Mechanical Ventilation in the Critically Ill Obese Patient

Antonio M. Esquinas Malcolm Lemyze Editors

123 Mechanical Ventilation in the Critically Ill Obese Patient Antonio M. Esquinas • Malcolm Lemyze Editors

Mechanical Ventilation in the Critically Ill Obese Patient Editors Antonio M. Esquinas Malcolm Lemyze Intensive Care and Non Invasive Department Respiratory and CC Medicine Ventilatory Unit Schaffner Hospital Hospital Morales Meseguer Lens Murcia France Spain

ISBN 978-3-319-49252-0 ISBN 978-3-319-49253-7 (eBook) https://doi.org/10.1007/978-3-319-49253-7

Library of Congress Control Number: 2017955688

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This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface

There is no doubt that obesity has become one of the leading public health threats worldwide. The number of obese subjects has doubled during the last 25 years to reach more than 600 million subjects in 2015. Considering the 100 million obese children in the world, obesity’s future is assured at least for the next generation. Of course, the continuously increasing incidence of the disease is problematic, but the new alarming phenomenon is the explosion of the cases of massively obese individuals. Indeed, the higher the severity of obesity according to body mass index, the higher the incidence of obesity-associated cardio-respiratory disorders and metabolic diseases. Obesity-induced chronic respiratory failure—commonly referred to as obesity hypoventilation syndrome—is encountered in more than half of the superobese patients with a BMI exceeding 50 kg·m−2. The management of these patients in the emergency setting is often challenging and raises specific problems that must be addressed and overcome at the bedside in a short time. At the interface between multiple health specialties, the obese patient usually requires a time- consuming multidisciplinary approach involving different stakeholders in respiratory care, cardiovascular diseases, endocrinology, surgery, anesthesiology, and also a necessary implication of the nursing staff. This book is intended to highlight the critically ill obese patient’s specificities that must be taken into account when mechanical ventilation is part of the therapeutic management of such a patient. Given the singularity of the massively obese critically ill patient, it can be assumed that an individualizing care approach is particularly adapted for this topic. Good knowledge of the respiratory physiology and cardio-respiratory interactions appears to be an essential prerequisite to the management of a critically ill obese patient, especially when oxygenation and mechanical ventilation are needed. The first part of the book is devoted to delivering insight into the basic understanding of the physiological characteristics of the respiratory system of the obese patient and their implications for mechanical ventilation. The second part deals with the comorbidities of the obese patient and the causes of acute respiratory failure that can impact on the outcome. The third part of the book includes chapters about preoxygenation, positioning, recruitment strategy, sedation and analgesia during invasive mechanical ventilation, and its associated complications. Another part is about noninvasive ventilation and the promising technique of high-flow oxygen via nasal cannula, which both have the potential to avoid the resort to invasive mechanical ventilation in many situations. Finally, nutritional support and outcome after mechanical

v vi Preface ventilation are two main issues that are developed in the last part. We are convinced that this book provides a useful didactic tool for an everyday practice of critical care medicine in obese patients with respiratory failure. Both editors are very grateful to all authors for their valuable contribution to the book. We are deeply aware of the time they spent in writing the chapters, making it possible to share their knowledge and expertise with the readers. We greatly appreciate having so many internationally recognized experts in the field of obesity and mechanical ventilation who accepted to participate in the writing of this book.

Lens, France Malcolm Lemyze, M.D. Murcia, Spain Antonio M. Esquinas, M.D., Ph.D. Contents

Part I Effects of Obesity on Respiratory Physiology

1 Control of Ventilation in Obesity �� 3 Nikolaos Markou, Heleni Stefanatou, and Maria Kanakaki 2 Obesity, Respiratory Mechanics and Its Impact on the Work of Breathing, Neural Respiratory Drive, Gas Exchange and the Development of Sleep-Disordered Breathing �� 15 Culadeeban Ratneswaran, Patrick Murphy, Nicholas Hart, and Joerg Steier 3 Implications of Obesity for Mechanical Ventilation �� 27 Paolo Formenti and John J. Marini

Part II Causes of Acute Respiratory Failure in the Obese Patient

4 Obesity and Comorbidities �� 43 Cintia Zappe Fiori, Denis Martinez, and Alicia Carissimi 5 Atelectasis �� 51 Sevinc Sarinc Ulasli 6 Obesity and Congestive Heart Failure �� 57 Stephan Steiner 7 Intra-abdominal Hypertension and Abdominal Compartment Syndrome: Consequences for Mechanical Ventilation �� 65 Peter D. Liebling and Behrouz Jafari 8 Impact of Sleep Breathing Disorders in Obese Critically Ill Patients �� 77 Moh’d Al-Halawani and Christine Won 9 Drugs and Medications �� 87 Clement Lee, Kate Millington, and Ari Manuel

vii viii Contents

Part III Invasive Mechanical Ventilation in the Critically Ill Obese Patient

10 Preoxygenation Before Intubation in the Critically Ill Obese Patient �� 99 Francesco Zarantonello, Carlo Ori, and Michele Carron 11 Analgesia in the Obese Patient �� 109 Preet Mohinder Singh and Adrian Alvarez 12 Sedation of the Obese Patient: Indications, Management, and Complications �� 123 Krysta Wolfe and John Kress 13 Positioning of the Critically Ill Obese Patient for Mechanical Ventilation �� 139 Malcolm Lemyze 14 Obesity and Positive End-Expiratory Pressure (PEEP)-Obesity and Recruitment Maneuvers During the Intraoperative Period �� 145 Seniyye Ulgen Zengin and Güniz Köksal 15 Complications Associated with Invasive Mechanical Ventilation in Obese Patients �� 151 Nishant Chauhan 16 Management of Ventilator-Induced Lung Injury �� 157 Sven Stieglitz 17 Ventilation Modes for Obese Patients Under Mechanical Ventilation �� 163 Rachel Jones, Jason Gittens, and Ari Manuel 18 Obesity and Tracheostomy: Indications, Timing, and Techniques �� 179 Bahman Saatian and Julie H. Lyou 19 Decannulation Process in the Tracheostomised Obese Patients �� 187 Pia Lebiedz, Martin Bachmann, and Stephan Braune

Part IV Noninvasive Ventilation and Oxygen Delivery in the Critically Ill Obese Patient

20 The Choice of Interface �� 193 Ahmed S. BaHammam, Tripat Singh, and Antonio M. Esquinas 21 The Choice of Ventilator and Ventilator Setting �� 199 Ebru Ortaç Ersoy 22 Obesity and Bi-level Positive Airway Pressure �� 205 Ayelet B. Hilewitz, Andrew L. Miller, and Bushra Mina Contents ix

23 High-Flow Nasal Cannula Therapy: Principles and Potential Use in Obese Patients �� 215 Emmanuel Besnier, Jean-Pierre Frat, and Christophe Girault 24 NIV in Type 2 (Hypercapnic) Acute Respiratory Failure �� 229 Shaden O. Qasrawi and Ahmed S. BaHammam 25 Prevention of Post-extubation Failure in Critically Ill Obese Patient �� 239 Ali A. El Solh 26 NIV in the Obese Patient After Surgery �� 251 Giuseppe Fiorentino, Antonio M. Esquinas, and Anna Annunziata 27 Determinants of NIV Success or Failure �� 259 Antonello Nicolini, Ines Maria Grazia Piroddi, Cornelius Barlascini, Gianluca Ferraioli, and Paolo Banfi 28 Chronic Ventilation in Obese Patients �� 265 Jean Christian Borel, Jean-Paul Janssens, Renaud Tamisier, Olivier Contal, Dan Adler, and Jean-Louis Pépin

Part V How to Support Nutritionally the Critically Ill Obese Patient

29 Nutritional Support in the Critically Ill Obese Ventilated Patient �� 281 Kasuen Mauldin and Janine W. Berta 30 Long-Term Outcomes After Mechanical Ventilation �� 287 Rose Franco and Rahul Nanchal

Index �� 307 Abbreviations

ABG Arterial blood gas AECOPD Acute exacerbation of chronic obstructive pulmonary disease AHI Apnea-hypopnea index AHRF Acute hypercapnic respiratory failure APACHE II Acute physiology and chronic health evaluation II ARF Acute respiratory failure ASPEN American Society for Parenteral and Enteral Nutrition ASV Adaptive servoventilation AVAPS Average volume-assured pressure support BMI Body mass index BNP Brain natriuretic peptide BPAP Bi-level positive airway pressure bpm Breath per minute CF Cystic fibrosis CHF Congestive heart failure CI Confidence interval CKD Chronic kidney disease

CO2 Carbon dioxide COPD Chronic obstructive pulmonary disease CPAP Continuous positive airway pressure CRF Chronic respiratory failure CSA Central sleep apnea CVEs Cardiovascular events DLCO Carbon monoxide diffusion capacity ECG Electrocardiogram EN Enteral nutrition EPAP Expiratory positive airway pressure ERV Expiratory reserve volume

ETO2 End-tidal oxygen concentration FAO2 Fraction of alveolar oxygen FEO2 Fraction of expired oxygen FEV1 Forced expiratory volume in 1 s FFM Full face mask

FiO2 Fraction of inspired oxygen

xi xii Abbreviations

FRC Functional residual capacity FVC Forced vital capacity HDU High dependency unit HF Heart failure HFNC High-flow nasal cannulae HFpEF Heart failure with preserved ejection fraction HFrEF Heart failure with reduced ejection fraction hsCRP High-sensitivity C-reactive protein IC Indirect calorimetry ICU Intensive care unit IMV Invasive mechanical ventilation IPAP Inspiratory positive airway pressure LVEF Left ventricular ejection fraction LVH Left ventricular hypertrophy MV Mechanical ventilation NIPPV Noninvasive positive pressure ventilation NIV Noninvasive ventilation NMD Neuromuscular diseases NPPV Noninvasive positive pressure ventilation OHS Obesity hypoventilation syndrome OR Operating room OSA Obstructive sleep apnea

PaCO2 Arterial partial pressure of carbon dioxide PACU Postanesthesia care unit PAD Peripheral artery disease

PaO2 Arterial partial pressure of oxygen PAP Positive airway pressure PE Pulmonary embolism PEEP Positive end-expiratory pressure PN Parenteral nutrition PSV Pressure support ventilation RCT Randomized controlled trials RM Recruitment maneuver RMs Recruitment maneuvers RR Risk ratio RV Residual volume SAP Safe apnea period SCCM Society of Critical Care Medicine

SpO2 Peripheral oxygen saturation SRBD Sleep-related breathing disorders TLC Total lung capacity TVB Tidal volume breathing VC Vital capacity VO2max Maximal oxygen consumption Vt Tidal volume VtPS Volume-targeted pressure support Part I Effects of Obesity on Respiratory Physiology Control of Ventilation in Obesity 1 Nikolaos Markou, Heleni Stefanatou, and Maria Kanakaki

1.1 Introduction

The literature on the control of ventilation in obesity suggests a fundamental dichot- omy: eucapnic subjects tend to maintain normal or augmented chemosensitivity, whereas hypercapnic subjects have a blunted chemosensitivity [1, 2]. Yet existing studies often pose methodological problems. Thus, they do not always take into account other factors which may also affect chemical control of breathing like gender or the coexistence of sleep-disordered breathing (SDB), which is very common in obese subjects. Furthermore, although most of these studies utilize rebreathing assessments of chemoreflex sensitivity, they do not always use the same rebreathing protocols. Additionally the output of the ventilatory center is not uniformly evaluated: some investigators measure minute ventilation (VE) alterations, while others evaluate neural drive more directly, in terms of alterations in mouth occlusion pressure (P0,1) or in diaphragmatic electromyogram activity (EMGdi). Finally, practi- cally all studies deal with chemical control of breathing only at the awake state, with very few data on chemosensitivity during sleep. In the rest of the chapter, we shall initially present data on the neural control of breathing at rest. Then we shall discuss data on the hypercapnic ventilatory response (HCVR) and the hypoxic ventilatory response (HOVR) in eucapnic and in hypercapnic obesity (obesity hypoventilation syndrome—OHS), with emphasis on studies accounting for the coexistence of obstructive sleep apnea (OSA). Finally we shall discuss the cause of alterations in the chemical control of breathing in OHS and the possible consequences of these alterations.

N. Markou, M.D. (*) • H. Stefanatou, M.D. ICU at Latseion Burn Center, General Hospital of Eleusis “Thriasion”, Athens, Greece e-mail: [email protected] M. Kanakaki, M.D. 1st University Clinic of Pulmonary Medicine, General Hospital of Diseases of the Chest “Sotiria”, Athens, Greece

© Springer International Publishing AG 2018 3 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_1 4 N. Markou et al.

1.2 Respiratory Neural Drive at Rest in Obesity

In otherwise healthy eucapnic obese adults, measurements of P0,1 and EMGdi suggest that respiratory neural drive at rest is increased compared to nonobese controls or to reference values [3–8]. Even in hypercapnic obesity, some limited data suggest that P0,1 at rest is not reduced and may even be increased relative to normal reference values [9, 10]. In eucapnic obesity, respiratory drive at rest seems to be closely related to indices of body weight [4, 7]. In a large cohort of 245 obese subjects with no obstructive or restrictive syndrome or neuromuscular impairment, P0,1 at rest was independently associated with severity of obesity (defined as percentage of body fat) and inversely associated with minimum oxygen saturation during sleep, total lung capacity, partial pressure of end-tidal CO2, and leptin levels [6]. In normal subjects, external elastic loading is known to augment neural drive by activating neural load-compensating mechanisms [11–13]. The increase of neural drive at rest in obesity seems to represent a similar compensatory mechanism in order to maintain an adequate minute ventilation in the face of increased mechanical loading due to weight gain [1, 2, 14]. From another viewpoint, an increased EMGdi in obesity might also indicate a reduced ventilatory reserve, that is, an inability in obese subjects to adequately augment their neural drive when needed, which might predispose to hypoventilation and hypercapnia in situations of increased work of breathing [7].

1.3 Chemical Control of Breathing in Eucapnic Obesity

In normal volunteers, the application of external elastic loading results in compensatory increases of neural drive responses to CO2 rebreathing and to exercise. The range of these neural adjustments may vary with load size and type of load—e.g., loading of the rib cage compartment might elicit more intense responses, than loading of the abdominal compartment [11–13, 15]. Similar compensatory mechanisms have been reported to be operative in eucapnic obesity as well [2, 16], and they probably contribute to the increased sensation of dyspnea often encountered in these subjects [17]. In spite of this neural adjustment, in obesity the final output in terms of minute ventilation response may remain unaffected or even decreased. Thus, Lopata et al. report that obese eucapnic subjects without OSA had an increased response of respiratory neural drive (evaluated as EMGdi) to CO2 rebreathing compared with normal controls, whereas the VE response was decreased. They conclude that compensatory adjustments in respiratory neural drive are not always adequate to completely overcome the increased mechanical load in obesity [3]. Eucapnic subjects with less preserved HCVR may be more prone to ventilatory compromise: Sampson et al. have observed an impairment of the VE response to

CO2 rebreathing in eucapnic massively obese patients who had previously suffered an episode of transient hypercapnia at the time of a respiratory insult, compared with carefully matched controls who had never been hypercapnic [4]. 1 Control of Ventilation in Obesity 5

Yet, perhaps because of methodological differences, not all studies on chemosensitivity in eucapnic obesity come to the same conclusions. A shortcoming of many of these studies is that they do not account for the frequent coexistence of obstructive sleep apnea (OSA) in obesity. Yet, OSA has also been associated with increased chemosensitivity [18–22]—although the literature again is not unanimous [23–27], with an increased gain of the central controller of breathing implicated in OSA pathogenesis [28–30]. In studies addressing the question of chemosensitivity in eucapnic obesity without taking into account the possible presence of sleep-disordered breathing (SDB), the HCVR has been reported to be normal [5, 31] or increased [4, 32, 33] or even gender-depended, with normal responses for males and increased responses for females [34]. An association has also been suggested between an increased HCVR in obesity and the percentage and distribution of body fat [32]. The HOVR has similarly been reported as normal [31] or increased [5, 32–34]. Before and after studies with weight loss after surgical treatment of obesity conclude that eucapnic obesity is associated with an augmented HCVR [17, 35]. Methodological problems are encountered in some of these studies, like a great imbalance as regards age and gender between obese subjects and normal controls [5] or the measurement of HCVR without a hyperoxic background mixture, which may have contributed to the finding of an augmented HCVR in another study [33].

1.4 Chemical Control of Breathing in Eucapnic Obesity Without OSA

Studies of eucapnic obese subjects in whom OSA had been rigorously excluded with polysomnography also provide somewhat conflicting data.

Thus, Lopata et al. [3] report a lower VE response to CO2 rebreathing compared with normal controls in spite of a normal or increased response in terms of mouth occlusion pressure and EMGdi. According to Narkiewicz et al., eucapnic obese subjects without OSA had a higher HCVR compared to normal controls matched for age and sex but a similar HOVR [36]. Buyse et al. on the other hand, compared the chemosensitivity of 138 healthy obese subjects without OSA (21 men and 117 women) of whom more than half had morbid obesity (BMI > 40), with reference values from their laboratory, and concluded that in obesity, chemosensitivity is affected by gender differences [37]. Obese women had an increased response of VE normalized for vital capacity and of P0,1 to hyperoxic hypercapnia and an even more increased response to hypoxia. HCVR and HOVR slopes correlated with BMI. On the contrary, obese men did not have an altered chemosensitivity. Women deemed to be menopausal in this study had lower HCVR and HOVR than women deemed to be premenopausal. Estrogen and progestin are known to augment respiratory drive [38], and an augmented chemosensitivity in obese women may be associated with increased estrogen production from fat tissue in the premenopausal period [37]. 6 N. Markou et al.

An interplay between weight increase and sex on chemosensitivity is further corroborated by the findings of Sin DD et al. in a large cohort of 219 patients (many of them obese) who underwent polysomnography under suspicion for OSA and in whom HCVR independently correlated with BMI in women and with age in men [39]. Finally, in a study of obese adolescents, it was found that after exclusion of OSA, obese subjects in the awake state had a higher VE response to CO2 than age-matched lean subjects but that this difference did not persist during sleep [40].

1.5 Chemical Control of Breathing in Eucapnic Obesity with OSA

Coexistence of OSA seems to blunt neural drive responses and to diminish the VE response to CO2 in the study of Lopata et al. [3]. A blunting effect of coexisting OSA on HCVR has also been confirmed by Gold et al. in eucapnic obese males, while HOVR was not affected by the coexistence of OSA [41]. On the other hand, in a case-control comparison of 21 men and 34 women with obesity and OSA matched 1:1 with obese subjects without OSA, on the basis of age, height, and BMI, coexistence of OSA resulted in a higher VE/VC and P0,1 response to hypoxia (but not hypercapnia) in women, while it did not affect chemosensitivity in obese men [37]. Finally, in obese adolescents, coexistence of OSA did not affect the HCVR in the awake state. Nevertheless, during sleep, obese subjects with OSA had blunted ventilatory responses to CO2 administration compared both to normal controls and to obese subjects without OSA, although the neural drive response was not evaluated [40]. The blunted response during sleep might conceivably result in prolonged respiratory events in these subjects (promoting nocturnal hypercapnia), while the enhanced response during wakefulness might lead to an inappropriately high ventilatory response upon arousal from apnea with concomitant ventilatory instability because of fluctuations in PaCO2 [40].

1.6 Chemical Control of Breathing in Hypercapnic Obesity (Obesity Hypoventilation Syndrome)

The simplest evidence for a defective central respiratory drive in OHS is that most of these patients are able to voluntarily hyperventilate to eucapnia, implying that impairments in respiratory system mechanics alone do not explain the hypoventilation [42]. This impression is further confirmed by several small studies that report a blunted HCVR in OHS compared to normal weight subjects [3, 43] or subjects with eucapnic obesity [44], at least in the absence of OSA [3]. Interestingly, Lopata et al. report that in eucapnic obesity coexisting with OSA, the HCVR is similarly blunted [3], but this finding has not been confirmed by Garay et al., who report a substantially higher HCVR in eucapnic obesity compared with OHS [23]. 1 Control of Ventilation in Obesity 7

Data on HOVR in OHS are fewer, but it seems that HOVR is also decreased compared with lean controls [43]. A trend for lower HOVR has also been observed in hypercapnic compared with eucapnic obese subjects with OSA [21], while in another study of OSA patients not necessarily obese, this difference in HOVR between hypercapnic and eucapnic subjects was significant [45]. This blunted chemosensitivity in OHS is not likely to be associated with genetic influences: HCVR and HOVR were similar between first-degree relatives of patients with OHS and controls matched for age and weight [46]. It should be noted that neither the decreased drive observed in hypercapnic OSA can be attributed to genetic influences [45]. The demonstration of increases in HCVR and HOVR as early as 2 weeks from initiation of treatment of OHS with continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NIPPV) [10, 46–48] constitutes additional evidence that blunting of chemosensitivity does not preexist but is a secondary effect of the syndrome, probably mediated by hypercapnia, which is similarly reversed with CPAP or NIPPV treatment. This improvement in HCVR is probably confined to subjects with substantially blunted chemosensitivity, in whom an increase of 47% has been reported after NIPPV [49]. Blunted HCVR has also been observed in patients with hypercapnic OSA (many of whom are obese and suffering in fact from OHS) compared with normal controls [19, 23] or with eucapnic OSA patients [45, 47, 48] and is similarly reversed— together with hypercapnia—by effective OSA treatment.

A weak but significant inverse association between HCVR and PaCO2 has been demonstrated in a large cohort of 219 patients who underwent polysomnography under suspicion of OSA, although only a few of them had severe obesity or hypercapnia [40]. Development of nocturnal hypercapnia is believed to be a critical factor toward the establishment of a blunted HCVR in obesity as well as in isolated OSA. Notably, the study of Chouri-Pontarollo N et al. confirms that in patients with OHS, the HCVR correlates moderately with the amount of nocturnal hypoventilation during REM sleep [49]. Obesity may promote nighttime hypercapnia by increasing metabolic rate and

CO2 production [50] while at the same time imposing increases in elastance and resistance of the respiratory system and perhaps impairing respiratory muscle function [1, 2]. During sleep these effects may promote nocturnal alveolar hypoventilation, more pronounced during REM sleep. Additionally, obesity often compromises upper airway patency causing OSA, which is in fact present in 90% of patients with OHS [1]. Most individuals with OSA can sufficiently hyperventilate after apneas to eliminate the accumulated CO2 and therefore can maintain overall eucapnia during sleep [51–53]. Yet in obesity, this interapnea elimination of CO2 can be impaired due to mass loading and reduced FRC, or because the ventilatory response to accumulated CO2 during sleep may be blunted [41, 52]. Once nocturnal hypercapnia develops, kidneys retain at night small amounts of bicarbonate to buffer the decrease in pH. This increase in serum bicarbonate is not always corrected before the next sleep period as the time constant of bicarbonate 8 N. Markou et al.

excretion is longer than that of CO2. The result will be a net gain of bicarbonate which will cause a secondary depression of central respiratory drive [53–55] and will promote further CO2 accumulation at night [51]. Thus a vicious circle begins, with more severe exposure to hypoxemia and hypercapnia and further attenuation of central drive, with a decreased HCVR during daytime and maintenance of the state of hypoventilation during the day as well [1, 2, 56]. A blunted HOVR may also contribute to daytime hypercapnia in obesity. Blunted HOVR may be caused by sleep desaturation in the settings of OSA or of alveolar hypoventilation during sleep: this nocturnal hypoxemia may lead to depression of HOVR, in way similar to that seen in high-altitude hypoxia [57]. Sustained hypoxia may also impair the arousal response to external resistive loading, and this may worsen sleep-associated airway occlusion [58]. Nocturnal hypoxemia in obese patients may thus further impair the compensatory hyperventilation between apneic events, contributing to nocturnal rise in CO2 [1]. There are some indirect indications of a poor correlation of central drive at the awake state with central drive during sleep [40, 51]. This might explain why some patients with OHS may still have normal HCVR. Regrettably data on respiratory drive during sleep are scarce in obesity [40] and nonexistent in OHS, and it remains unclear if what matters more is respiratory drive during wakefulness or during sleep. In addition to its contribution to the establishment and maintenance of OHS, an impaired chemosensitivity may be responsible for the worsening of hypercapnic acidosis observed in a randomized crossover study of patients with OHS after breathing an oxygen mixture with an FiO2 0,5 [59]. It has also been found that OHS patients with the lowest HCVR responses had a greater propensity for increased objective sleepiness, while they also demonstrated significant improvement in objective daytime sleepiness with NIPPV [49]. Respiratory stimulants (medroxyprogesterone, acetazolamide) have occasion- ally been used in the past in OHS in order to reverse CO2 retention [60–63]. Yet experience remains limited, and such drugs do not currently constitute a part of the mainstream approach in OHS, which remains based on application of CPAP or NIPPV during sleep.

1.7 The Role of Leptin in Alterations of Chemosensitivity in Obesity

Neurohormonal changes may also be implicated in alterations of chemosensitivity in obesity. In this context, the interplay between obesity, leptin, and ventilatory drive seems to play an important although not fully clarified role. Leptin is a satiety hormone produced by adipocytes that, in addition to reducing appetite and weight via receptors in the hypothalamus, increases ventilation in animal models by stimulating central respiratory centers after penetrating the blood- brain barrier [64]. 1 Control of Ventilation in Obesity 9

Leptin levels rise in proportion to body fat and obese subjects usually have high leptin levels, while hypoxia (in the context of OSA and OHS) also seems to exert an influence on leptin production 1[ , 2]. The association of leptin with chemosensitivity in humans is not absolutely clear. In mostly nonobese eucapnic OSA patients, both HCVR and leptin levels were higher than in matched healthy controls, and a significant correlation existed between HCVR and leptin levels [20]. Yet hypercapnic OSA patients, in spite of a significantly lower HCVR, had leptin levels similar to those found in eucapnic OSA [20]. High serum leptin concentrations have been associated with the presence of hypercapnia in obesity [65] and OSA [66]. In obese subjects leptin was a better predictor of hypercapnia than the degree of adiposity [65], while in OSA leptin was the only independent predictor of hypercapnia [66]. Furthermore, serum leptin levels are inversely associated with respiratory drive (P0,1) at rest in obese subjects [6]. In order to explain the paradox of a depressed ventilatory drive and hypercapnia in the presence of high leptin levels, it has been suggested that in some obese subjects, central resistance to ventilatory stimulatory effects of leptin may develop [2]. Leptin has to penetrate the blood-brain barrier in order to affect the respiratory center. The finding that obese individuals have leptin levels three times higher compared to lean controls while their leptin CSF/serum ratio is fourfold lower [67] suggests that such resistance may be the result of reduced leptin CSF penetration [1]. The observation that NIPPV use significantly reduces leptin levels [68] has led to the hypothesis that the improvement noted with positive pressure treatment in the central chemosensitivity of OHS patients [10, 47, 48] may be mediated through a reduced leptin resistance. Yet the hypothesis of leptin resistance is not uniformly supported by all studies. Redolfi et al. [69] found that leptin levels were considerably elevated in OHS patients compared with reference values but remained much lower than those observed in matched obese eucapnic controls. Several months after initiation of NIPPV, PaCO2 was normalized in these patients, HCVR was increased by 100%, and leptin levels were increased by 50%, although they still remained significantly lower than in eucapnic obesity. More study is therefore needed in order to clarify the exact role of leptin in the control of ventilation in obesity.

Conclusion Eucapnic obesity may be associated with an augmented chemosensitivity which represents a compensatory response to mass loading of the respiratory system. Yet, a small subset of obese subjects who develop daytime hypercapnia demonstrates a blunted respiratory drive. Although secondary to nocturnal hypoventilation and the subsequent development of daytime hypercapnia, this blunted chemosensitivity contributes to the establishment and maintenance of daytime hypercapnia. 10 N. Markou et al.

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Culadeeban Ratneswaran, Patrick Murphy, Nicholas Hart, and Joerg Steier

2.1 Respiratory Mechanics and Obesity

2.1.1 Background

Obesity reduces life expectancy and increases morbidity and mortality [1, 2]. It causes serious health risks including diabetes, cardiovascular disease and cancer [3]. Despite this, the worldwide prevalence of obesity has doubled since the 1980s [4]. Although there is extensive knowledge about the cardiovascular and metabolic risks of obesity, respiratory comorbidities of obesity are less well understood. The degree of obesity can be measured using the body mass index (BMI), often used due to its ease of use and correlation with adverse health outcomes. BMI, however, is not a good measure of body fat distribution. There is ongoing discussion whether indices of fat distribution may be better predictors of morbidity [5] and whether they are of greater relevance to the development of sleep-disordered breathing, but this has not been born out by prospective studies [6, 7].

2.1.2 Non-communicable Disease

According to the World Health Organization (WHO), non-communicable disease (NCD) contributes to the majority of mortality worldwide. NCD is commonly

C. Ratneswaran Lane Fox Unit, Guy’s & St Thomas’ NHS Foundation Trust, London, UK P. Murphy • N. Hart • J. Steier (*) Lane Fox Unit, Guy’s & St Thomas’ NHS Foundation Trust, London, UK King’s College London, Faculty of Life Sciences and Medicine, London, UK e-mail: [email protected]

© Springer International Publishing AG 2018 15 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_2 16 C. Ratneswaran et al. attributable to one of the following four factors: alcohol, tobacco, unhealthy diet and physical inactivity [8]. The trend to lead a more sedentary lifestyle with reduced metabolic needs, while energy intake increases, results in a general rise in body weight with age [9, 10]. The population most at risk of obesity-related ill health therefore tends to be middle-aged.

2.1.3 The Respiratory Muscle Pump

Effects of obesity can impact on the respiratory mechanics, as well as on neural respiratory drive. The respiratory muscle pump sums up all muscle groups that contribute to ventilation; it contains the diaphragm, chest wall muscles, neck and shoulder muscles and the abdominal muscles. Different parts of the respiratory muscle pump are active during inspiration, expiration, awake at rest, during exercise or while asleep. The most important muscle for inspiration is the diaphragm, which separates the thoracic from the abdominal cavity. It delivers the majority of the work of breathing in healthy individuals [11]. Due to its contribution to intrathoracic and intra-abdominal pressure swings while breathing, it impacts on various effects associated with ventilation. The diaphragm is made of three parts, the costal part, the crural part and a central tendon (Fig. 2.1).

Fig. 2.1 The human diaphragm (reproduced from Gray’s Anatomy, 20th US edition, originally published in 1918) 2 Obesity, Respiratory Physiology and Sleep-Disordered Breathing 17

Contraction of the diaphragm results in caudal movement of the dome-like structure in addition to expansion of the ribcage which is supported by other inspiratory muscle groups like the parasternal intercostal muscles, the scalenes and accessory muscle groups. The resulting negative intrathoracic pressure results in inspiratory airflow. In expiration, the diaphragm is largely relaxed and positive intra-abdominal pressures will push it back up into the thoracic cavity. Elevated intra-abdominal pressures in obesity significantly impact on the function of the diaphragm by increasing the load during inspiration and expiration (Fig. 2.2).

2.1.4 Gas Exchange in Obesity

Gas exchange is typically measured using the diffusing capacity of the lungs for carbon monoxide (DLCO). The DLCO is relatively well preserved in mild obesity [12–16], but the pattern in severe obesity is less well understood [16, 17]. However, intra-abdominal pressures in obesity impact on the diaphragm and the intrathoracic

Brain

Neural Obesity Sleep Respiratory OSA Drive OHS

EMG

Capacity Respiratory Load Muscles

Respiratory Failure ↓02, ↑CO2

Fig. 2.2 The load-capacity ratio of the respiratory muscle pump, simplified scheme. Multiple factors in obesity contribute to an increased load that leads to an elevated neural respiratory drive to recruit from the capacity of the respiratory muscle pump. If the elevated level of neural drive cannot be sustained (e.g., fatigue) or is influenced by other factors (e.g., sleep, drugs), an imbalance between load and capacity will develop and cause symptoms and respiratory failure when awake and sleep-disordered breathing when asleep 18 C. Ratneswaran et al. cavity, particularly in supine posture, and contribute to a ventilation-perfusion mismatch in the posterobasal compartments of the lung, and this mismatch contributes to the effect of alveolar hypoventilation.

2.1.5 Lung Volumes in Obesity

Lung volumes in obesity are either relatively normal or slightly reduced, indicating a restrictive ventilatory defect (Fig. 2.3). The forced expiratory volume in 1 s

(FEV1) is lower in obesity compared to nonobese subjects [19, 20], suggesting that in addition to an increased elastic load, obese subjects must overcome an increased airway resistance which is a consequence of the reduction in operational lung volumes (Figs. 2.4 and 2.5). The expiratory reserve volume (ERV) is low in morbidly obese subjects, and the functional residual capacity (FRC) is close to the residual volume (Fig. 2.3).

2.1.6 Respiratory Mechanics and Changes in Obesity

During normal inspiration, the diaphragm descends and the decrease in intrathoracic pressures initiates inspiratory airflow; in parallel, the diaphragm descent draws blood into the vena cava and the right side of the heart. During expiration, an increase in intrathoracic pressures leads to air being expelled from the lungs. While inspiration is generally an active process, expiration follows passively due to the elastic recoil of the chest compartment and positive intra-abdominal pressures, and, unless enforced, expiration does not require significant muscle activity in the normal subject at rest. In obesity, many factors related to the respiratory system change. Intra-abdominal pressures are high, particularly with visceral obesity, and this causes an increased preload on the diaphragm movement, specifically in supine posture. The abdominal pressures are transmitted to the thoracic cavity where they result in reduced transpulmonary pressures [18]. Due to the reduced pressure gradient, it is more likely that obese subjects breathe close to the residual volume (RV) with the functional residual capacity (Fig. 2.2) which leads to increased airway resistance due to the closing volume of the small airways [21]. This effect increases the work of breathing due to a low compliance [22] (Figs. 2.4 and 2.5). In supine posture, the work of breathing increases further [18, 23, 24], the intra-abdominal pressure impacts directly on the diaphragm, and an intrinsic positive end-expiratory pressure (PEEPi) develops [24, 25]. Neural respiratory drive increases to recruit force, but it can be offset by inflating the chest with continuous positive airway pressure (CPAP; Fig. 2.6) [24]. However, without noninvasive support, patients with obesity are prone to develop a restrictive spirometry. With sleep onset, neural respiratory drive falls and the required minute ventilation is no longer maintained, which results in hypoventilation and the development of hypercapnia. 2 Obesity, Respiratory Physiology and Sleep-Disordered Breathing 19

a TLC 6 Non-obese 6 Obese

IRV TLC

IRV

3 V1 3

ERV V1

Lung Volume (L) Lung Volume (L) ERV RV RV 0 0 seated supine seated supine

100 TLC 100

TLC 80 80

Non-obese IRV Obese

60 60 IRV

V1 olume (%predTLC) olume (%predTLC)

V 40 V 40 V1

Lung ERV Lung ERV

20 20

RV RV 0 0 seated supine seated supine

Fig. 2.3 Simplified schematic illustration of lung volumes seated and supine in normal and obese subjects, expressed as litres (upper panel) and per cent predicted TLC (lower panel). TLC total lung capacity, IRV inspiratory reserve volume, Vt tidal volume, ERV expiratory reserve volume, RV residual volume. With friendly permission from Thorax [18] 20 C. Ratneswaran et al.

PV seated, N9 + O1 140

120

100

60 Volume (%predTLC)

-40 -30 -20 -10010 20 30 40 50

Transpulmonary Pressure (cmH20)

Fig. 2.4 Pressure–volume (PV) curves seated of a normal (N9, male, 66 years, 1.72 m, body mass index (BMI) 23.3 kg/m2; filled circles) and matched obese (01, male, 60 years, 1.73 m, BMI 34.4 kg/m2; open circles) subject. Functional residual capacity (FRC) levels and dynamic compliance are indicated by bold grey bars. The PV curve in the obese is restricted in lung volume and diminished in slope, the FRC is low. Despite the differences in the slope of the static PV curves, the dynamic compliance, illustrated by the diagonal grey bars, is not substantially different between the obese and normal subject. With friendly permission from Thorax [18]

PV supine, N9 + O1 140

120

100

60 Volume (%predTLC) 20

0 -40 -30 -20 -10 01020304050

Transpulmonary Pressure (cmH20)

Fig. 2.5 Pressure–volume curves supine of a normal (N9, filled circles) and matched obese (01, open circles) subject. Compared with the seated posture, the slope of the curves is diminished, in the obese functional residual capacity approximates residual volume. Dynamic compliance is lower than when seated and more different between obese and normal subject. With friendly permission from Thorax [18] 2 Obesity, Respiratory Physiology and Sleep-Disordered Breathing 21

Sitting Supine Supine+CPAP EMGdi channel 5 EMGdi channel 5 EMGdi channel 5 400 µV O

2 Poes 3 Poes 2 Poes 1 20 cm H O 2

Pgas Pgas Pgas 0 cm H O2 2 Pdi Pdi Pdi 20 cm H O

2 Pmask Flow

40 I/min Flow 2 cm H

10 s10 s10 s

Fig. 2.6 Resting breathing in an obese subject (body mass index 42 kg/m2, neck circumference 43 cm) when seated (left), supine without CPAP (middle) and with CPAP (right). The change in end-expiratory oesophageal baseline pressure is reflected by thehorizontal dotted lines (nos 1–3).

There is PEEPi of approximately 6 cm H2O (vertical lines indicate the start of inspiratory flow, difference between horizontal dotted lines 2 and 4 = PEEPi). Zero flow is indicated by the horizontal line. The right panel shows the same patient supine breathing with CPAP of 6 cm H2O (full facemask). Neural respiratory drive to the diaphragm increases when changing posture from sitting to supine and decreases with CPAP; PEEPi is offset with CPAP and pressure swings of Poes and Pdi are smaller. Note that on the lower right trace we do not measure flow but mask pressure because flow is predominantly inspiratory when receiving CPAP. The inspiratory deflection in mask pressure was chosen instead of flow to mark the beginning of inspiration (vertical line). CPAP continuous positive airway pressure, EMGdi electromyogram of the diagram (channel 5 records the biggest EMG signal; Poes oesophageal pressure, Pgas gastric pressure; Pdi transdiaphragmatic pressure (Pdi = Pgas − Poes); PEEPi, intrinsic positive end-expiratory pressure; EMGdi in μV, all pressures in cm H2O, flow in l/min. With friendly permission from Thorax 24[ ]

2.2 Sleep-Disordered Breathing

2.2.1 Fat Distribution

Sleep-disordered breathing relates to abnormal breathing when asleep; the most common types of abnormal breathing during sleep in obesity are obstructive sleep apnoea (OSA), obesity hypoventilation syndrome (OHS) and an overlap syndrome (OSA/OHS). Neck circumference is a predictor of OSA which suggests that upper 22 C. Ratneswaran et al. body or central obesity contributes more to its pathogenesis than general weight gain [26]. Upper body obesity is thought to have a greater cardiovascular and metabolic risk than lower body obesity, and central obesity has a greater impact on spirometric results compared to the subcutaneous deposition of adipose tissue [27].

2.2.2 The Relationship of Weight Gain and Obesity with Poor Sleep

Obesity is directly related to poor sleep quality, through the development of diseases including obstructive sleep apnoea (OSA) and obesity hypoventilation syndrome (OHS). Weight gain is also known to cause poor sleep independent of other underlying conditions [28, 29]. Furthermore, poor sleep quality and reduced sleep quantity have been found to lead to weight gain, hence perpetuating a vicious cycle of poor sleep and obesity. Chronic sleep deprivation and the associated daytime sleepiness lead to reduced levels of exercise, and sleep deprivation is known to increase appetite and produce hyperphagia [30, 31]. These changes occur due to complex hormonal regulation including cortisol, an increased level of ghrelin and altered levels of leptin [30, 32]. Poor sleep quality and quantity have also been suggested to reduce energy expenditure due to abnormal thermoregulation and energy expenditure [33]. Adipose tissue is the largest endocrine organ, and it secretes leptin. Leptin par- ticipates in a number of metabolic pathways. It directly affects neuroendocrine functioning, and energy intake, via specific receptors in the hypothalamus, with one of its main roles being the reduction of appetite. Leptin levels increase exponentially with increasing levels of fat mass. However, obese individuals are thought to develop a ‘leptin resistance’ due to permanently increased levels of leptin [34], and obese patients with OSA have significantly higher levels of leptin than those without, independent of body fat [35]. These hormonal changes, in addition to changing the societal sleep pattern, perpetuate a cycle whereby poor sleep and weight gain are intrinsically related. The weight gain can lead to altered respiratory mechanics and, eventually, the development of sleep-disordered breathing.

2.2.3 Obstructive Sleep Apnoea

Obesity is a significant risk factor in the pathogenesis of OSA [26, 36]. OSA is a syndrome in which recurrent collapse of the upper airway leads to apnoeas and hypopnoeas during sleep [37]. Besides upper airway collapsibility, mechanical changes related to the respiratory muscle pump during obstructive respiratory events include increasing pleural pressure swings [38], decreased transpulmonary pressures [18], reductions in expiratory reserve volumes [18] and functional residual capacity [39] and decreased compliance [24, 40] compared to healthy individuals [25, 41]. Additionally, expiratory flow limitation and an intrinsic PEEP have been described [24, 25]. Most of these limitations are successfully counterbalanced by continuous positive airway pressure (CPAP; Fig. 2.6). 2 Obesity, Respiratory Physiology and Sleep-Disordered Breathing 23

2.2.4 Obesity Hypoventilation Syndrome

Obesity hypoventilation syndrome (OHS) [42] was historically known as the ‘Pickwickian’ syndrome after Charles Dicken’s stories that described the features in the character of fat boy ‘Joe’. These patients have a propensity towards a blunted neural respiratory drive which results in hypercapnia and hypoxia, whilst awake and more markedly during sleep. Obese patients tend to develop this condition as a consequence of the imposed mechanical limitations on their respiratory requirements secondary to the high intra-abdominal pressures caused by adipose tissue deposition. Problems caused by OHS are directly related to an increased body habitus, and weight loss can potentially reverse this condition. To improve the hypercapnic respiratory failure, patients benefit from noninvasive ventilatory support, typically offered at night. OHS has some clinical features of OSA, and many of these patients tend to have an overlap syndrome (OSA/OHS). With increasing prevalence of obesity, particularly morbid obesity, screening for sleep-disordered breathing becomes important. The majority of patients with morbid obesity have at least a mild degree of sleep-disordered breathing [43], while around a quarter of pre-bariatric patients who score >4 points on the STOP-BANG questionnaire [44] require CPAP therapy [45]. A restrictive spirometry (FVC <3.5 L in men and <2.3 L in women) and reduced daytime oxygenation (SpO2 <95% in men and <93% in women) can also be useful markers to indicate patients with features of nocturnal hypercapnia [46].

2.3 Summary

The load on the respiratory muscles in obesity is high, and this leads to an increased work of breathing and elevated levels of neural respiratory drive. High intra- abdominal pressures become more relevant with supine posture; they cause an intrinsic PEEP in morbidly obese subjects and impose an inspiratory preload on the diaphragm. Increased airway resistance due to the low operational volumes increases the work of breathing further and impacts on the compliance of the respiratory system. Lastly, the reduced transpulmonary pressures lead to a more restrictive lung function in obesity. Sleep-disordered breathing in obesity develops due to upper airway collapse (OSA) or hypoventilation (OHS) which is more likely with the increased load in obesity. With increasing neck circumference, the upper airway is more likely to collapse when asleep, and this explains the high prevalence of OSA in obesity. The impact of obesity on the intrathoracic compartment requires elevated levels of neural respiratory drive which are not maintained when falling asleep; the subsequent loss of the neuromuscular tone of the respiratory muscles leads to hypoventilation. The blood gas analysis and restrictive lung function parameters indicate the imbalance between load and capacity of the respiratory system and determine the likelihood of sleep-disordered breathing. Acknowledging pathophysiological changes is important in the context of screening for sleep-disordered breathing in this cohort. 24 C. Ratneswaran et al.

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Paolo Formenti and John J. Marini

3.1 Introduction

Recent data from the United States and Europe indicate that approximately one third of adult men and women are overweight, with body mass index (BMI) values exceeding 25. Results from studies that focused attention on the risks associated with overweight have reported conflicting results 1[ –4]. Improved medical management of obesity-related chronic diseases or differences between the US general population and populations in other studies may account for the findings of some reports that overweight was not associated with an excess risk of death [5]. However, a large prospective study reported that obesity was strongly associated with mortality risk and suggested that even moderate elevations in BMI portend an increased mortality risk [6]. Despite these conflicts, it is clear that obesity has potential to directly affect respiratory mechanics, since it increases oxygen consumption and carbon dioxide production while at the same time stiffens the chest wall, compresses the lungs, and increases the work of breathing. Adipose tissue around the rib cage and abdomen inhibits chest wall expansion and reduces functional residual capacity (FRC). For this and other reasons that we examine in the present chapter, ventilator settings should be adjusted to minimize potentially adverse consequences of obesity.

P. Formenti SC Anestesia e Terapia Intensiva, Università degli studi di Milano, Milan, Italy J.J. Marini (*) University of Minnesota, Minneapolis, MN, USA e-mail: [email protected]

© Springer International Publishing AG 2018 27 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_3 28 P. Formenti and J.J. Marini

3.2 Anatomic and Physiologic Considerations in Obesity (Fig. 3.1)

3.2.1 Non-pulmonary-Associated Alterations

Both excess adipose tissue and its distribution are considered obesity-associated risk factors for cardiovascular respiratory disease [7]. Centralized deposits of adipose tissue are metabolically more active than fat distributed in the periphery and are more highly associated with metabolic complications such as dyslipidemia, glucose intolerance, and diabetes mellitus [8]. Morbidly obese patients with a high proportion of visceral fat are also at greater risk from cardiovascular disease, left ventricular dysfunction, and stroke [9]. The exact mechanism for this increased attributable risk is not known, but recent studies focused on hormonal changes, inflammation, and circulatory impairment may help explain the correlation 10[ ]. Elevated body mass index seems to be associated with a deregulation of leptin and adiponectin secretion, two hormones that influence inflammation and oxidative stress regulation [11]. In fact, some experimental and clinical studies showed how these hormones are involved in the activation of macrophages, leukotriene synthesis, and inflammatory cytokine expression that increase airway responsiveness and smooth muscle activation of the vessels [12, 13], affecting both the right heart mass and volume and the pulmonary arteries [14]. Other obesity-related physiological

Small mouth opening Low FRC Short thyromental distance Increased intrapulmonary shunt Increased neck Decreased chest wall and lung circumference compliances Decreased neck motility Increased airway resistance Large breasts and tongue

Increased mechanical pressure increased metabolic demands simultaneously increase the work of breathing

Increased intrabdominal pressure Reduced diaphragmatic excursion Reduced chest wall compliance

Normal subject Obese subject

Fig. 3.1 (a) Anatomic challenges of obesity for ventilatory support. (b) Consequences of obesity for lung mechanics during passive ventilation 3 Implications of Obesity for Mechanical Ventilation 29 disturbances include menstrual disorders, irregular bleeding, and amenorrhea. Some studies demonstrate that obesity is associated with osteoarthritis, even if the central role of excess body weight in causing of this condition remains unconfirmed 15[ ]. Increased triglyceride stores are associated with a linear increase in the production of cholesterol. In turn, greater cholesterol production is associated with increased cholesterol secretion in bile and the development of gall bladder disease. Increased levels of circulating triacylglycerides in obesity are associated with decreased concentrations of high-density lipoprotein (HDL) cholesterol with the attendant predis- position to cardiovascular disease. Enhanced insulin resistance and increased insulin demand may promote diabetes mellitus, sodium retention, and hypertension [16].

3.2.2 Pulmonary Consequences of Obesity

Increased abdominal volume, intrathoracic fat, and obesity-associated chronic heart disease affect both lung volumes and gas exchange.

3.2.2.1 Upper Airway Anatomy Deposition of adipose tissue in the pharyngeal walls narrows the air passage, encourages upper airway collapse during spontaneous ventilation [17], and imposes difficulty in accomplishing mask ventilation and/or endotracheal intubation. Physical signs portending difficult mask ventilation or intubation include small mouth opening, short thyromental distance, increased neck circumference, decreased neck motility, and large breasts and tongue. For such patients optimal positioning is important, and advanced airway devices (such as fiberoptic bronchoscope, glidescope, and laryngeal mask) should be available to facilitate securing the airway. Availability of bronchial blockers and tube exchangers may help in cases of difficult single-lumen tube placement [18].

3.2.2.2 Lung Volume Morbid obesity is associated with reduced end-expiratory lung volumes (EELV) in mechanically ventilated patients, as FRC declines exponentially with increasing BMI. A low FRC, paired with increased intrapulmonary shunt, decreased chest wall and lung compliances, increased airway resistance, and atelectasis, predisposes the obese patient to rapid desaturation upon induction of anesthesia [19]. Abnormal upper airway anatomy aggravates the difficulty of effective mask ventilation and safe intubation, especially in the presence of OSA [20]. The supine position further decreases FRC, due to cephalad displacement of the diaphragm, airway closure in recumbency, and positional increase of pulmonary blood volume. Lung as well as chest wall compliances are decreased when supine, encouraging ventilation/perfusion mismatching [8].

3.2.2.3 Gas Exchange Oxygen consumption and carbon dioxide production tend to increase in the obese as a result of the metabolic activity of the excess fat and the increased energy 30 P. Formenti and J.J. Marini consumption of weight supporting skeletal muscle [21]. Moreover, normocapnia is usually maintained by increasing minute ventilation, a breathing burden that adds to the increased oxygen demand. Some patients, however, develop obesity hypoventilation syndrome (OHS), defined as chronic hypoventilation in the absence of lung, chest wall, and neurological disease [22]. In these, hypoventilation and apnea originate centrally due to progressive desensitization to hypercapnia, which leads to an increased dependence on the hypoxic drive to maintain respiration [23]. Even when impairment of oxygen exchange due to CO2 buildup is modest, relatively low perfusion of tissues due to inadequate blood flow per cell alters the oxidative response [24], perhaps contributing to the propensity of such patients to develop infection and atelectasis during their hospital stays [25].

3.2.2.4 Lung Elastance and Resistance Increased fat in the thorax and abdomen is associated with an exponential decline in respiratory compliance, which in some cases can fall to around 35% of predicted normal [26], especially when small tidal breaths are taken in the supine position [27]. Although accumulation of fat tissue in and around the chest wall leads to a modest increment in chest wall elastance, recent work suggests that the increment in total elastance is principally a consequence of an increased lung elastance [28]. Obesity is also associated with an increase in total respiratory resistance [29] indicating that the number and/or caliber of functioning airways is reduced throughout the tidal breathing cycle. However, although asthma and aspiration occur more commonly in the very obese, specific airway resistance (calculated by adjusting for the lung volume at which the measurements are made) generally remains within the normal range [30]. Thus, the apparent reduction in airway caliber in the obese might be attributable to the reduction in lung volumes rather than to airway obstruction [26]. It is also possible that airway structures could be remodeled by exposure to pro-inflammatory adipokines, or damaged by the continual opening and closing of small airways during the breathing cycle [31]. For the same minute ventilation, these derangements of lung elastance and resistance result in a relatively shallow and rapid breathing pattern, an increase in the work of breathing and a limitation of the maximum ventilatory capacity. In severe cases, breathing at low lung volume places the tidal flow volume loop into a region where it may encroach on the maximal flow-volume envelope, increasing the possibility of expiratory flow limitation during tidal breathing.

3.2.2.5 Respiratory Efficiency and Work of Breathing Increased mechanical pressure from the abdomen, increments in pulmonary elastance and resistance, and increased metabolic demands simultaneously burden the respiratory pump and increase the work of breathing. In normocapnic obese individuals at rest, this may be reflected in a modest 30% increase in the workload, but respiratory muscle inefficiency may limit the maximum ventilatory capacity and lead to relative hypoventilation at times of high metabolic activity [32]. In the obese individual with established daytime hypoventilation syndrome, work of breathing may approach four times than predicted. 3 Implications of Obesity for Mechanical Ventilation 31

Because an obese individual’s respiratory muscles must work constantly against a less compliant chest wall and higher airway resistance, it would be expected that they could generate normal or even increased pressures. An early study [33] examined the maximum inspiratory and expiratory pressures at different lung volumes in morbidly obese compared with nonobese patients. At all lung volumes, the pressures generated by obese patients were lower than those of the nonobese patients, despite chronically heightened demands for diaphragmatic work. This deficiency may result from diaphragm dysfunction due to increased abdominal and visceral deposits of adipose tissue. It has been suggested that the additional load causes a length-tension disadvantage for the diaphragm due to muscle fiber overstretching, which is accentuated while the individual is supine [34].

3.3 Mechanical Ventilation of the Obese Patient

The respiratory and non-respiratory changes described above require special attention during the management of obese individuals receiving ventilatory support, especially during deep sedation or anesthesia (Table 3.1). A key objective is to keep the lung open during the entire respiratory cycle.

Table 3.1 Special aspects of Body position ventilating the obese patient • Avoid the customary <30 ° recumbent posture • Upright • Beach Chair • Prone • Lateral • Reverse Trendelenburg During ventilation • Higher PEEP • Recruiting maneuvers • Minimize sedation

• Maintain patient’s baseline PaCO2 and pH Monitor • Mental alertness

• PECO2 • Oxygenation • Cautiously interpret –– Plateau pressure –– Driving pressure –– Stress index • Selected patients –– Transpulmonary pressure –– Bladder pressure Liberal post-extubation use of BiPAP 32 P. Formenti and J.J. Marini

3.3.1 Airway Management

Obesity significantly increases the complexity of airway management procedures. Patients with obesity present high risk for aspiration due to elevated intra-abdominal pressure and large gastric volume. A large neck with limited mobility, decreased mouth opening, big tongue, and short sternomental distance can pose serious challenges during endotracheal intubation attempts [35]. Any factor that contributes to difficult viewing of the airway opening increases the possibility of complications. Positioning the obese patient for intubation also presents unique challenges when compared to those of lower body weight. In patients of normal weight, intubation typically is performed while the patient is horizontal. However, in obese patients decreased functional residual capacity, increased airway resistance, and propensity for compressive airway closure often lead rapidly to hypoxemia in the supine, fully recumbent position. Various compensatory techniques, including CPAP and high- flow oxygen, may be employed to avoid desaturation during intubation attempts 36[ ]. Equipment selection must be carefully considered prior to airway procedures. Other than routine laryngoscope blades and endotracheal tubes, rapidly accessible equipment should include laryngeal mask airways, flexible bronchoscopes, and an emergency cricoidotomy kit. In addition, considerable operator strength may be required to open, maintain, and properly secure the airway of an extremely obese patient.

3.3.2 Ventilatory Support

Selected special aspects of ventilating the massively obese patient are highlighted in Table 3.1. Even more than in other patients in need of assistance for respiratory insufficiency or failure, care should be taken in these vulnerable patients to avoid injury to the lung parenchyma during ventilation. Advances in the understanding of the mechanisms of ventilator-induced lung injury from animal studies and randomized controlled trials in patients with uninjured lungs in intensive care unit and operation room have pushed anesthesiologists to consider lung-protective strategies during intraoperative ventilation [37]. Doing so has been linked to better outcomes in the postoperative period. There is general agreement that such approaches to lung protection should include the use of relatively low tidal volume. Whereas higher PEEP may not be universally helpful in patients of normal body mass, moderate PEEP may prevent intra- and perioperative atelectasis and attendant pulmonary complications in the obese. Protective effects, however, are currently ascribed more to low VT than to PEEP. In fact, the use of relatively high PEEP does not seem to protect against postoperative pulmonary complications in nonobese patients undergoing open abdominal surgery [38]. Furthermore, the role of driving pressure for titrating ventilation settings in patients with uninjured lungs remains to be carefully investigated, and virtually no data are available regarding driving pressures in the massively obese. A lung-protective strategy designed to minimize alveolar overdistention has been reported to decrease mortality by 20% compared with a traditional ventilator 3 Implications of Obesity for Mechanical Ventilation 33 strategy [39]. However, the commonly applied plateau pressure (Pplat) limit of

30 cmH2O may prove inadequate to accomplish adequate gas exchange in morbidly obese patients because of the increased elastance of the chest wall and altered lung volumes. Numeric guidelines for safe airway pressure in such patients may be misleading with regard to safe and effective ventilation, as the effects of obesity on the chest wall must be separated from those attributable to increased lung elastance. When selecting mechanical ventilator settings for obese patients, important physiological factors are critical to consider. Thus, under conditions of no flow that char- acterize the extremes of the tidal cycle, the pressure difference between airway opening and pleural space (transpulmonary pressure, Ptp) is the distending pressure across the lung. The Ptp is measurement useful in assessing the risk of ventilator- induced lung injury [40]. Impressive increases in airway pressure may be observed despite acceptable lung stresses and low injury potential because the excursions of pleural pressure are unusually high [41]. Pleural pressure approximated by the use of an esophageal balloon may help in PEEP selection and in determining the actual peak and driving pressures applied to the lung, especially during spontaneous breathing efforts [42]. A challenge at the bedside is that pleural pressure is not routinely measured, and therefore transpulmonary pressure is not known in most cases. Clinicians who rely on airway pressures alone must estimate what pleural pressures are in any given patient, and this limitation may lead to suboptimal ventilator management. In sample populations of patients with ALI/ARDS, one landmark randomized controlled trial has shown a net reduction in mortality risk across the studied population with the use of 6 mL/kg tidal volume compared with 12 mL/kg [43]. In supporting patients with obesity, it is especially important that tidal volume be calculated on the predicted body weight, rather than on the measured value so as to avoid the application of hazardous tidal volumes and resulting plateau and driving pressures. (Predicted body weight is based on height and gender, and the rationale for using it is that when a patient gains weight, the lung does not change in size.) Even when selection of tidal volume is appropriately based on predicted weight, regional over distension may occur. With changes in the impedance to ventilation, pressure-targeted modes may result unpredictably in inappropriately low tidal volumes in the massively obese. Conversely, pressure-targeted modes allow marked increases in tidal volume and transpulmonary driving pressures during vigorous spontaneous efforts. Such patients can generate large and potentially damaging Ptp that may not be obvious to the clinician focused on airway pressure alone.

3.3.2.1 Importance of Monitoring Respiratory Mechanics and Gas Exchange

High baseline values of PaCO2, a tendency to develop dependent atelectasis, and stiffness of the chest wall require that the clinician monitor gas exchange and mechanics carefully. Alterations in respiratory impedance caused by changes of body position or retention of airway secretions, for example, may have pronounced effects on the adequacy of ventilation. Apart from pulse 34 P. Formenti and J.J. Marini oximetry, capnography of the exhaled airstream may give early clues to developing hypercapnia and end-expiratory airway closure [44]. Close monitoring of mental status is also advisable during noninvasive ventilation and throughout the immediate pre- and post-extubation periods to forewarn against

progressive CO2 retention. Whether using a volume- or pressure-based approach to invasive mechanical ventilation, estimated lung stress should be considered and attempts made to moderate it in all patients with ALI/ARDS so as to avoid worsening of lung injury or retarding of healing. This mandate is particularly important to observe in obese patients who require elevated mechanical ventilation pressure settings. Interestingly, prone positioning tends to improve FRC and oxygenation in obese patients, just as it does in those with normal body habitus [45]. On the other hand, allowing PaCO2 to increase (“permissive hypercapnia”), a consequence of reduced driving pressures [46], may not be tolerated well by obese patients, many of whom already have elevated levels of arterial CO2 at baseline.

3.3.2.2 PEEP Setting PEEP functions to increase lung recruitment and prevent unstable lung units from collapsing in patients who are mechanically ventilated for ARDS. The level of PEEP required to achieve these benefits, however, is influenced by the properties both of the lung and of the chest wall 46[47]. Because chest wall elastance may be profoundly increased in morbid obesity, such characteristics increase the intrapleural pressure and decrease the Ptp resulting from any given airway pressure. Thus, the level of PEEP needed to support equivalent oxygenation may be higher in morbidly obese patients than in patients with normal BMI. A study finding that conventional levels of PEEP superimposed on high tidal volumes did not improve intraoperative arterial oxygenation of morbidly obese patients might support this concept [48]. Ineffectiveness of PEEP, however, may also be secondary to redistribution of blood flow to poorly or non-ventilated regions, resulting in increased venous admixture and intrapulmonary shunt, even in patients who have no intrinsic lung disease. Higher levels of PEEP may be more beneficial in obese patients with ALI/ARDS who receive lung-protective, low tidal volume ventilation [49]. Respiratory system mechanics have been studied in spontaneously breathing obese patients and in those who were paralyzed and/or deeply sedated during the postoperative period. Obese patients exhibit reduced EELV, increased lung elastance, and increased chest wall impedance [50]. FRC values in morbidly obese patients are often below closing volume, especially while in the supine position. This can result in sustained lung unit closure and/or expiratory gas trapping in the dependent lung zones, worsening hypoxemia [51]. Wang and colleagues [48] recently conducted a network meta-analysis with the intention to identify the optimal mechanical ventilation strategy for obese patients. The results of this meta- analysis show that using VCV associated with higher PEEP and single RM was superior to other strategies in improving oxygenation, intraoperative pulmonary compliance, and atelectasis in obese patients under anesthesia, whereas an alternative strategy (i.e., pressure-controlled ventilation with lower PEEP) was less effective. 3 Implications of Obesity for Mechanical Ventilation 35

3.3.2.3 Effects of Body Positioning In the supine obese patient, the cranial displacement of the diaphragm and the gravitational effect of the abdominal contents upon the diaphragm and the thoracic cavity reduce lung volumes [52, 53]. The use of paralytic agents and the subsequent decrease in diaphragmatic muscle tone further enhance the atelectasis induced by the abdominal contents. Morbidly obese patients (BMI 42 ± 5 kg/m2) undergoing laparoscopic gastric banding have a lower lung elastance and a greater end-expiratory lung volume (EELV) when in the beach chair position compared to supine position [54]. Lemyze and colleagues observed in critically ill mechanically ventilated obese patients (BMI 48.4 (95% confidence interval, 45–51.2) kg/m2) that the sitting position significantly diminishes expiratory flow limitation and leads to a significant drop in auto-PEEP compared to supine positioning [52]. In a study, prone positioning compared to supine positioning leads to an increase in FRC, an increase in lung compliance, and improved oxygenation in mechanically ventilated obese patients undergoing elective surgery in the prone position [45]. This increase in lung volume observed in the prone position might be most indicative of the influence upon the lungs of the mediastinal contents during supine positioning. The improvement of oxygenation is also a result of a more uniform distribution of pulmonary perfusion in the prone position that has been seen in studies with healthy nonobese volunteers [55, 56].

3.3.3 Extubation and Weaning Period

Certain postoperative complications (specifically, surgical site infection and atelectasis) occur more frequently among the obese population. Increased intra-abdominal pressure and venous stasis help explain the link between perioperative deep venous thrombosis, pulmonary embolism, and obesity. As expected, surgical procedures that involve prolonged immobility are associated with greater risk. Abdominal and thoracic operations pose significant risks to obese patients; atelectasis has been found in up to 45% of obese patients following upper abdominal surgery [57]. Early mobilization should be prioritized in obese patients to reduce the risk of pulmonary dysfunction as well as veno-thrombosis [58]. The relatively prolonged duration of mechanical ventilation and higher oxygen requirements of obese patients reflect their numerous physiologic alterations of pulmonary function [8]. Studies of respiratory function have uniformly shown reduced functional residual capacity due primarily to the cephalad intrusion of abdominal contents in the peri-diaphragmatic lung zones, particularly in the recumbent postures [32]. Liberation from mechanical ventilation also tends to be delayed in morbidly obese patients, due to increased work of breathing resulting from increased airway resistance, abnormal chest elasticity, and inefficiency of the respiratory muscles. It has been suggested that the reverse Trendelenburg positions at > = 45° can facilitate the weaning process by facilitating larger tidal volumes and lower respiratory rates. The beach chair position—a positioning angle of >60 ° from horizontal—has been demonstrated to improve gas exchange as it minimizes the gas trapping during tidal closure of dependent airways that otherwise is in evidence in other recumbent postures [51, 52, 58]. 36 P. Formenti and J.J. Marini

3.3.4 Indications for Tracheotomy

Critically ill morbidly obese patients are more likely to be intubated, to remain intubated, to stay in the ICU longer, and to encounter higher risk for in-hospital death when compared with their nonobese counterparts [59, 60]. Patients with obesity tend to require more sedation and store sedative medications that impede recovery of alertness once the full support period has ended. Strong consideration should be given to noninvasive ventilation in the period immediately following airway extubation so as to counter their heightened tendencies for OSA and CO2 retention. For reasons already given, maintaining an upright position is also helpful. As with patients with normal body habitus, the obese often require tracheotomy for prolonged mechanical ventilation. Some morbidly obese patients require tracheotomy to counter OHS and OSA, as well. The optimal timing of tracheotomy and its impact on weaning from mechanical ventilation in critically ill, morbidly obese patients remain controversial. Results from a retrospective study suggest that tracheotomy performed in morbidly obese subjects within the first 9 days may reduce the duration of MV but may not affect hospital mortality [59]. Although it can be safely performed when appropriate precautions are taken, obesity is a relative contraindication to percutaneous dilational tracheostomy (PDT) because precise identification of neck anatomy is frequently difficult [61]. The most common serious complication of tracheostomy is tube obstruction. Some procedures started percutaneously need to be converted to open tracheostomy procedures due to bleeding, inability to pass the guidewire, and loss of airway control. PDT was complicated by the inability to identify anatomic landmarks, by non-life-threatening hemorrhage, and by malpositioning of the tracheostomy tube that result in hypoxemia and bradycardia. Tube obstruction within the first 24 hours after surgery usually results from tube impingement on the posterior wall of the trachea, partial displacement into the mediastinum, occlusive blood clot, or mucus plug. In a study of 89 obese patients with tracheostomy [62], the incidence of complications due to the procedure was 25%, with an estimated mortality of 2%.

Conclusion Obesity presents numerous challenges to the safe and effective implementation of mechanical ventilation. Difficult access to the upper airway, chest wall restriction, positional gas trapping, atelectasis, impaired ventilatory drive, compromised gas exchange, and increased work of breathing are routinely encountered. Evaluation of underlying lung mechanics is often challenging when attempting to choose safe and effective machine settings, and the obese are at elevated risk for complications during and after invasive ventilatory support. Careful consideration of the patho-pathophysiology of this common condition serves to guide the selection of treatment approaches best suited to optimize ventilation throughout all stages of ventilatory support. 3 Implications of Obesity for Mechanical Ventilation 37

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4.1 Introduction

In 2014, worldwide, 13% of the adults aged 18 years and over were classified as obese [1, 2]. The relationship between obesity and the development of comorbidities is well established in the literature. The main comorbidities of obesity, according to the American Heart Association/American College of Cardiology Foundation guidelines for the Management of Overweight and Obesity in Adults, include hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, stroke, obstructive sleep apnea (OSA), and respiratory problems.

C.Z. Fiori, Ph.D. (*) Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil e-mail: [email protected] D. Martinez, M.D., Ph.D. Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil Graduate Program in Medicine, Medical Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil A. Carissimi, Ph.D. Graduate Program in Psychiatry and Behavioral Science, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil

© Springer International Publishing AG 2018 43 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_4 44 C.Z. Fiori et al.

4.1.1 Obesity and Comorbidities

The primary aim of this chapter is to perform a systematic literature review of the Medline and Cochrane databases. The search was based on a PICO (population, intervention, comparator, and outcome) strategy. From 75,900 articles retrieved, the filters listed in Table 4.1 allowed to identify 97 articles, further selected to our inclusion criteria. Eleven studies met inclusion criteria (Table 4.2).

Table 4.1 Search strategy Population Obese subjects Intervention Not applied Comparator Comorbidities (hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, stroke, sleep apnea, and respiratory problems) Outcome Obesity associated with adverse comorbidities Design Meta-analysis Excluded Age <18 years or ≥65 years; animal species; publication dates older than 5 years

Table 4.2 Summary of studies Author Number of Number of (year) studies patients Comorbidities Conclusion Zhang et al. 28 2403 Left ventricular Obesity is an independent (2014) [5] randomized hypertensive hypertrophy risk factor for left clinical trial patients (LVH) ventricular hypertrophy in (mean age hypertensive patients 43.8–66.7 years) Chen et al. 21 cohorts 1,124,897 (mean Cardiovascular Obesity is a risk factor for (2013) [11] age 53.4 years) disease, coronary mortality from overall heart disease, cardiovascular disease and stroke for specific diseases, including coronary heart disease, ischemic stroke, and hemorrhagic stroke Lytsy et al. 2 cohorts 6069 Hypertension Obesity has a strong (2014) [9] positive association with development of hypertension even in absence of insulin resistance Cuspidi et al. 22 cohorts 5486 (mean age Left ventricular LVH occurs in a high (2014) [4] range hypertrophy fraction of the obese 31–76 years population, as obesity- related LVH is a powerful risk factor for systolic/ diastolic dysfunction 4 Obesity and Comorbidities 45

Table 4.2 (continued) Author Number of Number of (year) studies patients Comorbidities Conclusion Padwal et al. 14 cohorts 23,967 (mean Heart failure (HF) In patients with chronic (2014) [6] age 66.8 years) HF, the obesity was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at BMI levels of 30–34.9 kg m2 Kivimäki 7 cohorts 102,128 (mean Coronary artery Obesity was associated et al. (2013) age disease (defined with an increased risk of [13] 44.3 ± 9 years) as first nonfatal coronary artery disease myocardial infarction or cardiac-related death) Cronin et al. 7 prospective 9319 patients Major Obesity is an independent (2013) [7] studies with peripheral cardiovascular risk factor for CVEs artery disease events (CVEs) (nonfatal myocardial (PAD) (mean infarction, nonfatal stroke, age 67–74) cardiovascular death) in patients with PAD Park et al. 11 23,181 patients Cardiovascular Low BMI was associated (2013) [10] prospective (mean age causes, nonfatal with increased risks of percutaneous 62 ± 10 years) myocardial major CVEs and death coronary infarction, stent intervention thrombosis, or studies stroke Juonala et al. 4 prospective 6328 patients Type 2 diabetes, Overweight or obese (2011 [3] cohort (mean age of hypertension, children who were obese studies 11.4 ± 4.0 years dyslipidemia, and as adults had increased at baseline. The carotid artery risks of type 2 diabetes, mean length of atherosclerosis hypertension, follow-up was dyslipidemia, and carotid 23.1 ± 3.3 years) artery atherosclerosis Thomas 11 30,146 adult Microalbuminuria Metabolic syndrome and et al. (2011) prospective participants with or proteinuria and its components are [12] cohort metabolic chronic kidney associated with the studies syndrome disease (CKD) development of CKD The 58 221,934 people Cardiovascular BMI, waist circumference, Emerging prospective in 17 countries disease and waist-to-hip ratio do Risk Factors cohort (age ≥40) not importantly improve Collaboration studies cardiovascular disease risk Wormser prediction in people in et al. (2011) developed countries when [8] additional information is available for systolic blood pressure, history of diabetes, and lipids BMI body mass index, CKD chronic kidney disease, CVEs cardiovascular events, HF heart failure, LVH left ventricular hypertrophy, OSA obstructive sleep apnea, PAD peripheral artery disease 46 C.Z. Fiori et al.

4.2 Discussion and Analysis

The risks for complications of obesity start in childhood. One meta-analysis included four prospective cohort studies with mean length of 23 years at follow-up of body mass index (BMI) from childhood to adult age. The mean prevalence of obesity observed among adults was 20.7%. The individuals classified as overweight or obese in childhood and obese as adults had increased risks of type 2 diabetes, hypertension, dyslipidemia, and carotid artery atherosclerosis [3]. Left ventricular hypertrophy is a common consequence of obesity, independently of hypertension. In 22 echocardiographic studies, with overall 5486 obese individuals of both sexes, in the pooled obese population, the prevalence of left ventricular hypertrophy was 56%. The likelihood of having left ventricular hypertrophy was 4.2-fold greater in obese than in their nonobese counterparts. A meta- regression analysis of 14 studies with 2214 persons showed a significantly direct correlation between BMI and left ventricular mass [4]. Zhang et al. [5] evaluated 28 randomized controlled trials comprising 2403 hypertensive patients. The overweight and obesity status were associated with left ventricular mass independently of hypertension. There was statistical heterogeneity among studies due to different blood pressure levels and left ventricular mass measurement methods at baseline. Heart failure is another major comorbidity, associated with elevated disability and mortality rates. A meta-analysis of 14 studies of individuals with heart failure with preserved versus reduced ejection fraction explored a relationship between BMI and survival of these patients. Interestingly, mortality in both heart failure subtypes was U-shaped, with a nadir at BMI levels of 30–34.9 kg m2, i.e., degree of obesity I [6]. The shape is present in most studies of the meta-analysis. Major cardiovascular events (CVEs) are often seen in obese individual, particularly when atherosclerotic phenomena are already present. Cronin et al. [7] reviewed seven prospective studies in patients with peripheral artery disease searching for an association between markers of obesity and major CVEs, defined as nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. The markers of obesity were BMI, waist circumference, or waist-to-hip ratio. In 1872 patients with peripheral artery disease, a mild positive association between combined measures of obesity and CVEs was found. Adiposity is the major modifiable determinant of cardiovascular disease, but several confounders need to be accounted. The Emerging Risk Factors Collaboration evaluated the risk of first-onset cardiovascular disease in 58 prospective studies. BMI, waist circumference, and waist-to-hip ratio did not importantly change the prediction of cardiovascular disease risk in developed countries when compared with systolic blood pressure, history of diabetes, and lipids [8]. The risk of incident hypertension is another example of the etiologic role of obesity on cardiovascular disease. In two prospective cohorts with a median of 10 years of follow-up, 884 (48%) persons developed hypertension and 1639 (39%) progressed to a higher blood pressure stage. Patients who are overweight or obese, 4 Obesity and Comorbidities 47 without insulin resistance, had 46% higher odds to develop high blood pressure and 32% higher odds of hypertension progression than those with normal weight and no insulin resistance [9]. Eleven prospective percutaneous coronary intervention studies evaluated the association between BMI and the risk of major CVEs, defined as death from cardiovascular causes, nonfatal myocardial infarction, stent thrombosis, or stroke, and death after percutaneous coronary intervention. The risk of major CVEs and mortality declined among patients with higher BMI [10]. As this analysis supports an inverse relationship of BMI with major CVEs and all-cause mortality, it is possible that more obese people are selected for resistance to coronary complications, having adapted and survived immense overloads. Less obese subjects, on the other hand, were not challenged to survive cardiac overworks, being exposed to early coronary problems and mortality. Chen et al. [11] analyzed 20 cohorts and identified 49,184 cardiovascular deaths after a mean follow-up of 9.7 years. East Asians with a BMI of 25 or above had a 9% higher risk of death from overall cardiovascular disease, compared with the reference range of 22.5–24.9 BMI. Compared to BMI ranges of 30–32.4, 32.5–34.9, and 35–50, the risk was increased by 59%, 74%, and 97%, respectively. Thomas et al. [12] included eleven studies in a meta-analysis that evaluated the development of microalbuminuria or proteinuria and/or chronic kidney disease in participants with metabolic syndrome. Nine studies evaluating 28,897 patients demonstrated that the obesity component was associated with an odds ratio increase to 19% for development of estimated glomerular filtration rate <60 ml/min per 1.73 m2. Kivimäki et al. [13] assessed the association of job strain and lifestyle risk factors with the risk of coronary artery disease in 14 prospective cohort studies with a mean follow-up time of 7.3 years. Obesity was one of four lifestyle risk factors. Compared to healthy controls, the risk of incident for coronary artery disease was 66% greater for participants with obesity and 113% for obese people reporting job strain. Our search strategy did not retrieve meta-analysis evidence evaluating obesity and respiratory system-related comorbidities. Obstructive and central sleep apnea, obesity hypoventilation syndrome, asthma, and chronic obstructive pulmonary disease are seriously impacted by obesity, but the evidence is mostly of low level. Irrespective of the search, it is important to highlight the epidemiological studies corroborating the OSA-obesity association [14–16]. Peppard et al. [14] evaluated the longitudinal association between weight change and OSA, in a sample from the Wisconsin Sleep Cohort Study of the natural history of OSA in 690 middle-aged adults. A 10% weight gain predicted an increase of approximately 32% in the apnea-hypopnea index (AHI). This weight gain increased sixfold the odds for AHI >15. A population-based investigation of more than one thousand people, from the Sao Paulo Epidemiologic Sleep Study, showed that one in three (32.8%) subjects investigated had an AHI >5. The risk for OSA was 2.6-fold higher among overweight subjects and 10.5-fold higher for obese subjects [15]. 48 C.Z. Fiori et al.

Brown et al. [16] investigated 3040 subjects of the Sleep Heart Health Study, in search of association between baseline OSA severity and increase in BMI after 5 years. While people with normal AHI had an increase of 0.34 kg/m2 in BMI, people with AHI 5–30 had a BMI increase of 0.55 kg/m2 and with AHI >30 of 0.85 kg/m2. This data represents an explanation for the difficulty of weight loss in people with comorbid OSA.

Conclusion Cardiovascular diseases were the comorbidities more often associated with obesity in meta-analysis studies. However, larger and more homogeneous studies and meta-analyses including respiratory comorbidities, such as OSA, are needed to improve evidence level.

4.3 Key Major Recommendations

• Meta-analyses of epidemiological studies and randomized trials are necessary to improve the evidence level of the literature on obesity and its consequences. • Obesity should not be regarded as a homogeneous state of increased body mass since differential effects of fat accumulation were seen in the reviewed literature. • Respiratory, including OSA, metabolic, osteoarticular, neoplastic, and even social consequences of obesity are seldom investigated and lack high level evidence.

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5.1 Introduction

Atelectasis is defined as the collapse of lung. Atelectasis can be classified according to the pathophysiologic mechanisms (obstructive, nonobstructive), the amount of collapsed lung (lobar, segmental, total), or the location (lobe or segment). Surgery, pain, mechanical ventilation, blockage in airway due to foreign object, mucus plug, lung cancer, a poorly placed endotracheal tube, smoking history, and obesity are the conditions of increasing atelectasis risk [1]. It has been well defined that obesity alters respiratory mechanics 2[ ]. Restrictive pattern with decreased compliance of respiratory system involving chest wall and lungs in obese patients favors atelectasis [3]. In this chapter acute respiratory failure due to atelectasis in obese patients will be discussed mainly focusing on the outcomes and prevention of atelectasis in obese critically ill patients.

5.2 Discussion and Analysis

5.2.1 Causes of Atelectasis in Critically Ill Obese Patients

Functional residual capacity is reduced in obese patients [4]. Supine position and longer bedbound periods also aggravate the reduction of functional residual capacity in critically ill obese patients. Reduced traction of airway passage due to decreased lung volumes causes airway collapse and atelectasis. Collapse of

S.S. Ulasli, M.D. Department of Pulmonary Diseases, Hacettepe University, School of Medicine, Sihhiye, 06100 Ankara, Turkey e-mail: [email protected]

© Springer International Publishing AG 2018 51 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_5 52 S.S. Ulasli posterior and basal segments of lungs is frequently seen when anesthesia reduces diaphragmatic tonus [5]. Moreover decreased residual capacity and increased closing volume during anesthesia, analgesia, and sedation also cause alveolar collapse. Alveolar collapse alters the distribution and synthesis of surfactant which accelerate atelectasis. Obese patients have also larger amount of atelectatic area when compared with lean patients [6]. In obese patients, suppression of cough and deep breathing due to pain or decreased mucociliary clearance as a result of intubation, anesthesia, and analgesia leads to the accumulation of secretions and atelectasis. Moreover obese patients frequently have respiratory comorbidities such as chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, or obesity hypoventilation syndrome which prolong hospital and intensive care unit stays [3].

5.2.2 Outcomes of Atelectasis in Critically Ill Obese Patients

Atelectasis reduces compliance and increases work of breath. Ventilation perfusion mismatch and intrapulmonary shunt due to atelectasis cause respiratory failure. The amount of atelectasis is related with pulmonary shunt and respiratory failure [2]. Atelectasis is often used as an explanation for otherwise unexplained postoperative fever. However their occurrence seems as a coincidence rather than causal. Lack of association between atelectasis and fever has been demonstrated [7]. Thus attribution of a postoperative fever to atelectasis leads to the misdiagnosis of fever origin.

5.2.3 Prevention and Treatment of Atelectasis in Critically Ill Obese Patients

It has been demonstrated that perioperative atelectasis is more frequent and atelectasis persists for longer (for up to 24 h after surgery) postoperatively in obese patients in comparison with full resolution in lean patients in a few hours [6]. In the study by Baltieri et al., prevalence of atelectasis in obese patients without respiratory comorbidities was found to be 37.8% at 48 h after bariatric surgery indicating the importance of interventions to prevent atelectasis formation [8]. In obese patients different approaches have been stated to prevent atelectasis during perioperative period and follow-up period in intensive cares [9]. From the beginning of mechanical ventilation and during the follow-up period under mechanical ventilation, optimal tidal volume and adequate level of end- expiratory pressure (PEEP) should be applied to prevent atelectasis. Optimal tidal volume should be between 6 mL/kg and 8 mL/kg of predicted body weight. The tidal volume setting must be guided by the patient’s height and not by their measured weight [3]. 5 Atelectasis 53

The easiest predicted body weight formula can be used as

Predicted bodyweight (kg) = height (cm)–100 for male. Predicted bodyweight (kg) = height (cm)–110 for female.

Higher PEEP decreases venous return and causes arterial hypotension with decreasing oxygenation [10]. Two thirds of intrinsic PEEP should be applied to subjects with auto-PEEP. Proper levels of PEEP and recruitment maneuvers (RMs) can be used to reopen collapsed lung area and to maintain the lungs fully aerated [11], whereas PEEP alone does not reduce atelectasis in morbid obesity after anesthesia induction, and recruitment maneuvers up to 55 cmH2O show only transient effects, a combination of recruitment maneuvers and PEEP improves oxygenation with reducing atelectasis for at least 20 min [12]. Recruitment maneuvers (RMs) improve gas exchange and increase transpulmonary pressure and intrathoracic blood volume. Optimal frequency of RMs is not estimated but can be applied with hemodynamic monitorization [13]. Moreover stepwise RMs, instead of abrupt RMs, should be used in obese patients. Treatment of atelectasis depends on the cause. Subjects with abundant secretions will benefit from chest physiotherapy (i.e., coughing, postural drainage, deep breathing exercises (incentive spirometry), and percussion), suctioning, and bronchoscopy. Noninvasive ventilation (NIV) is an option for patients with few secretions as demonstrated by a randomized controlled trial in which 60 obese patients undergoing minor peripheral surgery were randomly assigned to receive short-term NIV or supplemental oxygen via venturi mask during their postanesthesia care unit (PACU) stay [14]. NIV promoted more rapid recovery of postoperative lung function and oxygenation in the obese with 24 h lasting effect. Important limitations to this evidence are that the trial was unblinded and could not draw any conclusion regarding clinical outcome [14]. A recent meta-analysis described the benefits in oxygenation, clearance of carbon dioxide, and pulmonary function testing after general anesthesia with NIV compared with standard care in obese patients [15]. Postoperatively, NIV was found to be associated with a decreased risk of respiratory complications but not of reintubation after tracheal extubation and unplanned intensive care unit admission. NIV-related anastomotic leakage was not reported. NIV-related complications in obese patients were mainly due to intolerance and ranged from 7% to 28% of cases suggesting well tolerance and effectiveness of NIV in obese patients [15]. Fiberoptic bronchoscopy is frequently used in the treatment of atelectasis, but evidence suggests that it may be no more effective than standard chest physiotherapy. The role of flexible bronchoscopy for the treatment of atelectasis is also unclear in obese patients. In a recent prospective study by Khan et al., flexible bronchoscopy was found to be safe without increased needs for sedation in obese patients [16]. Moreover no difference in complications during fiberoptic bronchoscopy or 54 S.S. Ulasli procedural success based on obesity criteria was detected [16]. However there has been no study regarding the efficacy and safety of fiberoptic bronchoscopy for the treatment of atelectasis in critically ill obese patients. Mucolytics are commonly used to assist clearance of tenacious secretions; however, their efficacy in this setting has not been well documented. Nasotracheal suctioning of the nonintubated patient with a weak and ineffective cough is uncomfortable and transient in the meaning of clearing secretions from the tracheo- bronchial tree.

Conclusion Obese patients are more likely to develop atelectasis during the follow-up in intensive care. Interventions to prevent and treat atelectasis are very important to reduce mortality and morbidity in critically ill obese patients.

References

1. Kotlo RM. Chapter 104. Acute respiratory failure in the surgical patient. In: Fishman's pulmonary diseases and disorders. 5th ed. New York: McGraw-Hill Education; 2015. p. 1592–606. 2. Harris AT, Morell D, Bajaj Y, Martin-Hirsch DP. A discussion of airway and respiratory complications along with general considerations in obese patients. Int J Clin Pract. 2010;64(6):802–6. doi:10.1111/j.17421241.2010.02350.x. 3. Pépin JL, Timsit JF, Tamisier R, et al. Prevention and care of respiratory failure in obese patients. Lancet Respir Med. 2016;4(5):407–18. doi:10.1016/S2213-2600(16)00054-0. 4. Pelosi P, Croci M, Ravagnan I, et al. Respiratory system mechanics in sedated, paralyzed, morbidly obese patients. J Appl Physiol. 1997;82:811–8. 5. Magnusson L, Spahn DR. New concepts of atelectasis during general anaesthesia. Br J Anaesth. 2003;91(1):61–72. 6. Eichenberger A-S, Proietti S, Wicky S, et al. Morbid obesity and postoperative pulmonary atelectasis: an underestimated problem. Anesth Analg. 2002;95:1788–92. 7. Engoren M. Lack of association between atelectasis and fever. Chest. 1995;107:81–4. 8. Baltieri L, Peixoto-Souza FS, Rasera-Junior I, Montebelo MI, Costa D, Pazzianotto-Forti EM. Analysis of the prevalence of atelectasis in patients undergoing bariatric surgery. Braz J Anesthesiol. 2016;66(6):577–82. doi:10.1016/j.bjane.2014.11.016. 9. Fernandez-Bustamante A, Hashimoto S, Serpa Neto A, Moine P, Vidal Melo MF, Repine JE. Perioperative lung protective ventilation in obese patients. BMC Anesthesiol. 2015;15:56. 10. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303:865–73. 11. Pelosi P, Ravagnan I, Giurati G, et al. Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis. Anesthesiology. 1999;91:1221–31. 12. Reinius H, Jonsson L, Gustafsson S, et al. Prevention of atelectasis in morbidly obese patients during general anesthesia and paralysis: a computerized tomography study. Anesthesiology. 2009;111:979–87. 13. Futier E, Constantin JM, Pelosi P, et al. Noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during and after intubation of morbidly obese patients: a randomized controlled study. Anesthesiology. 2011;114:1354–63. 5 Atelectasis 55

14. Zoremba M, Kalmus G, Begemann D, et al. Short term non-invasive ventilation post-surgery improves arterial blood-gases in obese subjects compared to supplemental oxygen delivery - a randomized controlled trial. BMC Anesthesiol. 2011;11:10. 15. Carron M, Zarantonello F, Tellaroli P, Ori C. Perioperative noninvasive ventilation in obese patients: a qualitative review and meta-analysis. Surg Obes Relat Dis. 2016;12(3):681–91. doi:10.1016/j.soard.2015.12.013. Epub 2015 Dec 10 16. Khan I, Chatterjee AB, Bellinger CR, Haponik E. Sedation for bronchoscopy and complications in obese patients. Respiration. 2016;92(3):158–65. Obesity and Congestive Heart Failure 6 Stephan Steiner

6.1 Introduction

Obesity is known to be a main health problem in the industrial countries. Only one third of men and less than half of women have normal weight based on BMI measurements [1], and up to 40% of the ICU patients are obese [2]. Obesity is associated with an increased risk of cardiovascular disease [3–5], especially heart failure [3, 6, 7]. Some researches hypothesize that the steady increase of life expectancy might be stopped by the “obesity endemic” [4]. Consequently, intervention in obesity seems to be an advisable goal in the primary prevention of cardiovascular disease [4].

6.2 Definition and Diagnosis of Left Heart Failure

Heart failure is defined as a “complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood [8].” The AHA Guideline for the management of heart failure differentiates between heart failure with reduced (EF <40%, HFrEF) and those with preserved ejection fraction (HFpEF, EF >50%). Keeping in mind that there might be bias with respect to different methods of imaging (echocardiography, magnetic resonance imaging, ventricu- lography), patients between the above mentioned range are considered to have borderline HFpEF [8] (Table 6.1).

S. Steiner, Prof. Department of Cardiology, Pneumology and Intensive Care Medicine, St. Vincenz Hospital, Auf dem Schafsberg, 65549 Limburg/Lahn, Germany e-mail: [email protected]

Table 6.1 Definition of Heart failure with preserved ejection fraction (HFpEF) (EF >50%) heart failure [8] Borderline HFpEF (EF 40–50%) Heart failure with reduced ejection fraction (HFrEF) (EF <40%)

Diagnosis of heart failure might be complicated in obese patients. Obesity as well as heart failure can cause dyspnea, exercise intolerance, and edema [9, 10]. It seems that cardiorespiratory fitness is severely reduced in morbidly obeseindividuals— similar to those with HFrEF [11]. Nevertheless, as in non-obese patients, diagnosis is based on clinical examination, noninvasive methods (e.g., echocardiography, magnetic resonance tomography, cardiopulmonary exercise testing), and, in some cases, heart catheterization and myocardial biopsy, the latter allowing histological study of a myocardial specimen. With respect to obesity, it should be kept in mind that even the detection of brain natriuretic peptides, which are surrogate markers of myocardial wall stress, might be misleading. There is an inverse relationship between BMI and BNP, even in healthy people. Therefore it is not surprising that BNP levels are lower in obese patients with heart failure and that at least slight elevations in BNP might have implications for heart failure risk [12]. On the other hand, natriuretic peptides increase after weight loss [13]. Compared with HFrEF, diagnosis of HFpEF is even more complex. HFpEF has been diagnosed traditionally by Swan Ganz catheterization (pulmonary capillary wedge pressure as a marker of left ventricular filling pressure), E/A ratio quantified by Doppler echocardiography, or measuring left ventricular end-diastolic pressure during left heart catheterization. The European Society of Cardiology has added some challenging methods to improve categorization of HFpEF, for example, biomarkers and modern echocardiographic methods like speckle tracking [9].

6.3 Pathophysiology of Heart Failure with Respect to Obesity

Echocardiography has shown subclinical alterations of left ventricular myocardial characteristics related to the degree of obesity [14]. Using longitudinal strain analysis, Wang et al. noted longer longitudinal strain, greater dyssynchrony, and signs of early diastolic dysfunction in asymptomatic obese patients [15]. Even after adjusting for age, mean arterial pressure, left ventricular hypertrophy, or insulin levels, BMI was shown to be independently associated with left ventricular dysfunction [14], mild myocyte hypertrophy [16], increased myocardial triglyceride levels and epicardial fat [17], and the burden of atrial fibrillation [18]. Mahajan et al. [19] found that obesity results in global biatrial endocardial remodeling in an animal model. Remodeling has been characterized by left atrial enlargement and conduction abnormalities. Furthermore, left atrial muscle has been infiltrated by epicardial fat and fibrosis. These findings were thought to represent a unique substrate for atrial fibrillation [19]. In a small sample of healthy monozygotic twin pairs, who 6 Obesity and Congestive Heart Failure 59

Coronary artery disease “Framingham RF” Myocardial infarction – HTN, DM, DLP Sleep apnea (SRBD)

Small vessel disease

Obesity HFpEF HFrEF

Hyperdynamic circulation (↑SV, ↑HR) Heart metabolism – Fatty degeneration, – Inflammation

Fig. 6.1 Pathophysiology of heart failure in obese patients. There is a high prevalence of traditional cardiovascular risk factors (e.g., hyperlipidemia, arterial hypertension, coronary artery disease, and myocardial infarction). However, there are specific mechanisms associated with obesity which might lead to HFpEF and HFrEF. For detailed information, see [10, 14, 17]. HTN: Hypertension, DM: Diabetes mellitus, DLP: Dyslipidemia, SV: Stroke volume, HF: Heart rate were discordant for obesity, there was increased epicardial fat independent of genetic factors. Additionally, there was a close relationship between obesity and low-grade inflammation as a potential pathophysiological link to the development of cardiovascular disease [20]. Next to these pathomechanisms, comorbidities such as arterial hypertension, hypercholesterinemia, or coronary artery disease might raise or worsen heart failure. Sleep apnea is often associated with obesity and heart failure. Ongoing registry data on 6876 patients with clinically stable heart failure had demonstrated a prevalence of sleep-related breathing disorders (SRBD) of 36% in women and 49% in men [21]. Predictors for SRBD were age, BMI, and severity of heart failure. Therefore, nocturnal breathing disorders might play an additional role in the development of left heart failure [22] in obese patients because of arterial hypertension [23] and left ventricular hypertrophy [24]. The complex interaction between obesity and heart failure is summarized in Fig. 6.1 without a claim to be complete.

6.4 Association of Obesity and Right Ventricular Function

There is a complex pathophysiologic relationship between sleep-related breathing disorders, right ventricular dysfunction, and pulmonary hypertension [16, 25–27]. Chahal et al. [27] hypothesized that right ventricular functional and morphologic alterations are explained by an obesity-associated increase of right ventricular afterload, increased blood volume, hormonal effects, or specific obesity-related effects. Wong et al. used tissue Doppler imaging techniques to identify determinants of 60 S. Steiner right ventricular function in overweight and obese patients compared to a control group [28]. They conclude that BMI was associated with right ventricular dysfunction which interestingly has been independent of coexisting sleep apnea. Therefore, obesity itself seems to affect right ventricular geometry and worsens RV function which also might be negatively impacted by the occurrence of sleep-related breathing disorders (as a result of, e.g., hypoxemia, intrathoracal pressure changes).

6.5 Obesity Paradox

For decades it has been recognized that obese patients with heart failure and a very high BMI have shown a decreased mortality compared to those with normal weight, whereas patients with low BMI and CHF have a lower life expectancy [3]. These findings were confirmed even after heart transplantation where overweight patients were found to have an improved survival rate. These observations have been termed “obesity paradox” [29]. Shah [30] et al. studied 6142 heart failure patients with acute decompensation in a worldwide observational study. Without regional differences a higher BMI was protective. Aging, heart failure severity, and metabolism explained, at least in part, the obesity paradox in this study. With respect to acute decompensated heart failure, the authors summarized that a lower BMI might identify patients at particularly high risk.

6.6 Therapy of Heart Failure in Obese Patients

Therapy of heart failure does not differ between normal weight and obese patients, neither with respect to medication nor respective device therapy [9, 31]. Medication should be initiated with a starting dose on purpose to titrate the target dose which is defined in different controlled studies. Apart from some anticoagulants, e.g., dabi- gatran which is indicated in case of atrial fibrillation in order to prevent thromboem- bolism, dose adjustments are not recommended. Concerning body weight there is no consistent recommendation. In obese patients without manifest heart failure, weight loss is recommended [9] with a view to prevent heart failure [31] and symptom benefit. With respect to left and right ventricular geometry and performance, Alpert et al. summarized the positive effects of excessive weight in a detailed review of the literature [32]. Kitzman et al. studied the effect of a caloric restriction on peak oxygen consumption and the quality of life in 100 patients with preserved left ventricular ejection fraction and a BMI greater than 30 kg/m2 [33]. Further inclusion criteria were signs or symptoms of heart failure (HFpEF). After a study period of 20 weeks of diet, exercise, or both, they found an increase in VO2max. Nevertheless, the intervention was not associated to a better quality of life. Farrell et al. [34] examined the association among cardiovascular fitness, body mass index, and heart failure mortality. Between 1971 and 2010, a total of 44,674 individuals were included in the study. BMI was significantly associated with heart failure mortality, but mortality rates were lower in fit than in unfit men within each BMI stratum. 6 Obesity and Congestive Heart Failure 61

Obesity

Heart failure (HF)?

No Yes

Weight loss beneficial < 35 kg/m2 BMI > 35 kg/m2 (Prevention of HF)

Weight loss not Weight loss might recommended be considered (Worse prognosis) (Managing symptoms/ exercise capacity)

Fig. 6.2 Recommendation on weight loss in heart failure patients. There is no doubt that weight loss is beneficial in obese patients without manifest heart failure as a primary prevention. If heart failure is still present, weight loss is not recommended because of the “obesity paradox” and therefore worse prognosis. Except in severely symptomatic patients, weight loss might be considered in order to attenuate symptoms

Bariatric surgery can achieve marked weight loss and seems to be safe and effective in obese patients with heart failure. In a retrospective study, weight loss (−22.6% body weight) by bariatric surgery was associated with an increase of left ventricular ejection fraction (+5.1 ± 8.3%) [35]. Unfortunately the authors could not give information on quality of life and clinical course/prognosis of these patients because of the retrospective character of the study. In patients with overt heart failure, weight loss could not be recommended concerning prognosis. However, in some patients with advanced obesity, weight loss might help to manage symptoms and increase exercise capacity [9]. In obese individuals without heart failure, weight reduction should be pursued as soon as possible, even in adolescence as a primary prevention of heart failure. These recommendations are supported by a current Swedish study reporting a nearly ten- fold higher risk of early heart failure in those individuals with a BMI >35 kg/m2 compared with non-obese individuals [36]. Recommendations on weight loss in heart failure patients are illustrated in Fig. 6.2.

6.7 Meaning of Obesity in Cardiogenic Shock and Myocardial Infarction

Critically ill obese patients are at increased risk of mortality [37] due to prolonged mechanical ventilation and extended weaning. With reference to myocardial infarction, obese patients did not show worse outcomes compared with 62 S. Steiner non-obese patients [38]. Until now there is no evidence that obesity is associated with worse—or even better—outcomes in cardiogenic shock; nevertheless, clinical trials on mechanical support have excluded massive obese patients [10]. Concerning the efficacy of mechanical support, registry data on 1638 patients (INTERMACS, Interagency Registry for Mechanical Circulatory Support [39]) show that patients with a higher BMI more often have poor outcomes (death or poor quality of life).

Conclusion Obesity is associated with multiple negative effects on right and left ventricular geometry and poses function and an immense risk for the development of heart failure. Therefore, weight reduction should be recommended to prevent heart failure. If heart failure or even heart decompensation is present, weight reduction might be aimed with respect to physical capacity and improvement of symptoms (e.g., dyspnea). Nevertheless, because of the obesity paradox, there is no recommendation to lose weight in these patients.

6.8 Key Major Recommendations

• Obesity has negative impact on left/right heart geometry as well as myocardial function due to multiple mechanisms. • Be aware of obesity even in adolescents in order to recommend weight loss as a tool to prevent heart failure. • Weight loss might be beneficial in clinically stable obese patients with heart failure with respect to symptomatic benefit. • There is a partially explained “obesity paradox” which describes a better outcome in obese patients with severe heart failure compared with lean patients. Therefore, there is no recommendation for weight loss in these patients.

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Peter D. Liebling and Behrouz Jafari

7.1 Introduction

There is growing evidence showing that intra-abdominal hypertension (IAH) is extremely important in the care of critically ill patients. This phenomenon can evolve to the end-stage abdominal compartment syndrome (ACS) with a serious impact on the function of respiratory system and other vital organs. ACS can esca- late lung injury and increase intrathoracic pressures, leading to atelectasis, airway closure, and deterioration of respiratory mechanics and gas exchange. Abdominal compartment syndrome is a particular challenge for mechanical ventilation. It is the only extrathoracic entity that can significantly decrease the compliance of the respiratory system and is increasingly recognized in critically ill patients. In this chapter we will review in detail the consequences of raised intra-abdominal pressure as a cause of respiratory failure and comment on what is known about mechanical ventilation in these patients.

7.2 Definitions

The latest consensus definitions on IAH and ACS have been published by the World Society of Abdominal Compartment Syndrome (WSACS) in 2013. Table 7.1 summarizes these consensus definitions: a sustained increase in intra- abdominal pressure (IAP) equal to or above 12 mmHg defines IAH where ACS is defined by a sustained IAP above 20 mmHg with new-onset organ dysfunction [1] (Table 7.1).

P.D. Liebling, M.D. • B. Jafari, M.D. (*) Section of Pulmonary, Critical Care and Sleep Medicine, University of California-Irvine, School of Medicine, Irvine, CA, USA VA Long Beach Healthcare System, 5901 East 7th Street, Long Beach, CA 90822, USA e-mail: [email protected]

© Springer International Publishing AG 2018 65 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_7 66 P.D. Liebling and B. Jafari

Table 7.1 2013 consensus definitions of the World Society of the Abdominal Compartment Syndrome Definition Retained definitions from the original 2006 consensus statements 1. IAP is the steady-state pressure concealed within the abdominal cavity 2. The reference standard for intermittent IAP measurements is via the bladder with a maximal instillation volume of 25 mL of sterile saline 3. IAP should be expressed in mmHg and measured at end expiration in the supine position after ensuring that abdominal muscle contractions are absent and with the transducer zeroed at the level of the midaxillary line 4. IAP is approximately 5–7 mmHg in critically ill adults 5. IAH is defined by a sustained or repeated pathological elevation in IAP ≥12 mmHg 6. ACS is defined as a sustained IAP ˃20 mmHg (with or without an APP ˂60 mmHg) that is associated with new organ dysfunction/failure 7. IAH is graded as follows: Grade I, IAP 12–15 mmHg Grade II, IAP 16–20 mmHg Grade III, IAP 21–25 mmHg Grade IV, IAP ˃25 mmHg 8. Primary IAH or ACS is a condition associated with injury or disease in the abdominopelvic region that frequently requires early surgical or interventional radiological intervention 9. Secondary IAH or ACS refers to conditions that do not originate from the abdominopelvic region 10. Recurrent IAH or ACS refers to the condition in which IAH or ACS redevelops following previous surgical or medical treatment of primary or secondary IAH or ACS 11. APP = MAP − IAP New definitions accepted by the 2013 consensus panel 12. A polycompartment syndrome is a condition where two or more anatomical compartments have elevated compartmental pressures 13. Abdominal compliance is a measure of the ease of abdominal expansion, which is determined by the elasticity of the abdominal wall and diaphragm. It should be expressed as the change in intra-abdominal volume per change in IAP 14. The open abdomen is one that requires a temporary abdominal closure due to the skin and fascia not being closed after laparotomy 15. Lateralization of the abdominal wall is the phenomenon where the musculature and fascia of the abdominal wall, most exemplified by the rectus abdominis muscles and their enveloping fascia, move laterally away from the midline with time Abbreviations: ACS abdominal compartment syndrome, APP abdominal perfusion pressure, FG filtration gradient,GFP glomerular filtration pressure,IAH intra-abdominal hypertension, IAP intra-abdominal pressure, MAP mean arterial pressure, PTP proximal tubular pressure Adapted from Kirkpatrick A, et al. Intra-abdominal hypertension and the abdominal compartment syndrome: Updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med 2013;39(2):1190–1206 (with permission) 7 Intra-abdominal Hypertension and Abdominal Compartment Syndrome 67

7.3 Etiologies

There are several etiologies which can cause or contribute to IAH/ACS, including massive fluid resuscitation, ileus, abdominal infection, pancreatitis, pneumoperitoneum, and hemoperitoneum. WSACS categorized the causes of IAH/ACS into primary and secondary conditions [3]. Primary IAH or ACS is a condition associated with injury or disease in the abdominopelvic region that frequently requires early surgical or interventional radiological intervention. These include trauma, liver transplantation, ruptured abdominal aortic aneurysm, postoperative bleeding, retroperitoneal hemorrhage, intestinal obstruction, and bleeding pelvic fracture. By the other hand, the secondary causes refer to conditions that do not originate from the abdominopelvic region and do not require any surgical intervention, like sepsis, major burns, peritoneal dialysis, pregnancy, morbid obesity, large-volume fluid replacement, and intra-abdominal infection [3, 4].

7.4 Clinical Features

7.4.1 Symptoms

Patients may describe dyspnea, abdominal fullness or pain, nausea, and low urine output. However, most patients with ACS require mechanical ventilation and are unable to voice their symptoms.

7.4.2 Physical Examination

Vital sign abnormalities may include tachypnea, tachycardia, and hypoxemia. If intra-abdominal infection is present, fever can be present. The chest examination may include decreased breath sounds at the bases owing to bilateral elevated hemidiaphragms. Abdominal examination may reveal a distended abdomen, tense to pal- pation, with or without bowel sounds. Incision sites may be a clue to recent abdominal surgery which is the most frequent etiology of IAH. Unfortunately, the above findings are all very nonspecific, as the physical exam has both low sensitivity (61%) and specificity (81%) for elevations in IAP [5].

7.4.3 Hemodynamics

Increased IAP has been shown to decrease cardiac output, raise central venous pressure, and raise pulmonary artery pressure and pulmonary capillary wedge pressure [6]. Surprisingly, arterial blood pressure is usually preserved. 68 P.D. Liebling and B. Jafari

7.4.4 Laboratory

Chemistries in ACS will often demonstrate a lactic acidosis, elevated blood urea nitrogen, creatinine, and decreased bicarbonate. In cases of hemoperitoneum causing ACS, anemia can be found. Leukocytosis is common, and in the presence of pancreatitis, elevated lipase and amylase levels are often seen. Blood gasses often show concurrent metabolic acidosis and respiratory acidosis with hypoxemia and decreased PaO2/FiO2 ratio. The metabolic component is likely from abdominal hypoperfusion or global hypoperfusion from low cardiac output. The respiratory acidosis arises as the patient hypoventilates in the setting of elevated hemidiaphragms and decreased ability to maintain tidal volumes. Renin and aldosterone levels are also elevated in ACS but generally are not used for the diagnosis [7].

7.4.5 Imaging

The most common imaging abnormality in patients with IAH and ACS is elevated hemidiaphragms and low lung volumes on chest X-ray. Abdominal CT may show a “round abdomen sign” where the usual roughly oval-shaped abdomen becomes cir- cular, with an anteroposterior/transverse abdominal diameter ratio greater than 0.8 [8]. Other disease-specific imaging findings can be present, including air under the diaphragms in pneumoperitoneum, blood in the peritoneal or retroperitoneal space in the setting of intra-abdominal hemorrhage, evidence of acute pancreatitis, or dilated loops of bowel in the case of ileus.

7.5 Diagnosis

The diagnosis of IAH or ACS begins with clinical suspicion. If the history or physical examination includes risk factors for IAH, it is prudent to transduce a bladder pressure. Given the shortcomings of physical examination, diagnosis requires an elevation of transduced IAP. Historically there have been multiple modalities of transducing the intra- abdominal pressure. These have included gastric pressure transduced from a naso- gastric or orogastric tube, inferior vena cava pressure transduced from a femoral venous line placed in the vena cava, transduction of the insufflation pressure during laparoscopy, and direct transduction of peritoneal pressure via intraperitoneal catheters. The most clinically useful and easiest method however is transduction of a bladder pressure. This is done by inserting a Foley catheter, instilling 25 cm3 of sterile saline, clamping the drainage tube, and connecting the transducer to the flush port on the catheter. IAP should be expressed in mmHg and measured at end expiration in the supine position after ensuring that abdominal muscle contractions are absent and with the transducer zeroed at the level of the midaxillary line [9]. 7 Intra-abdominal Hypertension and Abdominal Compartment Syndrome 69

If elevated IAP is found, a comprehensive search for organ dysfunction should be undertaken. This should include assessment of respiratory insufficiency, record- ing of hourly urine output, close monitoring of vital signs, and serial measurements of the IAP. A laboratory evaluation should be completed including blood gas, chemistries, lactic acid, and blood counts.

7.6 Consequences

ICU patients with IAH on ICU day 1 have significantly higher mortality (38.8%) than those without IAH (22.2%). Predictors of mortality for patients with IAH include age, APACHE II score, medical compared to surgical ICU admission, and the presence of liver dysfunction [2].

7.7 Obesity and Intra-abdominal Hypertension/Abdominal Compartment Syndrome

7.7.1 IAH

IAP is significantly higher in obese patients compared to controls and is most closely correlated with sagittal abdominal diameter [10, 11]. Increases in IAP correlate with increasing number of obesity-related comorbidities. Interestingly, the increased IAP seen in morbidly obese patients is not alleviated by laparotomy incision, the usual method of decompressing the abdominal compartment. This suggests the elevated IAP in morbidly obese patients does not truly represent an ACS [12]. There is a significant elevation in plasma renin and aldosterone with elevation in IAP and in obesity [7]. This elevation is alleviated with weight loss in parallel with reduction in blood pressure, suggesting a possible underlying mechanism of systemic hypertension in morbidly obese patients [13, 14]. The correlation between elevated IAP and elevated renin and aldosterone specifically in obese patients has not been well studied.

7.7.2 ACS

There is no evidence that obesity is a risk factor for ACS or that prognosis is worse in obese patients with ACS. In a large epidemiologic study, there was no difference in BMI between survivors and non-survivors of ACS [2]. However, intraoperatively during laparoscopic Roux-en-Y gastric bypass surgery, anuria is sometimes seen during abdominal insufflation. This should be managed like any other ACS, and the abdomen should desufflated until urine output resumes 15[ ]. 70 P.D. Liebling and B. Jafari

7.8 Pulmonary Physiology in Intra-abdominal Hypertension/Abdominal Compartment Syndrome

As far back as the 1970s, animal studies of intra-abdominal hypertension demonstrated increased peak pressures at fixed tidal volume and decreased partial pressure of oxygen in dogs with artificially elevated intra-abdominal pressure 16[ ]. In a case series of patients with massively elevated IAP, who had very low dynamic compliance, elevated diaphragms, low lung volumes, and high positive end-expiratory pressure (PEEP), patients were required to maintain oxygenation [17]. In another animal study, the application of 10 cm H2O of positive end-expiratory pressure was associated with an exaggerated response to increasing intra-abdominal pressure on central venous pressure, pulmonary capillary wedge pressure, pulmonary artery pressure, pulmonary vascular resistance, and blood lactate levels [18]. However, in a case series of 15 patients with intra-abdominal hypertension, incremental increase in PEEP had no effect on intra-abdominal pressure. This is postulated to be due to the bulk of the PEEP being dissipated at the pulmonary transmural pressure gradient and not actually increasing the pleural pressure [19]. In mechanically ventilated patients without IAH, increases in PEEP do however demonstrate a mild but statistically significant increase in IAP [20]. Conversely, in a swine model, incremental increases in IAH increased peak inspiratory pressure markedly. This study also demonstrated that elevations in intra-abdominal pressure correlated with an increase in PaCO2 and a decrease in PaO2 [21]. In a study of 26 adult patients undergoing laparoscopic cholecystectomy, increased insufflation pressures markedly affected pulmonary compliance. With intra-abdominal pressure increases of 12 mmHg, the pulmonary compliance was halved [22]. These studies show an interesting relationship between the chest and the abdominal compartments (Table 7.2). Increases in pulmonary pressures are not communicated to the abdomen meaningfully, but increases in abdominal pressures are rapidly communicated to the chest. ACS not only affects the pulmonary and cardiovascular system but also results in other abnormalities such as renal dysfunction, hepatic impairment, and even immune dysfunction [23].

7.9 Management of Mechanical Ventilation in Intra-abdominal Hypertension/Abdominal Compartment Syndrome

7.9.1 Management of ACS

The first task when a diagnosis of abdominal compartment syndrome is made is to address the underlying cause and obtain surgical consultation for decompressive options. Surgical decompression reverses the deleterious effects of ACS on the respiratory, cardiovascular, and renal systems [24]. 7 Intra-abdominal Hypertension and Abdominal Compartment Syndrome 71

Table 7.2 Pulmonary System Parameter Effect physiologic parameters Cardiovascular Cardiac output affected by IAH ↓ Venous return ↓ Peripheral vascular resistance ↑ Intrathoracic pressure ↑ Heart rate ↑ Mean blood pressure – Pulmonary Pulmonary compliance ↓ Peak inspiratory pressure ↑ Pulmonary vascular ↑ resistance Total lung capacity ↓ Functional residual capacity ↓ Residual volume ↓ Renal Renal vascular resistance ↑ Renal arterial flow ↓ Glomerular filtration rate ↓ Abdominal viscera Splanchnic blood flow ↓ Abdominal wall Abdominal wall blood flow ↓ Abdominal wall compliance ↓ Intracranial Intracranial pressure ↑ Cerebral perfusion pressure ↓ Adapted from K.-M. Sieh, et al. Intra-abdominal hypertension and the abdominal compartment syndrome. Langenbeck’s Arch Surg 2001:386;53–61 (with permission)

7.9.2 Noninvasive Ventilation in ACS

There have been no formal trials of noninvasive ventilation in ACS. The use of noninvasive ventilator modes is probably ill-advised, as there is a significant risk of aerophagia-induced gastric distension which may further increase IAP. There is a case report of this exact phenomenon inducing ACS [25].

7.9.3 Invasive Mechanical Ventilation in ACS

7.9.3.1 Ventilator Mode There are no firm guidelines establishing the best ventilator mode in ACS. As such, conventional volume control or pressure control modes are acceptable, as long as the settings conform to the below recommended parameters. Even though elevations in PEEP are not communicated to the abdominal compartment in a meaningful way, transitioning from conventional ventilation to airway pressure release ventilation can significantly elevate IAP 26[ ]. 72 P.D. Liebling and B. Jafari

7.9.3.2 Tidal Volume It is common that patients who have abdominal compartment syndrome have concurrent acute respiratory distress syndrome (ARDS). There has only been one trial evaluating tidal volume goals in IAH. This was a rat model in which 6 cm3/kg vs. 10 cm3/kg tidal volumes were compared with and without IAH. In the IAH group, 10 cm3/kg tidal volume resulted in less inflammation in lung tissue samples compared to 6 cm3/kg. This has not been evaluated in human trials, and this is counter to current ARDS Network recommendations. Given the lack of human data to support this finding, these patients should be managed with a low tidal volume strategy as recommended by the ARDS Network guidelines [27]. This is certainly an area in which further research is needed.

7.9.3.3 Recruitment Maneuvers In the presence of ACS and increased chest wall elastance, the inspiratory pressure applied during recruitment maneuver should be higher, in order to achieve an inspiratory transpulmonary pressure that is large enough to reopen collapsed alveoli.

7.9.3.4 PEEP High PEEP is usually required in patients with IAH. Theoretically PEEP should be titrated to normalize the position of the diaphragm, which is shifted upward by increases in IAP [27]. This recommendation is supported by a swine study where IAP-matched PEEP decreased shunt, dead space ventilation, increased lung volumes, and improved oxygenation. Application of PEEP did however decrease cardiac output and chest wall elastance. However, independent of IAH, studies found that the “optimal” PEEP should be selected according to the “best” elastance of the respiratory system [28, 29]. The authors found that a reasonable compromise between the deleterious and beneficial effects of PEEP would be to use a strategy of setting it at 0.5 × IAP [28]. There are however multiple mentions in the literature of the best PEEP being equal to the IAP, but this should be considered expert opinion, as there have been no trials in humans to evaluate this recommendation.

7.9.3.5 Plateau Pressure Outside of the ARDS Network guidelines recommending a plateau pressure goal of ≤30 cmH2O, only expert opinion is available on the safe plateau pressure in IAH/ ACS. Several articles suggest that it is safe to allow plateau pressure to elevate to

30 cmH2O + IAP/2. Again, this has not been evaluated by trial data.

7.9.4 Positioning During Mechanical Ventilation

There is a growing body of evidence that shows a mortality benefit in patients placed in the prone position with ARDS. In a swine study, it was demonstrated that prone positioning improved PaO2/FiO2 ratio in pigs with increased intra-abdominal pressure more than those with normal abdominal pressures, suggesting an added 7 Intra-abdominal Hypertension and Abdominal Compartment Syndrome 73 therapeutic benefit to prone positioning in patients with concomitant ARDS and IAH [30]. There is a very reasonable concern however that placing a patient prone may in fact increase IAP and therefore worsen or precipitate ACS. This is reassuringly not the case, as demonstrated by a human study in which IAP did not significantly change from supine to prone positioning in ARDS patients [31]. However, a follow- up study did demonstrate a statistically significant increase in IAP from supine to prone. This study did not demonstrate any ill effects of this small 2 mmHg increase [32]. The support surface that patients are placed on when they are placed in the prone position does affect IAP. Foam mattresses increase IAP and specialty air support mattresses do not. However, the increase noted in the foam support surface did not result in a meaningful change in oxygenation, hemodynamic parameters, nor splanchnic circulation. Therefore there is not enough evidence to recommend an air support surface to prevent ACS when utilizing prone positioning in ARDS [33]. Positioning of the head of the bed (HOB) has also shown to change IAP. There is a linear relationship between IAH and increasing the HOB [34]. Whether this simply represents the column of abdominal contents being loaded above, the transduced location of the abdominal pressure in the bladder or a clinically significant increase related to compression of the abdomen by induction of kyphoscoliosis or the rib cage compressing the abdomen downward is unknown.

7.10 Summary

Mechanical ventilation is certainly a challenge in patients with IAH/ACS. However, several key factors need to be considered. ARDS protocol gives a good direction to ventilate these patients while considering IAP into account. This means use of protective tidal volume, recruitment maneuvers, and PEEP level is set according to the “best” compliance of the respiratory system while at the same time avoiding over- inflation of already well-aerated lung regions. Also the reverse Trendelenburg position as well as deep sedation with or without neuromuscular paralysis in severe ARDS cases may improve respiratory mechanics. There is still a general lack of clinical awareness in many ICUs, and no consensus exists on optimal timing of measurement or decompression. Given the effect of this syndrome on any aspect of vital organs, clinicians should measure IAP when any known risk factor for IAH/ACS is present in a critically ill or injured.

References

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25. De Keulenaer BL, De Backer A, Schepens DR, Daelemans R, Wilmer A, Malbrain MLNG. Abdominal compartment syndrome related to noninvasive ventilation. Intensive Care Med. 2003;29(7):1177–81. 26. Kollisch-Singule M, Emr B, Jain SV, et al. The effects of airway pressure release ventilation on respiratory mechanics in extrapulmonary lung injury. Intensive Care Med Exp. 2015;3(1):35. 27. De laet I, MLNG M. ICU management of the patient with intra-abdominal hypertension: what to do, when and to whom? Acta Clin Belg. 2007;62(Suppl 1):190–9. 28. Regli A, Mahendran R, Fysh ET, et al. Matching positive end-expiratory pressure to intra- abdominal pressure improves oxygenation in a porcine sick lung model of intra-abdominal hypertension. Crit Care. 2012;16(5):R208. 29. Staffieri F, Stripoli T, De Monte V, Crovace A, Sacchi M, De Michele M, Terragni PP, Ranieri VM, Grasso S. Physiological effects of an open lung ventilator strategy titrated on elastance- derived end-expiratory trans-pulmonary pressure: study in a pig model. Crit Care Med. 2012;40:2124–31. 30. Mure M, Glenny R, Domino K, Hlastala M. Pulmonary gas exchange improves in the prone position with abdominal distension. Am J Respir Crit Care Med. 1998;2:1785–90. 31. Comment PR. Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis. Surv Anesthesiol. 2000;44(6):360–1. 32. Hering R, Wrigge H, Vorwerk R, et al. The effects of prone positioning on intraabdominal pressure and cardiovascular and renal function in patients with acute lung injury. Anesth Analg. 2001;92(5):1226–31. 33. Michelet P, Roch A, Gainnier M, Sainty J-M, Auffray J-P, Papazian L. Influence of support on intra-abdominal pressure, hepatic kinetics of indocyanine green and extravascular lung water during prone positioning in patients with ARDS: a randomized crossover study. Crit Care. 2005;9(3):R251–7. 34. McBeth PB, Zygun DA, Widder S, et al. Effect of patient positioning on intra-abdominal pressure monitoring. Am J Surg. 2007;193(5):644–7. Impact of Sleep Breathing Disorders in Obese Critically Ill Patients 8

Moh’d Al-Halawani and Christine Won

8.1 Introduction

Sleep breathing disorders are a common but under-recognized cause of acute on chronic hypercapnic respiratory failure in the intensive care unit. Sleep disorders in the intensive care unit may present in the form of obesity hypoventilation syndrome (OHS), obstructive or central sleep apnea, or a combination of the former. Patients may present to the hospital with shortness of breath or acute on chronic hypercapnic respiratory failure and are likely to require monitoring in the intensive care unit [1]. In this section, we will discuss sleep-related breathing disorders that are commonly encountered by clinicians and affect obese patients in the intensive care setting.

8.2 Obesity Hypoventilation Syndrome and Obstructive Sleep Apnea Syndrome

8.2.1 Definitions

Obesity hypoventilation syndrome is a common ailment defined by a triad of obesity—characterized by a body mass index (BMI) more than 30 kg/m2, daytime hypoventilation, and sleep-disordered breathing. Daytime hypoventilation is defined by an arterial partial pressure of carbon dioxide (PaCO2) greater than 45 mmHg during wakefulness and an arterial partial pressure of oxygen (PaO2) lower than

M. Al-Halawani, M.D. • C. Won, M.D., M.S. (*) Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT 06520-8057, USA e-mail: [email protected]; [email protected]

© Springer International Publishing AG 2018 77 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_8 78 M. Al-Halawani and C. Won

70 mmHg. Sleep-disordered breathing occurs in two forms in OHS, one form being obstructive sleep apnea (OSA), which occurs in 70–90% of cases, and the other as nocturnal hypoventilation, occurring in 10–30% [2, 3]. Other causes that could account for daytime hypoventilation, such as neuromuscular disease, obstructive lung disease, and metabolic or central etiologies, must be ruled out [2, 4]. Obstructive sleep apnea syndrome is defined by recurrent episodes of upper airway narrowing or obstruction during sleep, leading to marked reduction or cessation of airflow, hypopneas, and apneas, respectively, associated with recurrent arousals and oxygen desaturation, which leads to sleep fragmentation and daytime symptoms. It is characterized by an Apnea-Hypopnea Index (a measure of the number of events per hour measured on a sleep study) of greater than five per hour of sleep in a symptomatic patient. Daytime symptoms may present as excessive daytime sleepiness, excessive fatigue, mood changes, and concentration difficulties 5[ , 6]. Patients with OHS and OSA usually suffer from severe OSA with AHI > 30 events per hour, with breathing events often associated with significant arterial oxygen desaturation [2, 3]. OSA is also a growing health concern with a prevalence estimate ranging between 3 and 24% in the general population and 10 and 50% in obese men and women. OHS is more prevalent in males, and most patients are diagnosed in their fifth or sixth decade of life. It has a reported prevalence of 10–20% in outpatients presenting to sleep clinics, with the prevalence increasing with BMI, and 30% in hospitalized obese patients [1, 4]. The prevalence of OSA in the intensive care unit population is unknown [2, 5, 6]. As the prevalence of obesity increases, so does the incidence of OHS. However, only a minority of obese individuals develop OHS, suggesting that other factors may be playing a role in its pathogenesis. The respiratory muscles’ response to mass loading due to obesity differs from one patient to another. Studies comparing patients with OHS with matched controls show that OHS patients had lower lung compliance, functional residual capacity, chest wall compliance, and higher lung resistance. This suggests that patient’s BMI and the mechanical load due to obesity may play an important but partial role and is only one factor among many others in the pathogenesis of OHS [3].

8.2.2 Pathophysiology

The pathophysiology of obesity hypoventilation syndrome is complex and not fully understood. Several mechanisms have been proposed in its pathogenesis, including abnormal respiratory system mechanics and restrictive lung disease due to obesity which leads to decreased lung compliance, functional residual capacity, chest wall compliance, and increased lung resistance; impaired central responsiveness to hypercapnia and hypoxemia and ventilatory drive; sleep-disordered breathing; and neurohormonal abnormalities (e.g., leptin resistance). During normal sleep, there is mild hypoventilation and PaCO2 levels increase by 3–5 mmHg. In patients with obesity hypoventilation syndrome, PaCO2 is often increased by greater than 10 mmHg [2, 3]. 8 Impact of Sleep Breathing Disorders in Obese Critically Ill Patients 79

8.2.3 Presentation and Diagnosis

Obesity hypoventilation syndrome and obstructive sleep apnea were first observed in patients with severe obesity. Patients present with nonspecific symptoms but may present with snoring, nocturnal gasping or choking, episodes of apnea, and excessive daytime sleepiness. Facial plethora, large neck circumference, rapid shallow respirations, a loud P2 on cardiac examination, and elevated jugular venous distension are findings on physical examination. The clinician who evaluates severely obese patients should always suspect OHS in individuals presenting with a serum bicarbonate level > 27 mEq/L and consider sleep-disordered breathing in patients with secondary erythrocytosis who present with the symptoms and signs mentioned earlier [2, 7, 8]. OHS patients may present for symptoms of shortness of breath or acute on chronic hypercapnic respiratory failure necessitating admission to the ICU; this diagnosis is usually missed and requires an intensivist with a high index of suspicion. It may be argued that obese patients are more susceptible to hypercapnic respiratory failure due to their tremendous baseline work of breathing and lack of respiratory reserve. These patients may be more susceptible to ventilatory failure when challenged by common hospital events such as atelectasis, aspiration, pneumonia, sepsis, and pulmonary edema. Likewise, patients may decompensate during the course of hospital treatment. For example, when given large amounts of narcotic pain medications or sedatives, metabolic alkalosis induced by diuretics or hyperoxic supplementation may predispose to acute hypercapnic respiratory failure in OHS patients [2]. The definitive test for hypoventilation is an arterial blood gas performed on room air done during wakefulness. The arterial blood gas in OHS demonstrates hypercapnia with PaCO2 > 45 mmHg, hypoxemia with PaO2 < 70 mmHg, and a relatively normal Alveolar-arterial (A-a) gradient. However, due to the ventilation and perfusion mismatch in the lung bases of obese patients (mainly due to atelectasis), there might be a slight increase in A-a gradient [2]. The diagnosis also becomes complicated in the acute setting, when underlying pulmonary injury or the use of sedatives or narcotics may affect arterial blood gas measurements. An astute clinician is able to interpret acute and chronic changes in blood gases and explore a stable-state medical history, to help make a diagnosis of sleep-disordered breathing. Pulmonary function testing reveals a mild-to-moderate restrictive ventilatory defect and a severely reduced expiratory reserve volume [8]. Obese individuals require more work for their ventilation as their breathing lies on a less compliant portion of the pressure-volume curve. They may also experience expiratory flow limitation with increased alveolar end-expiratory pressure due to incomplete expiration. Lung hyperinflation in severely obese individuals overstretches the diaphragm leading to inefficient respiration, as the oxygen consumption dedicated to the work of breathing increases by fivefold 3[ ]. Nocturnal polysomnography is the gold standard for the diagnosis of sleep- disordered breathing (e.g., OSA) that may accompany or occur independent of 80 M. Al-Halawani and C. Won

OHS. Home sleep testing is also an option for selected patients, especially those with high probability of straightforward OSA [9]. Some studies have shown the feasibility of performing overnight polysomnography in the ICU setting or in patients who had acute respiratory failure immediately after recovery for the diagnosis of sleep-related breathing disorders. Although it is challenging to diagnose OHS or OSA in the acute setting, evaluation and the initiation of treatment during hospitalization allow the patient to be discharged from the hospital with appropriate care and follow-up [2].

8.2.4 Clinical Implications

Untreated OSA or OHS may lead to significant morbidity to the patients and carry risks independent of obesity alone. Compared with obese controls, OHS patients are at greater risk for developing congestive heart failure, angina, and cor pulmonale. Patients with OHS also have higher rates of hospitalization, increased healthcare costs, intensive care unit admission, need for mechanical ventilation during hospitalization, and an overall worse quality of life [1, 2]. OHS is a systemic illness involving many organ systems with complicated interactions between these systems. Patients admitted to the ICU with OHS also have a high risk of severe obesity- related multisystem organ dysfunction. The organ system derangements include hypercapnic respiratory failure, systemic hypertension, left ventricular hypertrophy with diastolic dysfunction, right ventricular volume overload, pulmonary hypertension, chronic renal failure, and nonalcoholic steatohepatitis [4]. OSA has been identified as an important independent risk factor for cardiovascular disease. It also carries a high incidence of comorbid conditions that commonly present in patients admitted to the ICU, including diabetes mellitus, hypertension, ischemic heart disease, heart failure, and cerebrovascular disease. OSA-induced nocturnal hypoxemia has been shown to be a major contributor in the pathogenesis of pulmonary hypertension and is a risk factor for the development of arrhythmias including idiopathic atrial fibrillation, atrial flutter, ventricular tachycardia, and bradyarrhythmias in obese patients. Sleep-disordered breathing was also identified as a common contributing cause of hypercapnic respiratory failure in obese patients in the ICU setting with these patients being more likely to require intubation or noninvasive positive pressure ventilation. Patients with untreated OSA, given the association with the comorbidities listed above, may have a higher risk of morbidity and mortality in the ICU [5, 7]. Furthermore, obese patients with OHS or OSA have a higher rate of preoperative and postoperative cardiopulmonary complications compared to lean patients, and this risk increases with the number of associated comorbidities. This may be related in part to the effects of medications (e.g., anesthetics, sedatives, opiates) that affect the central nervous system, suppressing the breathing center and upper airway muscle tone and precipitating sleep-disordered breathing. This effect is seen mostly in the immediate postoperative period. In addition, on the first postoperative night, patients will have decreased to absent 8 Impact of Sleep Breathing Disorders in Obese Critically Ill Patients 81 rapid eye movement (REM) sleep; this is usually followed by REM rebound on subsequent nights. It is known that OSA may worsen in REM sleep, which leads to an increase in hypoxemic episodes about threefold on the second and third postoperative nights, increasing the risk of complications. Therefore, it is important to identify patients that have a high risk of having OSA in the preoperative period. One method is by using the STOP-BANG questionnaire, an easy-to- administer questionnaire that has been approved to identify patients with high risk of OSA. It consists of 8 yes or no questions related to the signs and symptoms of OSA including snoring, tiredness during the day, observed apneas, high blood pressure, body mass index > 35 Kg/m2, age > 50, neck circumference > 40 cm, and male gender. A STOP-BANG score higher than or equal to three suggests that the patient has a high risk of having OSA [9].

8.2.5 Management

Treatment of OHS in the critically ill patient should include acute management of respiratory failure as well as the planning of a long-term care strategy to deal with obesity, chronic respiratory failure, and other comorbidities. Continuous positive airway pressure (CPAP), bi-level positive airway pressure (BPAP), and average volume-assured pressure support (AVAPS) are all modes of noninvasive positive pressure ventilation (NIPPV) that are currently used to manage patients with OHS. NIPPV reduces the work of breathing and decreases respiratory muscle exertion during sleep. It provides positive end-expiratory pressure, which promotes alveolar recruitment and oxygenation, while eliminating obstructive apneas and hypopneas by maintaining airway patency, leading to improvements in oxygenation, arousals and sympathetic hyperactivity, and daytime function [3]. Bi-level positive airway pressure therapy may be a more attractive option for OHS treatment as BPAP augments ventilation during sleep in addition to treatment of sleep-disordered breathing [8]. Tracheostomy is often considered definitive therapy for OSA as it bypasses the upper airway. However, in patients with OHS, tracheostomy may improve but does not reliably eliminate hypoventilation, and positive airway pressure support may still be required [2]. The treatment of OHS and the accompanying sleep-disordered breathing using positive airway pressure (PAP) or tracheostomy can have significant improvements in daytime PaCO2 and PaO2 even in the absence of weight loss, with an effect that is more pronounced with greater hours of usage at night, although the effect reaches a plateau beyond 4.5 h of PAP usage. Every hour of PAP use improves the daytime PaCO2 by 2 mmHg and PaO2 by 3 mmHg, approximately. Moreover, the need for daytime oxygen supplementation decreases from 30 to 6% in patients treated with PAP. Improvement in the hypercapnic and hypoxemic ventilator responses is also noted after only 2 weeks of PAP therapy. Treatment of OHS is also associated with improved quality of life, sleep-related symptoms, pulmonary arterial pressures, erythrocytosis, and mortality. Nonetheless, the tendency to develop sleep-disordered breathing and chronic hypoventilation does not 82 M. Al-Halawani and C. Won reverse despite PAP therapy, and the negative effects will recur if OHS patients stop using PAP [3, 8]. Acute respiratory failure in patients with OHS may be managed with invasive and noninvasive ventilatory strategies. NIPPV (CPAP, BPAP, or AVAPS), oxygen, or both will possibly be needed at home to manage chronic respiratory failure. Critically ill OHS patients may have contraindications to the use of NIPPV via a nasal or oronasal interface and may require endotracheal intubation and receive mechanical ventilation. Reasons for invasive mechanical ventilation would include altered mental status, hemodynamic instability, multi-organ failure, and severe acidosis. Clinicians must be aware of the challenges that they may face when attempting invasive airway management of a critically ill obese patient. Endotracheal intubation may be difficult in this population owing to the limited neck mobility and mouth opening and rapid oxygen desaturation when obese patients assume the supine position, which occurs due to an additional decrease in the functional residual capacity and expiratory reserve volume. Therefore, intubation in obese critically ill patients requires technical skill and familiarity with advanced techniques [8]. Upon clinical stabilization, OHS patients may require a PAP titration (with CPAP, BPAP, or AVAPS) during overnight polysomnography to determine optimal PAP settings for treatment of their sleep-disordered breathing and hypoventilation. During the titration study, expiratory pressures are adjusted to eliminate OSA, and inspiratory pressures are adjusted to ensure adequate tidal volumes, CO2 levels, and oxygenation [2]. Other important aspects that should be considered in the chronic management of OHS patients include weight loss strategies and pharmacologic respiratory stimulation [8]. Weight loss is the most important element in the management of OHS, and treating OHS without achieving significant weight loss is unlikely to reduce the significant morbidity and mortality associated with this syndrome. Weight loss in morbidly obese persons has been shown to improve lung volumes, lung function, gas exchange, and pulmonary artery pressures. Respiratory muscle strength and performance are also improved by weight loss. It is difficult to achieve and maintain weight loss by dieting and medical management alone. Bariatric surgery is the most effective weight loss remedy, where patients lose weight quickly and maintain this weight loss over a long period of time. Bariatric surgery has thus been the focus of studies on OSA and obesity. Around 70% of bariatric surgery patients have OSA. Weight loss surgery leads to an average BMI reduction of 15 kg/m2, and this has been associated with improvements in AHI of >30 events per hour. In addition, bariatric surgery has been shown to improve pulmonary function, pulmonary hypertension, and reverse left ventricular hypertrophy [2, 4]. Tracheostomy may be an option for patients with refractory OHS who are intolerant or non-compliant to NIPPV, have severe cor pulmonale, or fail weaning off mechanical ventilation. Tracheostomy bypasses the upper airway, significantly decreasing the apneas and hypopneas related to airway obstruction. OSA and daytime hypercarbia improve but may not be reliably eliminated due to several factors 8 Impact of Sleep Breathing Disorders in Obese Critically Ill Patients 83 including anatomic (e.g., partial obstruction of the tracheostomy tube by redundant chin and neck skin), the emergence of central apneas, work of breathing through the tracheostomy, or persistent central hypoventilation [1, 2, 8]. Respiratory stimulants have been the most explored pharmacological treatment for OHS and are used as an adjunct to PAP therapy. Acetazolamide is a carbonic anhydrase inhibitor that decreases serum bicarbonate levels by 5 mEq/L within 24 h, decreasing the serum pH up to 0.1, thereby promoting increased minute ventilation by up to 15% and reducing PaCO2 by 5–6 mmHg. Medroxyprogesterone can also be used in some patients in conjunction with PAP therapy to promote ventilation [1, 2]. As mentioned earlier, there is a higher risk of perioperative complications in patients with sleep-disordered breathing and OHS. Several studies addressed the management of severely obese patients immediately after surgery. The primary issue in postoperative period is the interaction between the untreated sleep apnea, the recovery from anesthesia and sedation, and the need for postoperative pain management. In obese patients, there is evidence that NIPPV prevents respiratory failure immediately postextubation. Many patients with OSA use CPAP at home to maintain arterial oxygenation; therefore, the use of CPAP postoperatively in these patients is critical to maintain oxygenation [2, 7].

8.3 Central Sleep Apnea

Central sleep apnea (CSA) is characterized by apneas and hypopneas in the setting of a markedly decreased or absent breathing effort. Normally, the ventilatory drive during sleep is regulated by chemoreceptors in the brainstem and carotid bodies. The respiratory drive increases in response to elevated levels of PaCO2 maintaining its range within the normal limits. Patients with CSA have an abnormal regulation of breathing in the respiratory centers of the brainstem. Patients with heart failure (HF) are at high risk of developing CSA as they are inclined to have an exaggerated response to hypercapnia. This results in an inappropriate hyperventilation during sleep, which in turn results in hypocapnia and suppression of the central respiratory drive causing a central apnea. This tends to occur in cyclical waxing and waning pattern and is termed Cheyne-Stokes breathing. CSA and Cheyne-Stokes breathing were identified as a marker of poor prognosis in HF; studies have shown that patients with HF and CSA may have decreased survival compared to patients with HF alone and were at higher risk of recurrent hospital admissions. CSA is also associated with an increased sympathetic tone during sleep, peripheral vasoconstriction, tachycardia, and activation of the renin-angiotensin- aldosterone system which may have detrimental effects on patients with HF [10]. Treatment of CSA can be achieved by supplemental oxygen, CPAP, or adaptive servoventilation (ASV). Supplemental oxygen therapy has been shown to improve the nocturnal oxygen saturation and lessen the sympathetic activity associated with 84 M. Al-Halawani and C. Won

CSA. Similarly, treatment with CPAP has been associated with improvement in AHI, sympathetic tone, as well as improvement in the left ventricular ejection fraction (LVEF) in patients with HF and CSA. A more recent technology, ASV, is an advanced mode of NIPPV in which the device provides inspiratory support and additional breaths to overcome apneas and hypopneas and withdraws support during hyperventilation, while delivering a baseline positive airway pressure. ASV has been shown to be a more effective treatment modality for CSA and Cheyne-Stokes breathing than CPAP or oxygen therapy and is usually better tolerated by patients than CPAP. A recently published large randomized controlled trial, SERVE-HF, evaluated the effects of ASV on hospitalization, lifesaving cardiovascular intervention, or death in patients with symptomatic New York Heart Association class II–III systolic HF (with LVEF ≤ 45%) and CSA. ASV appeared to be highly efficacious in reducing AHI but was associated with an increased all-cause and cardiovascular mortality in this patient population. As a result of this study, ASV is no longer a recommended treatment for CSA in patients with symptomatic systolic HF with reduced LVEF (≤45%) [10]. The optimal treatment, and whether therapy is even required for this patient population, is currently unknown and requires further investigation.

Conclusion Sleep disorders in the critical care setting are often underdiagnosed and undertreated, leading to increased morbidity and mortality in the critically ill, obese population. Prompt diagnosis and treatment and long-term follow-up are essential for improved clinical outcomes.

8.4 Key Points

1. Sleep breathing disorders commonly affect obese patients in the critical care setting but are usually under-recognized or undertreated by clinicians. The most common forms are obesity hypoventilation syndrome, obstructive sleep apnea, or a combination of these. 2. Patients may present with acute on chronic hypercapnic respiratory failure that usually requires admission to the intensive care unit. 3. Diagnosis of OHS is made by arterial blood gases and pulmonary function test. Patients also require polysomnography to evaluate for sleep-disordered breathing. 4. Positive airway pressure using CPAP, BPAP, or AVAPS with or without supplemental oxygen is the treatment of choice in the acute setting. Weight loss is also important to consider as part of chronic management. 5. Central sleep apnea is usually seen in patients with heart failure. Treatment with supplemental oxygen, CPAP, or ASV may be considered in the appropriate patient. 8 Impact of Sleep Breathing Disorders in Obese Critically Ill Patients 85

References

1. Lee WY, Mokhlesi B. Diagnosis and management of obesity hypoventilation syndrome in the ICU. Crit Care Clin. 2008;24(3):533–49. vii 2. Won CM. Obesity hypoventilation syndrome: an impending epidemic. Clin Pulm Med. 2013;20(1):36–42. 3. Won CH, Kryger M. Sleep in patients with restrictive lung disease. Clin Chest Med. 2014;35(3):505–12. 4. Marik PE, Desai H. Characteristics of patients with the “malignant obesity hypoventilation syndrome” admitted to an ICU. J Intensive Care Med. 2013;28(2):124–30. 5. Bolona E, Hahn PY, Afessa B. Intensive care unit and hospital mortality in patients with obstructive sleep apnea. J Crit Care. 2015;30(1):178–80. 6. Karnatovskaia LV, et al. Obstructive sleep apnea, obesity, and the development of acute respiratory distress syndrome. J Clin Sleep Med. 2014;10(6):657–62. 7. Poirier P, et al. Cardiovascular evaluation and management of severely obese patients undergoing surgery: a science advisory from the American Heart Association. Circulation. 2009;120(1):86–95. 8. Jones SF, Brito V, Ghamande S. Obesity hypoventilation syndrome in the critically ill. Crit Care Clin. 2015;31(3):419–34. 9. Vasu TS, et al. Obstructive sleep apnea syndrome and postoperative complications: clinical use of the STOP-BANG questionnaire. Arch Otolaryngol Head Neck Surg. 2010;136(10):1020–4. 10. Pearse SG, Cowie MR. Sleep-disordered breathing in heart failure. Eur J Heart Fail. 2016;18(4):353–61. Drugs and Medications 9 Clement Lee, Kate Millington, and Ari Manuel

9.1 Introduction

Obesity is becoming one of the major health problems across the world [1]. The risks involved with being overweight or obese are related to the deposition of adipose tissue (adiposity) that is associated with increased risk of adverse health problems. Dosing medications in obese subjects is a challenge as these patients are often excluded from many premarketing clinical drug trials. Current dosage recommendations for most drugs for obese patients are most often inferred from normal-weight persons. As the pharmacokinetics (PK) and pharmacodynamics (PD) of many drugs are altered by the disproportional increase of adiposity relative to lean body mass in morbid obesity, dosing based on total body weight could lead to the risk of overdose and serious clinical complications. An individualised dosing scalar that takes into account the changed body composition should be used in MO patient, particularly in anaesthesia and intensive care.

9.1.1 Methods for Measuring Adiposity

Body mass index (BMI) is a very simple formula and still commonly used as a screening tool in assessing the total body adiposity. However, the calculation takes absolute body weight into account and cannot differentiate between fat and muscle mass. The simple formula has a pooled specificity of 90% and a

C. Lee (*) • K. Millington Department of Anaesthesia and Perioperative Medicine, Westmead Hospital, Westmead, NSW, Australia e-mail: [email protected]; [email protected] A. Manuel Oxford Sleep Unit, Respiratory Department, Churchil Hospital, Oxford OX3 7LE, UK e-mail: [email protected]

© Springer International Publishing AG 2018 87 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_9 88 C. Lee et al. pooled sensitivity of 50% to identify excess adiposity [2]. The poor sensitivity of the BMI criteria is because it is unable to take the variations of adiposity with different age groups, gender and ethnicity into account [3]. Body fat distribution can be estimated by waist circumference. It has excellent correlation with imaging techniques and is a good predictor of all-cause mortality. However, it does have some practical limitations including location of measurement and cut-off values. Various ratios such as waist-to-height and waist-to-thigh ratios have been introduced to predict the risk of metabolic disorders in obesity, but they have sparked debate and controversy. Gelber et al. and Taylor et al. could not identify enough clinical evidence to show these ratios were more accurate to predict adverse health events compared to BMI, and the routine use of ratios to assess adiposity is hence not recommended [4, 5]. Assessment of adipose tissue with CT and MRI is mainly restricted to research and limited by costs as well as the body size of severely obese patients.

9.1.2 Methods of Measuring Body Composition

Apart from measuring body fat, interest has been developing to measure other body composition like fat distribution, muscle mass, fat-free mass and bone mass. Several techniques can be used including anthropometry, skinfold thickness, near-infrared interactance, dual-energy X-ray absorptiometry, bioelectric impedance analysis (BIA) and CT/MRI. None of the methods stand out without error as most are extrapolated from normal-weight persons. Anthropometry and BIA are the most routinely used clinically. The other methods are expensive and require more expertise and training.

9.2 Which Weight Approaches Should Be Used for Calculating Drug Dosage?

9.2.1 Total Body Weight

Total body weight (TBW) is valid for dosing medications in normal-weight patients. However, blind use of TBW for dosing any drugs could lead to an overdose in obese patients. Generally, fat tissue increased proportionally with TBW, but the percentage of lean body tissue per kilogramme of TBW decreases. Highly lipophilic drugs tend to have an increased volume of distribution (Vd), but this relationship is not linear with TBW due to changes in other factors such as drug clearance and plasma protein binding in obesity. Less lipophilic or water-soluble agents show less significant or no change in Vd.

9.2.2 Ideal Body Weight

The term ideal body weight (IBW) was originally developed by the insurance industry to correlate maximum life expectancy with the ideal body weight, for 9 Drugs and Medications 89 each gender and height. IBW as a dosing scalar is irrational as all obese individuals with the same sex and height would receive the same dose, regardless of their body composition. IBW could be useful in patients up to a BMI of 40 kg/m2, but there is a risk of underdosing. Some practitioners correct this shortcoming by adding 40% of TBW to IBW in the dosage (adjusted body weight).

9.2.3 Lean Body Weight

Lean body weight (LBW), sometimes known as fat-free mass (FFM), describes weight without the adipose tissue. The formula is sex specific and included measures of TBW and BMI. The calculations have accurate predictive properties when compared to dual-energy X-ray absorptiometry, a gold standard for measurement of LBW. In obese patients, LBW is significantly correlated with cardiac output, an important factor for early drug distribution kinetics. Researchers suggest that drug dosage based on LBW is more appropriate since almost all metabolic activity in the body occurs in the LBW compartment, and drug clearance increases linearly with LBW.

9.2.4 Predicted Normal Weight

This formula is to predict the normal weight of an overweight or obese person. It works out the sum of an individual’s LBW and their predicted normal fat mass [6]. This has been specifically developed to characterise the pharmacokinetics of drugs.

Weight terms Formula

Total body weight Actual body weight of the person

Ideal body weight Female: Height (cm) –105 Male: Height (cm) –100

Adjusted body weight IBW (kg) + 0.4 (TBW (kg) – IBW (kg)

Lean body weight Female: 9270 x TBW/ (8780 +244x BMI) (Janmahasatian 2005) Male: 9270 x TBW/(6680 +216 x BMI) Predicted body weight Female: 1.75 x TBW – 0.0242 x BMI x TBW –12.6 Male: 1.57 x TBW – 0.0183 x BMI x TBW –10.5

Fig. 9.1 The five most useful terms for describing patients’ weight 90 C. Lee et al.

Total body 190 cm male weight (kg) (With 15% body fat, IBW 82 kg)

300

Excess fat

200

Fat mass

100 ‘Normal’ fat

Learn body mass

20 40 60 80 100 BMI (kg.m-2)

Fig. 9.2 Relationship between total body weight and body mass index (BMI) and lean body mass (Source: CE Nightingale Distributed under CC BY-NC-ND 3.0)

9.3 Pharmacokinetic Changes in Obesity

Oral absorption of drugs does not appear to change in obesity as suggested previously. Intramuscular administration should be avoided due to unpredictable pharmacokinetics. Obesity increases both adipose and lean tissue masses compared with nonobese subjects of the same age, height and sex. These changes in body composition alter the volume of distribution of many drugs. The volume of the central compartment is largely unchanged, but dosages of lipophilic and polar drugs need to be adjusted due to the increased volume of distribution. An increased in Vd could prolong the elimination half-life despite increased clearance. Metabolic changes are caused by high concentrations of the drug accumulating into adipose tissue that is relatively metabolically inactive. For the less fat-soluble drugs, the LBW should be used. MO patients have an increased cardiac output, and this alters the early pharmacokinetics of drug distribution. Obesity-induced cardiomyopathy may lead to heart failure which can affect tissue perfusion and drug distribution [7]. Drug metabolism and clearance may be affected by obesity-induced changes in hepatic and renal function. Hepatic clearance is usually unchanged or even 9 Drugs and Medications 91 increased in obese patients. Non-alcoholic steatohepatitis causes hepatocyte dysfunction [8] and affects drug elimination. Creatinine clearance increases in otherwise healthy obese subjects in proportion to their estimated LBW. Dosage of drugs dependent on renal excretion needs to be adjusted in individuals with chronic renal impairment. The effects of obesity on the binding of drugs to plasma proteins are still unclear. It has been reported increased concentrations of plasma protein and fatty acid molecules may interfere with protein binding of some drugs, increasing their free plasma concentrations [9]. On the other hand, the increase in concentrations of acute phase proteins, including α1-acid glycoprotein, may reduce the free plasma concentrations of certain drugs.

Volume of distribution

Decreased fraction of total body water

Increased adipose tissue

Increased lean body mass

Altered tissue protein binding

Increased blood volume and cardiac output

Plasma protein binding

Increased 1-acid glycoprotein and free fatty acids

Drug clearance

Increased renal blood flow

Increased GFR and tubular secretion

Abnormal liver function

Fig. 9.3 Factors affecting drug pharmacokinetics in obesity 92 C. Lee et al.

9.4 Impact of Obesity on Pharmacokinetics of Common Anaesthetic Drugs

9.4.1 Intravenous Induction Agents

9.4.1.1 Thiopental Thiopental is rapidly distributed from the blood to highly perfused tissues, followed by less inactive tissue depots such as muscles and fat. The induction dose for obese patients should be calculated based on LBW and not on TBW [10]. Limited information is available on the most appropriate weight scalar to use for continuous infusion as thiopental is very rarely used for maintenance of general anaesthesia because of its long context-sensitive half-life and prolonged recovery period.

9.4.1.2 Propofol Like thiopental, it is a highly lipophilic drug which distributes rapidly from the blood to tissues. The speed of onset and duration of effect are determined by the cardiac output. LBW is a more appropriate weight-based scalar than TBW for induction of general anaesthesia in MO patients. Propofol is ideally suited for maintenance infusions in MO patients due to its favourable pharmacokinetic profile [11]. In a study done in obese patients, Servin et al. demonstrated minimum propofol accumulation or delayed emergence when obese patients received continuous infusion based on their TBW [12].

9.4.1.3 Etomidate Induction with this induction agent may be preferable over thiopental and propofol in haemodynamically unstable MO patients. The standard induction dose is 0.3 mg/ kg (range 0.2–0.6 mg/kg). The PK and PD of etomidate in obese patient are lacking. Induction dose is justifiable to be based on LBW given that the drug has similar pharmacokinetics to propofol and thiopental.

9.4.1.4 Benzodiazepines Benzodiazepines are highly fat-soluble drugs, and the excess fat tissue in obese patients significantly influences their volume of distribution and elimination half-life. A single intravenous dose should be increased at least in proportion to TBW in MO patients because of the large volume of distribution. On the contrary, the dose should be adjusted to IBW rather than TBW if a continuous infusion is used as clearance is not significantly different compared to nonobese subjects [13]. Due to longer half-lives in obese critically ill patients, the time to awaken can be prolonged after 48 h of continuous infusion even when IBW is used as the dosing scalar.

9.4.1.5 Inhalational Anaesthetics The pharmacokinetics of modern volatile agents does not seem to be significantly influenced by obesity [14]. All halogenated agents have been used safely in obese patients. Desflurane and sevoflurane are both characterised by a more rapid cerebral 9 Drugs and Medications 93 wash-in and wash-out than other halogenated agents resulting in a more rapid recovery from anaesthesia. These agents have been marketed as the ‘anaesthetic of choice’ for obese patients. Desflurane has the lowest fat-to-blood solubility among all the commonly used inhalational agents. Its smaller blood/gas coefficient (0.42) suggests a more rapid kinetic profile 15[ ]. These properties make desflurane as a favourable agent to be used in MO patients especially for long procedures. One clinical study, however, demonstrated the low-fat solubility property of desflurane contributed to only a 2-min difference in time to awakening when compared to sevoflurane 16[ ].

9.4.1.6 Muscle Relaxants Muscle relaxants are polar and hydrophilic drugs. Succinylcholine is a rapid onset depolarising muscle relaxant with short duration of action. Due to increased plasma cholinesterase in MO patients, succinylcholine administration should be based on TBW as it has been shown to provide better intubating conditions when compared to dosing on LBW or IBW [17]. Non-depolarising muscle relaxants such as rocuronium and vecuronium are hydrophilic. They are primarily distributed in the central component, and dosing should be based on LBW to avoid a prolonged duration of action, particularly in MO patients [18]. Since cisatracurium is eliminated by Hoffman degradation, it had been suggested to be the neuromuscular-blocking drug of choice in obese patients [19] until sugammadex became widely available in recent years. Like other agents, dosing for cisatracurium should be based on IBW. Reported recovery times for rocuronium and all other muscle relaxants are highly variable in obese patients. Intraoperative neuromuscular monitoring is strongly recommended in all MO patients. Recovery from neuromuscular blockade is defined as a train-of-four (TOF) ratio > 0.9. Postoperative residual paralysis is one of the major causes for increased risk of these critical respiratory events. Even minimal degrees of neuromuscular blockade can result in functional impairment of the pharyngeal and oesophageal muscles resulting in aspiration.

9.4.1.7 Neuromuscular Block Reversal Agents The recommended dose of neostigmine is 0.04–0.8 mg/kg, not to exceed a total dose of 5.0 mg. The reversal effect appears within 1–2 min, and the maximum effect occurs within 6–10 min. Some studies demonstrated the maximum effect was more delayed in obese patients than in the normal-weight patients. The dose- response relationship of neostigmine in obese patient is not studied. Neostigmine/ glycopyrrolate combinations are not effective in reversing profound neuromuscular block. Sugammadex is a selective agent that encapsulates rocuronium and vecuronium. Although sugammadex has a lower affinity for vecuronium than for rocuronium, reversal of vecuronium is still effective because fewer vecuronium 94 C. Lee et al. molecules are present in vivo for equivalent blockade (vecuronium is approximately seven times more potent than rocuronium). The bound complex is excreted via kidneys. Since sugammadex only distributes in the extracellular fluid volume, a dose of 2–4 mg/kg based on IBW is recommended for an incomplete block [20].

9.4.1.8 Opioids New synthetic opioids (fentanyl/sufentanil/remifentanil) are widely used for pain treatment, but MO patients may be particularly susceptible to the side effects of this class of drugs due to altered pharmacokinetics of these drugs in these subjects. The high cardiac output in obese patients will result in lower fentanyl concentration in the initial phase of distribution. Both loading and maintenance dose of these drugs should be based on LBW because the drug clearance does not increase linearly with TBW in obese patients [21]. Using the TBW to calculate the dose of opioids may increase the risk of overdose and respiratory depression. Morphine is a hydrophilic opioid which is mainly distributed in the LBW compartment only [21]. The dosage for hydrophilic drug should be on IBW rather than on LBW. Patient age [22] and comorbidities such as the presence of obstructive sleep apnoea (OSA) and obesity hypoventilation syndrome (OHS) and chronic renal impairment must be considered when used in MO patients. There are case reports describing respiratory distress after initiation of morphine PCA postoperatively in MO patients [23]. For postoperative analgesia after major operations, patient-controlled analgesia (PCA) without background infusion is advised. PCA dosage and lockout time period should be individualised to each patient. All patients with known significant OSA and OHS will warrant continuous pulse oximetry monitoring in a level 2 unit [24]. In some cases, arterial lines will allow repeated blood gas sampling to detect rising carbon dioxide level. Percutaneous CO2 monitoring is a potential alternative. A multimodal approach to pain therapy that involves opioid-sparing adjuncts will be beneficial in MO patients. Epidural or regional nerve blocks (both intermittent and continuous) are effective techniques resulting in reduced postoperative opioid requirements [25, 26]. Given the range of comorbidities in MO patients, the potential benefits of multimodal approaches must weigh against the individual patient’s risk factors.

Conclusions Obesity is a rapidly growing global health problem. As the pharmacokinetics of many intravenous drugs are affected by obesity, the adaptation of drug dosages to obese patients is a subject of concern for many health practitioners. Future dose exposure-response studies are needed to provide evidence-based dosing instructions in drug labels for all classes of obese patients. 9 Drugs and Medications 95

References

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22. Macintyre PE, Jarvis DA. Age is the best predictor of postoperative morphine requirements. Pain. 1996;64:357–64. 23. Lotsch J, Dudziak R, Freynhagen R, et al. Fatal respiratory depression after multiple intravenous morphine injections. Clin Pharmacokinet. 2006;45:1051–60. 24. Gross JB, Bachenberg KL, Benumof JL, et al. Practice guidelines for the perioperative management of patients with obstructive sleep apnea: a report by the American Society of Anesthesiologists task force on perioperative management of patients with obstructive sleep apnea. Anesthesiology. 2006;104:1081–93. 25. Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J Anesth. 2001;87:62–72. 26. Von Ungern-Sternberg BS, Regli A, Reber A, Schneider MC. Effect of obesity and thoracic epidural analgesia on perioperative spirometry. Br J Anaesth. 2005;94:121–7. Part III Invasive Mechanical Ventilation in the Critically Ill Obese Patient Preoxygenation Before Intubation in the Critically Ill Obese Patient 10

Francesco Zarantonello, Carlo Ori, and Michele Carron

10.1 Introduction

10.1.1 The Impact of Obesity on the Respiratory System

Obese patients exhibit alterations both in lung volumes and respiratory mechanical properties that are inversely correlated with body mass index (BMI) [1]. With regard to lung volume, expiratory reserve volume (ERV) and functional residual capacity (FRC) are significantly decreased, and the supine position further decreases ERV and FRC in both awake and anesthetized obese patients [2]. This results in ventilation–perfusion mismatch and increased intrapulmonary shunting, which eventually leads to arterial hypoxemia and hypercapnia [1–3]. Both forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) may be reduced, particularly among morbidly obese patients [1], even if the FEV1/FVC ratio often remains unchanged [1–3]. Breathing effort, basal metabolic rate, and oxygen consumption are also increased in obese patients [1], contributing to a further decrease in respiratory reserve [4]. Obesity decreases the compliance and increases the resistance of the respiratory system. These alterations may be explained, at least in part, by the reduction in lung volume due to atelectasis formation and/or airway closure [1–3].

F. Zarantonello, M.D. (*) • C. Ori, M.D. • M. Carron, M.D. Department of Medicine, Anesthesiology and Intensive Care, University of Padova, Via C. Battisti, 267, 35121 Padova, Italy e-mail: [email protected]; [email protected]; [email protected]

© Springer International Publishing AG 2018 99 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_10 100 F. Zarantonello et al.

10.1.2 The Impact of Obesity on Airway Management in Obese Patients in Acute Care Settings

Obesity is associated with various clinical features including fat deposition in tissues surrounding the upper airway, at the occipitus and in the neck, as well as pharyngeal tissue inflammation. In patients with obstructive sleep apnea (OSA), all the aforementioned characteristics may lead to difficulty with face mask ventilation, endotracheal intubation, or both [1–3]. OSA, neck circumference > 42 cm, and BMI > 50 kg/m2 are independent predictors of difficult airway management in obese patients [5–7], and anatomic as well as physiopathologic alterations in respiratory function [8, 9] adversely affect the ability to maintain adequate oxygenation after loss of consciousness during intubation attempts [10]. Increased oxygen consumption and alterations of gas exchange due to lung disease, pulmonary edema, atelectasis, or acute respiratory distress syndrome in critically ill patients might make intubation even more difficult, especially in emergency situations [11]. A recent prospective observational study reported that the incidence of difficult intubation of obese patients was doubled in an intensive care unit (ICU) setting compared to the operating room (OR) (16.2% vs. 8.2%, risk ratio [RR] 1.9, 95% confidence interval [CI] 1.5–2.6,p < 0.0001). Severe life-threatening complications associated with intubation were also more frequent in the ICU than in the OR (41% vs. 2%, RR 21.6, 95% CI 15.4–30.3, p < 0.01) [11]. Intubation may expose critically ill patients to severe hypoxemia, especially when the procedure takes a long time or requires multiple attempts. Indeed, hypoxemia has been reported to occur in up to 20% of ICU patients during intubation, and multiple attempts at laryngoscopy were required in 10% of cases [12].

10.2 Discussion and Analysis

10.2.1 Preoxygenation

Preoxygenation aims to increase the oxygen reserve to extend the “safe apnea period” (SAP). The SAP is the time available before hypoxemia develops between anesthesia induction and the moment in which the airway is secured, and it represents the most critical period during intubation, particularly in critically ill obese patients [13, 14]. The main determinants of SAP length are the patient’s own oxygen reserve, which is contained mainly in the blood and lungs, and its consumption rate. Oxygen in the blood is either freely dissolved in plasma or bound to hemoglobin, but these reserves are barely enhanced by breathing pure oxygen as the hemoglobin is already fully saturated when the healthy individual breaths room air, while the content of oxygen dissolved in plasma is almost negligible [15]. The FRC is the most relevant oxygen store available in the lung, and in the normal patient it has a volume of about 2500–3000 mL. Breathing ambient air and having a fraction of alveolar oxygen

(FAO2) of 16%, a person is theoretically able to store up to 0.16 × 3000 = 480 mL 10 Preoxygenation Before Intubation in the Critically Ill Obese Patient 101

of oxygen. Breathing pure oxygen can hypothetically bring the FAO2 up to 95%, increasing the oxygen reserve stored in the FRC to 0.95 × 3000 = 2850 mL [16] and almost doubling SAP length in the lean patient [15]. Optimizing intubation conditions by improving oxygenation before tracheal intubation is therefore of crucial importance in critically ill obese patients.

10.2.2 Preoxygenation Strategies

10.2.2.1 Oxygen Supplementation During Spontaneous Breathing This strategy consists of supplying oxygen-rich gas while the patient continues to breathe spontaneously and can be either “slow” or “fast.” The “slow” method allows most of the patients to reach a good level of preoxygenation after 3 min of tidal volume breathing (TVB) at 100% fraction of inspired oxygen [17], while “fast” preoxygenation, which is based on four to eight deep vital capacity breaths, theoretically achieves the same result in 30–60 s [17]. A randomized clinical trial compared 3 min of TVB versus eight deep breaths in 1 min as preoxygenation methods in morbidly obese patients: no differences were found in end-tidal oxygen concentration or SAP length [18].

The fraction of expired oxygen (FEO2) is a good indicator to ensure adequate preoxygenation, which can be considered satisfactory when FEO2 is >90% [19]. In the ICU, the analysis of expired oxygen concentration is seldom available, and frequently clinicians only rely on peripheral oxygen saturation (SpO2). It is important to note that SpO2 does not reflect preoxygenation adequacy, because even if the lung reserve is not filled with oxygen, the SpO2 might already be 100% [16]. Whatever the technique, the key step for obtaining adequate preoxygenation depends on ensuring a tight seal between the mask and the patient’s face. In fact, failure in obtaining a tight seal results in 20% dilution of oxygen with air, and keeping the face mask just 1 cm from the patient’s face results in 40% dilution [20]. This can have detrimental consequences on the primary aim of preoxygenation, which is filling the FRC with oxygen-rich gas. When conventional preoxygenation is judged inadequate, further methods can be employed before proceeding with intubation, if time permits.

10.2.2.2 Noninvasive Positive Pressure Ventilation Severe ventilation–perfusion mismatch and significant intrapulmonary shunting may limit the increase in SpO2 during standard preoxygenation. Lung atelectasis, one cause of these alterations, may be managed by applying positive pressure to reduce the proportion of collapsed lung, improve the ventilation–perfusion ratio, and increase the FRC and oxygen reserve [19]. In a recent meta-analysis, noninvasive positive pressure ventilation (NPPV) compared with conventional preoxygenation in obese patients was associated with a significant improvement in partial arterial oxygen pressure (PaO2) (p < 0.0001) before tracheal intubation and in end-tidal oxygen concentration (ETO2) after tracheal intubation (p < 0.0001) [21]. 102 F. Zarantonello et al.

Harbut et al. found a significantly higher post-intubation PaO2 (p < 0.001) and fewer episodes of desaturation with pressure support ventilation (PSV) 5 cmH2O over continuous positive airway pressure (CPAP) 5 cmH2O for 2 min compared to conventional preoxygenation in morbidly obese patients [22].

Cressey et al. compared CPAP 7.5 cmH2O with a standard technique using the Mapleson A breathing system for 3 min in morbidly obese females. No statistically significant difference in mean time to desaturate to 90% after succinylcholine administration was observed in the CPAP group compared to the Mapleson A group

(240 ± 64 vs. 203 ± 31 s), and the mean lowest SpO2 values were similar in the two groups (SpO2 85%) [23]. Futier et al. compared 5 min of PSV and PSV plus recruitment maneuver (RM) to conventional preoxygenation. PSV was adjusted to attain an expiratory tidal volume of 8 mL/kg predicted body weight, a positive end-expiratory pressure (PEEP) level of 6–8 cmH2O, and an airway pressure (pressure support level + PEEP) of no more than 18 cmH2O [24]. A higher PaO2 was observed in PSV group and PSV plus RM group compared to TVB group (382 ± 87 mmHg and 375 ± 82 mmHg compared to 306 ± 51 mmHg, p < 0.001). A higher ETO2 was also found (95.6 ± 1.1% and 96 ± 1% compared to 92.3 ± 2.3%, p < 0.01) [25]. After intubation, PaO2 remained higher, and, compared to preanesthesia values, end-expiratory lung volume was greater in the PSV and PSV plus RM groups compared to the TVB group (88% and 87% compared to 58%, p = 0.002) [24].

Gander et al. compared PEEP 10 cmH2O applied 5 min before and 5 min after anesthesia induction with conventional preoxygenation without PEEP in morbidly obese patients. Patients in PEEP group had significantly higher PaO2 before apnea (376 ± 145 mmHg vs. 243 ± 136 mmHg, p = 0.038) and longer SAP (from intubation to an SpO2 of 92%, 188 ± 46 s vs. 127 ± 43 s, p = 0.002) compared with TVB group [26]. Comparing conventional preoxygenation to CPAP 4 cmH2O plus PSV 4 cmH2O for 3 min, Georgescu and colleagues showed that an FEO2 ≥ 90% was reached more frequently with NPPV (80%) than with TVB (60%) (p = 0.008) [27].

Coussa et al. compared the application of CPAP 10 cmH2O before intubation and mechanical ventilation (MV) with PEEP 10 cmH2O thereafter, versus TVB and MV without PEEP in morbidly obese patients. PaO2 after anesthesia induction was significantly higher in the PEEP group compared with the control group (457 ± 130 mmHg vs. 315 ± 100 mmHg, p = 0.035). In addition, control group patients had a significantly higher amount of lung atelectasis determined by computed tomography, compared to the PEEP group (10.4 ± 4.8% vs. 1.7 ± 1.3%, p < 0.001) [9]. Data on this topic are limited in the acute care setting. Baillard and colleagues randomized nonobese patients with acute respiratory failure who required intubation to be preoxygenated for 3 min with a nonrebreather bag-valve mask or PSV before a rapid sequence intubation in the ICU [25]. At the end of preoxygenation,

SpO2 was higher in the PSV group compared with the control group (98 ± 2% vs. 93 ± 6%, p < 0.001). During the intubation procedure, lower SpO2 values were observed in the control group (81 ± 15% vs. 93 ± 8%, p < 0.001), and fewer episodes of SpO2 < 80% were reported in the PSV group (2/27 vs. 12/26, p < 0.01). Five minutes after intubation, SpO2 values were still higher in the PSV group compared with the control group (98 ± 2% vs. 94 ± 6%, p < 0.01) [25]. 10 Preoxygenation Before Intubation in the Critically Ill Obese Patient 103

10.2.2.3 Apneic Oxygenation Apneic oxygenation is used to extend the SAP beyond that which can be achieved by preoxygenation alone. When the patient is apneic, oxygen constantly flows from the alveoli to the bloodstream at a rate of about 250 mL/min, while carbon dioxide is eliminated from the blood at a rate of 8–20 mL/min. This difference between oxygen and carbon dioxide generates a negative pressure that promotes the movement of air from the upper airway to the alveoli [28]. Theoretically, filling the pharyngeal space with oxygen in the presence of a patent airway might allow maintenance of adequate arterial oxygen saturation during the apnea period, as oxygen is gradually moved to the alveoli and thereafter to the bloodstream. Baraka et al. demonstrated that in morbidly obese patients placed in a 25° sitting position, preoxygenation alone is followed by a more rapid desaturation during the subsequent apnea, compared to preoxygenation with additional nasopharyngeal oxygen supplementation at 5 L/min [3]. The authors also found a significant negative correlation between the time to desaturation and BMI (r2 = 0.66, p < 0.05) [3]. Ramachandran et al. showed that apneic oxygenation with 5 L/min oxygen via nasal prongs compared to preoxygenation alone in patients in a 25° head-up position significantly prolonged the SAP (5.29 ± 1.02 vs. 3.49 ± 1.33 min, p < 0.05), and more patients in apneic oxygenation group had SpO2 > 95% at 6 min (8/15 vs. 1/15, p = 0.001) [29]. The lowest SpO2 reached after intubation was also significantly higher in the apneic oxygenation group (94.3 ± 4.4% vs. 87.7 ± 9.3%, p < 0.05) [30]. Cardiopulmonary alterations are nearly always present in the critical care setting, so the benefit gained with apneic oxygenation might be lower than that previously reported. In nonobese critical care patients, Miguel-Montanes et al. showed that oxygen administered via high-flow nasal cannulae (HFNC) significantly improved preoxygenation and reduced the prevalence of severe hypoxemia (2% vs. 14%, p = 0.03) compared with a nonrebreathing reservoir face mask during tracheal intubation of ICU patients with mild-to-moderate hypoxemia [31]. However, this benefit has not been always confirmed. In 119 critical care patients, Vourc’h and colleagues compared preoxygenation before intubation by means of HFNC with that by means of facial mask and found no difference in the rise of SpO2 (p = 0.98), the lowest SpO2 during the intubation (p = 0.44), or the incidence of severe desaturations (p = 0.70) [32]. Similarly, Semler et al. showed that apneic oxygenation with HFNC did not seem to increase the lowest arterial oxygen saturation during the endotracheal intubation of 150 critically ill patients compared with usual care [33]. The authors found no difference between apneic oxygenation with nasal high-flow oxygen (15 L/min) and usual care in incidence of SpO2 less than 90% (p = 0.87), SpO2 < 80% (p = 0.22), or decrease in SpO2 of more than 3% (p = 0.87) [33]. Due to the urgency with which intubation is usually performed in the intensive care setting, SAP was not an outcome of these studies; furthermore, results in the nonobese population are conflicting. At this time, no definite conclusion can be drawn regarding the use of apneic oxygenation during prolonged intubation attempts in the critically ill obese patient. 104 F. Zarantonello et al.

10.2.2.4 Patient Positioning The position of the obese patient has a relevant effect both on lung volumes, particularly the FRC, and on the work of breathing [2, 4]. This happens at least in part due to the upward displacement of abdominal contents that might decrease the effectiveness of preoxygenation and tolerance to apnea [34]. Altermatt et al. compared sitting and supine positions for preoxygenation. In the predetermined body position, preoxygenation was achieved with eight deep breaths within 60 s and an oxygen flow of 10 L/min. All patients were intubated after rapid sequence induction of anesthesia in the supine position and then left apneic and disconnected from the anesthesia circuit until SpO2 decreased to 90%. The SAP was almost 1 min longer in the sitting group (216 ± 35 s vs. 164 ± 38 s, p < 0.05) [34]. Dixon et al. explored preoxygenation with a 25° head-up position compared to a supine position in obese patients. After induction, ventilation was delayed until blood oxygen saturation reached 92%, and this desaturation safety period was recorded. The authors found that SAP was significantly longer in the 25° head-up position group (201 ± 56 s vs. 155 ± 70 s, p = 0.02) [29]. The authors reported that this “intermediate” position between sitting and supine was also more comfortable in terms of ease of intubation, as it allowed optimal head positioning during laryngoscopy [29]. Boyce et al. previously investigated a 30° reverse Trendelenburg, a supine- horizontal, and a 30° back-up Fowler position in obese patients. After intubation, subjects were ventilated for 5 min in a mixture of 50% oxygen/50% air and then disconnected from the ventilation circuit. The time required for SpO2 to decline from 100% to 92% was noted and identified as the SAP [35]. The authors found that higher BMI was associated with a reduced SAP and that a 30° reverse Trendelenburg was associated with the longest SAP compared to a supine-horizontal position and 30° back-up Fowler position (178 ± 55 s, 153 ± 63 s, 123 ± 24 s, p < 0.05) [35]. Pirrone et al. recently confirmed the benefit of elevating the head of the bed for increasing end-expiratory lung volumes and gas exchange after recruitment maneuvers followed by titrated positive end-expiratory pressure [36]. Using the beach chair or reverse Trendelenburg position may further improve lung volumes, respiratory system elastance, and oxygenation in critically ill, mechanically ventilated, morbidly obese patients [37].

Conclusion According to the most recent difficult airway management guidelines, all patients should receive preoxygenation before tracheal intubation [38] to increase the body’s oxygen reserve and prolong the SAP. Preoxygenation is even more important when there is an increased risk of hypoxemia due to difficult airway management or pulmonary alterations, such as in obese patient, particularly in the acute care setting. Due to concomitant problems and diseases, critically ill patients are at increased risk of severe hypoxemia during intubation [19]. Most of the evidence has been obtained in nonobese or otherwise healthy obese patients undergoing general anesthesia (Table 10.1); however, preoxygenation techniques should be carefully considered. Conventional preoxygenation might not be sufficient in the obese critically ill patient, while NPPV 10 Preoxygenation Before Intubation in the Critically Ill Obese Patient 105 - pres PSV high-flow high-flow HFNC , and EELV with , and EELV 2 and fewer desaturations and fewer and less lung atelectasis and longer SAP with PSV , ETO desaturations and fewer 2 2 2 2 2 of 90% more frequently with PSV 2 Longer SAP with head-up position No difference Higher PaO Longer SAP with sitting position No difference No difference Longest SAP with reverse Longest SAP with reverse Trendelenburg Longer SAP with apneic oxygenation Fewer episodes of severe hypoxemia hypoxemia episodes of severe Fewer with HNFC Higher PaO Higher PaO Higher PaO Higher SpO FEO Longer SAP with apneic oxygenation Main results with PSV with CPAP with CPAP PSV positive end-expiratory pressure, end-expiratory positive fraction of expired oxygen, fraction of expired PEEP FEO2 tidal volume breathing tidal volume TVB Supine/25° head up No oxygen during intubation/ HFNC during intubation TVB + no PEEP/ CPAP + PEEP Supine/sitting (90°) Facial mask/HFNC Facial TVB/CPAP Supine/back-up/reverse Supine/back-up/reverse Trendelenburg No oxygen/nasopharyngeal catheter Facial mask + nasal oxygen/ Facial HFNC TVB/CPAP TVB/PSV/PSV + RM TVB + no PEEP/PSV + PEEP TVB + no TVB/PSV TVB/PSV Techniques No oxygen/nasal oxygen 2 partial arterial oxygen pressure, 2 end-tidal oxygen concentration, 2 peripheral oxygen saturation, PaO 3 min Variable 5 min 1 min according Variable to ETO 4 min 3 min 5 min 3 min 3 min Preoxygenation 2 min 5 min 5 min 3 min 3 min ETO SpO2 not reported, Supine/25° head up Variable NR Sitting/supine 25° head up NR NR Supine/ back-up/reverse Trendelenburg 25° head up NR Position 25–30° head up Beach chair Ramped NR Supine NR safe apnea period, > 40 Nonobese > 35 > 35 30–35 Nonobese BMI > 35 26 ± 3 > 35 Nonobese > 35 > 40 > 35 Nonobese > 30 SAP end-expiratory lung volume, lung volume, end-expiratory EELV 42 150 18 40 30 119 Patients Number 20 26 34 101 44 66 30 52 30 noninvasive ventilation, ventilation, noninvasive NIV OR ICU OR Setting OR OR ICU OR OR OR ICU OR OR OR ICU OR recruitment maneuver, recruitment maneuver, RM not applicable, NA Dixon (2005) Semler (2016) Coussa (2004) Altermatt (2005) Ramachandran (2010) Vourc’h (2015) Vourc’h Author (year) Cressey (2001) Cressey Boyce (2003) Boyce Baraka (2007) Miguel-Montanes (2015) Harbut (2014) Harbut Futier (2011) Gander (2005) Baillard (2006) Georgescu (2012) Georgescu Summary of cited studies

Positive pressure (PP) pressure Positive (POS) Position (AO) oxygenation Apneic continuous positive airway pressure, airway continuous positive Intervention Table 10.1 Table CPAP nasal cannulae, sure support ventilation, sure support ventilation, 106 F. Zarantonello et al.

might grant some additional benefit. Regarding apneic oxygenation, results from critical care settings are conflicting at this time, and a specific evaluation of this technique in the obese population is missing. Optimization of the patient’s position, with a slight elevation of the thorax or the reverse Trendelenburg position, should be considered due to the advantages in terms of oxygenation, lung volumes, and SAP [11].

10.3 Key Major Recommendations

• Preoxygenation is recommended before intubating obese patients. • Noninvasive positive pressure ventilation increases oxygenation and lung volumes. It should be considered whenever possible for critically ill nonobese patients. • The benefit of apneic oxygenation needs to be confirmed in the critically ill obese population. • A slight back-up position provides a longer safe apnea period in obese patients.

Conflict of Interest The authors have no interests to disclose.

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12. Simpson GD, Ross MJ, McKeown DW, Ray DC. Tracheal intubation in the critically ill: a multi-centre national study of practice and complications. Br J Anaesth. 2012;108(5):792–9. 13. Berthoud MC, Peacock JE, Reilly CS. Effectiveness of preoxygenation in morbidly obese patients. Br J Anaesth. 1991;67(4):464–6. 14. Jense HG, SA D, Silverstein PI, O’Leary-Escolas U. Effect of obesity on safe duration of apnea in anesthetized humans. Anesth Analg. 1991;72(1):89–93. 15. Bouroche G, Bourgain JL. Preoxygenation and general anesthesia: a review. Minerva Anestesiol. 2015;81(8):910–20. 16. Tanoubi I, Drolet P, Donati F. Optimizing preoxygenation in adults. Can J Anaesth. 2009;56(6):449–66. 17. Tanoubi I. Oxygenation before anesthesia (preoxygenation) in adults. Anesthesiol Rounds. 2006;5(3) 18. Rapaport S, Joannes-Boyau O, Bazin R, Janvier G. Comparison of eight deep breaths and tidal volume breathing preoxygenation techniques in morbid obese patients. Ann Fr Anesth Reanim. 2004;23(12):1155–9. 19. De Jong A, Futier E, Millot A, et al. How to preoxygenate in operative room: healthy subjects and situations “at risk”. Ann Fr d’anesthèsie rèanimation. 2014;33(7–8):457–61. 20. McGowan P, Skinner A. Preoxygenation—the importance of a good face mask seal. Br J Anaesth. 1995;75(6):777–8. 21. Carron M, Zarantonello F, Tellaroli P, Ori C. Perioperative noninvasive ventilation in obese patients: a qualitative review and meta-analysis. Surg Obes Relat Dis. 2016;12(3):681–91. 22. Harbut P, Gozdzik W, Stjernfält E, Marsk R, Hesselvik JF. Continuous positive airway pressure/pressure support pre-oxygenation of morbidly obese patients. Acta Anaesthesiol Scand. 2014;58(6):675–80. 23. Cressey DM, Berthoud MC, Reilly CS. Effectiveness of continuous positive airway pressure to enhance pre-oxygenation in morbidly obese women. Anaesthesia. 2001;56(7):680–4. 24. Futier E, Constantin J-M, Pelosi P, et al. Noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during and after intubation of morbidly obese patients: a randomized controlled study. Anesthesiology. 2011;114(6):1354–63. 25. Baillard C, Fosse J-P, Sebbane M, et al. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am J Respir Crit Care Med. 2006;174(2):171–7. 26. Gander S, Frascarolo P, Suter M, Spahn DR, Magnusson L. Positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients. Anesth Analg. 2005;100(2):580–4. 27. Georgescu M, Tanoubi I, Fortier LP, Donati F, Drolet P. Efficacy of preoxygenation with noninvasive low positive pressure ventilation in obese patients: crossover physiological study. Ann Fr Anesth Reanim. 2012;31(9):e161–5. 28. Shah U, Wong J, Wong DT, Chung F. Preoxygenation and intraoperative ventilation strategies in obese patients: a comprehensive review. Curr Opin Anaesthesiol. 2016;29(1):109–18. 29. Dixon BJ, Dixon JB, Carden JR, et al. Preoxygenation is more effective in the 25 degrees head- up position than in the supine position in severely obese patients: a randomized controlled study. Anesthesiology. 2005;102(6):1110–5. 30. Ramachandran SK, Cosnowski A, Shanks A, Turner CR. Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. J Clin Anesth. 2010;22(3):164–8. 31. Miguel-Montanes R, Hajage D, Messika J, et al. Use of high-flow nasal cannula oxygen therapy to prevent desaturation during tracheal intubation of intensive care patients with mild-to- moderate hypoxemia. Crit Care Med. 2015;43(3):574–83. 32. Vourc’h M, Asfar P, Volteau C, et al. High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive Care Med. 2015;41(9):1538–48. 33. Semler MW, Janz DR, Lentz RJ, et al. Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill. Am J Respir Crit Care Med. 2016;193(3):273–80. 108 F. Zarantonello et al.

34. Altermatt FR, Muñoz HR, Delfino AE, Cortínez LI. Pre-oxygenation in the obese patient: effects of position on tolerance to apnoea. Br J Anaesth. 2005;95(5):706–9. 35. Boyce JR, Ness T, Castroman P, Gleysteen JJ. A preliminary study of the optimal anesthesia positioning for the morbidly obese patient. Obes Surg. 2003;13(1):4–9. 36. Pirrone M, Fisher D, Chipman D, et al. Recruitment maneuvers and positive end-expiratory pressure titration in morbidly obese ICU patients. Crit Care Med. 2016;44(2):300–7. 37. Carron M. Recruitment maneuvers and positive end-expiratory pressure titration in morbidly obese ICU patients: the role of positioning [Epub ahead of print]. Crit Care Med. 2016;44(9):e910. 38. Frerk C, Mitchell VS, McNarry AF, et al. Difficult airway society 2015 guidelines for management of unanticipated difficult intubation in adults. Br J Anaesth. 2015;115(6):827–48. Analgesia in the Obese Patient 11 Preet Mohinder Singh and Adrian Alvarez

11.1 Introduction

Obese patients pose unique challenges to the anesthesiologist for optimal perioperative management. The perioperative universal goal of comfortable yet safe surgery is no less than a double-edged sword in the morbidly obese. In order to achieve high patient satisfaction (directly related to quality of recovery and analgesia), the anesthesiologist has to strike a delicate balance between the life-threatening adverse events and analgesic potential of opioids. Further to compound the issue, the interindividual pharmacokinetic variations in opioid effects make this job almost next to impossible. Despite these safety hurdles and pharmacological barriers, a postsurgical obese patient in pain cannot be ethically or morally justified! Over the years, gradual progress has been made in analgesic management of the morbidly obese that not only resorts to alternative analgesic regimens but also strikes a safety balance for the use of “dangerous” opioids. The “danger” here is not by any stan- dards a misrepresentation as it can be adjudged by the fact that as per the American Society of Anesthesiologists (ASA) closed claim data, highest perioperative complications/mortality in obese occurs due to opioid-related airway complications [1]. Postoperative complications in morbidly obese have been repeatedly linked to increasing the body mass index (BMI). Evidence suggests that most of airway- related complications in fact possess a near-linear relationship with the increasing BMI. This can be attributed to the proportionate increase in obstructive sleep apnea

P.M. Singh Department of Anesthesia, All India Institute of Medical Sciences, New Delhi 110029, India e-mail: [email protected] A. Alvarez (*) Hospital Italiano de Buenos Aires, Avenida Medrano 364, First Floor, CABA, Buenos Aires 1179, Argentina e-mail: [email protected]

© Springer International Publishing AG 2018 109 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_11 110 P.M. Singh and A. Alvarez

(OSA) incidence with increasing BMI values [2]. Thus, in real context, the actual problem is to address the interaction of these high ceiling frontline perioperative analgesics (opioids) on OSA (or patients susceptible to OSA).

11.2 Opioids and Obese: What’s Wrong?

Opioid-related breathing problems are more strongly related to OSA; however, obese patients without OSA are also predisposed to the same. Ahmad et al. showed that in morbidly obese patients (with or without OSA), the perioperative desaturation rates were significantly higher than nonobese with the use of morphine-based patient–controlled analgesia [3]. Studies have also demonstrated that even the use of epidural or intrathecal opioids also depresses the respiratory frequency and depth to alarming limits and thus limiting the utility of this route as well [4]. Compared to nonobese patients, various physiological alterations account for the clinical predis- positions for complications.

11.2.1 Peripheral Mechanisms

Recent studies have proved the existence of mechanoreceptors on the laryngeal adductor motor neurons. After an opioid agonist binds to these receptors, the laryngeal adductors are activated and abductors are inhibited [5]. The density of these receptors increases with the increasing BMI, and clinically evident opioid-related obstruction could be attributed to this. Most induction agents actually enhance this obstructive potential of opioids, and the chances of airway collapse increase. Ehsan et al. also showed that dexmedetomidine is least likely to have effect on these peripheral receptors and complication rates would not actually rise. In view of these findings and in coherence with many other clinical trials, dexmedetomidine has emerged as an attractive opioid-sparing drug in morbidly obese patients. Both anatomical and physiological alterations in pharynx predispose to airway collapse in patients with morbid obesity. Opioids are well known to lower the pharyngeal tone as well, and this predisposes to airway collapse. In an interesting study by Wang et al., it was shown that nearly 30% of patients who received methadone for deaddiction eventually developed OSA-like symptoms [6]. It is expected that these opioid-related effects would be further magnified in patients actually suffering from OSA. Needless to say that opioids thus have potential to cause airway obstruction in obese with or even without OSA.

11.2.2 Central Effects

The evidence base for opioid-related central adverse effects in obese is much stron- ger. The direct effect of opioids when used as analgesics causes sedation, and precipitate OSA is already well established. These effects are compounded by further 11 Analgesia in the Obese Patient 111 decrease in sensitivity of respiratory centers to both hypoxic and hypercapnic stimulus. In OSA these reflexes are already dampened and thus on sedation further makes it worse. Studies have shown that the clinical effects actually persist beyond the pharmacological half-lives of the opioids. Opioids have shown to promote delayed sedation when used during the first 3 postoperative days (by direct central action). The pathophysiology of this is based on the fact that opioids alter the natural sleep architecture by promoting non-rapid eye movement (NREM) and suppression of rapid eye movement (REM) phase of sleep. During the phase of highest pain (initial 3 days after surgery), patients often receive highest amount of opioids. Subsequently following these days, patients tend to compensate for the REM sleep and the REM sleep rebounds. Thus in postoperative phase of recovery, the danger of life-threatening natural deep sleep-induced apnea again increases. As a result of the opioid use in obese with OSA, the incidence of airway obstruction not only increases during opioid therapy but also after cessation of opioids [7]. Obese patients have wide variations in weight and alterations in volume of distribution of drugs. This is even more variable for lipid-soluble drugs like opioids. Arguments can be made that with available technologies, estimates of the body fat percentage and subsequently the volume of distribution can be made. This would be something similar to the use of target-controlled infusions (TCIs) technology in the population. However, the actual problem extends beyond these pharmacokinetic issues. The crux of this trou- ble originates from the completely unpredictable yet highly variable pharmacodynamic effects of the opioids in the obese. There is strong evidence both in humans and animals that suggest that central nervous system has increased sensitivity toward opioid sedative propensity and eventually respiratory depression. Evaluating this pharmacological aspect of obesity, Colleen et al. demonstrated that obese patients undergoing abdominal surgeries require much less opioids for comparable levels of analgesia in contrast to the nonobese patients undergoing similar surgeries [8]. Thus, with all this said, the unwanted effects of opioid-based analgesia in obese patients may often outweigh the expected benefits. Not only it is likely to compromise the safety but also in long term adds to healthcare financial burden (more monitoring and staffing to prevent/monitor for complications). Keeping in mind that the frontline analgesics (opioids) are of limited use in obese, analgesic plans often need individualization. Targets should aim at use minimal to almost no opioids in these patients during the perioperative period.

11.3 The Ideal Strategy: A Multimodal Approach

Defining an ideal analgesic regimen eventually relies upon the use of combination of analgesics. The multimodal analgesia targets to prevent/treat pain at different levels in the pain pathway. Thus, drugs other than opioids should be targeted to prevent generation of pain, transmission, and eventual perception of pain. When drug combinations are used to target these aspects of pain, multimodal regimen is achieved. The present ASA task force guidelines for the perioperative management of OSA patients clearly advocate preferential use of regional analgesic techniques 112 P.M. Singh and A. Alvarez

Morbidly obese The multimodal approach Madulation

Sensory CNS Descending affronts perception inhibitory pathways

Spinal Peripheral Spinal Narcotics Adjuvants cord action cord • PCA/PCEA Adjuvants • Tramadol Regional • NSAIDS • IV • Paracetamol • Spinal/ • Narcotics Limited for MO • NMDA • Alpha–2 agonists Epidural • NMDA Antagonists • Nerve blocks Antagonists • 5HT3 antagonists • Infiltration • Gabapentinoids

NASIDS

Fig. 11.1 Analgesic regimens in obese patients

over systemic opioid analgesics. The guidelines also recommend exclusion of opioids even from neuraxial techniques favoring NSAIDs (nonsteroidal anti- inflammatory drugs) [9]. Local anesthetic-based regional blocks can certainly aid in achieving these targets. Evidence suggests that wherever opioids cannot be completely avoided in obese patients, extreme vigilance and monitoring can safeguard against complications [10]. A framework of useful drugs that form the basis of multimodal analgesia in obese is depicted in Fig. 11.1.

11.4 No Opioids: What’s the Alternative

Most perioperative care teams often develop a notion that the quality of opioid- based analgesia remains unmatched by that of non-opioid techniques. Literature however is replete with evidence contrary to this instinctive thinking. Mansour et al. demonstrated that non-opioid-based general anesthesia for bariatric surgery is as effective as opioid one. They resorted to multimodal analgesic regimens (without opioids) in one of the group, and pain scores were comparable to opioid-based analgesic group [11]. Similarly, Feld et al. compared intraoperative non-opioid analgesic regimen to fentanyl-based analgesia surgeries in morbidly obese patients undergoing gastric bypass. They concluded that well-titrated non-opioids (ketorolac, clonidine, and regional techniques) produced equivalent analgesia to opioid group. They also reported that non-opioid-based group showed lower sedation 11 Analgesia in the Obese Patient 113 scores postoperatively that was further associated with better hemodynamic stability. Additionally, multimodal group patients required lower total postoperative analgesic supplementation [12].

11.5 What Drugs for Analgesia?

A number of systemic alternatives exist for providing analgesia. These drugs can be either primary analgesics themselves or adjuvants that decrease the analgesic dose requirements. The frontline drugs that are used in perioperative period in obese are.

11.5.1 NSAIDs

NSAIDs inhibit the cyclooxygenase (COX), thus preventing conversion of arachi- donic acid to prostaglandins. These prostaglandins act as inflammatory mediators and sensitize the peripheral nerves to painful stimulus. With the advent of COX-2- specific inhibitors, the safety profile of these drugs has improved. The renal and gastric effects that complicated NSAID use are diminished. Patients undergoing bariatric surgery in particular have shown marked opioid-sparing effect with appropriate use of NSAIDs. Govindarajan et al. in morbidly obese undergoing laparoscopic surgery demonstrated significant reduction of narcotic requirements and further continued administration of ketorolac during the first 24 h postoperatively that led to improved patient satisfaction as well. This allowed active patient partici- pation in respiratory physical therapy and thus enhanced the recovery as well [13]. The limitation of most NSAIDs is that they are low ceiling analgesics and dose- response curve flattens after particular dose increments. Among the available NSADs, ketorolac has shown promising results. The pharmacological profile of this drug makes it a preferable analgesic in the perioperative period where opioids need to be avoided. It is one of the highest efficacy NSAID with potency equivalent to one-third to one-fifth of that of morphine. However, unlike morphine it has no respiratory effects that limit the use of morphine in bariatric patients. Yet another advantage that NSAIDs offer over opioids in obese is early return of bowel motility after surgery. As a result, most of the enhanced recovery after surgery (ERAS) protocols for bariatric surgery incorporate the use of NSAID analgesics as the frontline pain medications [14–16]. To attain optimal pain relief with NSAIDs, they must be used in combination with adjuvants (discussed subsequently) or regional techniques. This can allow cutting down opioid requirement to almost nil [17].

11.5.2 Paracetamol

Over the last decade, paracetamol has gained a lot of popularity as a potent analgesic with minimal adverse effects. It has unique mechanism of action that extends beyond inhibition of cyclooxygenase at the peripheral level alone. Pharmacological 114 P.M. Singh and A. Alvarez studies have demonstrated a unique ability to inhibit hypothalamic cyclooxygenase (called COX-3). In addition, it also alters the central serotonergic transmission as well that adds to its analgesic potency. It is free of bleeding, gastric, and renal side effects that limit the use of NSAIDs. Trials consistently have shown it to possess significant opioid-sparing effects [18, 19]. As per the conventional ideology, the paracetamol dose in obese needs to be based upon ideal body weight. However, recent study by van Rongen et al. demonstrated that obesity leads to lower acetaminophen concentration due to increased CYP2E1-mediated oxidation of acetaminophen in obese [20]. Paracetamol often needs to be supplemented with additional analgesics for the first few days after surgery to attain optimal pain relief.

11.5.3 Flupirtine

Flupirtine is an aminopyridine that is a non-opioid, non-NSAID analgesic. It is also an N-methyl-d-aspartate (NMDA) receptor antagonistic activity that adds to its analgesic potential. However, it has central analgesic action (like opioids), but it does not cause sedation, which is a desirable property in obese patients [21]. The present perioperative role of this drug is limited due to the lack of clinical experience/evidence. Preliminary trials have shown significant morphine-sparing effect in the perioperative period in non-bariatric surgeries [22].

11.6 Adjuvants

Most of the analgesic adjuvants work by lowering sensitivity of the central nervous system to the perception of pain. An ideal adjuvant is likely to have minimal sedative effect, and further on, its mechanism of action should preferably be different from the primary analgesic. For the purpose of opioid sparing, clinical evidence exists for the following pharmacological agents in the obese patients.

11.6.1 Ketamine

Ketamine is a NMDA receptor antagonist that has a well-established role in management of patients with chronic pain [23, 24]. Low-dose ketamine infusions lead to decrease in pain sensitivity without significant sedation or airway-related complications (which is a desired property in obese). Perioperatively, its use lowers the incidence of acute pain turning into a chronic pain syndrome [25]. Pharmacological studies have suggested that ketamine may have an additional anti-inflammatory property, which could be of great clinical relevance in the postoperative period [26]. Recently, Feld et al. reported significantly low patient-controlled analgesia (PCA) morphine requirements in morbidly obese patients receiving ketamine adjuvant [12]. Many randomized controlled trials evaluating the impact of ketamine infusion on opioid consumption after major abdominothoracic surgeries have reported a 11 Analgesia in the Obese Patient 115 notable reduction in morphine requirements postoperatively [27, 28]. The doses evaluated and found safe (free of hallucination, impairment of cognition) in various trials ranges from a 0.5 mg/kg bolus followed by a continuous infusion of 2.0– 2.5 mcg/kg/min for the first 48 h postoperatively 24[ ].

11.6.2 Alpha-Agonist

Most clinical experience exists for this class of drugs in terms of efficacy of analgesic potential. Antinociceptive action for this class is explained on the basis of antag- onism of alpha-2A receptors present on the substantia gelatinosa in the spinal cord. Available drugs in this subset include clonidine and dexmedetomidine. Among these, dexmedetomidine is much more selective in its action at alpha-2A receptors and thus has better analgesic potential. Bakhamees et al. recently concluded that an intraoperative infusion of dexmedetomidine decreases the total amount of propofol and fentanyl required to maintain anesthesia; it offers better control of intraoperative and postoperative hemodynamics. Further it decreases postoperative pain level, decreases the total amount of morphine consumed, and eventually leads to better recovery profile compared to placebo 29[ ]. Dexmedetomidine possesses additional desirable properties like it does not lead to loss of airway tone despite higher degree of sedation [30]. Another recent finding that makes it a preferred drug in obese is that it does not apparently suppress the REM sleep [31]. Such a property prevents the delayed REM rebound in obese patients and lowers airway-related complications in the postoperative phase. Presently, alternative routes (epidural, subarachnoid block) of dexmedetomidine are being explored, and the preliminary results are promising in terms of opioid-sparing action [32]. Both clonidine and dexmedetomidine can safely lower rescue analgesic requirements by 25 and 30%, respectively, in postoperative phase in morbidly obese [33].

11.6.3 Gabapentinoids

Gabapentinoids (gabapentin and pregabalin) were originally introduced as antiepi- leptics but have additional analgesic, anticonvulsant, and anxiolytic effects as well. Over the years, these drugs have shown very good patient acceptance and tolerance without significant side effects 34[ ]. In a recent study, Cabrera and colleagues concluded that a single preoperative oral dose of 150 mg pregabalin is useful for reducing morphine consumption after sleeve gastrectomy. It promotes effective and safe analgesia with a low incidence of sedation or airway-related side effects.

11.6.4 Magnesium

Much has been already written about analgesic potential of magnesium. A strong evidence base exists for nonobese patients for its perioperative opioid-sparing effect. 116 P.M. Singh and A. Alvarez

Although direct trials evaluating magnesium in obese could not be found at the time of writing, results from nonobese population are fairly encouraging. Magnesium by blocking NMDA receptors (at site different from ketamine) is known to suppress both intraoperative and postoperative analgesic/anesthetic requirements [35]. Steinlechner et al. demonstrated that magnesium gluconate moderately reduced the remifentanil consumption without serious side effects in patients undergoing cardiac surgery. Interestingly the opioid-sparing effect of magnesium was greater at higher pain intensities and further increased with dose escalation [36]. Studies recommend that magnesium at a dose of 50 mg/kg given at the time of induction is highly efficacious in improving quality of postoperative analgesia [37]. Being non-sedating along with capability to lower intraoperative anesthetic requirements (possibly translating into lesser residual effects of anesthesia in obese), magnesium is a promising agent for further clinical utility in obese patients. Being a water-soluble drug, it is advisable to dose it as per the ideal body weight rather than actual body weight.

11.7 Place of Regional Anesthesia in the Obese

Blocking the sensory affronts can certainly lower the pain or even sensation perception. As a result, it is understandable that analgesic requirements would drop exponentially in absence of sensory/pain stimulation. An optimally performed block can in fact cut down the opioid requirements to nearly zero. However, there are few ground realities that limit this idealistic outcome. Regional blocks rely on the local- ization of the nerves (by ultrasound or by stimulation) which would be a challenge in case of obese. Although ultrasound has almost revolutionized the field of regional anesthesia, yet it does require a learning curve. The deeper the nerves, the harder they may be to locate and in plane techniques would further require additional skills and expertise. The conventional central neuraxial blocks are also not as easy in obese. Location of the interspinous spaces may not be easy, and even ultrasound is not very helpful in these patients. Also, one needs to consider that most of the surgeries these days are preferably performed laparoscopically in the obese and no ideal block for this exists. The laparoscopic port sites (where highest somatic pain occurs) lie in widely varying dermatomal distribution, and a single block would fail to cover these effectively. The rationale of above discussion is not to discourage the use of regional anesthesia in obese but to prepare the anesthesiologist for possible limitations. Nevertheless, there is ample evidence that clearly demonstrates that clinically relevant opioid-sparing effect can be achieved with the use of regional techniques. Various blocks/regional techniques for which evidence presently exists are.

11.8 Peripheral Blocks

Patient satisfaction scores studied retrospectively in morbid obese have shown to be high with the use of regional anesthesia [38]. Regional anesthetic techniques in numerous studies have demonstrated to be highly efficient in reducing opioid 11 Analgesia in the Obese Patient 117 requirements and airway- or OSA-related complications [39, 40]. Franco et al. demonstrated once the learning curve is attained the actual success rates of blocks in morbidly obese (94.3%) may not be very different from nonobese (97.3%). They also suggested that the success rate improves with experience of the anesthesiologist [41]. One important aspect that should be kept in mind is that anesthesiologists must evaluate these patients preoperatively for nerve injuries/palsies or vitamin deficiencies that would have postoperative medicolegal significance. Blocks that have been evaluated in obese include brachial plexus, lumber plexus, truncal blocks, and abdominal wall blocks. Cotter et al. in their retrospective analysis of 9342 regional blocks used in patients with BMI > 25 kg/m2 found obesity as independent risk factor for block failure [42]. Ultrasound-guided transversus abdominis plane (TAP) block is particularly effective in blocking T10 to L1 segments and seems to be an attractive option for laparoscopic/open surgery. Bilateral TAP block in nonobese has shown efficacy for midline incisions [43] and can be a valid option in situations of failed/difficult epidurals in obese. Trials show much higher efficacy of thoracic epidurals when compared to TAP block 44[ ]; thus, we recommend thoracic epidurals to take priority over TAP block unless specific contraindications exist.

11.9 Surgical Site Infusions

Multi-orifice catheters have been used for infusion of local anesthetics at the surgical site for providing prolonged analgesia. Initial concerns existed for possible delay in wound healing; however, recent trials have concluded contrarily to the older thinking. Continuous bupivacaine infusion has been used to reduce the use of opioids in morbid obese undergoing laparoscopic bariatric surgery [45].

11.10 Intraperitoneal Infusions

Sherwinter et al. evaluated continuous infusion of intraperitoneal 0.375% bupivacaine in morbidly obese patients undergoing laparoscopic gastric banding. They reported a clinically relevant pain reduction that was not associated with any increase in adverse effects [46]. Studies have shown in nonobese patients that when small dose of opioid is added to the infusion analgesic efficacy significantly increases [47].

11.11 Central Neuraxial Block

It goes without saying that neuraxial blocks (epidural and subarachnoid) from the densest and most reliable of all the regional techniques. This would be true in both obese and nonobese population. In obese patients, there are multiple trials that illus- trate beneficial effects of epidural analgesia on respiratory functions by lowering postoperative pulmonary complications following abdominal surgeries [48–50]. 118 P.M. Singh and A. Alvarez

A congruent epidural (one put at the dermatomal distribution of surgical incision) achieves high-efficacy analgesic potential with local anesthetic (completely opioid- free) infusion. Many centers practice the use of thoracic epidurals in obese patients and recommend their use for enhanced patient recovery. Another, indirect benefit that exists with the use of neuraxial techniques is that the anesthesiologist can evade the difficult airway in these patients and thus improve overall safety. Literature has repeatedly documented that technical difficulties offset the common use of epidurals in obese. We however believe that these concerns are only opinion based. Supporting this Ellinas et al. found that technical difficulties of placing epidurals in obese pregnant patients are overrated and stressed upon use of optimal positioning prior to placement [51].

11.12 Future Strategies

Interesting trials by Nguyen et al. and Farley et al. have suggested that the use of warm humidified carbon dioxide for insufflation may be associated with analgesic properties. Exploring this further Savel et al. conducted a randomized controlled trial in morbidly obese patients addressing the same issue and eventually could not demonstrate an analgesic advantage [52–54]. Multimodal and combination techniques are the ideal and most appropriate analgesic regimens for obese patients. One may be very tempted to use opioids to achieve high analgesic levels but in doing so can subject the patient to catastrophic complications. We support the view that patient must be pain-free; however, there are other avenues that must be explored in obese for better recovery and safety profile.

Conflicts of Interest None.

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8. Rand CSW, Kuldau JM, Yost RL. Obesity and post-operative pain. J Psychosom Res. 1985;29(1):43–8. 9. Gross JB, Bachenberg KL, Benumof JL, Caplan RA, Connis RT, Coté CJ, et al. Practice guidelines for the perioperative management of patients with obstructive sleep apnea: a report by the American Society of Anesthesiologists Task Force on Perioperative Management of patients with obstructive sleep apnea. Anesthesiology. 2006;104(5):1081–1093–1118. 10. Thorell A, MacCormick AD, Awad S, Reynolds N, Roulin D, Demartines N, et al. Guidelines for perioperative care in bariatric surgery: enhanced recovery after surgery (ERAS) society recommendations. World J Surg. 2016;4:2065–83. 11. Mansour MA, Mahmoud AAA, Geddawy M. Nonopioid versus opioid based general anesthesia technique for bariatric surgery: a randomized double-blind study. Saudi J Anaesth. 2013;7(4):387–91. 12. Feld JM, Laurito CE, Beckerman M, Vincent J, Hoffman WE. Non-opioid analgesia improves pain relief and decreases sedation after gastric bypass surgery. Can J Anaesth. 2003;50(4):336–41. 13. Govindarajan R, Ghosh B, Sathyamoorthy MK, Kodali NS, Raza A, Aronsohn J, et al. Efficacy of ketorolac in lieu of narcotics in the operative management of laparoscopic surgery for morbid obesity. Surg Obes Relat Dis. 2005;1(6):530–535–536. 14. Lemanu DP, Srinivasa S, Singh PP, Johannsen S, MacCormick AD, Hill AG. Optimizing perioperative care in bariatric surgery patients. Obes Surg. 2012;22(6):979–90. 15. Hahl T, Peromaa-Haavisto P, Tarkiainen P, Knutar O, Victorzon M. Outcome of laparoscopic gastric bypass (LRYGB) with a program for enhanced recovery after surgery (ERAS). Obes Surg. 2016;26(3):505–11. 16. Mannaerts GHH, van Mil SR, Stepaniak PS, Dunkelgrün M, de Quelerij M, Verbrugge SJ, et al. Results of implementing an enhanced recovery after bariatric surgery (ERABS) protocol. Obes Surg. 2016;26(2):303–12. 17. Alvarez A, Singh PM, Sinha AC. Postoperative analgesia in morbid obesity. Obes Surg. 2014;24(4):652–9. 18. Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth. 2013;23(6):475–95. 19. Remy C, Marret E, Bonnet F. Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials. Br J Anaesth. 2005;94(4):505–13. 20. van Rongen A, Välitalo PAJ, Peeters MYM, Boerma D, Huisman FW, van Ramshorst B, et al. Morbidly obese patients exhibit increased CYP2E1-mediated oxidation of acetaminophen. Clin Pharmacokinet. 2016;55(7):833–47. 21. Singal R, Gupta P, Jain N, Gupta S. Role of flupirtine in the treatment of pain—chemistry and its effects. Maedica (Buchar). 2012;7(2):163–6. 22. Thapa D, Ahuja V, Dass C, Gombar S, Huria A. Effect of preoperative flupirtine on postoperative morphine sparing in patients undergoing total abdominal hysterectomy. Saudi J Anaesth. 2016;10(1):58–63. 23. Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. 2014;77(2):357–67. 24. Kurdi MS, Theerth KA, Deva RS. Ketamine: current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283–90. 25. McGreevy K, Bottros MM, Raja SN. Preventing chronic pain following acute pain: risk factors, preventive strategies, and their efficacy. Eur J Pain Suppl. 2011 11;5(2):365–72. 26. Hirota K, Zsigmond EK, Matsuki A, Rabito SF. Topical ketamine inhibits albumin extravasa- tion in chemical peritonitis in rats. Acta Anaesthesiol Scand. 1995;39(2):174–8. 27. Mathews TJ, Churchhouse AMD, Housden T, Dunning J. Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain? Interact Cardiovasc Thorac Surg. 2012;14(2):194–9. 28. Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M. Nefopam and ketamine comparably enhance postoperative analgesia. Anesth Analg. 2005;100(1):169–74. 120 P.M. Singh and A. Alvarez

29. Bakhamees HS, El-Halafawy YM, El-Kerdawy HM, Gouda NM, Altemyatt S. Effects of dexmedetomidine in morbidly obese patients undergoing laparoscopic gastric bypass. Middle East J Anaesthesiol. 2007;19(3):537–51. 30. Kaur M, Singh PM. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res. 2011;5(2):128–33. 31. Alexopoulou C, Kondili E, Diamantaki E, Psarologakis C, Kokkini S, Bolaki M, et al. Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study. Anesthesiology. 2014;121(4):801–7. 32. Grewal A. Dexmedetomidine: new avenues. J Anaesthesiol Clin Pharmacol. 2011;27(3):297. 33. Blaudszun G, Lysakowski C, Elia N, Tramèr MR. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta- analysis of randomized controlled trials. Anesthesiology. 2012;116(6):1312–22. 34. Imani F, Rahimzadeh P. Gabapentinoids: gabapentin and pregabalin for postoperative pain management. Anesth Pain Med. 2012;2(2):52–3. 35. Liu HT, Hollmann MW, Liu WH, Hoenemann CW, Durieux ME. Modulation of NMDA receptor function by ketamine and magnesium: Part I. Anesth Analg. 2001;92(5):1173–81. 36. Steinlechner B, Dworschak M, Birkenberg B, Grubhofer G, Weigl M, Schiferer A, et al. Magnesium moderately decreases remifentanil dosage required for pain management after cardiac surgery. Br J Anaesth. 2006;96(4):444–9. 37. Ryu J-H, Kang M-H, Park K-S, Do S-H. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100(3):397–403. 38. Davies KE, Houghton K, Montgomery JE. Obesity and day-case surgery. Anaesthesia. 2001;56(11):1112–5. 39. Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J Anaesth. 2001;87(1):62–72. 40. Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert A, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. BMJ. 2000;321(7275):1493. 41. Franco CD, Gloss FJ, Voronov G, Tyler SG, Stojiljkovic LS. Supraclavicular block in the obese population: an analysis of 2020 blocks. Anesth Analg. 2006;102(4):1252–4. 42. Cotter JT, Nielsen KC, Guller U, Steele SM, Klein SM, Greengrass RA, et al. Increased body mass index and ASA physical status IV are risk factors for block failure in ambulatory surgery–an analysis of 9,342 blocks. Can J Anaesth. 2004;51(8):810–6. 43. Abdallah FW, Chan VW, Brull R. Transversus abdominis plane block: a systematic review. Reg Anesth Pain Med. 2012;37(2):193–209. 44. Niraj G, Kelkar A, Jeyapalan I, Graff-Baker P, Williams O, Darbar A, et al. Comparison of analgesic efficacy of subcostal transversus abdominis plane blocks with epidural analgesia following upper abdominal surgery. Anaesthesia. 2011;66(6):465–71. 45. Cottam DR, Fisher B, Atkinson J, Link D, Volk P, Friesen C, et al. A randomized trial of bupivacaine pain pumps to eliminate the need for patient controlled analgesia pumps in primary laparoscopic Roux-en-Y gastric bypass. Obes Surg. 2007;17(5):595–600. 46. Sherwinter DA, Ghaznavi AM, Spinner D, Savel RH, Macura JM, Adler H. Continuous infusion of intraperitoneal bupivacaine after laparoscopic surgery: a randomized controlled trial. Obes Surg. 2008;18(12):1581–6. 47. Hernández-Palazón J, Tortosa JA, Nuño de la Rosa V, Giménez-Viudes J, Ramírez G, Robles R. Intraperitoneal application of bupivacaine plus morphine for pain relief after laparoscopic cholecystectomy. Eur J Anaesthesiol. 2003;20(11):891–6. 48. Buckley FP, Robinson NB, Simonowitz DA, Dellinger EP. Anaesthesia in the morbidly obese. A comparison of anaesthetic and analgesic regimens for upper abdominal surgery. Anaesthesia. 1983;38(9):840–51. 49. Smetana GW. Postoperative pulmonary complications: an update on risk assessment and reduction. Cleve Clin J Med. 2009;76(Suppl 4):S60–5. 11 Analgesia in the Obese Patient 121

50. Singh PM, Borle A, Shah D, Sinha A, Makkar JK, Trikha A, et al. Optimizing prophylactic CPAP in patients without obstructive sleep apnoea for high-risk abdominal surgeries: a meta- regression analysis. Lung. 2016;194(2):201–17. 51. Ellinas EH, Eastwood DC, Patel SN, Maitra-D’Cruze AM, Ebert TJ. The effect of obesity on neuraxial technique difficulty in pregnant patients: a prospective, observational study. Anesth Analg. 2009;109(4):1225–31. 52. Nguyen NT, Furdui G, Fleming NW, Lee SJ, Goldman CD, Singh A, et al. Effect of heated and humidified carbon dioxide gas on core temperature and postoperative pain: a randomized trial. Surg Endosc. 2002;16(7):1050–4. 53. Farley DR, Greenlee SM, Larson DR, Harrington JR. Double-blind, prospective, randomized study of warmed, humidified carbon dioxide insufflation vs standard carbon dioxide for patients undergoing laparoscopic cholecystectomy. Arch Surg. 2004;139(7):739–743–744. 54. Savel RH, Balasubramanya S, Lasheen S, Gaprindashvili T, Arabov E, Fazylov RM, et al. Beneficial effects of humidified, warmed carbon dioxide insufflation during laparoscopic -bar iatric surgery: a randomized clinical trial. Obes Surg. 2005;15(1):64–9. Sedation of the Obese Patient: Indications, Management, 12 and Complications

Krysta Wolfe and John Kress

12.1 Introduction

As the prevalence of obesity increases, so too does the number of obese patients being cared for in the critical care setting. Many patients will require the administration of analgesics and sedative medications during the course of their critical illness. Therefore, it is important for clinicians to recognize not only the effect of critical illness on the pharmacokinetics and pharmacodynamics of these medications but also how obesity further alters these effects. A lack of knowledge in these areas may lead to excessive or inadequate sedation.

12.2 Drug Dosing in Obese Patients

In general, dosing of medications for any patient in the intensive care unit may be erratic due to changes in organ function, volume of distribution, and other effects of critical illness. Obesity further adds to this variability. A major challenge in caring for critically ill obese patients is the lack of evidence guiding administration of common drugs. It remains unclear in many cases how obesity impacts drug han- dling. The physiologic changes associated with obesity may alter the distribution, metabolism, protein binding, and clearance of many drugs [1, 2].

12.2.1 Absorption

The oral absorption of drugs is unchanged in obese patients [3].

K. Wolfe • J. Kress (*) Medical ICU, Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago, 5841 S. Maryland Ave. MC 6026, Chicago, IL 60637, USA e-mail: [email protected]

© Springer International Publishing AG 2018 123 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_12 124 K. Wolfe and J. Kress

12.2.2 Protein Binding

Protein binding can be altered in the obese patient due to elevated levels of circulating lipoproteins, triglycerides, cholesterol, and free fatty acids that can bind serum proteins thus inhibiting protein binding of drugs. The clinical significance of this is unclear [4, 5].

12.2.3 Volume of Distribution

The volume of distribution of a drug depends on the amount of adipose tissue, lean body mass, blood volume, cardiac output, total body water, and lipophilicity of the drug [3, 6]. For lipophilic drugs such as benzodiazepines, the volume of distribution is very large in an obese patient.

12.2.4 Elimination

Obesity can impact drug clearance as well. Hepatic clearance of drugs is typically unchanged. More specifically, phase I reactions (oxidation, reduction, hydrolysis) may be unchanged or increased in obesity, and phase II reactions are consistently increased [7, 8]. Renal clearance is typically increased in the obese patient due to increased blood flow and glomerular filtration rate [9]. When renal dysfunction is present, it is important to base dosing of renally excreted drugs on the measured creatinine clearance as the calculated clearance correlates poorly with the measured creatinine clearance in obese patients [10]. The alterations described are not uniform and in combination with the wide variation in the pharmacodynamics of drugs commonly given in the ICU make a single dosing strategy impossible to implement. Therefore, all patients, and in particular obese patients with critical illness, should receive close monitoring of dosing based on clinical end points.

12.3 Analgesia: Indications and Monitoring

The experience of pain is common in the critical care setting, with approximately 80% of patients experiencing moderate to severe pain while in the ICU [11–13]. Common sources of pain include routine ICU care (such as turning), presence of an endotracheal tube, tissue injury (such as surgical or pressure wounds), vascular access, and prolonged immobility [14, 15]. Agitation is a common consequence of unrecognized pain, often leading to the use of non-analgesic sedatives instead of pain medications. Additional adverse effects of pain include increased endogenous catecholamine activity, myocardial ischemia, hypercoagulability, 12 Sedation of the Obese Patient: Indications, Management, and Complications 125 hypermetabolic states, hyperglycemia, sleep deprivation, anxiety, and delirium [16]. Non-pharmacologic interventions, such as optimal bed positioning, are useful and should be the first step in management but alone are often inadequate in relieving pain. Therefore, an aggressive approach to pain management is advocated by several published consensus opinions regarding sedation in the ICU [12, 17, 18]. Despite recommendations for aggressive pain management, treatment of pain in the ICU is often inadequate in practice [19]. Ineffective communication, due to physical barriers or an altered level of consciousness, is the main impediment to both recognition and treatment of pain in patients with critical illness. Other possible barriers include concerns over addiction to opiates, adverse cardiopulmonary effects of analgesics, and arbitrary limits on drug dosing [20]. Routine pain assessment aids in achieving optimal patient comfort by prompting increased recognition of pain and evaluation of response to interventions aimed at pain reduction. The use of routine assessment has been associated with decreased need for sedative medications and improved outcomes [21]. The best tool for assessment of pain is patient self-report, but due to a variety of reasons, this is often not possible in the ICU. Physiologic parameters, such as hypertension and tachycardia, correlate poorly with pain levels [22]. Therefore, tools such as the Visual Analog Scale (VAS), which has been shown to have very good reliability and validity, are utilized for routine and frequent pain assessment [23, 24]. The VAS consists of a horizontal line with the extremes of “no pain” and “severe pain” on the ends. The Numeric Rating Scale is also commonly used and utilizes a similar horizontal line with numeric markings from 1 to 10 indicating pain severity [25]. In patients that cannot self-report, tools that utilize behavioral or physiologic responses such as facial expression, body movements, muscle tension, and ventilator compliance have been validated. Examples of these tools include the behavioral pain score (BPS) and critical care pain observation tool (CPOT) [26, 27].

12.4 Analgesia: Management

Intravenous administration of analgesic medications is generally the preferred route in patients with acute pain in the ICU. Both continuous infusion and intermittent dosing strategies can be employed and tailored in a patient-specific manner. Patients alert enough to respond may benefit from patient-controlled analgesia. PCA provides effective analgesia in the obese, although close monitoring for respiratory depression is prudent [28]. Intramuscular injection is not preferred due to pain from the injection itself and inconsistent absorption in critically ill patients. Similarly, transdermal opiates may have altered absorption in the setting of critical illness. Oral administration can be limited by unpredictable absorption due to gastrointestinal dysfunction. There are limited studies guiding opiate choice and dosing requirements in obese patients. Widespread variability in morphine requirements has been reported in postoperative patients with obesity [29]. Therefore, regular pain assessments are necessary in managing analgesia in critically ill obese patients. 126 K. Wolfe and J. Kress

12.5 Analgesia: Medication Choice

An ideal analgesic medication has a rapid onset, rapid offset, lack of drug accumulation, and lack of side effects. Unfortunately, none of the available analgesic medications have all these attributes (Table 12.1); therefore, the properties of each drug must be considered in the context of each individual patient.

12.5.1 Opiates

Opiate receptors are found throughout the central nervous system and peripheral tissues. The primary effect of opioids is analgesia, which is predominantly mediated through the μ and к receptors. They also provide mild to moderate anxiolysis, but have no amnestic properties.

Table 12.1 Analgesics Fentanyl Morphine Hydromorphone Remifentanil Mechanism of μ-opioid μ-opioid agonist μ-opioid agonist μ-opioid action agonist agonist Onset 1–2 min 5–10 min 5–10 min 1–3 min Elimination 2–4 h 3–4 h 2–3 h 3–10 min half-life Metabolic pathway N-dealkylation Hepatic, Hepatic, Hydrolysis by CYP3A4/5 glucuronidation glucuronidation plasma substrate esterases Active metabolite None 6- and 3- None None glucuronide metabolite (renally excreted) Intermittent dosing 0.35–0.5 μg/ 2–4 mg IV 0.2–0.6 mg IV None kg IV q0.5–1 h q1–2 h q1–2 h Continuous 25–200 μg/h 2–30 mg/h 0.5–3 mg/h 1.5 μg/kg IV infusion loading dose; then 0.5–15 μg/ kg/h Side effects Less Accumulation Accumulation No hypotension; with hepatic/ with hepatic/ accumulation accumulation renal renal with organ with hepatic impairment, impairment dysfunction impairment histamine release Pharmacokinetics No significant No significant No significant No significant in obese patients change change change change Dosage in obese Based on Based on IBW Based on IBW Based on LBW patients LBW LBW lean body weight, IBW ideal body weight 12 Sedation of the Obese Patient: Indications, Management, and Complications 127

Opiates have a number of side effects, most notably dose-dependent centrally mediated respiratory depression. This is mediated by the μ2 receptors in the brainstem (medulla), leading to a decreased respiratory rate. Other side effects of opiates include CNS depression, hallucinations, hypotension, pruritus, peripheral vasodila- tion, nausea and vomiting, ileus, urinary retention, and in rare cases increased intracranial pressure. Patients receiving prolonged high daily opioid doses typically develop tolerance leading to a diminishing effect over time. Another consideration when using opiates for prolonged periods or in high doses is the risk of precipitating withdrawal when rapidly tapering or abruptly stopping these medications. In one study of mechanically ventilated trauma and surgical ICU patients receiving large doses of analgesic and sedative medications for over 7 days, symptoms of withdrawal were experienced by 32% [30]. Signs and symptoms of withdrawal are extensive and nonspecific. They include pupillary dilation, sweating, lacrimation, rhinorrhea, piloerection, tachycardia, vomiting, diarrhea, hypertension, yawning, fever, tachypnea, restlessness, irrita- bility, increased sensitivity to pain, nausea, cramps, muscle aches, dysphoria, insomnia, and anxiety [30]. It is not known if regular interruption of opiate administration or downward titration of doses is effective in preventing withdrawal. The use of longer-acting opiates, such as transdermal fentanyl or methadone, can be considered in patients in whom withdrawal is a concern. Because of the stigma around methadone and heroin addiction, transdermal fentanyl is currently used more frequently. Morphine: Intravenous morphine has an onset of action ranging from 5 to 10 min due to its low lipid solubility, which delays its movement across the blood-brain barrier. Its duration of action is approximately 2–4 h. If given repeatedly, morphine accumulates in peripheral tissues which may prolong its effect. This may be particularly relevant in obese patients. Importantly, morphine undergoes glucuronide conjugation in the liver, and its active metabolite, morphine-6-glucuronide, is eliminated by the kidney. Therefore, its effects may be prolonged in patients with renal failure. Hydromorphone: Intravenous hydromorphone has a similar onset of action as morphine with a shorter duration of action (2–3 h). Hydromorphone does not have active metabolites, which contributes to its relatively shorter duration of action. Fentanyl: Due to its high lipid solubility, fentanyl rapidly crosses the blood-brain barrier leading to a quick onset of action (1–2 min). Its duration of action is short (30–60 min) due to tissue redistribution. As with all opiates, tissue redistribution can lead to accumulation and prolongation of effect with repeated or prolonged exposure, particularly in obese patients. Remifentanil: Remifentanil is a highly lipid-soluble drug with a rapid onset of action (1–3 min). Its elimination half-life is very short leading to rapid recovery within minutes of cessation. This is due to metabolism through hydrolysis by plasma esterases. Therefore, its action is not affected by hepatic or renal function. The pharmacokinetics of remifentanil appears to be similar between obese and lean patients. It is recommended that dosing be based on ideal body weight instead of total body weight [31]. 128 K. Wolfe and J. Kress

12.6 Sedation: Indications and Monitoring

Once appropriate analgesia is obtained, some patients in the ICU will still experience varying degrees of agitation or unpleasant awareness. Common causes of this include anxiety; frustration; lack of homeostasis due to thirst, hunger, or dyspnea; ventilator dyssynchrony; inability to communicate; or need for physical restraints. Once the need for sedation has been established, it is important to then determine the desired level of sedation for an individual patient. The level of desired sedation is dependent on a patient’s underlying condition. Indications for continuous deep sedation include treatment of intracranial hypertension, severe respiratory failure, refractory status epilepticus, and prevention of awareness in all patients treated with neuromuscular blockade. The majority of patients treated in the ICU do not have one of these indications, and for these patients, the goal is to minimize the use of sedatives. Ideally a patient is kept in a pain-free state where he/she is lucid and able to interact and cooperate with care providers. Reaching this goal may be difficult and requires close monitoring of the sedation level. In many instances the level of sedation reached is suboptimal, with a tendency toward providing oversedation [32, 33]. Several tools have been developed to help standardize sedation monitoring. The most commonly used scales are the Riker Sedation-Agitation Scale (SAS) (Table 12.2) and Richmond Agitation-Sedation Scale (RASS) (Table 12.3) [34, 35]. Both the SAS and RASS have been evaluated extensively for validity and reliability and performed similarly in a direct comparison [36]. They can be used to detect changes in level of sedation over repeated assessments and correlate well to dosage of sedative and analgesic medication administered. For most patients, a goal level of sedation (calm and interactive) is represented by a RASS score of 0 or −1 and a SAS score of 3 or 4 (Table 12.2 and 12.3).

Table 12.2 Riker Sedation-Agitation Scale (SAS) Score Term Description 7 Dangerous Pulling at endotracheal tube, trying to remove catheters, agitation climbing over bed rail, striking at staff, thrashing from side to side 6 Very agitated Requiring restraint and frequent verbal reminding of limits, biting endotracheal tube 5 Agitated Anxious or physically agitated, calming at verbal instruction 4 Calm and Calm, easily arousable, follows commands cooperative 3 Sedated Difficult to arouse but awakens to verbal stimuli or gentle shaking, follows simple commands but drifts off again 2 Very sedated Arouses to physical stimuli but does not communicate or follow commands, may move spontaneously 1 Cannot be Minimal or no response to noxious stimuli, does not aroused communicate or follow commands 12 Sedation of the Obese Patient: Indications, Management, and Complications 129

Table 12.3 Richmond Agitation-Sedation Scale (RASS) Score Term Description +4 Combative Overtly combative, violent, immediate danger to staff +3 Very agitated Pulls or removes tubes or catheters; aggressive +2 Agitated Frequent non-purposeful movement, fights ventilator +1 Restless Anxious but movements not aggressive or vigorous 0 Alert and calm −1 Drowsy but has sustained (>10 s) awakening, with eye opening in response to verbal command −2 Light sedation Awakens briefly (<10 s) with eye contact to verbal command −3 Moderate Any movement, except eye contact, in response to command sedation −4 Deep sedation No response to voice, but any movement to physical stimulation −5 Unarousable No response

An additional property of many sedative medications is amnesia. The importance of amnesia in ICU patients is less well established than the anxiolytic property of sedative medications. It is clearly indicated and considered mandatory during the administration of neuromuscular blockade. In short periods, such as during an unpleasant intervention, amnesia appears to be desirable, but prolonged periods of amnesia may be detrimental. [37, 38].

12.7 Sedation: Management

The choice and dosage of sedative medication needed to maintain an optimal sedation level may vary widely between patients and even for the same patient at different points in his or her care. Dosing of sedative medications in the ICU is highly variable due to altered pharmacokinetics and pharmacodynamics of drugs during critical illness, particularly in the setting of obesity [39]. Important considerations in dosing include volume of distribution, clearance, altered protein binding, and organ function. The alterations in pharmacology due to critical illness are often unpredictable; therefore, there cannot be a uniform dosing strategy for critically ill patients, but rather dosing and titration must be against discernible clinical end points. In order to reach the optimal sedation level for a patient, either an intermittent or continuous method of administration can be utilized. While a continuous infusion may result in fewer fluctuations in medication levels and be less demanding on nursing, it can also lead to increased drug accumulation. The 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit recommend the practice of analgosedation, which promotes the use of lighter sedation whenever possible [12]. This recommendation is based on a substantial body of evidence that lower cumulative sedative doses are associated with decreased risk of negative short- and long-term outcomes. 130 K. Wolfe and J. Kress

A landmark study that compared routine daily interruption of sedation with dis- cretionary interruption by the treating physician found that patients randomized to daily interruption received less total sedation and had a shorter duration of mechanical ventilation and ICU length of stay [40]. A large, multicenter trial of daily interruption of sedation paired with daily spontaneous breathing trials showed that interruption of sedation was associated with decreased administration of benzodiazepines, reduced duration of mechanical ventilation, reduced ICU length of stay, and significantly increased survival 41[ ]. A 2012 study that evaluated the addition of daily interruption of sedation to a protocol that minimized the level of sedation found no clinical benefit to the addition of a daily interruption [42]. In a trial of mechanically ventilated patients receiving analgesia with morphine, a comparison of no sedation versus sedation with daily interruption found that no sedation was associated with shorter ICU and hospital length of stay and decreased duration of mechanical ventilation [43]. Depth of sedation has been independently associated with the duration of mechanical ventilation, in-hospital mortality, and rates of death within 180 days [44]. A clear and consistent message from the evidence available is that minimization of sedation in the ICU results in clinical benefit. Reaching this goal requires careful monitoring of the level of sedation provided. Protocol-driven sedation strategies aid in the careful monitoring required by incorporating continuous reassessment of sedation level and response to sedative medications [45]. In addition to the evidence supporting the use of light sedation when possible, it is important to consider the limits deep sedation places on the ability to perform a neurologic exam. Brain injury can be a devastating consequence of critical illness, and the ability to do a mental status examination to assess brain function is critical. Early detection of acute cerebral dysfunction may allow for the ability to correct the underlying process if possible before permanent injury takes place (Table 12.3).

12.8 Choice of Medication: Sedation

The most commonly used sedative medications in the ICU are propofol and dexmedetomidine. Benzodiazepines have largely fallen out of favor. Knowledge of the pharmacokinetics and associated effects of sedative medications is imperative in choosing a sedation strategy that provides an optimal level of patient comfort while simultaneously minimizing the depth and duration of sedation (Table 12.4). While there have been numerous studies comparing sedative regimens, there is a paucity of evidence guiding this choice in obese patients. Clearly, an important consideration when formulating a sedation strategy for all patients is the impact of medication choice on critical care outcomes. In a meta- analysis of randomized trials, the use of either a dexmedetomidine- or propofol- based sedation regimen compared to a benzodiazepine-based sedation regimen was 12 Sedation of the Obese Patient: Indications, Management, and Complications 131 agonist A Lorazepam GABA 15–20 min 8–15 h Hepatic, glucuronidation None Respiratory depression, glycol-related propylene acidosis, renal failure 0.5–2 mg of Increased volume increased distribution, terminal elimination half-life, prolonged duration of action with infusion Loading dose based on maintenance TBW, dosing based on IBW agonist A Midazolam GABA 3–5 min 2–6 h, duration < 2 h (dose dependent) Hepatic CYP3A4 1-hydroxymidazolam Yes, (accumulates with prolonged infusion, renally excreted) Respiratory depression 0.5–2 mg of Increased volume increased distribution, terminal elimination half-life, prolonged duration of action with infusion TBW, Loading dose based on maintenance dosing based on IBW ideal body weight IBW g/kg/min increase risk agonist (with other μ A g/kg/min (doses greater μ total body weight, Propofol GABA effects) 1–2 min 26–32 h Hepatic, CYP2B6 None Hypotension, respiratory depression, hypertriglyceridemia, pain on injection, pancreatitis, PRIS 5–50 than 80 of HTG and PRIS) No significant change Based on TBW TBW g/kg/h μ -agonist 2 propofol infusion syndrome, Dexmedetomidine α 5–10 min Up to 3 h, duration 60–120 min Hepatic, N-glucuronidation CYP2A6 and N-methylation, None Bradycardia, hypotension, xerostomia 0.2–1.5 No studies No specific dosing recommendations. TBW based on Typically PRIS Sedatives

hypertriglyceridemia, hypertriglyceridemia, Mechanism of action Onset Half-life Metabolism metabolite Active effects Adverse Dose Pharmacokinetics in obese patients Dosage in obese patients Table 12.4 Table HTG 132 K. Wolfe and J. Kress associated with a shorter ICU length of stay and duration of mechanical ventilation [46]. When comparing long-acting benzodiazepines with propofol, there was no difference in mortality, but there was a reduction in the length of stay in the ICU [47]. In a randomized trial of ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was associated with reduced duration of mechanical ventilation compared to midazolam. Its use was also associated with an improved ability to communicate pain level when compared to midazolam or propofol [48]. Delirium in mechanically ventilated patients in the ICU is common. Sedative use is consistently linked to the development of delirium [49–51]. Delirium, defined as a disturbance of consciousness characterized by acute onset and fluctuating course of impaired cognitive functioning, is associated with increased mortality, prolonged duration of mechanical ventilation, increased hospital length of stay, and higher risk of cognitive impairment [52–54]. Therefore, minimizing the risk of delirium is imperative to improving patient outcomes. In a randomized trial of sedation with dexmedetomidine versus midazolam, the group receiving dexmedetomidine had a reduced risk of delirium and shorter duration of mechanical ventilation despite comparable sedation levels [55]. In a study of dexmedetomidine compared with lorazepam infusion, the use of dexmedetomidine was associated with longer survival without delirium or coma [56]. Propofol: Propofol is a short-acting intravenous anesthetic agent. Its exact mechanism of action is unknown but is thought to act through the GABA receptor. It is highly lipid soluble and rapidly crosses the blood-brain barrier, leading to an onset of action of 1–5 min. The duration of action is short due to rapid distribution to peripheral tissues [57, 58]. Its duration of action may increase with higher doses used but typically remains short. Once propofol is stopped, it is redistributed back into the plasma from fat tissue, but usually not in clinically significant levels. It appears to have similar pharmacokinetics in obese and nonobese patients [59]. Propofol is a hypnotic agent that leads to dose-dependent suppression of awareness. It also has potent anxiolytic and amnestic properties [60]. It does not provide analgesia. In addition to its CNS effects, propofol causes respiratory depression and significant hemodynamic changes. Hypotension is caused by dilation of venous capacitance vessels leading to a reduction in preload. It is also associated with mild myocardial depression. Propofol is delivered by an intralipid carrier; therefore, continuous infusions can lead to hypertriglyceridemia [61]. It is recommended that triglyceride levels are checked every 48–72 h while receiving propofol, and it should be stopped if hypertriglyceridemia (> 500 mg/dL) occurs. A rare adverse effect is propofol infusion syndrome. This typically occurs with infusions over 48 h and high doses (> 80 μg/kg/min) and is characterized by metabolic acidosis, rhabdomyolysis, hyperkalemia, dysrhythmias, and renal and heart failure [62, 63]. Dexmedetomidine: Dexmedetomidine is a highly selective α2 agonist that has sedative, anxiolytic, and analgesic properties [64–66]. Its distribution half-life is 12 Sedation of the Obese Patient: Indications, Management, and Complications 133

6 min with a terminal half-life of 2 h. It undergoes hepatic metabolism; therefore, hepatic impairment significantly reduces its clearance 67[ ]. Dexmedetomidine provides light sedation allowing the patient to be more interactive and communicative resulting in improved ability to participate in routine care and, importantly, the neurologic exam. Additionally, it does not cause respiratory depression, allowing its use in non-intubated patients. Due to its analgesic effects, the use of dexmedetomidine is associated with decreased requirements for opiate analgesia [68]. Adverse effects of dexmedetomidine include xerostomia, bradycardia, and hypotension [48, 55]. Benzodiazepines: Benzodiazepines act through the γ-aminobutyric acid (GABA) receptor leading to inhibition of the central nervous system and dose-dependent suppression of awareness. They are potent anxiolytic and amnestic agents [69, 70]. Additionally, all benzodiazepines have anticonvulsant properties [71]. They cause a dose-dependent, centrally mediated respiratory depression that is less potent than opiates. This manifests as smaller tidal volumes and an increased respiratory rate with a decreased ventilator response to hypoxia. Benzodiazepines have minimal hemodynamic effects but may cause hypotension in hypovolemic patients. All benzodiazepines are lipid soluble with a large volume of distribution. The duration of action of various benzodiazepines depends on the rate of redistribution to peripheral tissues, especially adipose tissue. Maintenance dosing of benzodiazepines in obese patients should be based on ideal body weight [72]. Midazolam: Intravenous midazolam has a rapid onset of action (0.5–5 min) and duration of action of approximately 2 h. It undergoes hepatic metabolism and renal excretion. In the presence of renal failure, the active metabolite alpha-hydroxymidazolam can accumulate leading to prolonged effects. When given as a continuous infusion, it accumulates in peripheral tissues, leading to prolonged duration of clinical effect after discontinuation [73]. Midazolam has an increased volume of distribution in obese patients, and its terminal elimination half-life is prolonged [74, 75]. Lorazepam: Intravenous lorazepam has lower lipid solubility than midazolam leading to a slower onset of action (5–20 min). Its lower lipid solubility leads to decreased peripheral tissue redistribution and a longer duration of action (6–10 h). High doses of lorazepam (> 6 mg/h for more than 48 h) increases the risk of propylene glycol toxicity, which presents as metabolic acidosis (increased lactate) and renal failure.

Conclusion Appropriate use of sedation and analgesia is an important component in the management of mechanically ventilated critically ill patients. There is significant variation in medication requirements based on a patient’s underlying disease, physiology, and the drug’s pharmacology. In obese patients this variation is further increased. Directing treatment to individualized goals and implementation of a strategy (Figure 12.1) that includes frequent and standardized assessment of pain and sedation level will ensure that patient needs are met. 134 K. Wolfe and J. Kress

Pain Assessment

- Numeric Pain Rating Scale - Begavioral Pain Scale - Critical Care Pain Observation Tool

- Nonverbal Pain Scale

Treat Pain if Present

- Hydromorphone - Morphine - Fentanyl

- Remifenantil

Choose Sedation Strategy - Daily Interruption of Sedation - Sedation Scale-based Protocol (Target to a RASS score -2 to 0) - No sedation

Choose Sedative

- Dexmedetomidin e - Propofol - Midazolam

Fig. 12.1 Analgesia and sedation algorithm 12 Sedation of the Obese Patient: Indications, Management, and Complications 135

References

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Malcolm Lemyze

13.1 Introduction

Positioning of the critically ill obese patient is often considered by the attending clinician after the other therapeutic targets have been reached, while actually obese patients’ position drastically impacts on mechanical ventilation success or failure and may be a main determinant of the obese patients’ outcome.

13.2 Supine Position and Trendelenburg Position

When massively obese patients are allowed to lie completely flat, the abdomen pushes the diaphragm upward, which leads to both an increase in intrathoracic pressures and an extending airway collapse of the dependent parts of the lungs [1], promoting expiratory flow limitation, gas trapping, auto-positive end-expiratory pressure (auto-PEEP) [2–4], and severe hypoxemia [5, 6]. As demonstrated in supine pregnant women [7], extrinsic compression of the inferior vena cava by the abdominal weight may dangerously impair cardiac preload especially in hypovolemic patients with massive abdominal obesity. The combination of all these deleterious hemodynamic effects—the increased cardiac afterload, the decreased cardiac preload, and an insufficient oxygen supply to the heart—is the winning recipe to culminate in cardiac arrest. This scenario has been called “obesity supine death syndrome” to describe the fulminant cardiorespiratory failure that results from the supine positioning of a massively obese patient [8, 9]. Although rarely reported, it is certainly underrecognized and misdiagnosed in clinical practice. Morbidly obese patients in acute respiratory failure should therefore be assisted by noninvasive

M. Lemyze, M.D. Department of Respiratory and Critical Care Medicine, Schaffner Hospital, 99 Route de la Bassée, Lens, France e-mail: [email protected]

Fig. 13.1 Panel (a): The classic “sniff position” offers poor conditions for intubation of the massively obese patient. Panel (b): The HELP or ramped position improves oxygenation and facilitates laryngoscopy by placing the obese patient in 30 degrees reverse Trendelenburg in order to obtain a horizontal alignment between the external auditory meatus and the sternal notch mechanical ventilation each time they need to be kept supine (Fig. 13.1, Panel a), and this should be limited in time to prevent the catastrophic syndrome described above.

13.3 The Ramped Position or “HELP” Position for Intubation

Several anatomical characteristics of the morbidly obese patient increase the risk of difficult intubation especially in the commonly used “sniff position” (Fig. 13.1, Panel a). It cannot be emphasized enough that massively obese patients can become 13 Positioning of the Critically Ill Obese Patient for Mechanical Ventilation 141 severely hypoxemic immediately after they are placed in the supine position [5, 6]. The HELP (head-elevated laryngoscopy position) facilitates bag mask ventilation and enhances the rate of successful intubation [10]. This position also called “ramped position” is achieved by placing the patient in 30° reverse Trendelenburg in order to obtain a horizontal alignment between the external auditory meatus and the sternal notch, which significantly improves direct laryngoscopy (Fig. 13.1, Panel b). Furthermore, it prolongs the “safe apnea time”—the delay between anesthetic induction and hemoglobin desaturation below 90%—which gives the clinician some more time to intubate the patient safely [11].

13.4 Prone Position

In the obese patient, impaired pulmonary gas exchange mainly results from ventilation-perfusion mismatch. The cephalad displacement of the diaphragm and the extrinsic compression exerted by the thoracoabdominal wall reduce ventilation of the lower posterior parts of the lungs. These dependent parts of the lungs are well perfused especially in the supine position which results in a drop of ventilation- perfusion ratio (shunt effect) that generates severe hypoxemia [12]. Proning the obese patient may facilitate alveolar recruitment of the dependent parts of the lungs, improves perfusion of the most aerated lung area, and thus may substantially improves pulmonary gas exchange. Pelosi et al. demonstrated that prone position significantly increases functional residual capacity, lung compliance, and oxygenation during general anesthesia [12]. This is especially interesting for the most hypoxemic obese patients—those exhibiting ARDS or extensive atelectasis—under invasive mechanical ventilation. One special hurdle that needs to be overcome in order to get the most benefit from this strategy is to alleviate thoracoabdominal wall compression. Pillows may be placed under the patient’s upper chest and pelvis in order to maintain an abdomen-free position [12]. When executed by a well-trained team with at least 5–6 individuals per obese patient during the procedure, prone positioning does not result in more complication than in non-obese patients with a greater benefit in terms of increase in PaO2/FiO2 ratio and a better survival [13].

13.5 Lateral Decubitus Position

Lateral decubitus position probably relieves the diaphragm and the large intra- abdominal vessels from the weight of the panniculus. Objectively, it diminishes auto-PEEP and reverses expiratory flow limitation phenomenon that is commonly encountered in supine obese patients [2]. However, during mechanical ventilation, this position exposes the most obese patients to the risk of developing extensive atelectasis of the dependent lung which then promotes severe hypoxemia and super- infection. A more appealing strategy would be based on a periodical rotation alter- nating right lateral with left lateral decubitus position in case of absolute contraindication to the sitting position. 142 M. Lemyze

13.6 Sitting Position or “Cardiac Chair Position”

Sitting position (Fig. 13.2) reverses expiratory flow limitation of the obese patient and relieves the respiratory system from the additional elastic load induced by auto-PEEP in the supine position [3, 4]. It could therefore avoid the unnecessary use of inefficient but potentially dangerous drugs (high doses of corticosteroids or bronchodilators, for instance) or useless risky interventions (high increase in PEEP level, fiber optic bronchoscopy) in the morbidly obese patient in acute respiratory failure [4, 14]. The excursion course of the diaphragm is also facilitated by the gravitational forces in the sitting or upright position, while the abdomen crushes the diaphragm in supine morbidly obese patients (Fig. 13.1, Panel a). A change in posture from sitting to supine causes an increase in neural drive with higher esophageal pressure swings and electromyogram activity of the diaphragm [15]. On the opposite, all intrathoracic pressures—including plateau pressure and intrinsic PEEP—are reduced when the obese patient is seated [4]. Sitting position offers better conditions for the application of noninvasive ventilation and for the weaning process from mechanical ventilation and may be part of the protective

a b

Fig. 13.2 Panel (a): Sitting position during the weaning process from mechanical ventilation in a critically ill morbidly obese woman. Panel (b): The successful combination of noninvasive ventilation and cardiac chair position is applied immediately after extubation 13 Positioning of the Critically Ill Obese Patient for Mechanical Ventilation 143 ventilation strategy that is currently recommended in acute lung injuries. By limiting auto-PEEP and reducing inspiratory efforts, it can be assumed that sitting position decreases pleural pressure swings and thus transpulmonary pressure during insufflation 4[ , 15]. Combining sitting position and high external PEEP may keep transpulmonary pressure positive at expiration and thus may prevent airway collapse. Of course, critically ill obese patients should be regularly repositioned to ensure that they tolerate the sitting position for a few hours straight and to prevent them from slipping off the bed. One solution is to place the critically ill obese patient in a chair as soon as possible (Fig. 13.2, Panel b). Attention should be paid on not compressing the patient’s abdomen by maintaining slightly open legs in the sitting posture. An early rehabilitation program can be safely implemented in the most critically ill patients, although nearly 90% of them exhibit a situation that is commonly regarded as a major barrier to physical therapy and mobilization during mechanical ventilation [16]. Obesity is usually considered as one of these potential barriers that hinder early mobilization [16]. However, providing that bariatric equipment and a high caregivers-to-patients ratio are available—two conditions that are generally fulfilled in the ICU—sitting position should be easily achieved in most of the massively obese patients in acute respiratory failure.

Conclusion Based on physiological considerations, good positioning of the morbidly obese patient in acute respiratory failure should be regarded as a main therapeutic target as important as the settings of the ventilator, the choice of antibiotics, the volume of fluids, or any other treatment that can impact obese patients’ outcome in the emergency setting. When this will be figured out, physicians will do everything in their power to convince their staff to implement sitting position and early rehabilitation in critically ill obese patients.

13.7 Key Messages

1. More than for any other critically ill patients, obese patients’ positioning is a key determinant of mechanical ventilation success or failure and drastically impacts on obese patients’ outcome. 2. Everything should be done to avoid supine position and Trendelenburg position in critically ill patients with massive android obesity. 3. The ramped position or “HELP” (head-elevated laryngoscopy position) facilitates obese patients’ intubation. 4. For the more severely hypoxemic obese patients, prone position has proved safe and effective in recruiting the atelectatic dependent parts of the lungs during mechanical ventilation. 5. Sitting position is the optimal position to provide noninvasive ventilation, to facilitate the weaning process from mechanical ventilation, and to prevent atelectasis and acute respiratory failure episodes in massively obese patients. 144 M. Lemyze

References

1. Eichenberger AS, Proitti S, Frascarolo P, et al. Morbid obesity and postoperative pulmonary atelectasis: an underestimated problem. Anesth Analg. 2002;95:1788–92. 2. Pankow W, Podszus T, Gutheil T, Penzel T, Peter J, Von Wichert P. Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity. J Appl Physiol (1985). 1998;85:1236–43. 3. Ferretti A, Giampiccolo P, Cavalli A, et al. Expiratory flow limitation and orthopnea in massively obese subjects. Chest. 2001;119:1401–8. 4. Lemyze M, Mallat J, Duhamel A, et al. Effects of sitting position and applied positive end- expiratory pressure on respiratory mechanics of critically ill obese patients receiving mechanical ventilation. Crit Care Med. 2013;41:2592–9. 5. Yamane T, Date T, Tokuda M, et al. Hypoxemia in inferior pulmonary veins in supine position is dependent on obesity. Am J Respir Crit Care Med. 2008;178:295–9. 6. Pelosi P, Croci M, Ravagnan I, et al. Respiratory system mechanics in sedated, paralyzed, morbidly obese patients. J Appl Physiol. 1997;82:811–8. 7. Wright L. Postural hypotension in late pregnancy. “The supine hypotensive syndrome”. Br Med J. 1962;1:760–2. 8. Tsueda K, Debrand M, Zeok SS, et al. Obesity supine death syndrome: reports of two morbidly obese patients. Anesth Analg. 1979;58:345–7. 9. Lemyze M, Guerry MJ, Mallat J, Thevenin D. Obesity supine death syndrome revisited. Eur Respir J. 2012;40:1568–9. 10. Collins JS, Lemmens HJ, Brodsky JB, et al. Laryngoscopy and morbid obesity: a comparison of the “sniff” and “ramped” positions. Obes Surg. 2004;14:1171–5. 11. Boyce JR, Ness T, Castroman P, et al. A preliminary study of the optimal anesthesia positioning for the morbidly obese patient. Obes Surg. 2003;13:4–9. 12. Pelosi P, Croci M, Calappi E, et al. Prone positioning improves pulmonary function in obese patients during general anesthesia. Anesth Analg. 1996;83:578–83. 13. De Jong A, Molinari N, Sebbane M, Prades A, Futier E, Jung B, Chanques G, Jaber S. Feasibility and effectiveness of prone position in morbidly obese patients with ARDS: a case-control clinical study. Chest. 2013;143:1554–61. 14. Fortis S, Kittah J, De Aguirre M, et al. Perseverant, nonindicated treatment of obese patients for obstructive lung disease. BMC Pulm Med. 2013;13:68. 15. Steier J, Jolley CJ, Seymour J, et al. Neural respiratory drive in obesity. Thorax. 2009;64:719–25. 16. Pohlman MC, Schweickert WD, Pohlman AS, Nigos C, et al. Feasibility of physical and occupational therapy beginning from initiation of mechanical ventilation. Crit Care Med. 2010;38:2089–94. Obesity and Positive End-Expiratory Pressure (PEEP)-Obesity 14 and Recruitment Maneuvers During the Intraoperative Period

Seniyye Ulgen Zengin and Güniz Köksal

14.1 Introduction

Obesity is a global and growing public health problem. Worldwide obesity has more than doubled since the 1980s with around 600 million people being obese [1]. There has been a steady increase in the number of obese patients undergoing both bariatric and non-bariatric surgeries, and it seems likely that there will be more obese patients undergoing surgery in the future. Obesity is a risk factor for the onset of intra- and postoperative respiratory complications when compared to non-obese individuals [2]. Due to excessive weight load on the chest wall and intra-abdominal and intrathoracic compartments, there is a decrease in lung volumes and pulmonary compliance that causes restrictive pulmonary physiology. Every unit of BMI increase can be expected to reduce residual volume, total lung capacity, and vital capacity by 0.5%. Even at a BMI of 30 kg/m2, the EVR and functional residual capacity (FRC) can be reduced by 53 and 25%, respectively. It is possible that with reduced FRC and EVR, tidal volume is closer to RV. In the upright position, the lower part of the lungs of the obese is overperfused and underventilated. So with these findings, obese patients more easily lead to airway closure during tidal breathing, atelectasis, and ventilation—perfusion mismatch and shunt formation lending impairment of gas exchange [2]. In anesthetic patient, a 20% reduction in FRC in non-obese subjects compared with a 50% FRC reduction in the obese was demonstrated [3].

S.U. Zengin, M.D. (*) Department of Anesthesiology and Reanimation, Bezmialem Vakif University Faculty of Medicine, Istanbul, Turkey e-mail: [email protected] G. Köksal, M.D. Department of Anesthesiology and Reanimation, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey e-mail: [email protected]

© Springer International Publishing AG 2018 145 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_14 146 S.U. Zengin and G. Köksal

Respiratory complications occur within minutes after the induction of anesthesia in 85–90% of patients, and the adverse effects persist during the postoperative period, affecting the patient’s recovery. Furthermore, it has been demonstrated that obesity is a risk factor for postoperative tracheal re-intubation, morbidity, and mortality. Several strategies have reported about the benefits of respiratory physiotherapy in the pre- and postoperative periods of these patients, thus preventing the pulmonary complications related to surgeries [4]. These ventilation strategies would be expected to optimize gas exchange and pulmonary mechanics and to minimize the risk of postoperative respiratory complications.

14.2 Intraoperative Techniques

Different ventilation strategies including PEEP (positive end-expiratory pressure), RM (recruitment maneuver), ventilation modes, and high tidal volume are used to reduce pulmonary complications. However, the ideal ventilation strategy in obese patients undergoing surgery under general anesthesia has not yet been established. Positive end-expiratory pressure (PEEP) is an easily implemented intervention that can be used in ventilating a patient with positive pressure ventilation. It is a mechanical maneuver that positive pressure is exerted in the lungs at the end of each exhalation [4]. This end-expiratory pressure increases the functional residual capacity (FRC) and prevents collapse of the small airways, thereby reducing atelectasis. In patients with healthy lungs, PEEP leads to improved lung compliance, decreased shunting, and higher arterial oxygen pressure (PaO2). Coussa et al. ventilated the patients with PEEP at 10 cm H2O during surgery and observed the prevention of intraoperative atelectasis [5]. However, there was no follow-up of these patients in the postoperative period. In a study Baltieri et al. confirmed that high levels of PEEP during surgery can maintain lung expansion for up to 48 h after extubation, as confirmed by the decreased prevalence of atelectasis shown on the chest radiographies on the second day after surgery [6]. Timing of the PEEP is another controversial aspect. In a recent study, PEEP decreased the prevalence of postoperative atelectasis, but the most effective treatment for this purpose was observed with the use of positive pressure immediately after surgery, in which case the incidence of atelectasis was null [6]. Using PEEP like two-edged sword, in damaged lungs, PEEP may cause overdistension of normal lung areas without improvement in abnormal areas [7]. So it is possible that PEEP may actually impair respiratory function. The risk of barotrauma may increase because of increased intrapleural pressure caused by PEEP and may induce negative cardiovascular effects. Cardiovascular effects can change the intraoperative management of a patient’s condition, sometimes causing an increase in the need for cardiovascular support. Pelosi et al. found that 10 cm H2O PEEP improved oxygenation in obese but not in normal subjects [8]. The application of PEEP resulted in greater alveolar recruitment in obese patients. The unchanged oxygenation in normal patients is attributed to decreased cardiac output associated with PEEP. 14 Recruitment Maneuver 147

The RM most commonly described in the literature is sustained inflation, with a rapid increase in pressure to 40 cm H2O that is applied for a period of 40–60 s. Different types of recruitment maneuvers are described in the literature [9]: prolonged recruitment maneuvers with low pressure and increased positive end- expiratory pressure (PEEP) to 15 cm H2O, associated with expiratory pauses of 7 s twice per minute for 15 min; [2] incremental increases in PEEP, limiting the maximum inspiratory pressure; and [3] ventilation with constant controlled pressure with PEEP staggering. There is no clear consensus about the optimal duration or time of application of recruitment maneuver. Recent studies have been summited where a single recruitment maneuver was applied either after induction of anesthesia, after abdominal opening, after pneumoperitoneum, or after suture of abdominal aponeurosis [9–11]. Rothen et al. represent that reopening of the alveoli occurs within first 7–8 s of vital capacity maneuver in healthy anesthetized subjects with no previous lung disease [12]. More studies are needed to determine the optimal timing of application of recruitment maneuver and its duration. Repetition is also another factor that influences the effectiveness of RM, so increasing the frequency of the maneuver is important. Ahmed et al. aimed to represent the effect of RM repetition with respect to oxygenation and the reduction of atelectasis [13]. To do so, 60 patients were randomly divided into 3 groups: conventional ventilation, single RM (40 cm H2O for 7 s), and ARM repeated every 30 min. All groups were treated with PEEP set at 10 cm H2O. In addition to improving gas exchange and respiratory mechanics, repeated RM maintained its beneficial effects during the postoperative period [13]. RM in the presence of PEEP, and compared with PEEP alone, has a beneficial effect on oxygenation and compliance in obese patients undergoing surgery. The mechanism is how the combination of RM and PEEP works, and the positive effect could be that RM opens the collapsed alveoli and PEEP keeps them open. When a recruitment maneuver was applied without PEEP, the effect was short lasting. 20 min after the recruitment maneuver, no beneficial effects remained. This is in contrast to what has been observed in normal-weight patients in whom a recruitment maneuver followed by ZEEP (zero PEEP) reduced atelectasis significantly for at least 20 min if FIO2 was kept at 0.4. This observation suggests that the application of PEEP in morbidly obese patients is necessary to keep the lung open and improve respiratory function after an effective recruitment maneuver. It was observed that repeated inspiratory pressure maneuver combined with

10 cm H2O of PEEP increased respiratory system compliance and PaO2 and decreased PaCO2 in obese patients undergoing laparoscopic gastric banding without adverse effects and the positive effects on oxygenation continued into the early recovery period [6]. In a study Reinus et al. reported lung recruitment using inspiratory pressure of 40 cm H2O for 15 s repeated every 10 min and combined with PEEP of 10 cm H2O was associated with the best respiratory system compliance and best PaO2 in obese patients undergoing laparoscopic bariatric surgery, when compared with PEEP of 10 cm H2O alone, inspiratory pressure of 40 cm H2O applied once for 15 s, or both. 148 S.U. Zengin and G. Köksal

Although barotrauma is a major problem in patients treated with RM, only two randomized trials reported on this complication, and both analyzed the effect of RM plus PEEP. In those trials, patients (n = 92) were ventilated with different RM regimens and none was reported to suffer from barotrauma [2, 14]. This does not exclude the risk of barotrauma in obese surgical patients who are ventilated with RM. But, there were similar data from critical care patients with ALI. One of the important problems is in hypovolemic patients’ recruitment maneuver with excessive pressure may cause hemodynamic instability [10]. In addition RM can decrease the venous return by increasing intrathoracic pressure, which can cause venous stasis, especially in the low the lower extremities, increasing the risk of deep vein thrombosis [6]. In conclusion, studies indicate that anesthesia in morbidly obese patients induces atelectasis formation and impairment in oxygenation. An effective recruitment maneuver followed by PEEP was the good choice to reduce the amount of atelectasis and improve oxygenation for a prolonged period of time. However, PEEP or recruitment maneuver alone was not effective to reach a sustained improvement of respiratory function.

References

1. Obesity Facts & Figures – World Health Organisation Fact sheet No. 311 [Internet]. 2015. http://easo.org/education-portal/obesity-facts-figures/. Accessed 6 June 2015. 2. Shah U, Wong J, Wong D, Chung F. Preoxygenation and intraoperative ventilation strategies in obese patients: a comprehensive review. Curr Opin Anesthesiol. 2016;29:109–18. 3. Schumann R. Pulmonary physiology of the morbidly obese and the effects of anesthesia. Int Anesthesiol Clin. 2013;51(3):41–51. 4. Barbosa FT, Castro AA, de Sousa-Rodrigues CF. Positive end-expiratory pressure (PEEP) during anaesthesia for prevention of mortality and postoperative pulmonary complications. Cochrane Database Syst Rev. 2014;(6):CD007922. doi:10.1002/14651858.CD007922.pub3. 5. Coussa M, Proietti S, Schnyder P, et al. Prevention of atelectasis formation during the induction of general anesthesia in morbidly obese patients. Anesth Analg. 2004;98(5):1491–5. 6. Baltıerı L, Santos L, Rasera-Junıor I, et al. Use of positive pressure in the bariatrıc surgery and effects on pulmonary function and prevalence of atelectasis: randomızed and blinded clinical trıal. Arq Bras Cir Dig. 2014;27(Suppl 1):26–30. 7. Carvalho AR, Jandre FC, Pino AV, et al. Effects of descending positive end-expiratory pressure on lung mechanics and aeration in healthy anaesthetized piglets. Crit Care. 2006;10(4):R122. 8. Pelosi P, Ravagnan I, Giurati G, et al. Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis. Anesthesiology. 1999;91:1221–31. 9. Forgiarini Júnior LA, Rezende JC, Forgiarini SG. Alveolar recruitment maneuver and perioperative ventilatory support in obese patients undergoing abdominal surgery. Rev Bras Ter Intensiva. 2013;25(4):312–8. 10. Bohm SH, Thamm OC, von Sandersleben A, et al. Alveolar recruitment strategy and high positive end-expiratory pressure levels do not affect hemodynamics in morbidly obese intravascular volume-loaded patients. Anesth Analg. 2009;109:160–3. 11. De Souza AP, Buschpigel M, Mathias LA, et al. Analysis of the effects of the alveolar recruitment maneuver on blood oxygenation during bariatric surgery. Rev Bras Anesthesiol. 2009;59:177–86. 14 Recruitment Maneuver 149

12. Rothen HU, Neumann P, Berglund JE, et al. Dynamics of re-expansion of atelectasis during general anaesthesia. Br J Anaesth. 1999;82:551–6. 13. Ahmed WG, Abu-Elnasr NE, Ghoneim SH. The effects of single vs. repeated vital capacity maneuver on arterial oxygenation and compliance in obese patients presenting for laparoscopic bariatric surgery. Ain Shams J Anesthesiol. 2012;5(1):121–32. 14. Talab HF, Zabani IA, Abdelrahman HS, et al. Intraoperative ventilatory strategies for prevention of pulmonary atelectasis in obese patients undergoing laparoscopic bariatric surgery. Anesth Analg. 2009;109:1511–6. Complications Associated with Invasive Mechanical Ventilation in Obese Patients 15

Nishant Chauhan

15.1 Introduction

Obesity is not a problem of any particular geographic area. With rising living stan- dards, changing lifestyles and dietary habits, the prevalence of obesity has increased world over. Obesity has more than doubled since 1980, and most of the world’s population live in countries where overweight and obesity leads to more mortality than underweight [1]. Not only does obesity pose a problem in managing a particular critical illness but also in areas related to invasive mechanical ventilation (IMV), hemodynamic monitoring, etc. Obesity-related respiratory morbidity arises mainly from derangements in control of breathing and chest wall mechanics. It is associated with reduction in respiratory drive, decreased lung volumes, reduced respiratory muscle strength and increased work of breathing [2, 3]. Respiratory system compliance is usually reduced in obese patients and is primarily attributed to decrease in lung compliance. This leads to risk of developing atelectasis. Some of the morbidly obese patients show increased airway resistance, causing airflow limitation and development of intrinsic positive end-expiratory pressure (iPEEP). Respiratory muscle strength and endurance are generally well preserved in simple obesity but reduced in morbidly obese patients. This leads to decrease in total lung capacity (TLC) in these patients. Upper airway collapsibility seen during sleep causes episodic apnoeas and desaturations in patients of obstructive sleep apnoea (OSA).Ventilatory response to hypoxia and hypercapnia is reduced to some extent in simple obesity but more so in obesity hypoventilation syndrome (OHS) patients [4]. This fact has to be kept in mind while mechanically ventilating as well as weaning obese patients from ventilation.

N. Chauhan Pulmonary Medicine, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan 342005, India e-mail: [email protected]

15.2 Discussion

Before we dwell into the complications associated with IMV in obese patients, we should know about the effects of obesity on lung volumes and lung functions. Two medical conditions causing sleep-disordered breathing, OSA and OHS, are highly prevalent in obese and morbidly obese patients, respectively. Unless we are able to recognise these conditions prior to or during mechanical ventilation, there are higher chances of complications related to the disease itself in addition to inefficient ventilator settings.

15.2.1 Lung Volumes and Functions

It has been found that the greatest impact of obesity is on functional residual capacity (FRC) and the expiratory reserve volume (ERV), affecting total lung capacity (TLC) and vital capacity (VC) to a lesser extent. TLC is reduced in morbidly obese patients who have reduced muscle strength and endurance. Obesity also affects airway resistance. According to the Poiseuille equation, the pressure-flow characteristics of laminar flow depend on the length and the radius of the tube and viscosity of the gas [5]. This signifies the importance of airway in determining the driving pressure for a given flow, so that if the radius of the tube (airway in this case) is halved, the pressure that is required to maintain a given flow rate must be increased 16-fold. Since airway size is a function of lung volume, lower lung volumes are related with reduced airway size leading to increase in airway resistance. This is clinically important in choosing ventilator settings in obese patients and not simply or solely relating this increased airway resistance to asthma or any other obstructive lung disorder. Since obesity itself is a systemic inflammatory disorder, this inflammation may act on distal airways causing increased airway responsiveness. Respiratory system compliance is also reduced in obese patients which is mainly attributed to reduction in lung compliance.

15.2.2 Sleep-Disordered Breathing

Obesity is a major risk factor for the development of sleep-disordered breathing which primarily includes OSA and OHS. A proper evaluation of relevant clinical symptoms and signs along with sleep history is essential to suspect these entities in an obese patient who is being mechanically ventilated. Since a detailed description of these two disorders is beyond the scope of this chapter, a brief mention is being made. OSA is characterised by repeated episodes of apnoea or hypopnoeas during sleep, leading to intermittent hypoxemia and sleep fragmentation. Apnoeas and hypopnoeas are due to episodes of airway collapsibility seen in these patients which occur only during sleep. Another spectrum of obese patients with higher BMI is those which may be suffering from what is known as OHS which consists of daytime and nocturnal hypoventilation after excluding other causes of alveolar 15 Complications Associated with Invasive Mechanical Ventilation in Obese Patients 153 hypoventilation, such as chronic obstructive pulmonary disease (COPD) and parenchymal and extraparenchymal restrictive respiratory disorders. In arterial blood gas

(ABG), we find that OHS patients have daytime and nocturnal PCO2 >45 mm Hg with more elevation of PCO2 during sleep. These patients are at risk to present in the ICU or emergency room with acute or chronic respiratory failure. Once the patient has been intubated and connected to the ventilator all the above facts should be borne in mind while ventilating an obese patient. The following parameters need special consideration: [1] optimum tidal volume delivery (VT), [2] optimum PEEP and [3] application of recruitment manoeuvres. Many studies have shown that lung protection strategies used for ventilating adult respiratory distress syndrome (ARDS) patients suit well for obese patients as well. Due to increased mechanical load on the chest wall and reduced compliance of the respiratory system in obese patients, the dependent posterior segments of the lungs of obese patients are prone to hypoventilation and atelectasis [6]. Due to low lung volumes, the distal most airways have a tendency to remain collapsed with sudden and repeated opening and collapse with each ventilator breaths leading to “recruitment-derecruitment phenomenon” causing atelectrauma. This will not only trigger but also enhance the ongoing lung inflammation, known as biotrauma, histologically seen as diffuse alveolar damage. Experimental laboratory study has shown histological evidences of lung injury due to repeated derecruitments during mechanical ventilation [7]. As of now, there are no clear guidelines for setting VT in patients without ARDS. Most of the studies show the association of higher VT and ARDS, suggesting that low tidal volume lung protection strategies, VT of 6–8 mL/Kg predicted body weight (PBW), are useful for obese patients as well. The use of PBW instead of actual body weight is preferred because lung volumes are proportional to height but independent of body weight. Ventilating obese patients and limiting airway plateau pressure (Pplat) ≤30 cm H2O are difficult due to reduced chest wall and lung compliance. Transpulmonary pressure (TPP) defined as the difference between airway and pleural pressures is important in gauging the risk of barotrauma. Use of pleural pressure which is measured by oesophageal manometry can be used in advanced ICU settings. Alveolar overdistension can be prevented during inspiration by keeping the TPP below 25 cm

H2O. There is a tendency for the gravity-dependent segments of the lung to undergo atelectasis during the expiratory phase of respiratory cycle. There are some lung units which are open, and some are collapsed leading to heterogeneity in ventilated areas of the lungs. Alveolar overdistension and cyclical opening and collapse of the alveoli lead to atelectrauma. One of the ways to counteract this lung damaging phenomenon is to apply appropriate PEEP to keep the alveoli open throughout the phase of respiratory cycle. This also leads to homogeneity in lung ventilation and reduction in the number of atelectatic lung units. As explained above, obese patients have higher pleural pressure on end expiration so higher levels of PEEP are required in such patients. Optimum PEEP calculation can be done by setting the PEEP to maintain TPP of 0–10 cm H2O at end expiration. There are other methods like best lung compliance, gas exchange method, etc. The aim is to keep the alveoli distended at end expiration with minimal positive pressure that will not allow derecruitment to 154 N. Chauhan occur and maintain adequate oxygenation. It has been shown in various studies that recruitment manoeuvres reduce atelectasis and lung compliance, thereby improving oxygenation in the mechanically ventilated obese patients. Application of PEEP after a recruitment manoeuvre would prevent alveolar collapse in obese patients. The adverse effects associated with these manoeuvres are transient desaturation, hypotension, arrhythmias and barotrauma. Close monitoring for anticipation and occurrence of these complications is required. Obese patients with underlying OSA have a tendency of going into repetitive episodes of apnoeas and desaturations when they are being ventilated on assist control or pressure support modes while they are sedated. This is due to upper airway collapsibility during sleep or under general anaesthesia. Application of PEEP/continuous positive airway pressure (CPAP) adequate enough to provide splinting action on the upper airway will abort these apnoeic events, thus easing the process of liberating them from mechanical ventilation. Inability to diagnose or suspect OSA would lead to inadvertent increase in fractional inhalation of oxygen

(FiO2) delivery which would further deteriorate the condition by increasing the length of apnoeas duration and risk of causing hypercarbia. On the other hand, OHS patients additionally hypoventilate as evidenced by raised PCO2 levels. A simple way to treat this is to provide pressure support or bilevel positive airway pressure (BiPAP) support to such patients which would deliver them adequate tidal volume, thereby preventing hypoventilation. A high index of suspicion should be kept for the possibility of these sleep disorders in obese patients. This would lead to reduction of duration of mechanical ventilation once the primary illness has been treated. Any prolongation due to these conditions will put the patient at risk for both ventilator- and non-ventilator-associated complications during the ICU stay. Various changes described in the respiratory physiology along with the related problem are mentioned in Table 15.1. The pharmacokinetics of sedatives and

Table 15.1 Changes in the respiratory physiology along with the related problem Changes in respiratory physiology Problem Excessive oropharyngeal fat Upper airway obstruction leading to difficult intubation and ventilation Reduced chest wall and lung compliance Inadequate tidal volume delivery in pressure control mode Reduced FRC and ERV Risk of atelectasis and hypoxemia Alveolar collapse Hypoxemia Increased airway resistance Increased airway pressures Increased body weight Difficulty in changing positions, including prone positioning Airway collapsibility Recurrent episodes of apnoea during weaning seen in OSA patients Reduced respiratory drive and airway Episodes of hypercapnia seen in OHS patients collapsibility Auto PEEP due to airway closure during Increased work of breathing expiration 15 Complications Associated with Invasive Mechanical Ventilation in Obese Patients 155 neuromuscular blockers (NMBs) is affected by the mass of adipose tissue which is more in an obese patient, producing a prolonged and less predictable effect causing difficulty in arousal assessment 8[ ] while the patient is on mechanical ventilation and at the time of liberation from mechanical ventilation.

15.2.3 Weaning from Mechanical Ventilation

Due to excess fat deposition and deranged physiology, obese patients are at risk of prolonged ventilation and difficult weaning. Use of non-invasive positive pressure ventilation (NIPPV) early after extubation has shown to significantly reduce the duration of mechanical ventilation and prevent reintubation. Reversal to spontaneous breathing and arousal state may be delayed after stopping the infusion of sedative and NMBs in obese patients due to altered pharmacokinetics as mentioned earlier. Recognition of sleep disorders such as OSA and OHS is important especially more so when planning to liberate these patient from the ventilator.

Conclusion The increase in the proportion of obese patients requiring mechanical ventilation for different medical conditions is a challenge for the anaesthesiologists, pulmonologists and critical care physicians. Mechanical ventilation of critically ill obese patients requires detailed knowledge of the altered respiratory physiology and related complications seen in these patients. Two important sleep disorders to suspect in obese patients are OSA and OHS. Appropriate tidal volume delivery and optimal PEEP to avoid ventilator-induced lung injury, including barotrauma and atelectrauma, are the primary objectives. Consideration must be given to combine recruitment manoeuvres in the ventilator management rather than reserving it as a last resort. Weaning with the use of CPAP/NIPPV/BiPAP has shown good results in multiple studies and must be tried when indicated.

15.3 Key Major Recommendations

• Knowledge of the impact of obesity on respiratory physiology is the key component in providing better ventilatory support to critically ill obese patients. • Optimised tidal volume delivery along with application of PEEP and recruitment manoeuvres would minimise volutrauma, atelectrauma and nonhomogeneous ventilation in different parts of the lungs. • Early recognition of sleep disorders like OSA and OHS would help in choosing better modes of mechanical ventilation. • Use of CPAP/NIPPV in select group of obese patients during weaning process is likely to avoid prolonged ventilation and ICU stay. 156 N. Chauhan

References

1. World Health Organisation 2016, Obesity and overweight fact sheet. 2. Piper AJ, Grunstein RR. Big breathing: the complex interaction of obesity, hypoventilation, weight loss, and respiratory function. J Appl Physiol. 2010;108:199–205. 3. Salome CM, King GG, Berend N. Physiology of obesity and effects on lung function. J Appl Physiol. 2010;108:206–11. 4. Sampson MG, Grassino K. Neuromechanical properties in obese patients during carbon dioxide rebreathing. Am J Med. 1983;75:81–90. 5. Grippi MA, Elias JA, Fishman JA, Kotloff RM, et al. Fishman’s pulmonary diseases and disorders. 5th ed. New York: McGraw-Hill Education; 2015. p. 142. 6. Suratt PM, Wilhoit SC, Hsiao HS, et al. Compliance of chest wall in obese subjects. J Appl Physiol. 1984;57:403–7. 7. Suh GY, Koh Y, Chung MP, An CH, et al. Repeated derecruitments accentuate lung injury during mechanical ventilation. Crit Care Med. 2002;30:1848–53. 8. Hughes CG, McGrane S, Pandharipande PP. Sedation in the intensive care setting. Clin Pharmacol. 2012;4:53–63. Management of Ventilator-Induced Lung Injury 16

Sven Stieglitz

The study from Dreyfuss in 1985 demonstrated impressively that ventilation alone may harm and destroy even healthy lungs [1]. The reason is that ventilation itself may damage the lung by developing a ventilator-induced lung injury (VILI).

16.1 What Is the Characterization of VILI?

Initially, the development of VILI was explained by two different mechanisms: firstly baro- and volutrauma due to overdistension and rupture of alveolar walls in non-dependent lung regions by high inspiratory pressure and/or high volume and secondly cyclical reopening (tidal recruitment) of the alveoli during inspiration followed by the next expiration leading to shear stress and atelectrauma, a phenomenon occurring in dependent lung regions due to insufficient PEEP. The volutrauma rather leads to pulmonary edema with persistent inflammation followed by fibrosis and atelectrauma to alveolar capillary damage with surfactant dysfunction leading to alveolar collapse. The relation between PEEP and inspiratory pressure is described by the driving pressure ΔP = VT/C (VT = tidal volume, C = compliance) or plateau pressure minus PEEP (in controlled ventilation only) [2]. These pathomechanisms are not integrating dynamic aspects of stress and strain. In fact, dynamic strain (ratio between tidal volume and functional residual capacity) seems to be worse than static strain [3]. A high strain (amplitude) rate (velocity) is a risk factor for ventilator-induced pulmonary edema, possibly because it amplifies lung viscoelastic behavior [4]. Recently, the dynamic predictors of VILI risk were assessed by the key values of ventilator settings [5]: the mechanical power measured by the pressure–volume loops and its components tidal volume (TV)/driving

S. Stieglitz Clinic for Pneumology, Allergology, Sleep und Intensive Care Medicine at Petrus Hospital Wuppertal, Wuppertal, Germany e-mail: [email protected]

© Springer International Publishing AG 2018 157 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_16 158 S. Stieglitz pressure (ΔPaw), flow, positive end-expiratory pressure (PEEP), and respiratory rate (RR) [6]. Since ventilation and perfusion are distributed heterogeneously already in the healthy lung, the ventilation-perfusion mismatch is even marked in obesity. The inhomogeneity of the lung in ARDS dictates an inhomogeneous distribution not only of alveolar gases but also of forces and mechanical power, which is likely the main lung-dependent cause of VILI [6]. The initial local inflammation of the lung may finally damage the whole lung and even can lead to multi-organ failure

(MOV) and sepsis [7]. In rats an increase of white blood cell count, H2O2, interleukin-1, tumor necrosis factor alpha, and macrophage inflammatory protein-2 in bron- choalveolar lavage may be observed [8]. The damage-associated molecular pattern linked to VILI is characterized by activation of recognition receptors, releasing pro- inflammatory cytokines and chemokines [9], and may trigger MOV.

16.2 Which Kind of Respiratory Mechanics Are Altered in Obese Patients and Is Obesity a Risk Factor for Developing VILI During Invasive Ventilation?

Since there are no data about the prevalence of VILI in obese patients, we first shall have a look at the respiratory mechanics in obesity. Surprisingly, lung function in obesity is hardly changed both at rest and during exercise. The most common finding is a decrease in functional residual capacity (FRC) and a decrease of the expiratory reserve volume (ERV). This leads to a more common expiratory flow limitation with development of intrinsic positive end-expiratory pressure (iPEEP). All changes of lung function are marked in supine position which is important for understanding ventilation strategies in obese patients [10]. Ventilation-perfusion mismatch is a leading finding in obesity which reduces gas exchange and contributes to hypoxemia, which is also marked in the supine patient. Breathing with a reduced FRC means breathing on the flat part of the pressure-volume curve (with low compliance), which requires a higher work of breathing to overcome the thorax wall that is thickened anyway (reducing the compliance furthermore). These factors increase the work of breathing which seemed to be doubled in the supine compared with the upper position [11]. All these factors impair the function or respiratory muscles [12]. The typical breathing pattern in obese patients is characterized by a low tidal volume and a higher breathing rate. Moreover, fatty deposits increase the pharyngeal collapsibility which together with a blunted ventilatory drive, an increase of bicarbonate and leptin [13] concentration and other neurohu- moral influences lead to the development of sleep apnea and obesity hypoventilation syndrome (OHS). Summarizing the pathophysiology of respiratory mechanics in obesity, theoretically there is an increased risk for VILI by cyclical reopening (tidal recruitment) of alveoli during inspiration (shear stress) due to the lower FRC in combination of higher necessary IPAP due to an elevated abdominal pressure which counteracts the motion of the diaphragm. Hypoxemia may either be caused by hypoventilation or due to ventilation- perfusion mismatch. Treating the hypoxemia with high inspiratory oxygen 16 Management of Ventilator-Induced Lung Injury 159 concentration may also harm [14] since it triggers inflammation and edema of the lung (Lorrain-Smith effect) and aggravates atelectasis by absorption.

16.3 VILI: Which Treatment?

There are some animal studies on medical treatment of VILI. N-acetylcysteine [15] and apocynin [16] in a rat lung model, inhaled interleukin-10 [17], as well as airway instal- lation of budesonide in rats [15] ameliorate VILI and/or even improve outcome. Since there is no established medical treatment against VILI in man, ventilator strategies to avoid the development of VILI are the most important measures. Ventilating the lung with low volume but high positive end-expiratory pressure (PEEP) has been proven to be less harmful (“lung protective” is a critical term since ventilation itself never can be protective but remains always a risk for the lung) in several outcome studies since the milestone set by the first ARDS network trial [18]. The effect of ventilation with low volume and higher PEEP is attributed to a reduction in volutrauma. The major consideration in ventilating obese patients is a higher PEEP than usual (≥7 cmH2O) to antag- onize the iPEEP, to increase the FRC, to recruit the lung, and to keep the lung open. The oxygenation is optimized by PEEP titration and supporting the ventilation rather than increasing the oxygen supply. There are numerous ways to achieve alveolar recruitment, and still there is no gold standard to set PEEP [19], an issue which is not discussed in this chapter. A bedside test to estimate the contribution of hypoventilation to hypoxemia is the alveolar gas equation: it answers the question if the hypoxemia is explained by the hypercapnia. The alveolar PAO2 is calculated by PIO2–PaCO2/R. Breathing room air, PIO2 may be estimated being 149 mmHg. Otherwise PIO2 has to be calculated by Patm–PH2O × FiO2 ≈ 713 × FiO2. R is the respiratory exchange ratio which usually is 0.8. The PaCO2 and the PaO2 can be obtained by blood gas analysis. For example, if the PaCO2 is 65 mmHg, then the alveolar PAO2 is 149–65/0.8 = 67.75 (breathing room air). The normal alveolar- arterial PO2 difference is no more than <10 mmHg. In our example a PaO2 ≥57.75 mmHg would be explained by hypercapnia alone. This consideration is important as hypoxemia is a common finding in obesity but not always the treatment when oxygen is appropriate: ventilation-perfusion inhomogeneity usually needs no treatment, and hypoxemia due to hypercapnic failure rather requires ventilation. The situation is entirely different when a hypoxemic respiratory failure develops in an obese patient (e.g., pneumonia).

Prone positioning is recommended in severe (PaO2:FiO2 ratio <150 mmHg) ARDS since early prone positioning reduces mortality when performed for at least 16 h by homogenizing the distribution of stress and strain within the lungs [20]. Nevertheless, this is difficult to perform in obesity, and prone positioning in obese patients with ARDS increases the risk of sclerosing cholangitis which is an unfavorable complication of ICU therapy [21]. Additionally, there is experience with obese patients with BMI even greater than 40 and 50 kg/m2 and ARDS who were treated by extracorporeal membrane oxygenation (ECMO) support with the same outcome as other patients [22]. Therefore, ECMO seems also to be a treatment option in obesity allowing defensive ventilator settings. 160 S. Stieglitz

16.4 What Are the Clinical Data of Obese Patients with ARDS or VILI?

A large prospective study analyzed the outcome of more than four million morbidly obese patients with invasive ventilation (patients with NIV were excluded). Those patients with solely a respiratory failure had a normal prognosis compared to patients with normal weight. Even the rate of prolonged mechanical ventilation was unchanged. Nevertheless, if more organs failed, morbidly obese people showed an increased risk for mortality [23]. Taking these facts into account, one may have the impression that regarding the outcome ventilation of obese patients is not more sophisticated than ventilating other patients. Concerning ARDS, obesity is a risk factor for the occurrence of ARDS. Nevertheless, the outcome is improved compared to patients with normal body weight [24] whereas obstructive sleep apnea, a common feature of obesity, itself is not an independent risk factor for the development of ARDS [25]. Therefore it is unlikely that obesity is a risk factor for VILI when the outcome is even better. There are no epidemiological data regarding the prevalence of VILI in obesity.

References

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Rachel Jones, Jason Gittens, and Ari Manuel

17.1 Introduction

Obesity puts stresses on all body systems, including the respiratory system. There have been a number of studies to look at obese patients’ outcomes in the ICU. There is no conclusive evidence to show that they have poorer outcomes [1].

17.2 Obesity Applied Pathophysiology

Obesity is associated with low-grade chronic inflammation and airway inflammation. “The majority of the forty cross-sectional studies published to date report a modest positive association between obesity and asthma, with odds ratios of 1.5– 3.5” [3]. This can have an effect on airway pressure and physiology and affect ventilation mode choices. Morbid obesity is known to severely reduce functional residual capacity (FRC) and expiratory reserve volume (ERV). It has minimal impact on TLC or VC. Jones et al. have shown that this effect can happen even at BMI less than 30 kg/m2 [24]. Intra-abdominal pressure is increased by the fat deposition resulting in upward shift of the diaphragm, which, in combination with increased chest wall elastance, leads

R. Jones Intesive Care Unit, Papworth Hospital, Cambridge, UK e-mail: [email protected] J. Gittens Respiratory Department, Aintree Hospital, Liverpool, UK e-mail: [email protected] A. Manuel (*) Respiratory Department, Bristol Royal Infirmary, Bristol, UK e-mail: [email protected]; [email protected]

© Springer International Publishing AG 2018 163 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_17 164 R. Jones et al. to higher resting pleural pressure. The combined effects of a low FRC and high pleural pressure will cause early closure of smaller airways, contributing to pulmonary atelectasis and reducing lung compliance. This will inevitably lead to a worsening perfusion and ventilation mismatch due to the dependent areas being poorly ventilated with no change in the distribution of pulmonary perfusion placing the patient at risk of hypoxaemia. The patient placed in the supine position will compound these effects. Obesity causes a well-recognised restrictive deficit manifesting in decreased

FVC and forced expiratory volume 1 (FEV1). This is multifactorial due in part to increased chest wall mass from adipose tissue [3] as well as increased pulmonary blood flow leading to low pulmonary compliance. In addition, morbidly obese patients have been found to require a greater proportion of the total oxygen consumption (VO2) for respiratory work [4]. The VO2 for respiratory work in non-obese patients at rest is small and is thought to be less than

3% of the total body O2 consumption. Kres et al. found that the VO2 was reduced in obese patients requiring mechanical ventilation, which was not reciprocated in nonobese patients [5]. There have been a number of estimations in literature on the estimated VO2 for the work of breathing on obese patients ranging from 60 to 70% compared to non-obese patients [6]. This concludes the high risk of respiratory failure in obese patients arising from the greater baseline requirement of a high oxygen consumption for breathing in combination with reduced respiratory reserve.

17.3 Ventilation

The need for mechanical ventilation will be the result of respiratory pathophysiological changes that occur in obese patients in combination with the increased risks of underlying obesity hypoventilation syndrome, obstructive sleep apnoea, pulmonary hypertension and pre-existing comorbidities. Post-operatively obese patients may require ongoing support due to the prolonged effects of sedation, development of pulmonary atelectasis and hypoxaemia during anaesthesia. Overall there is a general view that morbidly obese patients may be protective during mechanical ventilation and have a mortality benefit. Nevertheless there is a recognition of past studies that was pointed out recently that highlights the problems with the study designs. The general recommendation for ventilating in obese patients with a BMI greater than 40 would be between 15 and 21 breaths [7]. This is also mirrored by the British Thoracic Society (BTS) recent guidelines published in 2016 on hypercapnia respiratory failure recommended PCV with an initial set rate of 20 [8]. Further adjustments to the ventilatory settings should be guided by dynamic compliance plateau pressures and patient comfort. Similar to patients on NIV, it was noted that high inspiratory pressures and PEEP may be required in OHS [8]. 17 Ventilation Modes for Obese Patients Under Mechanical Ventilation 165

17.4 Modes of Ventilation

There is a scarcity of research on the modes of ventilation for obese patients in the critical care setting. Extrapolation is therefore made from the intraoperative research in bariatric and non-bariatric surgery. This information limits its interpretation in the critical care setting as tidal volume targets are commonly different with 8–10 mL ideal body weight (IBW) in anaesthetics compared to 4–6 mL IBW in critical care. Furthermore, the duration of ventilation in many of the studies is short and not reflec- tive of the critical care population. Pressure-controlled ventilation (PCV) and volume- controlled ventilation (VCV) are commonly referred to in many of the research papers.

17.4.1 Pressure-Controlled Ventilation (PCV)

PCV selects a target pressure and cycled by time mode with an inspiratory flow pattern decreasing exponentially with reducing peak pressures [9]. This mode of ventilation may be preferred in critical care because of the heterogeneity of the time constants of alveoli optimising gas exchange, particularly in ARDS. Therefore, the theoretical advantage will be recruitment of additional lung units and improved ventilation among alveoli with prolonged time constants. It is believed that this leads to laminar airflow at the end of inspiration, with a more even distribution of ventilation [10]. However, the target tidal volume may not be achieved, which in obese patients with poor lung compliance and increased airway resistance will result in a reduction in the minute volume.

17.4.2 Volume-Controlled Ventilation (VCV)

Volume-controlled ventilation (VCV) selects a target volume which is delivered regardless of the pressure. This can lead to difficulties with barotrauma but can ensure that constant minute ventilation is achieved. Nevertheless, there is a risk of alveolar overdistension.

17.4.3 Comparing VCV and PCV

A review article comparing data on ventilation strategies in obese patients undergoing operations showed no difference between VCV and PCV modes. It looked at four randomised controlled trials when comparing intraoperative PaO2/FIO2 ratio, intraoperative tidal volume or mean airway pressure [11]. There was also no evidence of any difference in mean arterial pressure or mean heart rate. There was not enough data on other outcomes to comment on any other aspects [11]. This echoes other work on patients with ARDS or on non-obese patients undergoing thoracic surgery which also showed no difference between the two modes. 166 R. Jones et al.

In studies looking at morbidly obese patients undergoing laparoscopic gastric banding, De Baerdemaeker et al. [12] and Hans et al. [13] showed that volume- controlled ventilation (VCV) as compared to pressure-controlled ventilation (PCV) showed no difference in outcomes and gas exchange. Recently there was a large systematic review and network meta-analysis suggesting that a combination of VCV, high PEEP and a single recruitment manoeuvre may be the superior option [14]. This was compared with 12 ventilation options comparing the PaO2/FiO2 ratio, optimal intraoperative pulmonary compliance and decreased intraoperative atelectasis as measure of success.

17.4.4 Pressure-Controlled Ventilation Volume Guaranteed (PCV-VG)

Pressure-controlled ventilation volume guaranteed (PCV-VG) is a hybrid mode of ventilation in anaesthesia, using time mode, a preset tidal volume but pressure- regulated with variable inspiratory flow. PCV-VG will deliver the preset tidal volume for each breath cycle using the lowest pressure possible and thus in theory minimising the peak inspiratory pressure (PIP). Dion et al. [15] looked at 20 severely obese young patients during laparoscopic-assisted bariatric surgery who received 20 min of ventilation with VCV, PCV or PCV-VG. The main finding from the study was a lower PIP with PCV and PCV-VG modes as compared with VCV. There was no advantage with oxygenation or ventilation between the modes. This was also concluded in a study comparing VCV with PCV-VG where 30 patients undergoing abdominal surgery received PCV for 45 min and then alter- nating to PCV-VG modes [16]. No difference was found with plateau pressure, mean airway pressure or oxygenation [16]. This went against the authors’ initial hypothesis that the dual mode ventilation may alter the flow pattern improving oxygenation. There was no conclusive reason for this finding. Overall it remains difficult to interpret with small numbers included and the crossover format of the study design.

17.4.5 Pressure-Regulated Controlled Volume (PRCV)

There are no large randomised controlled trials assessing PRCV in general anaesthesia or intensive care evaluating its efficacy. In 2014 [17] there was an article published which looked at 79 patients receiving PRCV for a range of aetiologies both in type I and type II respiratory failure. Thirteen of these patients in this study who presented with acute on chronic respiratory failure were labelled as having obesity hypoventilation syndrome and obstructive sleep apnoea syndrome (OHS-OSAS). The study did not compare other ventilation modes. The main conclusion from this study was early improvement in oxygenation [17]. This result was also found in a small paediatric critical care study of 28 patients comparing VCV and PRCV, which demonstrated improved oxygenation through 17 Ventilation Modes for Obese Patients Under Mechanical Ventilation 167

changes in PaO2 and PaO2/FiO2 in initial stages of ventilation [18]. It is recognised that randomised clinical trials are required to determine PRCV mode in critical care for respiratory failure as well as for obese patients requiring mechanical ventilation [17, 18].

17.4.6 Pressure Support Mode in Invasive Mechanical Ventilation

Pressure support ventilation (PSV) is essentially a spontaneous breathing mode supported by a set inspiratory pressure and cycled by a change in the inspiratory flow. The benefit of PSV is the reduction of atelectasis, which is thought to be due to the optimal diaphragmatic contraction of the posterior portion of the diaphragm [4, 6]. This concept of diaphragmatic activity has been looked at by Hedenstierna et al. [19], who demonstrated that phrenic nerve stimulation resulted in reduced atelectasis particularly after PEEP application. Another advantage is the avoidance of the need for neuromuscular blocking agents. PSV may theoretically offer an advantage when the patient is in the supine position through better ventilation in dependent lung regions when compared with controlled mode ventilation. A German study looked into 68 moderately obese (BMI 25–35) patients [20] intraoperatively and showed that PSV was superior to PCV in terms of oxygenating patients but had a trade-off of raised pCO2. The author concluded that the improved oxygenation was a result of better ventilation and perfusion matching through better diaphragmatic contraction and reduced alveolar compression [20]. With the advent of new ventilation modes, Pepin et al. [7] in the review article suggest studies comparing them with PSV. In obese patients, there have been concerns that spontaneous breathing leads to increased intra- abdominal pressure from the increased thoracic activity [20]. The long-term outcomes and potential adverse effects of using PSV in patients who have undergone major abdominal surgery remain unknown. The BMI of the patient has been found to be linked to the degree of intra-abdominal pressure (IAP) [21]. The IAP transmitted to the thoracic cavity and the ultimate pleural pressure cannot be predicted and thus has no role as a surrogate marker. Fluid accumulation has also been found to complicate things [22]. Using PSV for ventilation brings the risk of a variable minute volume, and therefore it should not be used when near-total ventilation support is required.

17.4.7 Open Lung Ventilation

Open lung ventilation involves combining PEEP with low tidal volumes to create a protective ventilation strategy. It should maximise alveolar recruitment and reduce atelectasis. Lower tidal volumes should protect from trauma. There is no formally agreed open lung strategy, but a meta-analysis [23] of several approaches showed a mortality benefit in patients with ARDS. This is a standard of care in ARDS, but its role outside of this category is not yet clarified. 168 R. Jones et al.

17.4.8 Airway Pressure Release Ventilation (APRV)

This method of ventilation was first described by Stock in the 1980s with currently its main application within critical care as an advanced mode of ventilation for patients with ARDS. APRV is a type of pressure control ventilation using time mode providing high and low PEEP at inverse ratio so that the majority of time is at a high pressure with set timed interval releases to a lower pressure. APRV is considered to be a mode of ventilation to achieve open lung ventilation. There remains no standard strategy for setting the APRV parameters, and its explanation goes beyond the remit of this chapter. On APRV patients are able to spontaneously breathe with optimal ventilator synchrony by the presence of a dynamic expiratory valve. This provides the means of reducing the sedation requirements and promoting protective lung ventilation.The advantages of this technique include alveolar recruitment and improved oxygenation. The spontaneous breathing will also offer physiological benefit to include better ventilation and perfusion matching and improved central venous return and transmural pressure. The explanation is thought to improve arterial oxygenation and reduce pulmonary vascular resistance (PVR). In a case study [25] of a patient with pulmonary hypertension and abdominal compartment syndrome, it was demonstrated that APRV improved the oxygenation, increased mean airway pressure, reduced transmural pressure and improved lung compliance, though at the time the patient had received nitrous oxide which would also improve ventilation perfusion matching [25]. It is also recognised that PVR may be increased in APRV as a result of prolonged time spent with lung volumes that are greater than the patient’s FRC [25]. The disadvantages include the risk of volume trauma. If the patient is allowed spontaneous breaths, then there is also the potential issue of increased work of breathing and energy expenditure. In addition, achieving the 6 mL/kg IBW target will become challenging in the spontaneous mode. Other considerations include increased right ventricular afterload exacerbating pulmonary hypertension. It can also cause a reduction of right ventricular venous return which can exacerbate the intracranial hypertension and reduces cardiac output in circumstances with hypovo- laemia and the risk of dynamic hyperinflation. Dynamic hyperinflation could be an issue in patients with chronic obstructive pulmonary disease (COPD) [26]. There was a case report published by Arshad et al. [50] who demonstrated success in using APRV in a COPD patient. In their patient, the inverse ratio was not used, but Arshad et al. concluded the physiological benefits of APRV with the mean airway pressure kept at the lower infection point, reducing overdistension in addition to maintaining the FRC optimised ventilation and gas exchange [50]. There are no randomised trials that determine the role of APRV in obese critical care patients, but there are single and case series reports concluding its efficacy. Hirani et al. [27] show the successful use of APRV in treating a morbidly obese patient with ARDS. Transthoracic echo performed on the patient showed normal cardiac function. APRV increased lung recruitment but prevented over distention. 17 Ventilation Modes for Obese Patients Under Mechanical Ventilation 169

There is no data to indicate the APRV mortality. Testerman et al. [28], in their case series of 12 general surgical and trauma patients, demonstrated no deaths from hypoxaemic respiratory failure without the need for additional rescue therapies, including muscle paralysis. A recently published review [29] on APRV highlights the challenges over the last three decades in regard to this mode of ventilation and the optimal settings. The first problem is there is no one criterion or setting in defining APRV [29]. Currently, they can be broadly divided into fixed modes and personalised modes (adjusting settings depending on lung mechanics) with variation in the settings used in experimental studies and in clinical practice, making comparisons difficult. The timing of applying APRV for critical care patients has also been ques- tioned. Authors from an animal model which compared early APRV application with low tidal ventilation strategy demonstrated clinically and histologically that systemically inflammatory reaction syndrome (SIRS)-induced ARDS was prevented with APRV [30]. There remains further work to be done to determine the optimal APRV parameters and timing with this mode of ventilation, before its application in critical care obese patient can be fully determined.

17.4.9 Noninvasive Positive Pressure Ventilation (NIPPV)

NIPPV in critical care may be used as a type of ventilation in obese patients presenting with acute hypercapnia failure, to allow early liberation from invasive mechanical ventilation and post extubation failure. The role of NIPPV in hypoxaemic respiratory failure is yet to be defined in the general critical care population and has a significant failure rate. In the subgroup of critically ill obese patients, there remain no randomised controlled trials with regard to NIV in critical care for respiratory failure. There are numerous NIPPV ventilation strategies available; the most commonly used is the pressure support ventilation. The difference between the inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) provides the pressure support. Pressure support is usually delivered through a spontaneous/time (S/T) ventilatory mode where the patients’ breath triggers the ventilator and a set pressure is delivered. This mode allows patients to take spontaneous breaths with a backup rate ensuring that if the respiratory rate falls below this set rate, then an automatic breath is delivered by the ventilator. Having this S/T ventilatory mode feature is recommended as the obese patient may be at risk of having underlying breathing-related sleep disorders causing central sleep apnoea. Having this additional option can theoretically allow the operator to adjust the minute ventilation [31]. Nevertheless, this may be at the risk of increasing the possibility of ventilation and patient dyssynchrony. Time-mode options of ventilation in NIPPV may include either pressure control (difference between the IPAP and EPAP) or volume control. Average volume- assured pressure support (AVAPS) is a hybrid mode of NIPPV. In a dynamic real- life setting, the respiratory compliance will change and this model reflects this. In 170 R. Jones et al. this mode, the IPAP varies in order to achieve a present tidal volume, which is usually set at 7–10 mL per kg of ideal body weight. This mode was compared in a randomised controlled trial [32] to standard pressure support in patients with super obesity (average BMI = 50). This mode theoretically has the advantage of more consistent ventilation as shown by stable nocturnal transcutaneous CO2 monitoring, but this can also disrupt sleep [32], therefore negating this improvement. In the trial no difference in outcome was demonstrated between automated AVAPS mode and fixed-level PS. Currently there remains no study which demonstrates superiority with regard to the choice of ventilation mode for acute NIV for obese patients presenting in critical care with acute hypercapnia failure. There is no agreed optimal ventilation setting though a review article in 2016 [31] that recognised that an IPAP of 18 ± 3 cm H2O and EPAP of 7 ± 3 cm H2O were commonly used in numerous studies in this population group. The BTS guidelines 2016 on hypercapnia respiratory failure [8] recognises the lack of randomised controlled trials. The guidelines on NIV settings recommend a prolonged inspiratory time (I:E ratio of 1:1) to optimise tidal volume, positioning the patient upright and using a high EPAP ranging between 10 and 15 cm H2O [8]. The document also acknowledges that an IPAP in excess of 30 cm H2O and an EPAP greater than 8 cm H2O may be required for optimal ventilation [8]. One author performed a retrospective study of 73 obese patients receiving NIV for hypercapnic failure in ICU for various medical causes [33]. The main conclusion is that using a higher PEEP and a longer duration receiving ventilation was found to successfully reverse hypercapnia in obese patients [33]. The obesity arm of the study was mixed and included patients with OSA and overlap syndrome, which may also reflect the need for a higher PEEP. It is important to note in this study that the medical condition for admission when comparing the obese patients with the non-obese patients is that pulmonary oedema was more common (p = 0.003) and pulmonary infection less common (p = 0.043) in the former group. It was noted that the duration to achieve a pCO2 below 6.6 was 4 days longer in the obese patients compared to those with a BMI of less than 35. There was a direct link between the

BMI and the duration of NIV for normalising CO2 [33]. In contrast to Lemyze et al.’s study, Gursel and the team used APACHE II score for assessing the severity of the patient which had no correlation to the outcome [33]. There was a small retrospective study of 20 patients which also identified a similar conclusion that higher PEEP and prolonged ventilation may be required [34]. An important consideration is that the patients who normally sit upright are at risk of developing a respiratory decompensation or difficulty in becoming liberated from the NIPPV as patients in critical care are placed in the supine position. El-Solh et al. [35] conducted a prospective study measuring respiratory failure at 48 h post extubation as the primary endpoint comparing NIV with conventional therapy and found a 16% absolute risk reduction in the rate of respiratory failure with the former. The author identified that on subgroup analysis there was a reduced hospital mortality in the NIV group [35]. This suggests that NIV may be of benefit, though the actual patient criteria are still not fully recognised. 17 Ventilation Modes for Obese Patients Under Mechanical Ventilation 171

17.4.10 Obesity Hypoventilation Syndrome (OHS)

There is no conclusion in the current literature on the optimal delivery of respiratory support when comparing NIV with CPAP for the management of OHS. Though there is greater literature referencing NIV, CPAP is thought to be the preferred mode when OSA is the predominant feature. However, an explanation for the lack of difference in CPAP and NIV may be that the trials used very conservative ventilatory strategies—with low IPAP and EPAP such as the Piper study [36]. Carrillo et al. [37] in 2012 demonstrated through a prospective study the efficacy of NIV in managing patients with OHS. The study compared COPD and OHS patients in acute type II respiratory failure. The number of patients in the COPD arm of the study was 543 vs 173 in the OHS group. The OHS patients had a 1-year survival rate of an odds ratio of 1.83, 95% CI 1.24–2.69, P = 0.002 [37], though when adjusted for cofounders both COPD and OHS group had a similar outcome. Furthermore, the subgroup of patients with COPD with OHS had fewer late NIV failure. The author went on to conclude from this that overall OHS had a better outcome with NIV compared to COPD [37]. The BTS guidelines refer the management of patients with OHS to include not only the acute respiratory failure but also the need for domiciliary NIV [8]. The long-term management of OHS also includes lifestyle changes in combination with domiciliary NIV [38]. The aim of Pickwick study [39] (2015) was to compare NIV with CPAP in patients with OHS using daytime partial pressure of carbon dioxide as the main outcome measure. The consensus is that NIV is likely to be better than CPAP in restoring physiological parameters, though the information is difficult to extrapolate as the study population was outside of critical care. This trial remains ongoing and will delineate cardiovascular mortality which is the leading cause of death in OHS. The duration at which patients with OHS improve from their type II respiratory failure has been found to differ from the non-obese patient. A longer duration on NIV was required which may be explained by an altered response to hypoxia and hypercapnia in obese patients that was demonstrated in a small study by Zwillich et al. in 1975 [40]. Obese patients without OHS have shown in numerous studies to have an increased central ventilatory drive which is in contrast to OHS. Lemyze et al. [41] conducted a study that showed a good outcome from using NIV in hypercapnia respiratory failure. Out of the total of 76 obese patients, only 7 failed to reverse their respiratory failure. The main taking points from the study were that patients’ success in reversing the respiratory failure was likely with decompensated OHS and hypercapnia on admission. A better outcome was also noted in patients with idiopathic decompensated hypercapnia failure [41]. NIV failure was defined as the need for intubation and was found to occur in patients with pneumonia (n = 12/13, 92% vs n = 9/63, 14%; p < 0.0001), high SOFA (10 vs 5; p < 0.0001) and SAPS2 score (63 vs 39; p < 0.0001) on admission [41]. This would support the view that when OHS patients present in respiratory failure, with additional pulmonary pathology, or another organ dysfunction, the potential outcome with NIV is less clear. 172 R. Jones et al.

17.4.11 Oesophageal Pressure-Guided Mechanical Ventilation

Oesophageal pressure (Pes)-guided mechanical ventilation in respiratory failure can be used to set the optimal level of PEEP throughout the respiratory cycle. Currently, its use in critical care has mainly been applied as a research tool. The respiratory changes in Pes are representative of change in plateau pressure applied to the lung surface. The resting pleural pressure in obese patients in the supine position is raised; therefore, there is the risk of the operator applying suboptimal PEEP settings resulting in lower tidal volumes and the development of atelectasis. One recent study [42] looked at morbidly obese patients in critical care setting and used oesophageal pressure via NG tube to act as a surrogate for pleural pressure. In order to have a positive pressure throughout the respiratory cycle, PEEP should at least equal the end-expiratory oesophageal pressure. This showed the optimum PEEP was around

21 cm H2O [42]. This in turn improved end-expiratory lung volumes and oxygenation. Using this monitoring to generate Pes values could be applied in the clinical setting. One immediate benefit would allow for an alteration in the target plateau pressure, and as the paper demonstrated, higher pressures could be applied [42, 43]. Doubt remains as to whether oesophageal pressure is a reliable surrogate measure of the pleural pressure. This may be because the Pes is influenced by many factors, and our understanding of how this impacts on the value remains limited [43]. Nevertheless, it has been recognised that the pleural pressure may not be uniform throughout the space because of variable gravitational gradients and regional differences of the pleural architecture [43]. Measuring the Pes may overcome these factors. In determining whether higher plateau pressures could be applied, there remains no study which endorses this concept in the obese population requiring mechanical ventilation. Therefore, safe ventilation settings as evidenced by the ARDS trials are recommended [43]. There continues to be work led by the pleural pressure working group into better defining the role of oesophageal pressure monitoring in clinical practice.

17.4.11.1 Recruitment Manoeuvres Recruitment manoeuvres are used as an adjunct to achieving open lung for mechanical ventilation. The objective is to reopen alveoli which are collapsed in conjunction with PEEP to ensure the alveoli are not subjected to further collapse on each ventilatory cycle. Decruitment remains an ongoing risk for specifically obese patients but also as a result of a change in respiratory mechanics during anaesthesia which includes the use of high fraction of oxygen, low tidal volumes and inadequate PEEP. There are various recruitment strategies, but all leading to an increase in the transpulmonary pressure, commonly using a high inspiratory pressure of up to

40 cm H2O for at least 15 s. This can be as an isolated episode or as part of ramped increased pressure ventilation leading to sustained high pressure. There are some concerns that the increased intrathoracic pressure may reduce cardiac output as shown in animal models [44]. In an anaesthetic review article [11], recruitment manoeuvres and PEEP were shown to be superior to PEEP alone in intraoperative PaO2/FIO2 ratio and 17 Ventilation Modes for Obese Patients Under Mechanical Ventilation 173 respiratory compliance. There was no effect on mean arterial pressure [11]. They were not sufficiently homogeneous to comment on barotrauma. Most of this data is gathered preoperatively or intraoperatively. The IMPROVE study by Futier et al. [45] was a large randomised controlled study of 400 patients that looked at protected lung ventilation with PEEP and recruitment manoeuvre versus nonprotected lung ventilation in patients receiving major abdominal surgery. The mode of ventilation was volume controlled. The primary outcome was to compare pulmonary and extrapulmonary complications within the first 7 days. The main finding from the protected lung group with higher PEEP and recruitment manoeuvres had a relative risk of 0.40; 95% confidence interval [CI], 0.24–0.68; p = 0.001. In the secondary outcomes, the protected lung patient group had a reduced length of stay in hospital. The study is difficult to conclude for the critical care population as the PEEP used in the IMPROVE study 6–8 cm H2O is low in comparison to usual practice, and nonprotective lung ventilation does not apply. Other studies that have looked at ventilation strategies in the intraoperative period include Jaber et al. [47], which was a large observational multicentre trial of 2900 patients. It demonstrated that higher tidal volumes were administered greater than 10 mL/kg of IBW in patients [47]. This study demonstrates the operator’s tendency for higher tidal volumes during mechanical ventilation with patients presenting higher BMIs. The author went on to recognise that the previous practice from work published in the 1960s which had advocated using high tidal volumes as a strategy for improving oxygenation was a recognised strategy. Their study did find that recruitment manoeuvres were more common in patients with a high BMI, but overall this intervention was not commonly used [46]. As mentioned in the previous section on oesophageal pressure, the study published in February 2016 [46] remains the one study which specifically looked at recruitment manoeuvres of the critical care population. The author suggests that current practice in targeting PEEP in the obese population is inadequate [46]. There remains the need for large randomised controlled studies on outcome in the obese critical care group with respect to mortality, number of days requiring mechanical ventilation, number of ventilation free days and the risk of pulmonary and extrapulmonary complications. Furthermore, to conclude, there remains no guidance on the frequency in performing the recruitment manoeuvre during mechanical ventilation.

17.5 Patients Positioning

17.5.1 Reverse Trendelenburg

Reverse Trendelenburg is achieved by tilting the bed enabling the head to be higher than the feet. This helps relieve the effect of the intra-abdominal pressure on the diaphragm reducing intrathoracic pressure and improving lung compliance. Preliminary studies in positioning in bariatric surgery [48] showed that it was a safer position compared to the 30° backup Fowler and horizontal-supine positions (length of apnoea and time to recover to Sat greater than 97%). 174 R. Jones et al.

There is also evidence that ventilator-associated pneumonia (VAP) is lower. This may relate to gravity and intra-abdominal pressure. VAP is a well-recognised major complication of invasive mechanical ventilation.

17.5.1.1 Proning Proning is changing the patient position from the usual supine position onto their front, lying face down. This strategy traditionally used in ARDS can help with oxygenation. Morbid obesity carries increased risk with position change. Positioning patients in a prone position, while being IMV, reduces atelectasis and improves oxygenation. It has proven outcomes in ARDS with a review article in 2010 [49] showing an absolute mortality reduction of around 10%. In obesity, there is also some evidence that proning can be effective as seen in the French Montpellier Study where it was associated with survival benefit and no increased complication rate [49]. The physiology in obesity (decreased FRC and increased atelectasis) may have even a better outcome in proning patients than in those patients who are non-obese. There are risks associated with proning ventilation. Some are generic to all patients, such as endotracheal tube displacement. Others, such as intra-abdominal hypertension (IAH), are linked to morbid obesity. In a review article looking at the subject, there is mixed evidence regarding proning which appears to have the potential to either exacerbate or ameliorate IAH, depending on the technique.

Conclusion Obesity has a number of effects on respiratory physiology which can be a challenge to ventilation techniques. Overall goals should be to maximise airway recruitment and minimise atelectasis while avoiding barotrauma and ventilation- induced lung injury. VCV and PCV have advantages and disadvantages but have similar outcomes in studies. The hybrid modes of ventilation are increasingly being used in anaesthetics. The limiting factor is that very few trials have been performed in the critical care setting. Patients’ physiology should help guide an individualised approach when formulating a ventilation strategy. Tidal volumes delivered should be 6–8 mL/kg with the aim of reducing barotrauma. The objective should be to provide adequate oxygenation and ventilation which may not immediately normalise their respiratory physiology. In ARDS APRV can be considered to increase lung recruitment while pro- tecting the airway from barotrauma. The role APRV has still needs to be defined and better standardised through conducting randomised controlled trials. PEEP should be used to increase lung recruitment and avoid atelectasis. NIV is increasingly being used in critical care with good outcomes with hypercapnia respiratory failure in OHS. Patients with OHS have a clearer benefit with NIV for hypercapnia failure when there is no other organ failure. There continues to be a need for randomised controlled trials to determine the superiority of the traditional and hybrid modes of NIV. Recruitment manoeuvres also have shown 17 Ventilation Modes for Obese Patients Under Mechanical Ventilation 175

additional benefits and may be used alongside if effective. The use of oesophageal guide to aid mechanical ventilation may have a role in obese patients requiring IMV, aiding the operator in using higher pressures without the risk of inducing barotrauma. Nevertheless caution remains about using liberal plateau pressures without the support of a randomised controlled study. The use of patient position should be optimised ideally in a reverse Trendelenburg initially, and if not successful, one should consider proning the patient. The clinician should be aware of the risks associated with this position in certain patient groups.

References

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Bahman Saatian and Julie H. Lyou

18.1 Introduction

Obesity has become a major health issue in the United States and Europe [1]. It is estimated that more than one-third of the population in the United States is obese [2]. Obesity and morbid obesity are defined as body mass index (BMI)≥ 30—<40 kg·m−2 and ≥40 kg·m−2, respectively. A broad range of health issues such as cardiac disease, hypertension, stroke, type 2 diabetes mellitus, obstructive sleep apnea, and obesity hypoventilation syndrome are associated with obesity. All of the latter consequently increase the risk of hospitalization and a need for higher level of care. A recent study showed obesity was associated with significantly higher all-cause mortality relative to normal weight population [3]. From a pulmonary standpoint, lung physiology is significantly altered in the obese patient, including respiratory muscle insufficiency, reduced functional residual capacity (FRC), expiratory reserve volume (ERV), and lung compliance [4]. Ventilation and perfusion (V/Q) matching is altered due to a small airway closure caused by a lower ERV. When compared with nonobese controls, reduced chest wall compliance due to adipose tissue in the chest wall and abdomen leads to an increase in airway resistance. Furthermore, these changes in pulmonary physiology lead to a prolonged need for mechanical ventilation which increases the length of intensive care unit (ICU) stay [4]. During any airway intervention such as endotracheal intubation, excess soft tissue in the hypopharynx and altered respiratory physiology may also result in the rapid onset of hypoxemia and slow recovery in obese patients. It has been shown that higher BMI leads to higher likelihood of ICU admission, mechanical ventilation, and tracheostomy in hospitalized obese patients [5].

B. Saatian, M.D. (*) UC Irvine, School of Medicine, Irvine, CA, USA Veterans Affair Long Beach Healthcare System, Long Beach, CA, USA e-mail: [email protected] J.H. Lyou, M.D. UC Irvine, School of Medicine, Irvine, CA, USA

© Springer International Publishing AG 2018 179 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_18 180 B. Saatian and J.H. Lyou

Tracheostomy is one of the oldest surgical procedures dating back 3500 BC [6]. Tracheostomy is a commonly performed procedure that establishes a long-term secure airway for patients who require extended mechanical ventilation from a variety of disease processes. More than 100,000 tracheostomies are performed in the United States annually [7]. The procedure can be performed either in the operating room or at the bedside. Although newer techniques and instruments have evolved over the years, some studies suggest morbid obesity is a risk factor for tracheostomy regardless of utilized technique (percutaneous versus surgical) [6, 8]. Technique and optimal timing of tracheostomy in obese patients remain a subject of debate. The current recommendations suggest an individualized approach taking in consideration the reason for prolonged mechanical ventilation, the underlying comorbidities, and the potential risk factors that increase the incidence of complications [9].

18.2 Indications

Obese and morbidly obese patients are at higher risk for medical comorbidities, hospitalization, and admission to critical care units when compared to nonobese counterparts. The likelihood of intubation and the persistence of mechanical ventilation are higher in this patient population due to altered lung physiology and variety of medical comorbidities. The potential benefits and outcomes of tracheostomy should be assessed with a patient-centered approach. Tracheostomy should be considered if it is consistent with the patient’s wishes and preferences. Patients who have good prognosis with meaningful recovery from underlying illness are more likely to benefit from tracheostomy. It is proposed that tracheostomy decreases the length of ICU and hospital stay, improves patient comfort, and reduces mortality. However there is no consistent data to support the aforementioned benefits. Similar to the general population, the main reason for tracheostomy in critically ill and obese patients is the need for prolonged mechanical ventilation and failure to wean from mechanical ventilation. Other indications for tracheostomy include chronic respiratory failure, upper airway obstruction, obstructive sleep apnea, copious secretion [10, 11], chronic neurologic disorders resulting in respiratory muscle weakness such as amyotrophic lateral sclerosis (ALS) and cerebral palsy (CP), spinal cord injury, and traumatic and non-traumatic brain injuries (Table 18.1).

Table 18.1 Indications and contraindications of tracheostomy Indications Relative contraindications Absolute contraindications Prolonged mechanical High ventilatory demand Inexperienced practitioner ventilation Hemodynamic instability Unstable cervical spine Chronic respiratory failure Radiation therapy to neck Prior major neck surgery Obstructive sleep apnea Enlarged thyroid gland Pediatric age <8 years Upper airway stenosis Coagulopathy Trauma Inability to extend neck Excessive secretion Elevated intracranial pressure Neurologic disease High-riding innominate artery Local skin infection Gross distortion of the neck anatomy 18 Obesity and Tracheostomy: Indications, Timing, and Techniques 181

Tracheostomy (surgical or percutaneous) should be performed by an experienced physician, especially for those patients with relative contraindications. De Leyn et al. specified skin infection and prior major neck surgery which completely obscures the anatomy as relative contraindications to tracheostomy [10].

18.3 Timing

The optimal timing for elective tracheostomy is still a subject of debate. In the1980s, tracheostomy was considered “early” if it was performed within 21 days of endotracheal intubation. Otorhinolaryngology literatures recommended performance of tracheostomy within 3 days of intubation to prevent vocal cord damage from endotracheal intubation [12]. Several studies have shown early tracheostomy (within 7 days) reduced the duration of mechanical ventilation and the length of ICU stay as well as overall hospital length of stay in trauma patients [13]. The early tracheostomy group had a statistically significant lower incidence of pneumonia (78% vs. 96%, p < 0.05) compared to late tracheostomy (greater than 7 days) [13–15]. It is believed that the reduced rate of pneumonia is attributed to the normal closure of vocal cords following removal of the endotracheal tube. A multicenter randomized clinical trial comparing early (within 4 days) versus late (after 10 days) tracheostomy showed no improvement in 30 day all-cause mortality, mortality at critical care unit and hospital discharge at 1 and 2 years [16]. Two other multicenter randomized studies on early versus late tracheostomy also demonstrated no difference in 28 day mortality and pneumonia [17, 18]. A single center study by Rumbac and colleagues found mortality benefit in the medical ICU patients with early tracheostomy (within 48 h) as compared to delayed tracheostomy (14–16 days) patients [19]. Majority of the studies has not found a survival benefit from early tracheostomy [14, 20]. Lack of strong evidence for early versus late tracheostomy hindered an expert consensus on a standardized timeframe for tracheostomy placement. Liberation from mechanical ventilation in critically ill morbidly obese patients is more challenging due to increased work of breathing secondary to altered respiratory mechanics, impaired ventilatory drive, and higher prevalence of obstructive sleep apnea. Potential procedural complications are also higher in the obese patients. Therefore, the decision for timing of tracheostomy placement should be made on case by case basis.

18.4 Techniques

The technique by which tracheostomy is performed in obese patient remains controversial. The technical difficulty in performing tracheostomy in obese patients has been examined in several studies in the past decade. Selection of proper tracheostomy technique depends on several factors, necessitating a thorough pre-procedural assessment of the patient’s anatomy and relevant comorbidities. Anatomic variations, including excessive submental and upper thoracic tissue obstructing the surgical field, difficulty palpating the landmarks due to excess adipose tissue overlying 182 B. Saatian and J.H. Lyou the trachea, short neck displacing the airway structures inferiorly into the chest, limited neck extension, and prior tracheostomy, are important procedural factors that must be considered prior to the procedure [21]. These anatomic concerns are added to medical comorbidities, severity of acute illness, and anesthetic risks. There are two major techniques, percutaneous dilational tracheostomy (PDT) and traditional open surgical tracheostomy (ST). Multiple studies and reviews have compared the percutaneous and open tracheostomy techniques. A meta-analysis by Higgins identified 15 prospective, randomized controlled studies involving nearly 1000 patients [22]. This study demonstrated significantly fewer complications in percutaneous tracheostomy group with respect to wound infection and unfavorable scaring. The rate of decannulation and obstruction was higher in the percutaneous tracheostomy group [22]. False passage, minor and major bleeding, and subglottic stenosis were not significantly different between the two groups [22]. The complication rates in high-risk patients including the obese were not reported in this meta-analysis, and bronchoscopy was only used in seven of the studies. A large study by Dennis et al. reported a complication rate of 1% with percutaneous tracheostomy without bronchoscopy guidance in obese patients [23]. In 2008, Aldawood and colleagues showed a higher rate of major complications in obese patients who underwent PDT compared to nonobese patients [24]. Byhahn reported increased life-threatening complications (9.6% vs. 0.7%, P < 0.001) in obese patients who underwent bronchoscopy-assisted PDT compared to nonobese patients [25]. Obese patients had a 2.7-fold increased risk for operative complications and a 4.9-fold increased risk for serious complications [25]. In contrast, Blankenship showed there were no significant differences in procedure time, estimated blood loss, and postoperative complications between morbidly obese and nonobese patients [26]. In 2007, El Solh et al. found that conventional open surgical tracheostomy was associated with an increased risk of perioperative complications in the critically ill morbidly obese patients compared to non-morbidly obese patients [27]. The reported outcomes were in favor of PDT compared to surgical tracheostomy and those included wound infections, smaller incision scars, shorter operation time, and reduction in cost with PDT [28]. Despite this, open tracheostomy is still being performed in cases where PDT is thought to be difficult or where there is insufficient expertise of those who can perform PDT.

18.5 Percutaneous Tracheostomy

Percutaneous dilational tracheostomy (PDT) has become the widely accepted procedure of choice for tracheostomy in intensive care units [29]. Percutaneous tracheostomy was initially described by Shelden in 1955, and subsequently Ciaglia introduced his technique of serial dilation in 1985. The six major types of PDT that are currently being performed are the following: Slight modification of the dilational technique with a single tapered dilator (Ciaglia Blue Rhino) Forceps dilation referred to as the Griggs’ technique Translaryngeal tracheotomy (also known as the Fantoni technique) 18 Obesity and Tracheostomy: Indications, Timing, and Techniques 183

Variation of the dilational technique with a screw-in dilator T-shaped dilator (Ambesh) Balloon-facilitated dilational tracheostomy (Ciaglia Blue Dolphin) [12, 28] In a systematic review of 13 randomized trials looking at the six different techniques, the single-step dilation technique had fewer failures than the rotational dilation and fewer complications compared to the balloon dilation and guidewire dilating forceps method [28]. Based on expert opinion and case reports, recommendations for anesthesia for PDT include intravenous general anesthesia, neuromuscular blockade, or local analgesia [30]. Inhalation anesthesia is not suggested since there is gas leakage during the procedure. Appropriate positioning in obese patients, while difficult, is a sentinel step in the success of this technique. The patient should be positioned with the upper back elevated and the neck hyperextended, which may make direct laryngoscopy difficult. The endotracheal tube is then retracted until the cuff is below the vocal cords, and then the trachea is punctured with the introducing needle. An alternative method is to remove the endotracheal tube and place a laryngeal mask airway, which carries the risks of pulmonary aspiration, air leakage, and compromised ventilation [30]. Typically, two physicians are needed to allow for bronchoscopy guidance and management of airway complications. The operator begins by palpating the cricoid and tracheal rings. The optimal site is between the second and third tracheal ring under the cricoid cartilage. Locations that are more proximal increase the risk of tracheal stenosis while distal locations increase the risk of erosion of the great vessels in the mediastinum [30]. Ultrasound can be used to identify the intended level of puncture site. An 8–12 mm skin incision is made at the chosen level. The cuff of the endotracheal tube is deflated, and the trachea is punctured with the introducing needle. The guidewire is introduced, and the stoma is dilated with one or more dilators and possible use of dilating forceps. The cannula is then placed and guidewire is removed. Minor bleeding is managed with manual compression, subcutaneous infiltration with adrenaline-contain- ing local analgesic, and compression with gauze soaked in adrenaline solution (1 mg adrenaline, 4 ml sterile water). Major bleeding requiring transfusion requires an emergent surgery consult for exploration, suture, and cautery. Notably, four of the nine prior nonrandomized studies on tracheostomy in obese patients which bronchoscopy guidance was not consistently used demonstrated no significant increase in periprocedural complications [24, 27, 31]. Although there are no randomized controlled trials comparing PDT with and without bronchoscopy guidance, a literature review of published mortality related to PDT identified the lack of use of bronchoscopy guidance to be a major risk factor [30, 32]. Randomized controlled studies are warranted to assess safety of tracheostomy without bronchoscopy guidance.

18.6 Rigid Bronchoscopy-Guided Tracheostomy

Although flexible bronchoscopy-guided PDT is an acceptable and commonly used technique, it has inherent limitations such as loss of airway, inadequate ventilation due to occlusion of endotracheal tube, inadequate ability to provide suction in case 184 B. Saatian and J.H. Lyou of major bleed, and inadvertent puncture of cuff and posterior tracheal membrane. Suspension laryngoscopy-assisted PDT and rigid bronchoscopy-guided PDT have been advocated to avoid these potential complications in high-risk patients [6, 33]. Rigid bronchoscopy-guided PDT can be utilized in patients who have relative contraindications to having standard PDT performed, including morbid obesity, prior neck surgery, distorted airway anatomy, and uncorrected coagulopathy [33]. In a retrospective case series of 35 patients who underwent rigid bronchoscopy-guided PDT, there were no periprocedural complications or mortality associated with the procedure [33]. The advantage of utilizing the rigid bronchoscope over the flexible bronchoscope is airway security and protection of posterior tracheal membrane. The rigid bronchoscope also allows for adequate ventilation and suctioning throughout the entire procedure. In comparison to PDT with flexible bronchoscopy, rigid bronchoscopy allows for full visibility of the subglottic space and displacement of the trachea anteriorly for ease of accessibility. The procedure is performed in the operating room with the patient in the supine position. The upper back is elevated with a towel roll placed between the scapulae, extending the neck. The rigid bronchoscope is advanced to the posterior pharynx and glottis and then positioned just distal to the true vocal cords. At this point the endotracheal tube is removed from the airway and the rigid bronchoscope is advanced into the subglottic area. After establishing a sterile field, the thyroid and cricoid cartilages are palpated to mark the site of incision. The skin and subcutaneous tissue are anesthetized with lidocaine and epinephrine. A small vertical incision (1 cm) is made, and a Kelly clamp is used to dissect the tissue. The finder needle is then introduced through the trachea under the guidance of the bronchoscope. The guiding angiocath is then inserted and the needle is removed. The guidewire is introduced through the angiocath, which is then withdrawn. Sequential dilation is performed with a punch dilator followed by the Blue Rhino tapered dilator into the stoma. Finally, the tracheostomy tube is introduced onto a dilator and advanced into the trachea, with the dilator and guidewire being withdrawn. The tube is then secured in place with sutures on both sides.

18.7 Ultrasound-Guided Tracheostomy

Recently, use of real-time ultrasound guidance (RUSG) was shown to reduce the complications of PDT in patients with risk factors such as morbid obesity, short neck, deviated trachea, massive goiter, edema, and subcutaneous emphysema [16, 34]. It has been demonstrated that real-time ultrasound guidance improves the procedure safety by identifying the intended level of penetration, avoiding the posterior membrane damage, and improving the rate of first-pass puncture accuracy [17, 34]. Ultrasound can be used as an adjunct to PDT to evaluate the anatomy of the major vessels and the thyroid gland in relation to the tracheostomy site, especially in obese patients. A linear array probe is utilized to avoid vascular structures during tracheal puncture and to confirm guidewire entry. Lung sliding can be assessed after tracheostomy placement as well. In morbidly obese patients with increased neck girth, 18 Obesity and Tracheostomy: Indications, Timing, and Techniques 185 ultrasound can be used to assess pretracheal tissue thickness while placing the head in neutral position in order to select the tracheostomy tube length and size.

18.8 Surgical Tracheostomy

Surgical tracheostomy takes place in the operating room, most often by otolaryn- gologists (ENT), followed by general or thoracic surgeons. Standard technique rec- ommends a horizontal incision, but this is a matter of debate as a vertical incision may assist with tracheostomy tube mobility during swallowing [12, 21]. The lower rates of wound infection in PDT are thought to be due to the smaller incision (1–1.5 cm), in comparison to the larger (up to 4 cm) incision performed in surgical tracheostomy. In conclusion, tracheotomy tube placement can be challenging in obese patients. Proper tracheostomy technique should be selected after evaluating the patient’s airway anatomy, risk factors, and potential complications. Standard tracheostomy tubes are usually functionally inadequate in the obese patients due to length limitations. The curvature mismatch between the standard size tracheostomy tube and the increased distance between the skin of anterior neck and tracheal wall can lead to complications such as accidental decannulation and extratracheal tube misplace- ment. Therefore, tracheostomy tubes with extra length are commercially available for this purpose. The utility of flexible bronchoscopy, ultrasound, and rigid bronchoscopy has made PDT become a safer and more feasible procedure to perform in high-risk patients who were previously considered to have relative contraindications for PDT.

References

1. National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity and health risk. Arch Intern Med. 2000;160:898–904. 2. Sturm R, Hattori A. Morbid obesity rates continue to rise rapidly in the United States. Int J Obesity. 2013;37(6):889–91. 3. Flegal KM, Kit BK, Orpana H, et al. Association of all-cause mortality with overweight and obesity using standard body mass index categories.A systematic review and meta-analysis. JAMA. 2013;309(1):71–82. 4. Jones RL, Nzekwu MM. The effect of body mass index on lung volumes. Chest. 2006;130(3):827–33. 5. Westerly BD, Dabbagh O. Morbidity and mortality characteristics of morbidly obese patients admitted to hospital and intensive care units. J Crit Care. 2011;26:180–5. 6. White HN, Sharp DB, Castellanos PF. Suspension laryngoscopy-assisted percutaneous dilatational tracheostomy in high-risk patients. Laryngoscope. 2010;120:2423–9. 7. Yu M. Tracheostomy patients on the ward: multiple benefits from a multidisciplinary team? Crit Care. 2010;14(1):109. 8. McCague A, Aljanabi H, Wong DT. Safety analysis of percutaneous dilational tracheostomies with bronchoscopy in the obese patient. Laryngoscope. 2012;122:1031–4. 9. Akinnusi ME, Pineda AL, El Solh AA. Effect of obesity on intensive care morbidity and mortality: a meta-analysis. Crit Care Med. 2008;36(1):151–8. 186 B. Saatian and J.H. Lyou

10. De Leyn P, Bedert L, Delcroix M, et al. Tracheotomy: clinical review and guidelines. Eur J Cardiothorac Surg. 2007;32(3):412–21. 11. Rana S, Pendem S, Pogodzinski MS, et al. Tracheostomy in critically ill patients. Mayo Clin Proc. 2005;80(12):1632–8. 12. McWhorter AJ. Tracheotomy: timing and techniques. Curr Opin Otolaryngol Head Neck Surg. 2003;11(6):473–9. 13. Michele H, Dunham M, Brautigan R, et al. Practice management guidelines for timing of tracheostomy: the EAST practice management guidelines work group. J Trauma. 2009;67(4):870–4. 14. Rodriguez JL, Steinberg SM, Luchetti FA, et al. Early tracheostomy for primary airway management in the surgical critical care setting. Surgery. 1990;108:655–9. 15. Jeon YT, Hwang JW, Lim YJ, et al. Effect of tracheostomy timing on clinical outcome in neu- rosurgical patients: early versus late tracheostomy. J Neurosurg Anesthesiol. 2014;26(1):22–6. 16. Young D, Harrison D, Cuthbertson B, Rowan K. Effect of early versus late tracheostomy placement on survival in patients receiving mechanical ventilation. The TracMan randomized trial. JAMA. 2013;309(20):2121–9. 17. Terragni PP, Antonelli M, Fumagalli R, et al. Early versus late tracheostomy for prevention of pneumonia in mechanically ventilated adult ICU patients. A randomized controlled trial. JAMA. 2010;303(15):1483–9. 18. Blot F, Similowski T, Trouillet JL, et al. Early tracheostomy versus prolonged endotracheal intubation in unselected severely ill ICU patients. Intensive Care Med. 2008;34(10):1779–87. 19. Rumbak M, Newton M, Truncale T, et al. A prospective, randomized study comparing early percutaneous dilational tracheotomy to prolonged translaryngeal intubation (delayed tracheotomy) in critically ill medical patients. Crit Care Med. 2004;32:1689–94. 20. Saffle JR, Morris SE, Edelman L. Early tracheostomy does not improve outcome in burn patients. J Burn Care Rehabil. 2002;23:431–8. 21. Walts PA, Murthy SC, DeCamp MM. Techniques of surgical tracheostomy. Clin Chest Med. 2003;24:413–22. 22. Higgins KM, Punthakee X. Meta-analysis comparison of open versus percutaneous tracheostomy. Laryncoscope. 2007;117(3):447–54. 23. Dennis BM, Eckert MJ, Gunter OL, Morris JA Jr. Safety of bedside percutaneous tracheostomy in the critically ill: evaluation of more than 3000 procedures. J Am Coll Surg. 2013;216(4):858–65. 24. Aldawood AS, Arabi YM, Haddad S. Safety of percutaneous tracheostomy in obese critically ill patients: a prospective cohort study. Anaesth Intensive Care. 2008;36:69–73. 25. Byhahn C, Lischke V, Meininger D, et al. Perioperative complications during percutaneous tracheostomy in obese patients. Anesthesia. 2005;60:12–5. 26. Blankenship DR, Kullbersh BD, Gourin CG, et al. High-risk tracheostomy: exploring the limits of the percutaneous tracheostomy. Laryngoscope. 2005;115:987–9. 27. El Solh AA, Jaafar W. A comparative study of the complications of surgical tracheostomy in morbidly obese critically ill patients. Crit Care. 2007;11(1) 28. Cheung NH, Napolitano LM. Tracheostomy: epidemiology, indications, timing, technique, and outcomes. Respir Care. 2014;59(6):895–919. 29. Freeman BD, Morris PE. Tracheostomy practice in adults with acute respiratory failure. Crit Care Med. 2012;40:2890–6. 30. Madsen KR, Guldager H, et al. Danish guidelines 2015 for percutaneous dilatational tracheostomy in the intensive care unit. Dan Med J. 2015:1–8. 31. Mansharamani NG, Koziel H, Garland R, et al. Safety of bedside percutaneous dilatational tracheostomy in obese patients in the ICU. Chest. 2000;117(5):1426–9. 32. Simon M, Metschke M, Braune SA, et al. Death after percutaneous dilatational tracheostomy: a systematic review and analysis of risk factors. Crit Care. 2013;17(5):R258. 33. Majid A, Cheng GZ, et al. Evaluation of rigid bronchoscopy-guided percutaneous dilation tracheostomy: a pilot study. Ann Am Thorac Soc. 2014;11:789–94. 34. Rajajee V, Williamson CA, West BT. Impact of real-time ultrasound guidance on complications of percutaneous dilatational tracheostomy: a propensity score analysis. Crit Care. 2015;19:198. Decannulation Process in the Tracheostomised Obese Patients 19

Pia Lebiedz, Martin Bachmann, and Stephan Braune

The decannulation process of critically ill obese patients can be more difficult than that of nonobese patients. A recent study showed a high rate of persistent invasive mechanical ventilation at hospital discharge (49%) in obese tracheostomised patients [1]. Surgical tracheotomy, African American ethnicity, obstructive sleep apnoea and pulmonary hypertension were associated with decannulation failure [1]. Therefore, risk factors for decannulation of obese patients must be identified and optimal conditions established before decannulation in addition to general criteria of clinical and respiratory stability and exclusion of neurological disorders such as swallowing problems [2]. Moreover, a careful history taking from patients and/or their next of kin will have to clarify the existence of any diagnosed or suspected pre-existing obstructive sleep apnoea (OSA) or obesity hypoventilation syndrome (OHS).

19.1 Spontaneous Breathing Trial

Prior to decannulation, the ability for sufficient spontaneous breathing must be assessed. Sufficient spontaneous breathing capacity can be assumed, if the patient is able to breathe without significant mechanical support, such as T-piece, CPAP without pressure support or assisted mechanical ventilation with low pressure support [3].

P. Lebiedz (*) Department of Cardiovascular Medicine, University Hospital of Münster, Münster, Germany e-mail: [email protected] M. Bachmann Department of Intensive Care and Ventilatory Medicine, Asklepios Klinikum Hamburg- Harburg, Hamburg, Germany S. Braune, M.P.H. Department of Medical Intensive Care and Emergency Medicine, St. Franziskus Hospital Münster, Münster, Germany

© Springer International Publishing AG 2018 187 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_19 188 P. Lebiedz et al.

Due to high pleural pressures caused by low chest wall compliance and abdominal hypertension, obesity is associated with pulmonary restriction and reduced functional residual capacity. These factors lead to a higher risk of hypoxemic and/or ventilatory failure than in nonobese patients. The ventilatory capacity and the work of breathing in obese patients can be assessed by a spontaneous breathing trial via T-piece or on assisted ventilation with or without low pressure support before extubation or decannulation [4].

19.2 Positioning

Optimal positioning of the patient in upright position, sitting or beach chair position is crucial to facilitate mechanical ventilation of obese patients [5]. Due to the above mentioned changes in respiratory physiology caused by obesity and due to the often accompanying obstructive upper airway diseases, we recommend optimal positioning as described above before decannulation of obese patients.

19.3 Percutaneous Dilatational Versus Surgical Tracheotomy

Particularly in obese patients, recannulation after failure of decannulation is techni- cally significantly easier in surgically tracheotomised patients compared to percutaneously tracheotomised patients. After decannulation of a percutaneous dilatational tracheostoma, shifting of multiple subcutaneous tissue layers can lead to closure of tracheotomy and make recannulation impossible. This is the reason why a difficult airway for conventional intubation is a contraindication for percutaneous tracheostomy. Thus, physicians must always be aware of the patients’ airway anatomy before decannulation of percutaneously tracheotomised obese patients in case of decannulation failure and subsequent necessity for conventional (emergency) reintubation. A tracheal button or a downsizing cannula to maintain tracheal access should be used in the decannulation process in obese patients [6]. With a well-fitted placeholder device, NIV can be effectively applied, and at the same time, this leaves an access for deep tracheal suctioning and facilitates recannulation in case of NIV failure. Due to the above described risk, surgical tracheotomy may seem more reasonable for obese patients. However, surgical tracheotomy carries other risks such as higher tracheostomy infection rates [7]. Furthermore, obesity has been reported to be a risk factor for development of tracheal stenosis after surgical tracheotomy [8].

19.4 Non-invasive Ventilation After Decannulation

Because of the altered respiratory physiology of obese patients with reduced functional residual capacity caused by atelectasis and higher risk of ventilatory failure due to functional pulmonary restriction as well as the higher prevalence of OSA, the pre- emptive application of non-invasive ventilation (NIV) shortly after decannulation 19 Decannulation Process in the Tracheostomised Obese Patients 189 seems reasonable to minimise the risk of decannulation failure as has been shown for extubation of obese patients [9]. The mechanisms responsible for these positive effects are adequate positive end-expiratory pressures (PEEP) aiming for a positive end-expiratory transpulmonary pressure to counterbalance atelectasis and to treat OSA as well as to apply adequate driving pressures to reduce work of breathing.

Conclusions Decannulation of tracheotomised obese patients requires careful planning and optimal setting. This includes testing for sufficient unassisted ventilatory capacity, optimal positioning and the pre-emptive application of NIV post-decannulation.

19.5 Key Major Recommendations

• Pre-assessment of unassisted ventilatory capacity before decannulation • Sitting or beach chair positioning on decannulation • Pre-emptive NIV after decannulation

References

1. Byrd JK, Ranasinghe VJ, Day KE, Wolf BJ, Lentsch EJ. Predictors of clinical outcome after tracheotomy in critically ill obese patients. Laryngoscope. 2014;124:1118–22. 2. Ceriana P, Carlucci A, Navalesi P, Rampulla C, Delmastro M, Piaggi G, De Mattia E, Nava S. Weaning from tracheotomy in long-term mechanically ventilated patients: feasibility of a decisional flowchart and clinical outcome. Intensive Care Med. 2003;29:845–8. 3. Thille AW, Richard JC, Brochard L. The decision to extubate in the intensive care unit. Am J Respir Crit Care Med. 2013;187:1294–302. 4. Mahul M, Jung B, Galia F, Molinari N, de Jong A, Coisel Y, Vaschetto R, Matecki S, Chanques G, Brochard L, Jaber S. Spontaneous breathing trial and post-extubation work of breathing in morbidly obese critically ill patients. Crit Care. 2016;20:346. 5. Lemyze M, Mallat J, Duhamel A, Pepy F, Gasan G, Barrailler S, Vangrunderbeeck N, Tronchon L, Thevenin D. Effects of sitting position and applied positive end-expiratory pressure on respiratory mechanics of critically ill obese patients receiving mechanical ventilation. Crit Care Med. 2013;41:2592–9. 6. Marchese S, Corrado A, Scala R, Corrao S, Ambrosino N, Intensive Care Study Group, Italian Association of Hospital Pulmonologists (AIPO). Tracheostomy in patients with long-term mechanical ventilation: a survey. Respir Med. 2010;104:749–53. 7. Delaney A, Bagshaw SM, Nalos M. Percutaneous dilatational tracheostomy versus surgical tracheostomy in critically ill patients: a systematic review and meta-analysis. Crit Care. 2006;10:R55. 8. Halum SL, Ting JY, Plowman EK, Belafsky PC, Harbarger CF, Postma GN, Pitman MJ, LaMonica D, Moscatello A, Khosla S, Cauley CE, Maronian NC, Melki S, Wick C, Sinacori JT, White Z, Younes A, Ekbom DC, Sardesai MG, Merati AL. A multi-institutional analysis of tracheotomy complications. Laryngoscope. 2012;122:38–45. 9. El-Solh AA, Aquilina A, Pineda L, Dhanvantri V, Grant B, Bouquin P. Noninvasive ventilation for prevention of post-extubation respiratory failure in obese patients. Eur Respir J. 2006;28:588–95. Part IV Noninvasive Ventilation and Oxygen Delivery in the Critically Ill Obese Patient The Choice of Interface 20 Ahmed S. BaHammam, Tripat Singh, and Antonio M. Esquinas

20.1 Introduction

Noninvasive ventilation (NIV) applied through different interfaces is increasingly used in the treatment of acute respiratory failure (ARF) and in some chronic respiratory disorders such as sleep-disordered breathing (e.g., obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS)). Despite the great improvement in NIV technology and experience of the medical staff, the failure rate of NIV in the acute setting remains high ranging between 18 and 40% [1]. The success of NIV depends on the underlying pathology, patients’ cooperation, and staff experience. Nevertheless, success of therapy depends to a large extent on the selection of the proper interface.

20.2 Types of Interfaces for NIV

Choosing the right mask for patients with ARF involves patient preference, finding the right size, and fit of the mask. There are six available types of masks that can be used to deliver NIV therapy in the acute setting:

A.S. BaHammam, F.R.C.P., F.C.C.P. (*) Department of Medicine, The University Sleep Disorders Center, College of Medicine, King Saud University, Box 225503, Riyadh 11324, Saudi Arabia Strategic Technologies Program of the National Plan for Sciences and Technology and Innovation in the Kingdom of Saudi Arabia, Riyadh, Saudi Arabia e-mail: [email protected]; [email protected] T. Singh, M.D. Philips, Respironics, Delhi, India A.M. Esquinas, M.D., Ph.D. Intensive Care Unit, Hospital Morales Meseguer, Murcia, Spain

© Springer International Publishing AG 2018 193 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_20 194 A.S. BaHammam et al.

1. Nasal masks. This type of mask covers the nose only while resting on the upper lip, sides of the nose, and on the nasal bridge. 2. Oronasal masks. It is also referred to as full-face masks. This type of masks covers the nose and mouth while resting on the chin, sides of the nose and mouth, and on the nasal bridge. 3. Nasal pillows. This type of mask rests on the rim of the nostrils. They are a good option for people who find nasal or oronasal mask too obtrusive and who have skin breakdown on the nasal bridge. 4. Oral masks. This type fits in the mouth between the teeth and lips. It also has a tongue guide to prevent tongue obstructing the passage of airway. This type is not common in practice. 5. Total face mask. It covers the entire face and used mainly in patients with ARF [2]. 6. Helmet. The helmet is used as an alternative to oronasal mask in patients with acute hypoxemic respiratory failure or acute cardiogenic pulmonary edema in certain countries [3]. It is not commonly used in patients with acute hypercapnic respiratory failure.

Masks are made of a variety of materials but the commonly used material is sili- cone, and some manufacturers have gel masks as well. The advantage of gel masks is that they adapt to the contours of the face. The availability of several types of interfaces makes the choice of the appropriate interface for the patient with ARF a great challenge. NIV in the form of continuous positive airway pressure (CPAP), bi-level positive airway pressure (BPAP), or other pressure- and volume-limited ventilatory modes is used in patients with ARF. For all modes of NIV, a good fit interface is needed.

20.3 Difference Between Nasal and Oronasal Masks

In ARF, NIV efficacy is more important than patient’s comfort, yet appropriate mask fitting and care are essential to increase patient tolerance and subsequently improve NIV outcome [4]. Although there is no ideal NIV interface, choosing an interface needs thorough evaluation of patient’s features, ventilatory modes, and respiratory failure type [5, 6]. The choice of the proper interface is influenced by the patient’s face shape, mouth/nose breathing pattern, patient preference, and experience of the staff. Limited number of studies has assessed the impact of different interfaces on the success of treatment in patients with ARF and the improvements in respiratory parameters, i.e., respiratory rate, dyspnea, and arterial blood gases. Two randomized controlled trials that compared oronasal mask with the use of nasal mask in patients who had ARF showed no evidence that one type of interface is consistently better than the other in terms of clinical efficiency [7, 8]. Since mouth breathing is predominant in patients with ARF, full-face mask (oronasal mask) is considered to be the most suitable and effective interface followed by nasal mask, helmet, and mouthpiece [5, 7, 8]. Therefore, the most commonly used interface 20 The Choice of Interface 195 in patients with ARF is oronasal mask. This was revealed in a large web-based survey in North America and Europe, which showed that oronasal mask was used in 70% of the patients followed by total face masks, nasal masks, and helmets [9]. To accommodate the variability in the human face shape, full-face mask comes in a different range of shapes and sizes [5].

20.4 Mask Type and Upper Airway Obstruction

As most obese patients with ARF have an element of upper airway obstruction during sleep, it is important in this context to discuss the effect of different routes of interface on the upper airway patency. As oronasal and nasal masks are the most commonly used masks during ARF [9], we will review the studies that assessed the effect of each type on upper airway dynamics. Upper airway dynamics differ when we breathe through the nose than when we breathe through the mouth [10]. Upper airway resistance and propensity to develop OSA are higher when breathing occurs through the mouth as compared to breathing through the nose. Mouth opening is associated with a significant reduction in the retropalatal and retroglossal cross-sectional areas in awake subjects, as well as a reduction in the positive pharyngeal critical closing pressure during natural sleep [11]. Oronasal mask violates the Starling resistor model as pressure applied through the mouth and nose simultaneously may lead to collapse of the airway [12]. In 18 severe OSA patients treated with nasal CPAP, when the CPAP flow route was shifted from nasal to oronasal or oral route, there was a significant and progressive reduction in the distance between the epiglottis and tongue base and the retroglossal area, respectively [13]. The study demonstrated that patients showed upper airway obstruction during oronasal CPAP despite being predominantly breathing through the nose preceding the obstructive event [13]. The authors speculated that positive pressure applied through the mouth pushed the tongue posteriorly resulting in occlusion of the upper airway [13]. Moreover, they proposed that oronasal CPAP applies equal positive pressure in both nasopharyngeal and oropharyngeal compartments, which eliminates pressure gradient and hence allows gravity to displace the soft palate and tongue backward, resulting in airway obstruction [13]. Similar results were reported by Smith et al. who showed that oronasal CPAP was unable to open the upper airway even with CPAP pressure above the pharyngeal critical closing pressure obtained when nasal mask was applied [14]. Borel et al. [15] in a large prospective cohort study involving 2311 OSA patients confirmed the above findings, demonstrating that CPAP pressure is higher with oronasal mask as compared to nasal mask or nasal pillow. The above findings of the effect of oronasal masks on upper airway anatomy have been corroborated with radiological investigations of the upper airway in OSA patients. In ten OSA patients who were treated with CPAP using nasal and oronasal masks, upper airway was evaluated by cMRI while using CPAP [16]. In mouth breathers, applying CPAP at pressure of 15 cm H2O via oronasal mask produced significantly less airway opening in the retropalatal region of upper airway compared with nasal mask at the same CPAP pressure [16]. 196 A.S. BaHammam et al.

The above differences in the efficacy of positive airway pressure applied via nasal and oronasal masks may influence the effectiveness of NIV therapy particularly in patients with OHS who present with AHRF.

20.4.1 Fitting the Mask

Correct mask fitting is essential for the success of NIV therapy. Therefore, most masks come with a fitting guage to assure the choice of the correct size mask to improve acceptance and avoid complications. If a significant leak is detected or patients could not tolerate the mask, the interface should be changed to avoid NIV failure. However, when a different mask is used, trigger sensitivity, pressurization level, and compatibility with the circuitry must be checked [1]. Once the patient is stable and mouth leak is not present, nasal mask can be tried as it is less claustro- phobic and has lower risk of skin problems. Straps should not be overtightened to avoid pressure ulcers. In general, when the headgear is fixed, it should be possible to permit two fingers beneath it (the two-finger rule)17 [ ].

20.5 Type of Ventilator and Interface Choice

NIV can be applied through a close double-tube circuit or an open single-tube circuit. A double-tube circuit has one tube for inhalation and another for exhalation and a built-in exhalation port or filter for CO2 removal. Therefore, a non-vented mask is used to maintain the closed circuit. On the other hand, the open single-tube circuit uses one tube only; therefore, it requires a vented mask with a built-in exhalation port. If a non-vented mask is used, an additional exhalation valve in the circuit to allow CO2 removal must be added. Clinicians must be aware of this important difference between ventilators, because the use of non-vented mask in an open single-tube system without exhalation port in the system can be disastrous [1]. It is worth mentioning that the interface itself acts as a dead space, which theoretically may increase the risk of CO2 rebreathing and retention particularly in acute hypercapnic respiratory failure. The dead space is related to the internal volume of the interface [18]. Nevertheless, an in vivo study showed that the internal volume of the masks had no apparent short-term dead space effect on gas exchange, minute ventilation, or patient’s effort, suggesting that the interfaces may be interchangeable in clinical practice with the exception of the helmet [19].

20.5.1 Oxygen (O2) Supply and Interface

When using an ICU ventilator, the fraction of inspired oxygen (FiO2) can be precisely controlled. However, in some portable ventilators that are used outside the ICU setting, there is no oxygen control, and thus supplemental oxygen is bled into the mask or the ventilator circuit. Usually, low flow oxygen is bled into the circuit, 20 The Choice of Interface 197

and this results in variable FiO2. In contrast to ICU ventilators that have an inhalation tube and an exhalation tube, portable devices for NIV operate with one tube only. Therefore, an additional exhalation port is added to the circuit. The actual inspired FiO2 when oxygen is bled into the circuit or the mask is variable and is influenced by several factors such as intentional and unintentional leak through the mask or the circuit, inspiratory and expiratory pressure settings of the NIV, the interface, oxygen flow, and the oxygen administration site [20–22]. Frequently, oxygen supply is bled into an oxygen port already built into the frame of the mask. The site of oxygen delivery into the circuit is the most important factor in determining inspired FiO2 [20]. Administering oxygen into the mask results in exhaustion of oxygen out of the exhalation port [22]. Moreover, oxygen may leak unintentionally between the mask and the face resulting in low inspired oxygen concentration and hence low arterial partial pressure of oxygen (PaO2) and oxygen saturation. Consequently, when oxygen is bled directly into a mask with a leak port, patients may receive very low oxygen concentrations, which may result in low oxygen saturation in the blood [21, 22]. Therefore, during NIV of patients with ARF, it is recommended to use a ventilator in which FiO2 can be precisely controlled.

20.6 Summary

The best mask is the one that patient will wear. It is important to let the patient try different types of masks and choose the most comfortable mask. Aside from patient preference, oronasal masks are preferred in patients with ARF. Experience with mask fitting and prevention of mask-related problems such as air leak, skin irrita- tion, and pressure ulcers are essential for NIV therapy success. Once stable, patients may be shifted to nasal masks.

Acknowledgment This project was partially funded by The Strategic Technologies Program of the National Plan for Sciences and Technology and Innovation in the Kingdom of Saudi Arabia.

Conflict of Interest AB and AE have no conflict of interest to declare. TS is an employee of Philips, Respironics.

References

1. Brill A-K. How to avoid interface problems in acute noninvasive ventilation. Breathe. 2014;10:231–42. 2. Ozsancak A, Sidhom SS, Liesching TN, Howard W, Hill NS. Evaluation of the total face mask for noninvasive ventilation to treat acute respiratory failure. Chest. 2011 May;139(5):1034–41. 3. Esquinas Rodriguez AM, Papadakos PJ, Carron M, Cosentini R, Chiumello D. Clinical review: helmet and non-invasive mechanical ventilation in critically ill patients. Crit Care. 2013;17(2):223. 4. Brill AK. How to avoid interface problems in acute noninvasive ventilation. Breathe. 2014;10:231–42. 198 A.S. BaHammam et al.

5. Davidson AC, Banham S, Elliott M, Kennedy D, Gelder C, Glossop A, et al. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax. 2016;71(Suppl 2):ii1–ii35. 6. Nava S, Navalesi P, Gregoretti C. Interfaces and humidification for noninvasive mechanical ventilation. Respir Care. 2009;54(1):71–84. 7. Kwok H, McCormack J, Cece R, Houtchens J, Hill NS. Controlled trial of oronasal versus nasal mask ventilation in the treatment of acute respiratory failure. Crit Care Med. 2003;31(2):468–73. 8. Girault C, Briel A, Benichou J, Hellot MF, Dachraoui F, Tamion F, et al. Interface strategy during noninvasive positive pressure ventilation for hypercapnic acute respiratory failure. Crit Care Med. 2009;37(1):124–31. 9. Crimi C, Noto A, Princi P, Esquinas A, Nava S. A European survey of noninvasive ventilation practices. Eur Respir J. 2010;36(2):362–9. 10. Ayappa I, Rapoport DM. The upper airway in sleep: physiology of the pharynx. Sleep Med Rev. 2003;7(1):9–33. 11. Jefferson Y. Mouth breathing: adverse effects on facial growth, health, academics, and behavior. Gen Dent. 2010;58(1):18–25. quiz 6–7, 79–80 12. Andrade RG, Piccin VS, Nascimento JA, Viana FM, Genta PR, Lorenzi-Filho G. Impact of the type of mask on the effectiveness of and adherence to continuous positive airway pressure treatment for obstructive sleep apnea. J Bras Pneumol. 2014;40(6):658–68. 13. Andrade RG, Madeiro F, Piccin VS, Moriya HT, Schorr F, Sardinha PS, et al. Impact of acute changes in CPAP flow route in sleep apnea treatment. Chest. 2016;50(6):1194–201. 14. Smith PL, Wise RA, Gold AR, Schwartz AR, Permutt S. Upper airway pressure-flow relationships in obstructive sleep apnea. J Appl Physiol (1985). 1988;64(2):789–95. 15. Borel JC, Tamisier R, Dias-Domingos S, Sapene M, Martin F, Stach B, et al. Type of mask may impact on continuous positive airway pressure adherence in apneic patients. PLoS One. 2013;8(5):e64382. 16. Ebben MR, Milrad S, Dyke JP, Phillips CD, Krieger AC. Comparison of the upper airway dynamics of oronasal and nasal masks with positive airway pressure treatment using cine magnetic resonance imaging. Sleep Breath. 2016;20(1):79–85. 17. Meduri GU, Abou-Shala N, Fox RC, Jones CB, Leeper KV, Wunderink RG. Noninvasive face mask mechanical ventilation in patients with acute hypercapnic respiratory failure. Chest. 1991;100(2):445–54. 18. Schettino GP, Chatmongkolchart S, Hess DR, Kacmarek RM. Position of exhalation port and mask design affect CO2 rebreathing during noninvasive positive pressure ventilation. Crit Care Med. 2003;31(8):2178–82. 19. Fraticelli AT, Lellouche F, L'Her E, Taille S, Mancebo J, Brochard L. Physiological effects of different interfaces during noninvasive ventilation for acute respiratory failure. Crit Care Med. 2009;37(3):939–45. 20. Dai B, Kang J, Yu N, Tan W, Zhao HW. Oxygen injection site affects FIO2 during noninvasive ventilation. Respir Care. 2013;58(10):1630–6. 21. Schwartz AR, Kacmarek RM, Hess DR. Factors affecting oxygen delivery with bi-level positive airway pressure. Respir Care. 2004;49(3):270–5. 22. Storre JH, Huttmann SE, Ekkernkamp E, Walterspacher S, Schmoor C, Dreher M, et al. Oxygen supplementation in noninvasive home mechanical ventilation: the crucial roles of CO2 exhalation systems and leakages. Respir Care. 2014;59(1):113–20. The Choice of Ventilator and Ventilator Setting 21

Ebru Ortaç Ersoy

21.1 Introduction

Obesity is highly prevalent throughout the world. There have been multiple studies about obese critically ill patients, and the prevalence of obesity in intensive care unit (ICU) is estimated at 25%. Critically ill morbidly obese patients have higher ICU mortality compared to nonobese patients; morbid obesity is associated with prolonged mechanical ventilation and extended “weaning” period. Obesity results in anatomic and physiologic alterations in the face, neck, larynx, lungs, and chest wall and also affects pulmonary system function especially in critically ill patients by increasing work of breathing and by increasing respiratory system compliance and resistance [1, 2]. Excess facial fat may compromise fit of mask for ventilation, while pharyngeal fat increases upper airway resistance. Respiratory mechanics are markedly altered in obese patients; functional residual capacity is about one third of normal, and lung compliance is reduced for about 50%. Total lung resistance is threefold higher in obese patients. In summary, both elastic and resistive work of breathing are significantly higher [3]. Effective treatment strategies must relieve upper airway obstruction and increase alveolar ventilation in obese critical patients affected by respiratory failure. Morbid obesity is associated with an increase in work of breathing and oxygen cost of breathing and a decrease in compliance of the respiratory system, lung volumes, ventilatory drive, and respiratory muscle dysfunction [3]. Therefore, choosing ventilator and managing settings is important in obese patients in ICU. NIV can be applied with volume-limited or pressure-limited devices. Both ICU ventilators and portable noninvasive ventilators can be used.

E.O. Ersoy Medical Intensive Care Unit, Hacettepe University Hospital, Ankara, Turkey e-mail: [email protected]

Positioning of obese patient is also important. In this chapter, the choice of ventilator and ventilator settings will be described in obese ICU patients.

21.2 Ventilator Type

The choice of a ventilator can be important for the success of NIV in the obese patients for acute settings, because intolerance is especially important for NIV success. NIV can be delivered via standard type of ventilators found in the ICU: regular ICU ventilators with no NIV algorithms, ICU ventilators with NIV algorithms, or portable ventilators that are used for NIV only. Standard ICU ventilators have some advantages. An accurate concentration of oxygen can be delivered by ICU ventilators, separate inspiratory and expiratory tubing minimizes the rebreathing of CO2 (it is important especially in obesity hypoventilation patients), monitoring of alarms is better, and certain modes can only be delivered with standard ICU ventilators. But in ICU ventilators, leak compensation is poor. If leak is great, the ventilator leak alarm may be activated and leak can abort the breath of patient. Critical care ventilators have traditionally been designed for invasive ventilation, but newer generations have NIV modes. For critical care ventilators, dual-limb circuits are used, and these have inspiratory and expiratory valves and separate hoses for the inspiratory gas and the expiratory gas. Several recent studies have evaluated the ability of critical care ventilators to compensate for leaks. Vignaux et al. [4] found that leaks interfere with the function of ICU ventilators and that NIV modes can correct this problem but with wide variations between ventilators. In a follow-up study, Vignaux et al. [5] reported that NIV modes on ICU ventilators decreased the incidence of asynchrony typically associated with leaks. In a laboratory and clinical study, Carteaux et al. [6] suggested that, as a group, bi-level ventilators outperform critical care ventilators for NIV. However, the NIV modes on some, but not all, critical care ventilators improve synchrony in the presence of leaks. Some critical care ventilators also allow clinicians to make adjustments to improve synchrony. These embellishments include an adjustable trigger type and sensitivity, an adjustable flow cycle criteria with PSV, and a maximal inspiratory time during PSV. Due to the differences in the ability to compensate for leaks among ventilators used for NIV, it is important for clinicians to appreciate the unique characteristics of the ventilators they use [7]. Either pressure- or volume-cycled ventilators may be used to deliver NIV. The ventilatory mode used by pressure-cycled ventilators is also known as bi- level positive airway pressure (BPAP). It delivers both a preset inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP). The assist- control mode is used for volume-cycled ventilators. Additional “hybrid” modes such as average volume-assured pressure support (AVAPS) mode or intelligent volume-assured pressure support (iVPAPS) are available for NIV, and these hybrid modes can be used even in ICU. In difficult ventilated obese patients, hybrid modes may be used especially in patients with acute on chronic respiratory failure, e.g., OHS, OSA, and scoliosis. 21 The Choice of Ventilator and Ventilator Setting 201

Evidence to guide ventilator selection is lacking, but most practitioners prescribe pressure-cycled ventilators. Regardless of whether a volume- or pressure-cycled device is used, though, the initial priority should be to achieve patient comfort and acceptance rather than any particular level of improvement in gas exchange.

21.3 Ventilator Settings

Before maintaining the settings of ventilators, positioning of obese patient is important. Obese patients are at risk for severe oxygen desaturation that can occur precipitously because of lower functional capacity and atelectasis that is exacerbated in the supine position. Sitting position prevents gravitational atelectasis, unloads the diaphragm, and reduces work of breathing. In morbidly obese patients, elevated abdominal pressure can affect pulmonary function in sitting position. NIV should be administered at ramped position to obese ICU patients. Reverse Trendelenburg position in 30–45° is important [8, 9]. NIV can be delivered using the same modes with invasive ventilation. Especially with the ICU ventilators, more frequently used modes are the following:

1. Assist control (AC): The most common mode chosen for guaranteed minute ventilation. In an obese patient, it can be difficult to use AC mode because of high airway resistance and patient intolerance. 2. Pressure support ventilation (PSV): The most common mode for patient comfort and synchrony. Obese ICU patients can easily tolerate this mode for NIV. PSV is used most commonly for NIV applications in patients with acute respiratory failure. With a critical care ventilator, the level of PSV is applied as a pressure above the baseline PEEP. However, the approach is different with bi-level ventilators, where an inspiratory positive airway pressure and expiratory airway pressure are set. In this configuration, the difference between the inspiratory and expiratory airway pressure is the level of PSV [10]. 3. Continuous positive airway pressure (CPAP): Often used for patients with acute respiratory failure due to pulmonary edema and with obstructive sleep apnea (OSA). Especially in postoperative morbidly obese patients, CPAP can prevent atelectasis. 4. BPAP: The most common mode in patients with hypercapnic respiratory failure. 5. Proportional assist ventilation (PAV): Delivers an inspiratory pressure that is proportional to patient effort and may be helpful in patients who do not tolerate PSV or CPAP. 6. Hybrid modes: Average volume-assured pressure support (AVAPS). In this mode, the IPAP varies in order to achieve a present tidal volume. This mode can be used with portable NIV ventilators [11].

In ICU ventilators selected mode determines which parameters need to be set. The initial settings for NIV are similar to those for invasive ventilation. There is not any universal approach for initial settings especially for obese ICU patients. NIV settings have to be patient based. The goal of initial settings is to provide a modest 202 E.O. Ersoy amount of ventilatory support, while allowing the patient to become acclimated to NIV. The ventilator setting should be different in obese patients. Theoretically, the recommended Vt should be calculated according to the predicted body weight based solely on height and gender and should be adjusted for inflation pressure and gas exchange [12]. Tolerance of bi-level positive airway pressure devices is facilitated by using low initial pressures. Pressures should be titrated slowly to allow the patient to accli- mate the device. Initial inspiratory positive airway pressure (IPAP) is typically

8–10 cm H2O and expiratory positive airway pressure (EPAP) 4–5 cm H2O (thus providing inspiratory pressure support [IPAP minus EPAP] (pressure boost) of approximately 4–6 cm H2O). Indeed, the respiratory compliance of obese patients is decreased. Brochard et al. [13] used a pressure boost between 12 and 20 cm H2O in patients with acute exacerbation of COPD. In a patient with acute restrictive respiratory failure, a 6 cm H2O pressure boost significantly reduced diaphragmatic activity and allowed recovery of normal thoracoabdominal motion. When the pressure boost was increased to 11 cm H2O, diaphragmatic activity disappeared [14]. This suggests that pressure boost must reach a threshold to place the diaphragm at rest. This threshold may differ, depending on the stage and the type of respiratory disease, as well as the respiratory compliance due to severity of obesity. The IPAP can be increased until there is an acceptable level of steady oxygenation (SaO2 >92%). To achieve adequate ventilation in BPAP, the IPAP should be at least 8–10 cm H2O greater than EPAP [15]. Initial tidal volumes of 6–10 mL/kg (ideal body weight) are employed when using a volume-cycled ventilator, starting at the low end of the range and increasing, as needed. These volumes may be higher than those commonly used for invasive ventilation, because of the frequent need to compensate for air leaks during noninvasive ventilation. Positive end-expiratory pressure (PEEP) is usually provided at

4–5 cm H2O; slightly higher PEEP levels may be needed for patients with concomitant chronic obstructive pulmonary disease (COPD). In obese patients, Vt based on patients’ actual body weight is likely to result in high airway pressure and alveolar overdistention. In settings usage of ideal body weight is advised. In clinical practice, obese patients in ARF need high levels of IPAP (12–25 cm

H2O) and PEEP (5–13 cm H2O) [16]. Refractory hypoxemia is the main determinant of NIV failure. For volume-controlled NIV, the ventilator mode, respiratory rate, tidal volume, and PEEP must be selected. The largest tidal volume that consistently maintains an airway pressure less than 3 cm H2O is generally chosen. And respiratory rate is then set to achieve minute ventilation of 6–10 L/min. In acute decompensated obese patient with respiratory failure, NIV should be used as BPAP or volume-controlled NIV instead of CPAP, although BPAP is usually preferred unless it is insufficient to maintain an open upper airway or to overcome the decreased respiratory system compliance in obese patients [17]. In postoperative morbidly obese patients in the ICU, NIV is mostly used for preventing respiratory failure. CPAP provides ventilatory support to restore and maintain the lung volumes by recruiting atelectatic lung which, in turn, improves oxygenation and reduces 21 The Choice of Ventilator and Ventilator Setting 203 work of breathing in these patients. Animal studies have shown that minimizing lung atelectasis decreases bacterial growth and translocation of organisms to the bloodstream by reducing the permeability of the epithelial-endothelial barrier [18, 19]. A meta-analysis [20] has shown that postoperative CPAP following abdominal surgery significantly reduced post-pulmonary complications, atelectasis, and pneumonia which is in contrast with a more recent Cochrane review concluding that the evidence to support the use of CPAP to reduce pneumonia and re-intubation is of low quality [21, 22]. Although humidification necessary during NIV is controversial, humidification should be considered during NIV [23]. During NIV, unidirectional flow dries the upper airway and increases nasal airway resistance. Upper airway drying contributes to discomfort of patient and may affect tolerance to NIV. It can be done either actively by heated humidifiers (HH) or passively by heat and moisture exchangers (HME) in ICU settings. A heat and moisture exchanger is not recommended for use with NIV, because the additional dead space decreases carbon dioxide elimination, particularly in patients with hypercapnia [24, 25].

Conclusion The number of obese patients in ICU is increasing. It is important to pay special attention during mechanical ventilation in these patients because of lung dynamics and comorbidities. The choice of ventilator and setting is especially important especially in NIV. There is no any recommended setting. We have to choose ventilator and setting according to our critical patient and the medical problem of the patient.

References

1. Pelosi P, Croci M, Ravagnan I, Vicardi P, Gattinoni L. Total respiratory system, lung, and chest wall mechanics in sedated-paralyzed postoperative morbidly obese patients. Chest. 1996;109:144–51. 2. Harris RS. Pressure-volume curves of the respiratory system. Respir Care. 2005;50:78–98. 3. Janssens J-P, Pepin J-L, Guo YF. NIV and chronic respiratory failure secondary to obesity. Eur Respir Mon. 2008;41:251–64. 4. Vignaux L, Tassaux D, Jolliet P. Performance of noninvasive ventilation modes on ICU ventilators during pressure support: a bench model study. Intensive Care Med. 2007;33(8):1444–51. 5. Vignaux L, Tassaux D, Carteaux G, Roeseler J, Piquilloud L, Brochard L, et al. Performance of noninvasive ventilation algorithms on ICU ventilators during pressure support: a clinical study. Intensive Care Med. 2010;36(12):2053–9. 6. Carteaux G, Lyazidi A, Cordoba-Izquierdo A, Vignaux L, Jolliet P, Thille AW, et al. Patient- ventilator asynchrony during noninvasive ventilation: a bench and clinical study. Chest. 2012;142(2):367–76. 7. Hess DR, Branson RD. Know your ventilator to beat the leak. Chest. 2012;142(2):274–5. 8. Lemyze M, Guerry MJ, Mallat J, Thevenin D. Obesity supine death syndrome revisited. Eur Respir J. 2012;40:1568–9. 9. Burns SM, Egloff MB, Ryan B, et al. Effect of body position on spontaneous respiratory rate and tidal volume in patients with obesity, abdominal distension and ascites. Am J Crit Care. 1994;3(2):102–6. 204 E.O. Ersoy

10. Hess DR. Noninvasive ventilation for acute respiratory failure. Respir Care. 2013;58:6. 11. Storre JH, Seuthe B, Fiechter R, et al. Average volume-assured pressure support in obesity hypoventilation: a randomized crossover trial. Chest. 2006;130:815–21. 12. Marik P, Varon J. The obese patient in the ICU. Chest. 1998;113:492–8. 13. Brochard L, Isabey D, Piquet J, et al. Reversal of exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask. N Engl J Med. 1990;323:1523–30. 14. Carrey Z, Gottfried SB, Levy RD. Ventilatory muscle support in respiratory failure with nasal positive pressure ventilation. Chest. 1990;97:150–5831. 15. Perez de Llano LA, Golpe R, Ortiz Piquer M, et al. Short term and long term effects of nasal intermittent positive pressure ventilation in patients with obesity hypoventilation syndrome. Chest. 2005;128:587–94. 16. Lemyze M, Taufour P, Duhamel A, et al. Determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure. PLoS One. 9(5):e97563. 17. Piper AJ, Wang D, Yee BJ, et al. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax. 2008;63:395. 18. Duggan M, McCaul CL, McNamara PJ, et al. Atelectasis causes vascular leak and lethal right ventricular failure in uninjured rat lungs. Am J Respir Crit Care Med. 2003;167:1633–40. 19. van Kaam AH, Lachmann RA, Herting E, et al. Reducing atelectasis attenuates bacterial growth and translocation in experimental pneumonia. Am J Respir Crit Care Med. 2004;169:1046–53. 20. Ferreyra GP, Baussano I, Squadrone V, et al. Continuous positive airway pressure for treatment of respiratory complications after abdominal surgery: a systematic review and meta-analysis. Ann Surg. 2008;247:617–26. 21. Battisti A, Michotte JB, Tassaux D, et al. Non-invasive ventilation in the recovery room for postoperative respiratory failure: a feasibility study. Swiss Med Wkly. 2005;135:339–43. 22. Ireland CJ, Chapman TM, Mathew SF, et al. Continuous positive airway pressure (CPAP) during the postoperative period for prevention of postoperative morbidity and mortality following major abdominal surgery. Cochrane Database Syst Rev. 2014;8:CD008930. 23. Respeto RD, Walsh BK. AARC Practice Guideline. Humidification during invasive and non invasive mechanical ventilation. Respir Care. 2012;57(5):782–8. 24. Branson RD, Gentile MA. Is humidification always necessary during noninvasive ventilation in the hospital? Respir Care. 2010;55(2):209–16. 25. Lellouche F, Maggiore SM, Lyazidi A, Deye N, Taillé S, Brochard L. Water content of delivered gases during non-invasive ventilation in healthy subjects. Intensive Care Med. 2009;35(6):987–95. Obesity and Bi-level Positive Airway Pressure 22

Ayelet B. Hilewitz, Andrew L. Miller, and Bushra Mina

22.1 Introduction

Obesity has become an increasingly concerning global epidemic. Obesity, defined as a body mass index (BMI) more than 30 kg/m2, is classified based on severity with BMI 30–39.9 kg/m2 classified as obesity and BMI >40 kg/m2 classified as morbid or severe obesity. Obesity is a major risk factor for many acute and chronic diseases. It worsens chronic conditions including hypertension, dyslipidemia, type 2 diabetes mellitus, cholelithiasis, and osteoarthritis and is known to increase all-cause mortality. Obesity also has significant negative effects on the respiratory system and causes profound changes to the physiology of breathing, pulmonary mechanics, and gas exchange. A brief review of some of the changes will be discussed. One important change is the decrease in total respiratory system compliance. Compliance can be decreased by as much as two-thirds the normal value. This is likely due to accumulation of fat in and around the ribs, the diaphragm, and the abdomen [1]. Recumbency further worsens compliance in obese patients and is almost entirely due to decreased compliance of the chest wall. Increased work of breathing in obese patients is caused by this decrease in compliance, but more importantly is secondary to an increase in nonelastic work of the respiratory muscles [1]. Airway resistance is also significantly increased likely as a result of reduction in lung volumes due to obesity itself.

A.B. Hilewitz, M.D. (*) Division of Pulmonary, Hosftra Northwell School of Medicine, Northwell Health, Critical Care and Sleep Medicine, New Hyde Park, NY, USA e-mail: [email protected] A.L. Miller, M.D. Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver, CO, USA B. Mina, M.D. Northwell Health, Lenox Hill Hospital, New York, NY, USA

© Springer International Publishing AG 2018 205 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_22 206 A.B. Hilewitz et al.

Another important effect is changes in pulmonary function tests. The most common pulmonary function abnormality is reduction in expiratory reserve volume (ERV) [1]. ERV is likely the most sensitive indicator of obesity on lung function. This takes place due to mass loading, causing a decrease in functional reserve capacity (FRC), and since residual volume (RV) does not change in these patients, the ERV decreases. ERV decreases the most when the patient is supine, which causes the diaphragm to ascend and the weight of the lower thorax and abdomen to be applied to the lungs. When it reaches this stage, the ERV may come close to or surpass the closing volume, and gas may be trapped in the chest [1]. It has been shown that the decrease in FRC and ERV is proportionate to the degree of obesity. Of note, vital capacity (VC), total lung capacity (TLC), and other spirometric measures tend to be within normal limits in mild obesity. However, as BMI increases especially to the extreme (i.e., severe obesity), there is a decrease in expiratory flow and decreases in both forced expiratory volume in 1 second (FEV1) and forced viral capacity (FVC), as well as decreases in TLC and VC [1]. An additional change is an increased carbon monoxide diffusion capacity (DLCO). This is thought to be due to increased pulmonary blood flow. However, it should be noted that DLCO is directly proportional to lung volumes, so any decrease in lung volumes, such as those seen with high BMIs causing atelectasis, will lead to a low to normal DLCO [1]. A further effect of obesity is the distribution of ventilation and perfusion. In nonobese patients, ventilation is greatest in the dependent lung zones and decreases in the nondependent lung zones. In obese patients, however, there seems to be increased ventilation of the upper nondependent lung zones, leading to hypoxemia. The mechanism behind this ventilation perfusion mismatch is thought to be due to airway closure and atelectasis in the peripheral lung zones and smaller airways [1, 3]. Obesity is also associated with increased dyspnea on exertion and poor performance on 6-min walk test. Obesity causes additional stress to ventilation during exercise directly resulting from increased body mass requiring greater metabolic expenditure, as well as from functional impairment of the respiratory system [1]. Lastly, dyspnea on exertion, which is a prevalent complaint in obese patients, has been found to increase with increasing BMI. The cause is multifactorial, including increased work of breathing, airflow obstruction especially at low lung volumes, and respiratory muscle fatigue and weakness, among others [1]. There is a subset of obese patients who develop obesity hypoventilation syndrome (OHS). These patients tend to be morbidly obese and have the hallmark finding of daytime hypercapnia. It is unclear why certain obese patients develop this syndrome and others do not. The definition of OHS is obesity defined as BMI >30 kg/m2 and awake arterial hypercapnia (arterial pressure of carbon dioxide

PACO 2 > 45 mmHg) in the absence of other known causes of hypoventilation, including pulmonary, thoracic, metabolic, or neuromuscular disorders [2]. The reported prevalence of OHS is 10–20% of the obese population, and more than 50% of hospitalized patients with a BMI more than 50 meet diagnostic criteria for OHS [5]. Patients typically present with excessive daytime sleepiness, morning headaches, and fatigue. It is important to note that these patients have daytime hypercapnia and hypoxemia, which is strongly associated with pulmonary hypertension and 22 Obesity and Bi-level Positive Airway Pressure 207 subsequent cor pulmonale. In addition, many patients develop polycythemia. There is significant morbidity and mortality associated with this disease. Daytime hypercapnia in obesity is significantly associated with higher BMI levels and degree of restrictive chest wall mechanics, specifically lower VC and TLC 9[ ]. The majority of patients with OHS have concurrent obstructive sleep apnea (OSA). The exact pathophysiology of OHS has not been elucidated fully, but it likely results from intricate interplays among defective respiratory mechanics, neurohormonal abnormalities, sleep-disordered breathing, and an abnormal central ventilatory control [2]. Abnormal ventilatory drive is probably one of the more important factors in its development [1]. These patients lack compensatory hyperventilation mechanisms to overcome the mechanical abnormalities of obesity. It has been postulated that OSA may be an important contributor to this depressed ventilatory response and resultant hypoventilation. Chronic exposure to hypoxia and sleep fragmentation, as seen in OSA, has been found to lessen central ventilatory drive [2]. Patients with these concurrent syndromes get stuck in a vicious cycle where continued apnea-induced hypoxemia and hypercapnia cause more sleep fragmentation, leading to worsening of the ventilatory drive, impeding ventilatory compensation in post-apneic period, causing more severe hypoxemia further diminishing central ventilatory drive, and so on [2]. OHS is commonly underrecognized and is frequently diagnosed when a patient presents with an episode of acute respiratory failure (ARF), and it has been reported that OHS is frequently overlooked as a possible cause of ARF, thus leading to inappropriate treatment [3]. Studies have found that more than 75% of OHS exacerbations have been erroneously diagnosed and treated for asthma or chronic obstructive pulmonary disease (COPD) exacerbation [5]. Therefore, physicians should maintain a low index of suspicion. Bi-level positive airway pressure (BPAP) improves many aspects of respiratory mechanics and physiology. The inspiratory positive airway pressure (IPAP) augments tidal volume, while the expiratory positive airway pressure (EPAP) maintains airway pressures keeping airways open, as well as recruits collapsed alveolar units, thereby improving oxygenation. The difference between the IPAP and EPAP is the pressure support which enhances ventilation, thereby treating hypercapnia. It also improves work of breathing and improves diaphragmatic function. Data pertaining to BPAP use in the general obese population is sparse. The discussion will focus on its use in patients with OHS, as the overwhelming majority of the literature describes its use in this population. The use of continuous positive airway pressure (CPAP) has been well described as a treatment modality for patients with OSA. However, patients with OHS require ventilatory support to help correct their hypercapnia and will require BPAP. Morbid obesity puts patients at risk for both acute and chronic respiratory failure. Many OHS patients develop acute respiratory failure secondary to their disease, as well as many other common disease states, and can be treated with BPAP. Furthermore, many of these patients who recover from their acute event will continue to require ventilatory support. Most OHS patients will have chronic respiratory failure (CRF), as demonstrated by their symptoms and blood gas abnormalities, and will benefit from the BPAP use, as will be discussed below, preventing the need for tracheostomy. 208 A.B. Hilewitz et al.

22.2 Discussion

22.2.1 OHS and Acute Respiratory Failure

The prevalence of obesity in ICU patients ranges from 9 to 26% and morbid obesity ranges from 1.4 to 7% [3]. Obese patients with all of their associated changes to respiratory physiology have a diminished respiratory reserve, thus predisposing them to respiratory failure. Treating acute respiratory failure in obese patients represents a new challenge for healthcare providers. For many years, noninvasive positive pressure ventilation (NIPPV) has been a popular mode of ventilator support in many acute pulmonary disease processes, such as COPD, acute cardiogenic pulmonary edema, and pneumonia, among others. Only more recently, with the growing obese population has BPAP been considered in this group. There is strong evidence to support the use of BPAP, when no contraindications exist, as first-line therapy for ARF, particularly hypercapnic failure in obese patients, in order to avoid endotracheal intubations and all of its associated complications. Early recognition is especially important. Of note, acute hypoxemic respiratory failure is less likely to respond to supplemental oxygen and NIPPV, such as BPAP, and will frequently require mechanical ventilation. However, BPAP can be attempted in these patients particularly if the etiology of ARF is cardiogenic pulmonary edema, as NIPPV has been shown to be successful in this subset of patients [3]. NIPPV improves upper airway patency, reduces work of breathing, increases the FRC, unloads respiratory muscles, improves perfusion ventilation mismatching, and resolves the alveolar hypoventilation by augmenting tidal volume [3]. A prospective observational study was performed to evaluate if patients with OHS and acute hypercapnic respiratory failure would respond to NIPPV with the same efficacy as those with COPD, where BPAP has been shown to be effective in acute hypercapnic respiratory failure. Overall patients with OHS had lower rates of late BPAP failure, readmissions to the ICU, and ICU and hospital mortality and lower PACO2 on discharge as compared to those with COPD. The results showed that BPAP was highly effective in patients with OHS and acute hypercapnic respiratory failure and even had better outcomes, particularly survival, which will be discussed in more detail in the next section [4]. Another recent prospective observational study was performed to identify the factors associated with BPAP failure or success in the OHS population with acute hypercapnic respiratory failure no matter the cause of ARF. It was found that BPAP failed in only 17% of the population. Additionally, patients who were more likely to have early BPAP failure were more likely to be male and have a diagnosis of pneumonia and multisystem organ failure at admission, hypoxemic respiratory failure, lower PACO2 and serum bicarbonate levels, and higher severity scores at admission. Factors associated with successful response to BPAP were high PACO2 and bicarbonate levels at admission and idiopathic hypercapnic OHS exacerbation [5]. An interesting finding of the study concerned a delayed response to BPAP in patients with hypercapnic ARF. ABGs were improved significantly over the first 48 h. About half the patients would have been considered poor responders given their 22 Obesity and Bi-level Positive Airway Pressure 209

unimproved PACO2 and pH after the initial trial of BPAP, but were continued on BPAP because they failed to meet criteria for BPAP failure as set by the study. None of these patients were eventually intubated. These findings advocate for further NIPPV rather than immediate intubation and should be considered for morbidly obese patients with persistently severe acute hypercapnic respiratory failure after the first several hours of NIPPV [5]. The decreased responsiveness of the ventilatory drive may explain why these patients need more time to correct their acid-base derangements. Patients who present with ARF suspicious for OHS should be started on BPAP before performing a sleep study. Bahammam and Al-Jawder suggested a treatment algorithm with BPAP as follows: initiate EPAP of 4–6 cm H2O and IPAP of 8–10 cm H2O. EPAP should be gradually titrated up by 1–2 cm H2O until snoring, witnessed apneas and dips in oxygen saturation cease; IPAP should be gradually titrated up by

1–2 cm H2O until oxygen saturation is maintained in a range of 90–92% and should usually be 4–8 cm H2O above EPAP to maintain alveolar ventilation [3]. Most patients during ARF will require supplemental oxygen. It should be noted that the vast majority of the studies did not contain a control group of patients, as it was believed that it is unethical to withhold BPAP, which is considered the standard of therapy. In addition, most studies were performed on a small sample size. However, attempting BPAP is safe in these patients and should be tried first prior to endotracheal intubation. Caution should always be taken that patients do not meet any of the known contraindications to BPAP use. This noninvasive intervention should be started in the emergency room or general medicine floors. All these patients require close monitoring of vital signs, mental status, pattern of breathing, and serial blood gas monitoring and should be moved to an ICU.

22.2.2 OHS and Chronic Respiratory Failure

OHS causes many derangements to normal respiratory physiology, as described above, having many downstream effects causing significant morbidity and mortality. The resultant hypoxia can cause pulmonary vasoconstriction and eventual pulmonary hypertension, as well as many other cardiovascular effects, and polycythemia. Treating this disease is becoming more important as the rates of obesity continue to rise worldwide. BPAP can help reverse some of these abnormalities and has been suggested as a long-term treatment for these patients. CPAP alone cannot correct alveolar hypoventilation that occurs in OHS. There is the need for both inspiratory and expiratory pressures to help support ventilation. Several studies have been performed to evaluate the utility of nighttime BPAP in chronic respiratory failure due to OHS. Masa et al. performed a study in 2001 looking at the effectiveness of BPAP in patients with OHS compared to patients with kyphoscoliosis, in which BPAP has previously been shown to be successful. Overall the results showed that BPAP is effective in improving symptoms and reversing respiratory failure in patients with OHS, similar to the effect seen in patients with kyphoscoliosis [6]. 210 A.B. Hilewitz et al.

It is postulated that nighttime BPAP can help reverse daytime hypercapnia by improving chemoreceptor sensitivity to arterial pressure of oxygen (PAO2) and PACO 2, in addition to increases in lung volume and compliance, as well as improved efficiency of respiratory muscles 6[ ]. Other studies have shown improvement in

PAO 2 and PACO2 levels. In severely obese patients, BPAP has also been shown to unload the inspiratory muscles [7]. Heinemann et al. showed normalization of

PACO 2 during daytime spontaneous breathing without supplemental oxygen, accompanied by a significant improvement in hypoxemia after both 12 and 24 months of treatment with BPAP [8]. The degree of change was positively correlated with compliance with therapy. Meaning, the daily use of BPAP more than

4 hours per night was correlated with decreases in PACO2 after 12 and 24 months. This study also looked at changes in pulmonary function tests. After 12 months of therapy, there was a normalization of the restrictive ventilatory defect with a significant increase in TLC and VC. ERV also showed a significant increase 8[ ]. These findings were present independent of weight changes. Sleep architecture is also known to improve due to normalization of ventilation with increases in REM sleep and decreases in stage 1 and 2 sleep [9]. There have been several positive long-term outcomes found in those patients who use BPAP consistently. Studies have shown decreased emergency room visits and hospital admissions in OHS patients treated with BPAP compared with untreated OHS patients [3, 4, 7]. Again, compliance is essential for good outcomes. Studies have shown that patients discharged from the hospital after hypercapnic ARF had increased mortality if they refused BPAP with one study showing 6% mortality in the treated group vs. 46% mortality in those who refused [3]. In addition, improvements in hemoglobin and subsequent polycythemia have been reported. This change is not related to supplemental oxygen usage [3]. Another positive effect of BPAP is eliminating the use of daytime supplemental oxygen over time. Most OHS patients will require supplemental oxygen despite both inspiratory and expiratory pressure provided, as well as during the day. Studies have demonstrated that after several months of BPAP use, these patients may no longer require daytime oxygen with decreases in pulmonary artery pressures [3]. Subjective symptoms have also been shown to improve. Dyspnea, daytime somnolence, headaches, and general quality of life all improved in this population. In addition, many patients are able to be titrated from BPAP therapy to CPAP after several months of therapy [7]. Many of the studies above have compared BPAP use in OHS to BPAP use in patients with other chest wall or pulmonary diseases. There have been very few true control trials in CRF, as stated above, due to the BPAP being standard of care in this population. However, one study was performed evaluating whether nocturnal BPAP use in OHS vs. a control group, which received lifestyle counseling, could be effective on sleep structure, daytime somnolence, and inflammatory, metabolic, and cardiovascular consequences [9]. The OHS patients were characterized as having mild disease. It was a short-term study following patients for 1 month. As expected, the

BPAP group had improvements in diurnal PACO2, serum bicarbonate, and pH, as 22 Obesity and Bi-level Positive Airway Pressure 211 well as nocturnal oxygen measurements. Sleep architecture also improved significantly, as did subjective daytime sleepiness, although this was nonsignificant after 1 month. A significant reduction in BMI was seen in the lifestyle modification group. More importantly, no changes were seen on any metabolic parameters in either group despite improvement in oxygenation. The markers that were studied included several anti-inflammatory and inflammatory cytokines, high-sensitivity C-reactive protein (hsCRP), as well as measures on vascular endothelial function and arterial wall stiffness, blood pressure, lipid panel, fasting glucose, and hemoglobin A1C [9]. This is an important point as BPAP cannot be the only intervention for these patients to improve their cardiovascular and metabolic risk factors. OHS patients need intensive physical and pulmonary rehabilitation programs, as well as weight loss reduction plans, and should be considered for bariatric surgical interventions as well.

Conclusion Overweight and obesity have become a widespread global disease affecting mil- lions of people across all age groups. It has significant morbidity and mortality, causing cardiovascular, metabolic, pulmonary, and musculoskeletal derangements. Some of the effects on the pulmonary system include decreased compliance, ventilation/perfusion mismatching, changes in static lung volumes, as well as increased work of breathing and dyspnea. A proportion of severely obese patients develop OHS, where patients characteristically have daytime hypercapnia. These patients have worse morbidity and mortality, especially the development of pulmonary hypertension and cor pulmonale, as well as secondary polycythemia, than is observed in the general obese population. OHS is commonly underrecognized, misdiagnosed, and undertreated and has a high prevalence among hospitalized patients, especially ICU patients. Its recognition and treatment is becoming more important as the prevalence increases in the general population. BPAP is a well-known mode of noninvasive ventilation that has been proven useful in several acute and chronic disease states, such as COPD, acute cardiogenic pulmonary edema, kyphoscoliosis, as well as others. It provides both inspiratory and expiratory support, aiding in both ventilation and oxygenation, with which OHS patients have issues. Data over the last 20 years suggests that OHS patients with both acute and chronic hypercapnic respiratory failure will benefit from BPAP use. Patients with ARF benefit from the more immediate improvements in gas exchange and decreased work of breathing, and BPAP can safely be used in this population to prevent endotracheal intubation. Of note, patients with acute hypoxemic respiratory failure may not improve with BPAP and many progress to endotracheal intubation, but BPAP is still a reasonable initial ventilation modality. In CRF, long-term nighttime use has shown benefits, with decreases in mortality, hospitalizations, gas exchange abnormalities, as well as subjective symptoms, such as daytime somnolence and headaches. As stated previously, there is little data on the use of BPAP in the general obese population, but it is safe to extrapolate its safety in this group. Presumably, BPAP would be a good 212 A.B. Hilewitz et al.

choice for patients with ARF in the non-OHS obese population who are at baseline less severely ill, just as in the OHS population where patients may be more severely ill at baseline. The benefits of BPAP use would outweigh the risks. Avoiding endotracheal intubation in ARF is paramount, as mechanical ventilation in obese patients has a host of challenges and complications. Caution must always be used that patients are appropriate for this mode of ventilation and patients must be closely monitored in an ICU setting. In CRF, the use of BPAP in the non-OHS obese population is not as clear-cut, as many of these patients do not have the blood gas abnormalities that would necessitate the use of nighttime BPAP. Compliance with BPAP in both the acute and chronic setting cannot be under- stated. Poor compliance or patients not being able to tolerate the mask is a well- known contraindication to its use in the acute setting. In the CRF population, long-term studies have shown that patients who did not comply with the minimal amount of nighttime use had poor outcomes and did not reap the benefits that BPAP provided and were more similar to the group of patients who did not use BPAP at all. Education of patients and their family members is vital in this population so that they understand its importance and its benefits. Lastly, despite the positive short- and long-term effects of BPAP in the OHS population, weight loss cannot be ignored. Weight loss is the conclusive cure for OHS. This must be emphasized in this population. Patients must be referred to weight loss programs and/or should strongly be considered for bariatric surgical procedures. BPAP helps improve many of the abnormalities that are caused by hypoventilation and hypoxemia and will eventually help optimize them for any surgical procedures. However, the excess adipose tissue with all of its known negative effects cannot be resolved by BPAP alone.

22.3 Key Major Recommendations

• Obesity is a growing worldwide epidemic with significant morbidity and mortality, with a small proportion of patients developing OHS. • BPAP is a reasonable mode of NIPPV to attempt in obese and OHS patients with acute respiratory failure, especially hypercapnic failure, to prevent endotracheal intubation. • In chronic respiratory failure in OHS patients, the use of nocturnal BPAP has been shown to decrease mortality and hospitalizations and improve subjective symptoms and should be used in this population. • Compliance with BPAP must be emphasized in OHS patients ensuring that they reap the benefits that BPAP provides. • Weight loss is an imperative part of treatment in these patients. 22 Obesity and Bi-level Positive Airway Pressure 213

References

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Emmanuel Besnier, Jean-Pierre Frat, and Christophe Girault

Oxygen therapy is probably one of the most frequent treatments administrated in hospital setting. Its main goal is to correct or prevent the occurrence of hypoxemia, potentially provider of cellular or tissue hypoxia. A large panel of devices is currently available to administer conventional oxygen therapy (COT) using various interfaces and/or flows. However, some cases can catch out its use, and some major disadvantages can limit the expected benefits. Since few years, a new technique of oxygen therapy has been developed as an alternative to COT, the high-flow nasal cannula (HFNC) oxygen therapy. The HFNC consists of an air/oxygen blender connected via an active heated humidifier to specific nasal cannula and allows adjustment of the inspired fraction of oxygen (FIO2: 21–100%) independently from the gas mixture flow rate (up to 70 L/min in adults). In this chapter, we will discuss on the main limits of COT before focusing on the principles of HFNC and its potential interest in adult obese patients.

E. Besnier, M.D. Department of Anesthesia and Critical Care, Charles Nicolle University Hospital, Rouen University, 76031 Rouen Cedex, France J.-P. Frat, M.D. Department of Medical Intensive Care, Poitiers University Hospital, Poitiers University, 86021 Poitiers, France INSERM, CIC-1402, 5 ALIVE Team, Poitiers University, 86021 Poitiers, France C. Girault, M.D. (*) Department of Medical Intensive Care, Charles Nicolle University Hospital, Rouen University, 76031 Rouen Cedex, France UPRES EA 3830-IRIB, Institute for Biomedical Research and Innovation, Rouen University, 76031 Rouen Cedex, France Service de Réanimation Médicale, Hôpital Charles Nicolle, Centre Hospitalier Universitaire- Hôpitaux de Rouen, 1, rue de Germont, 76031 Rouen Cedex, France e-mail: [email protected]

© Springer International Publishing AG 2018 215 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_23 216 E. Besnier et al.

23.1 Conventional Oxygen Therapy

23.1.1 Rational for Using Oxygen Therapy

Normal composition of room air is approximately 21% of oxygen and 79% of diazote with an insignificant proportion of CO2. This proportion of oxygen is sufficient in current life situations but may be faulted in some pathological conditions, leading to a decrease in arterial concentration of oxygen, itself potentially provider of tissue hypoxia and possible subsequent complications on organ functions and prognosis. Indeed, Bowton et al. [1] identified that the occurrence of at least one episode of hypoxemia during hospitalization in medical patients was strongly associated with an increased risk of mortality within the 6 following months (RR 3.3 [1.41–8.2]) [1]. Oxygen therapy is consequently indicated in all situations with potential or existing hypoxemia in order to enhance arterial concentration of oxygen and therefore to optimize its transport to tissues. Current guidelines recommend a sufficient flow to obtain a transcutaneous oxygen arterial saturation (SpO2) comprised between 94 and 98% in acute respiratory failure (ARF) [2]. In order to achieve this objective, multiple interfaces are currently available allowing different flows of oxygen. Usually for COT, we distinguish low flows (<6 L/min) and high flows (> 6–15 L/min) of oxygen. The low-flow COT can be achieved through simple nasal prongs, whereas high-flow COT can be obtained thanks to non-rebreathing face masks with or without reservoir bags or Venturi device enhancing their efficacy.

23.1.2 Main Limits of Conventional Oxygen Therapy

23.1.2.1 Dilution of FiO2 The aim of oxygen administration is to raise the FiO2 in order to increase the pressure gradient between alveoli and pulmonary capillaries. Nevertheless, the actual

FiO2 delivered to alveoli depends on the patient’s breathing pattern, peak inspiratory flow rate (PIFR), delivery system, and mask characteristics 3[ ]. Moreover, patients with ARF often have high PIFR that substantially exceed the flow rates of COT delivery devices [3]. Consequently, the inadequacy between needs and oxygen delivery can induce a dilution of FiO2 with COT. For example, a patient presenting with ARF may generate a peak inspiratory flow of 40 L/min or more. Whether he is treated with 8 L/min of COT through facemask, this flow will not cover the PIFR, and, consequently, 32 L/min of the remaining gas mixture will be taken from the entrained room air, leading to a dilution of FiO2 down to approximately 35% [3]. The decrease in expected alveolar concentration of oxygen can be therefore highly deleterious in most severe patient, notably during ARF, with exaggerated work of breathing, increased oxygen consumption, and hypoxemia.

23.1.2.2 Humidification and Heating of Inspired Gases The important vascularization of upper airways, particularly in the nasopharyngeal space, increases the temperature and water content of inspired gases [4, 5]. Indeed, 23 High-Flow Nasal Cannula Therapy: Principles and Potential Use in Obese Patients 217

ambient air usually presents a relative humidity of 50%, corresponding to 10 mg H2O/L at 22 °C. Inspired gases are progressively warmed and water saturated along airways until the temperature and water gradients become null between the airways and the blood content. This equilibrium point is called the isothermic saturation boundary and usually obtained between the third and the fifth bronchial subdivision. Beneath this point, a 37 °C temperature with a water content of 44 mg H2O/L (absolute humidity) is observed. Conversely, expired gases cool down all along the airways and thus produce condensation. The evaporated water is incorporated into the mucosa allowing an optimal fluidity for the mucociliary function. In front of these features, inspiration of a dry and cold gas mixture can induce a desiccation of mucosa with elevated viscosity and potentially an alteration of ciliary movement, a perturbed clearance of bronchial secretions and then the formation of bronchial clots and atelectasis. Moreover, the inhalation of cold and/or dry gases can lead to a rise in airways resistance mediated through ther- mic or osmoreceptors located in the nasopharyngeal cavity [6]. Because of all these physiological points, humidification and heating of gas mixture appear to be beneficial for oxygen therapy. Most frequently, COT is administrated directly from oxygen reservoir through piping connected to a wall outlet. The gas mixture is dry and cold with a 15–20 °C temperature and thus can induce injuries in mucociliary function. Humidification of inspired gases is strongly recommended for flow above 4 L/min to limit the drying of mucosa [3]. A usual device for COT humidification is the bubble humidifier where oxygen flow bullheads and becomes saturated with non-heated water. In these conditions, unfortunately, humidification turns of poor quality with an absolute water content of 13 mg/L at 15 °C, corresponding to a relative humidity of only 29% at 37 °C. In addition, this low yield worsens with increasing flow. Conversely, heated humidifiers provide a flow of oxygen warmed in a specific chamber filled of water. Their use has been demonstrated to improve respiratory comfort in patients treated with COT of at least 5 L/min, reducing mouth and throat dryness [7]. Moreover, a recent animal study showed that humidification and heating at 40 °C in mechanically ventilated rabbits could reduce pulmonary inflammation and preserve ciliary integrity [8]. All these data strongly argue, therefore, for an optimal conditioning of inspired gases by heating and humidification during oxygen therapy.

23.2 High-Flow Nasal Cannula Oxygen Therapy

23.2.1 Technical Characteristics

HFNC has been developed as an alternative to COT, notably in specific setting such as ICU or neonatology. Thanks to a high-flow generator, HFNC can deliver an oxygen flow up to 70 L/min (and even more in some recent ICU ventilators) with a controlled FiO2 ranging from 21 to 100%. It is working in association with a separated humidification-heating chamber to provide an optimized conditioning of inspired gases. The gas mixture is conveyed through a single-branch system to a simple nasal cannula interface (Fig. 23.1). Because of these high-quality perfor- mances, several benefits can be expected, therefore, from the HFNC use. 218 E. Besnier et al.

HFNC : highflow nasal cannula

Fig. 23.1 HFNC device (Optiflow™, Fisher & Paykel©) 23 High-Flow Nasal Cannula Therapy: Principles and Potential Use in Obese Patients 219

23.2.2 Main Advantages of HFNC

23.2.2.1 Reduction in FiO2 Dilution As stated above, patients with ARF often generate a high PIFR, exceeding, most of the time, the capacity of COT delivery devices [3]. The high flow generated by HFNC is most often able to cover this increased PIFR, limiting room air entrainment and mixing of inspired gases, avoiding thus a reduction in delivered FiO2 [9, 10]. In addition, this better performance of HFNC can be maximal with closed- mouth breathing as compared to open-mouth breathing [9, 10].

23.2.2.2 PEEP and PIP Effects The use of a sufficient gas flow can generate a low to moderate level of positive end- expiratory pressure (PEEP) in the pharyngeal space. Indeed, PEEP recorded in pharyngeal space has been shown to be comprised between 3 and 7 cm H2O [10–12] and directly correlated to the magnitude of the flow applied with a 0.6 cmH2O increase every 10 L/min of flow 10[ ]. Best results were observed for nasal closed-mouth breathing as compared to open-mouth breathing which reduced by twofold the pharyngeal PEEP effect. These results were first demonstrated on healthy volunteers 11[ ], but also subsequently in patients after cardiac surgery [12], with chronic obstructive pulmonary disease (COPD) or fibrosis 13[ ], suggesting new perspectives in such pathologic conditions. Moreover, a close relationship has been demonstrated between oropharyngeal pressures induced by HFNC and the end-expiratory lung volume, suggesting that HFNC can generate a mild PEEP effect in distal airways, responsible for alveolar recruitment [14]. Nevertheless, the efficiency of HFNC to generate a PEEP effect depends not only on the mouth closure but also on the leakage around nasal cannula, requiring a special attention in the choice of cannula size, designed to fit with nostril diameters [15]. In addition, the PEEP effect may depends, in part, on the gender with higher levels for female, as well as on the height with a small decrease every 10 cm [11]. Moreover, a small positive inspiratory pressure (PIP) could be observed regardless of the mouth opening. This pressure has been shown to be low, less than

3 cm H2O despite a 50 L/min of gas flow but could be somewhat helpful in providing little inspiratory assistance [11, 12]. However, this PIP effect appears small, and inspiratory assistance provided is far from being compared with noninvasive ventilation (NIV).

23.2.2.3 Humidification and Heating of Gas Mixture The presence within the circuit of a device specifically dedicated to humidification and warming improves the conditioning of inspired gases, resulting in a 100% of water saturated mixture at a 37 °C temperature. Because dry gas induces an early alteration of mucus and bronchial epithelium functions, an optimized humidification could protect mucociliary function and fluidity, facilitate clearance of mucus and therefore local host defense, and limit the bronchial resistance to flow. Indeed, high-quality humidification at 37 °C has been demonstrated to improve mucosal clearance of patients with bronchiectasis [16] and to reduce inflammatory stress during mechanical ventilation [8]. Thus, its use through HFNC could be helpful 220 E. Besnier et al. during acute pulmonary inflammation, especially during pneumonia, as well as in patients with altered mucosal secretion such as COPD. Moreover, heated humidifiers have been demonstrated to reduce the intensity of throat and mouth dryness and improve global comfort in ICU patients [7, 17].

23.2.2.4 Dead Space Washout Due to the high-flow use of fresh gases, HFNC has been suggested to decrease the re-inhalation of exhaled CO2 by flushing the upper airways gases and, thus, a part of the airway dead space [18, 19]. Consequently, no change or even an improvement in

PaCO2 and/or pH may be expected with the use of HFNC. In an experimental model of acute lung injury, HFNC reduced PaCO2 in a flow dependent manner with a concomitant rise in PaO2 [20]. In a recent report, a COPD patient intolerant to noninvasive ventilation (NIV) with acute hypercapnic exacerbation exhibited a decrease in respiratory symptoms and PaCO2 with HFNC therapy [21]. Also, a retrospective analysis of 46 patients with hypercapnic respiratory failure observed a small (−6 mmHg) but significant reduction in PaCO2 after 24 h of HFNC therapy [22]. Another study, including “do-not intubate” patients with ARF and a moderate respiratory acidosis

(pH > 7.28 and PaCO2 < 65 mmHg), reported that the use of HFNC did not result in a rise of PaCO2 over time and even a trend toward reduction [23]. In an open-labeled prospective trial, HFNC use for hypoxemia after cardiac surgery was associated with a better oxygenation and a mild reduction in PaCO2 levels (−3 mmHg) during the first 24 h [24]. All these data represent strong arguments for a CO2 washout effect and suggest a potential benefit of HFNC in cases of hypercapnia, such as in exacerbation of COPD or obese patient with restrictive or overlap syndrome.

23.2.3 Indications of HFNC

23.2.3.1 Hypoxemic Acute Respiratory Failure HFNC has now been extensively used in hypoxemic ARF patients because of all its beneficial features exposed previously. First clinical observational studies dealt mainly with the efficacy and feasibility of HFNC in hypoxemic ARF. HFNC has been shown to rapidly improve comfort, tolerance, respiratory rate, symptoms of distress, and oxygenation in ICU [25] and emergency department [26] patients. HFNC could also be used sequentially with NIV in ARF to avoid alveolar derecruitment and impairment in oxygenation during spontaneous breathing period, with a better tolerance than NIV [27]. In a multicenter randomized trial, Frat et al. [28] have compared facemask COT, HFNC alone, and NIV with HFNC in 310 medical patients with hypoxemic ARF. HFNC alone was found a better strategy to decrease intubation rate and mortality in more hypoxemic patients (PaO2/FiO2 ratio ≤ 200 mmHg). Consequently, NIV was considered as potentially deleterious by delivering a higher expired tidal volume (>9 mL/kg) than expected, increasing thus the risk of intubation and mortality. A recent post hoc analysis of immunocompromised patients included in the previous trial has confirmed these results [29]. These findings were also suggested in a randomized controlled trial involving only 23 High-Flow Nasal Cannula Therapy: Principles and Potential Use in Obese Patients 221 immunocompromised patients and comparing NIV with oxygen support including HFNC [30]. Finally, based on the positive results of HFNC in hypoxemic ARF, ICU clinician should certainly be cautious with the use of NIV in this indication.

23.2.3.2 Postoperative Period Major surgery exposes to numerous postoperative complications including pain, diaphragmatic dysfunction, atelectasis, and impaired oxygenation requiring to be prevented at the best [31]. Thus, the prophylactic and curative use of continuous positive airway pressure (CPAP) or NIV has been demonstrated to improve oxygenation and outcomes after major thoracic, abdominal, or cardiac surgeries [32–35]. Like CPAP or NIV, HFNC could be a simpler technique in preventing or treating postoperative ARF. Parke et al. [36] randomized 60 patients with moderate hypoxemic ARF after cardiac surgery to receive either HFNC or COT with facemask. HFNC was associated with less need for NIV and fewer desaturations. In another multicenter randomized controlled trial, Stephan et al. [37] did not show any difference between NIV and HFNC applied to 810 patients presenting ARF (or at risk of ARF) after cardiac surgery, suggesting that HFNC may be a valuable alternative to NIV for postoperative ARF. Skin lesions were also reduced in HFNC group. Few data concerning the prophylactic use of HFNC are available. Parke et al. have evaluated its use in 340 patients after cardiac surgery in comparison with conventional therapy. Despite a lack of difference regarding oxygenation, HFNC reduced the escalation in respiratory support with less requirements for NIV or reintubation and a small reduction in PaCO2 [38]. Thus, as demonstrated for standard ARF, strong data support the use of HFNC during postoperative ARF. Its benefit as a prophylactic strategy is suggested, but further trials are required. Nevertheless, the use of NIV in the postoperative setting cannot be ruled out, notably in patients at risk of atelectasis. The association of both therapies could be complementary as the use of HFNC between NIV periods by improving oxygenation could also limit alveolar de-recruitment and enhance NIV tolerance by reducing its duration.

23.2.3.3 Post-extubation Support Post-extubation period after prolonged invasive mechanical ventilation is at high risk of failure in ICU patients. Reasons for this unsuccessful weaning are numerous: airway obstruction, excess of respiratory secretions, insufficient cough, pneumonia, heart failure, or comatose status. NIV has been proposed with success for patients at high risk of reintubation [39, 40]. Some recent studies explored the use of HFNC in such situations. Maggiore et al. [41] applied HNFC or Venturi mask to 105 patients with a 240 mmHg PaO2/FiO2 ratio just before extubation. HFNC was associated with a better oxygenation and comfort, a reduction in mask displacements and therefore in desaturation events, and a fewer cases of reintubation. Similarly, Hernandez et al. [42] showed that HFNC after extubation in ICU patients at low risk of extubation failure strongly decreases the reintubation rate within 72 h. Nevertheless, no study has compared yet HFNC and NIV during post-extubation period, and further clinical trials should be designed to define the respective indication of each device. 222 E. Besnier et al.

23.2.3.4 Preoxygenation Before Endotracheal Intubation Endotracheal intubation is a potential high-risk situation of desaturation, hypoxemia, and even mortality, particularly in ICU patients. NIV has been proposed as an alternative technique to non-rebreathing facemask (NRFM) to prevent the risk of severe hypoxemia during ETI. As compared to NRFM, NIV has been shown to optimize preoxygenation and reduce per-procedure desaturation in severe hypoxemic ARF patients [43], as well as in obese patients [44]. However, to perform laryngoscopy, NIV needs to be interrupted leading to the absence of oxygenation during the apneic phase of ETI, and thus, to the potential occurrence of severe desaturation. Two recent studies explored the use of HFNC as a preoxygenation technique with contradictory results. The first one from Miguel-Montanes et al. [45] compared a before period (NRFM) with an after period (HFNC) with a reduction in severe hypoxemia per-procedure in a non-selected ICU population. The second one was a randomized clinical trial and did not identify any difference between the two groups concerning severe desaturation [46]. Nevertheless, the absence of difference in this later could be related to a possible technical bias like the absence of mandibu- lar subluxation during the preoxygenation procedure. More recently, an observational study has compared the use of HFNC versus NIV for preoxygenation in non-selected ICU patients [47]. No difference was observed regarding severe desaturation or complications during the procedure, suggesting that HFNC could be a simpler alternative than NIV for preoxygenation. Currently, a French multicenter randomized clinical trial is ongoing to explore the respective role of these two strategies in this indication.

23.3 HFNC Therapy in Obese Patients

Obese patients exhibit many physiological modifications related to the excess of adipose tissue. Some of them may impact the respiratory function and deserve com- ments [48]. First, patients have an increased overall oxygen consumption leading to a rise in minute ventilation and, therefore, in the work of breathing, with enhanced production of CO2. Second, a restrictive syndrome is observed with a reduction in pulmonary volumes, inversely correlated with the body mass index (BMI). Indeed, a diminution in functional residual capacity, end-expiratory lung volume (EELV), expiratory reserve volume, and vital capacity is often observed and can be responsible for atelectasis in obesity hypoventilation syndrome. The reduction in lung volumes can even lead to a rise in lower airway resistances with an increased risk of asthma and/or overlap syndrome. Moreover, adipose infiltration in pharyngeal structures leads to a rise in upper airway resistances and, at worse, to an obstructive sleep apnea syndrome, which can negatively affect postoperative outcomes. All these physiological modifications can worsen prognosis and outcomes in obese patients admitted to the ICU or during the perioperative period. Due to these obesity- related comorbidities, the use of CPAP or NIV has been found associated with improved oxygenation and lung volumes in morbid obese patients after bariatric surgery [49, 50]. 23 High-Flow Nasal Cannula Therapy: Principles and Potential Use in Obese Patients 223

Fig. 23.2 High flow nasal cannula oxygen therapy via an ICU ventilator in an obese patient

Table 23.1 Potential physiological advantages of high-flow nasal cannula oxygen therapy in obese patients Dead space Oxygenation PEEP effect PIP effect Heated humidification washout Reduced room Prevention of Mild Improved respiratory Limitation of air oropharyngeal inspiratory comfort respiratory entrainment collapse support Preserved mucociliary acidosis and a Controlled Alveolar Decrease in function PaCO2 FiO2 recruitment with the work of Limitation of dry increase Improved increased EELV breathing gas-induced oxygenation Prevention of bronchoconstrictiona atelectasis aTheorical effects with no clinical demonstration as yet PEEP positive end-expiratory pressure, PIP positive inspiratory pressure, COPD chronic obstructive pulmonary disease, EELV end-expiratory lung volume

As discussed above, HFNC exhibits physiological effects which could be of benefit in obese patients (Fig. 23.2): the high flow of oxygen can cover the high minute ventilation and the enhanced oxygen consumption; the moderate PEEP effect may prevent the occurrence of atelectasis and collapse of upper airways, especially in patients with underlying obstructive sleep apnea syndrome; the mild PIP may provide ventilator support; the dead space washout may reduce PaCO2; and the humidification of inspired gases could prevent reduction in inferior airways caliber as compared to COT. These potential benefits of HFNC in obese patients are resumed in Table 23.1. Unfortunately, although numerous studies have included some obese patients, only few studies have specifically explored the reality of these physiological effects as well as the clinical use of HFNC in this particular population. A crossover study has evaluated the effects of COT and HFNC on pulmonary function after cardiac surgery in obese patients [14]. HFNC increased the EELV and tidal volume in comparison with COT. Benefits were particularly marked for higher BMI, with a 13.3% 224 E. Besnier et al. mean increase of EELV for BMI of 25 kg/m2 and a 24.4% mean increase for BMI of 40 kg/m2 [14]. The same team recently compared HFNC with COT as a prophylactic strategy after cardiac surgery. One hundred and fifty-five obese patients were randomized but, surprisingly, no difference in the atelectasis score, PaO2/FiO2 ratio or respiratory rate was observed between both strategies [51]. Nevertheless, some study limitations have to be underlined: the small number of patients included as regard to the frequency of respiratory complications in this population, the duration of HFNC use limited to 8 h post-extubation, and the small proportion of morbid obese patients (mean BMI of 35 and 36 kg/m2). Moreover, the choice of HFNC as compared to NIV as a prophylactic therapy could be questionable. Indeed, NIV has been demonstrated to be superior to CPAP in preventing atelectasis after major surgery [52]. As HFNC represents, from a physiological point of view, a respiratory support closer to CPAP than NIV, its use can logically be expected as inferior to NIV to prevent ARF in obese patients. As yet, no study has specifically explored the use of HFNC in obese patients with hypoxemic or hypercapnic ARF and in the post- extubation period. Further studies are warranted therefore in these indications. Meanwhile, the use of HFNC as an alternative to NIV in case of patient intolerance or refusal could be considered in these settings. Moreover, alternate HFNC periods with NIV27 could be considered as a promising strategy in this specific population. Another field of interest for HFNC could be the preoxygenation for intubation in obese patients. Indeed, airway management of these patients is frequently difficult with a higher risk of complications and hypoxemia [53]. A recent randomized study has evaluated preoxygenation with COT, CPAP, or HFNC in 33 morbidly obese patients [54]. A higher PaO2 was reported with HFNC, but neither the apnea duration without desaturation nor the occurrence of atelectasis was evaluated. In addition, the role of HFNC as a potential alternative to NIV preoxygenation in obese patients remains to be demonstrated [44]. In conclusion, HFNC oxygen therapy is a recent technique with potential benefits on morbidity and mortality in ICU patients. Its use in obese patients remains poorly investigated but could theoretically and potentially improve physiological parameters and patient outcome. Before implementing HFNC in the routine management of obese patients, further studies are obviously needed. Clinicians should also keep in mind that NIV remains an efficient respiratory support in these patients in numerous indications. In addition, like NIV, HFNC should never delay the intubation time whatever its indication since its unreasonable use can dramatically worsen the patient prognosis [55].

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Shaden O. Qasrawi and Ahmed S. BaHammam

24.1 Introduction

Noninvasive ventilation (NIV) refers to providing ventilatory support using a mask or a similar device without the use of invasive artificial airway (endotracheal tube or tracheostomy tube). The use of NIV has markedly increased in the recent years and is currently considered to be essential in the management of acute respiratory failure and in particular acute hypercapnic respiratory failure (AHRF) [1, 2]. AHRF results from inadequate alveolar ventilation, which is needed to maintain normal arterial oxygen and carbon dioxide levels [3]. Conventionally, pH <7.35 and arterial partial pressure of carbon dioxide (PaCO2) >6.5 kPa (>50 mmHg) define acute respiratory acidemia and AHRF [3]. In general, if AHRF persists despite initial medical therapy, those values have been used as a threshold for considering commencing NIV [3]. AHRF could complicate many respiratory disorders including chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, bronchiectasis, and neuromuscular and chest wall diseases, including morbid obesity and kyphoscoliosis (see Table 24.1) [3]. This section aims to discuss AHRF in obese patients. However, as obese patients may develop AHRF secondary to several respiratory disorders, we will cover briefly the utility of NIV in different respiratory disorders that cause AHRF and then will focus on AHRF in patients with obesity hypoventilation syndrome (OHS).

S.O. Qasrawi, M.B.B.S., M.R.C.P. • A.S. BaHammam, M.D., F.A.C.P. (*) University Sleep Disorders Center, College of Medicine, King Saud University, Box 225503, Riyadh 11324, Saudi Arabia e-mail: [email protected]; [email protected]

© Springer International Publishing AG 2018 229 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_24 230 S.O. Qasrawi and A.S. BaHammam

Table 24.1 Causes of hypercapnic respiratory failure • Chronic obstructive pulmonary disease (COPD) • Acute severe asthma • Bronchiectasis • Cystic fibrosis • Obstructive sleep apnea • Kyphoscoliosis • Morbid obesity • Opioid and sedative drugs • Neuromuscular diseases (e.g., cervical cord lesions, Guillain–Barré syndrome, myasthenia gravis, muscular dystrophy)

24.2 Indications and Contraindications to NIV in AHRF

The indications for NIV are variable based on the underlying cause, its severity, and the associated comorbidities. Clinical manifestations that support the early use of NIV include moderate to severe dyspnea, tachypnea (>24 breaths per min in obstructive lung diseases, >30 per min in restrictive lung diseases), and signs suggestive of increased work of breathing including accessory muscle use and thoracoabdominal paradox [4]. Other indications are usually based on investigations showing impaired gas exchange reflecting acute or acute on chronic ventilatory failure with raised

PaCO2 and acidemia [5, 6]. Table 24.2 summarizes the indications and contraindication to NIV. Application of NIV could be difficult in patients with severe facial deformity, fixed upper airway obstruction, or facial burns [4]. There are a number of other potential contraindications; however, most of those have been employed as exclusion criteria in clinical trials rather than being proven to be associated with worse outcome [3, 7].

24.3 Chronic Obstructive Lung Disease (COPD)

Acute exacerbations of COPD account for a significant number of annual admissions worldwide [8]. Of these, many present with hypercapnia [9], which increases the risk of mortality [10, 11]. Developing AHRF in COPD is usually multifactorial with many underlying causes such as infection, mucosal edema, bronchospasm, sputum retention, sedation, pneumothorax, pulmonary embolism, left ventricular failure, and excessive oxygen therapy. There is now strong evidence showing that uncontrolled oxygen therapy increases acidemia and subsequently mortality in acute exacerbations of COPD (AECOPD) [10]. This oxygen-induced hypercapnia applies with variable degree, to other causes of AHRF [3]. Hence, in managing all patients at a risk for AHRF, controlled oxygen therapy with oxygen saturation target of 88–92% is recommended initially [3]. 24 NIV in Type 2 (Hypercapnic) Acute Respiratory Failure 231

Table 24.2 Indications and Indications contraindications for NIV Clinical manifestations • Moderate to severe dyspnea • Tachypnea (>24 bpm in obstructive, >30 bpm in restrictive) • Signs of increased work of breathing (e.g., accessory muscle use and abdominal paradox) Gas exchange • Acute or acute on chronic ventilatory failure

(PaCO2 > 6.5, kPa, pH < 7.35) • Hypoxemia Contraindicationsa • Respiratory or cardiac arrest • Inability to fit the mask (e.g., severe facial deformity or facial burns) • Fixed upper airway obstruction • Hypotensive shock • Uncontrolled upper gastrointestinal bleeding • Agitation/confusion • Inability to protect the upper airway • Swallowing impairment • Excessive secretions not managed by secretion clearance techniques • Multiple (i.e., two or more) organ failure • Recent upper airway or upper gastrointestinal surgery aSome are relative contraindications

The use of NIV in AECOPD has increased markedly, and its use is currently viewed as a part of the standard therapy for patients who have persistent respiratory acidemia despite receiving standard medical therapy [12, 13]. The use of NIV in AECOPD has reduced the need for IMV, thereby reducing complications and cutting hospital costs associated with IMV, in addition to improving survival [13]. Hence, NIV is currently considered as a major progress in the management of AECOPD [13]. Severe acidemia alone is not a contraindication for NIV trial in an appropriately equipped setting where shifting the patient to IMV can be rapidly achieved. Nevertheless, the use of NIV should not delay commencing IMV when needed [3]. The treating team should keep in mind other possible causes of AHRF that may coexist with COPD such as obstructive sleep apnea (OSA) and OHS [3, 14]. Obese patients with COPD may have coexisting sleep-disordered breathing, which is called overlap syndrome. For patients with overlap syndrome, NIV should aim to correct both hypoventilation and upper airway obstruction. An improvement in physiological parameters such as pH and respiratory rate within 1–2 h of initiating treatment is usually a predictor of success of NIV, whereas 232 S.O. Qasrawi and A.S. BaHammam

Table 24.3 Predictors for Predictors for NIV success/failure in AHRF in COPD NIV success/failure in Predictors for treatment success patients with COPD pH 7.25–7.35, PaCO > 6.5 kPa exacerbation and AHRF 2 GCS > 14 Respiratory rate 24–30/min Response to NIV within 1–2 h APACHE II < 29 Predictors for treatment failure pH <7.25 GCS ≤ 11 Respiratory rate > 30/min Additional pneumonia Severe mask leakage Patient-ventilator asynchrony Agitation or intolerance Inability to clear secretions APACHE II >29 worsening of those parameters is predictive of failure of NIV with increased risk for intubation or mortality [3]. Table 24.3 shows the predictors of NIV success in patients with COPD exacerbation and AHRF [3, 15–20].

Monitoring of PaCO2 serves as a useful guide in planning the withdrawal of NIV, and transcutaneous PaCO2 measurement serves as a convenient alternative to arterial or capillary sampling [3].

24.4 Acute Exacerbation of Asthma

Patients with acute attack of asthma present usually with hypoxemic respiratory failure. However, in advanced cases, patients may present with AHRF. Nevertheless, the use of NIV in acute exacerbation of asthma remains a controversial topic, and reports of NIV use in patients with severe acute asthma are limited. A few RCTs have explored the utility of NIV in hypoxemic respiratory failure in patients with acute exacerbation of asthma [21]. However, the existing evidence is equivocal and limited by a small number of published trials with methodological problems [21]. Moreover, at present, there is no strong evidence to support NIV use in asth- matics with AHRF. The two studies reporting clear beneficial effect of NIV use in AHRF asthma were retrospective studies with methodological limitations [22, 23]. One of them included population who seem more likely a COPD than asth- matic population [24]. At present, there is limited evidence to recommend the use of NIV in patients with asthma exacerbation and respiratory failure. Larger, prospective RCTs of properly selected patients and a good methodological design are needed. 24 NIV in Type 2 (Hypercapnic) Acute Respiratory Failure 233

24.5 Non-CF Bronchiectasis

Patients who suffer from non-CF bronchiectasis can present with recurrent episodes of hypercapnic respiratory failure [3]. Despite little data, there is no evidence that patients with non-CF bronchiectasis presenting with AHRF do worse on NIV compared to those commenced on IMV [25]. Therefore, NIV is indicated in the presence of respiratory acidemia using the same criteria applicable in AECOPD [3]. It is not unusual to find sleep-disordered breathing in obese patients with bronchiectasis [26]. Such patients should be managed with NIV to improve ventilation and eliminate the obstructive events during sleep. Although managing and clearing excessive sputum while on NIV can be challenging, NIV could actually assist by improving dyspnea and hence help patients to participate more effectively in physiotherapy [27].

24.6 Extrapulmonary Restrictive Lung Diseases

Severe chest wall deformity and neuromuscular diseases (NMD) can markedly impair the respiratory muscles function and hence result in a restrictive lung function pattern characterized by reduced vital capacity (VC), total lung capacity, and functional residual capacity, which in turn can lead to AHRF [28]. Such patients will usually present with chronic hypercapnia and acute respiratory failure that is commonly precipitated by infection [28]. The risk of hypercapnic respiratory failure increases when the VC falls below 1–1.5 L [29]. Obese patients with neuromuscular diseases are at an increased risk for sleep-disordered breathing, and those with bulbar dysfunction are at a higher risk for OSA [30].There are no available RCTs comparing NIV with IMV in the management of AHRF complicating extrapulmonary restrictive lung diseases, and the current recommendations are extended from the evidence available for AECOPD management [3, 28]. Generally, NIV should be tried in patients presenting with hypercapnia without waiting for the development of acidemia, but if NIV fails, intubation should not be delayed unless IMV is not desired for whatever valid reason. In patients with NMD with bulbar dysfunction and communication difficulties, NIV is usually difficult. Moreover, patients with bulbar dysfunction have an increased risk of aspiration. In general, patients with NMD and chest wall deformities need an overnight sleep study once stable and might require nocturnal NIV at home [3].

24.7 Obesity Hypoventilation Syndrome (OHS)

Hypercapnia in hospitalized obese patients is associated with increased morbidity and mortality [31]. OHS is generally underdiagnosed and undertreated [32]. It is also not uncommon for chronic hypercapnia to be discovered when obese patients 234 S.O. Qasrawi and A.S. BaHammam who are otherwise not known to have OHS are assessed for emergency or elective operations. However, patients with OHS commonly present with acute on top of chronic hypercapnic respiratory failure [33]. A recent study has shown that approximately 40% of patients with OHS present for the first time with AHRF 34[ ]. Additionally, OHS patients admitted with AHRF have a high rate of in-hospital mortality (18%) [35]. Therefore, it is important to keep in mind the possibility of OHS as a cause of AHRF in the morbidly obese patients. OHS is the second most frequent indication (after COPD) for NIV treatment among hospitalized patients with AHRF [36, 37]. It is recommended to initiate NIV in all patients suspected of having AHRF secondary to OHS, before performing sleep study, since early initiation of NIV may obviate the need for IMV [2]. Nevertheless, there is no enough evidence to provide a guidance for the use of NIV in the treatment of both chronic hypercapnia and AHRF in obese patients [2]. The majority of patients with OHS have coexisting severe OSA [38]. In general, NIV will be needed as an emergency treatment in all patients with OHS presenting with AHRF [2]. In addition, NIV can be considered in admitted patients with raised

PaCO2 and excessive daytime sleepiness, sleep-disordered breathing, and/or right heart failure even when acidemia is absent [39]. Pressure- and volume-limited ventilation have been reported in patients with AHRF; however, we recommend initiating treatment with bi-level PAP (BPAP) ventilation as there is no evidence indicating that other ventilatory modes are superior to BPAP [2]. During NIV therapy, observation and monitoring of the level of consciousness, vital signs, respiratory pattern, oxygen saturation, and arterial blood gases are crucial [2, 40]. As most patients with OHS have coexisting OSA, EPAP should be increased gradually until snoring, witnessed apneas, and dips in oxygen saturation are eliminated. IPAP should be gradually increased to ensure optimal ventilation until an acceptable level of steady-state oxygen saturation (≥ 90%) is attained [33]. Figure 24.1 shows a proposed algorithm for the NIV management of OHS patients with AHRF [2]. In patients who do not respond to BPAP mode, volume-targeted pressure support (VtPS) can be attempted [41]. VtPS is a hybrid mode that combines the advantages of pressure-limited and volume-limited modes of ventilation into one ventilation mode. Studies concerning the use of volume-targeted pressure support mode to treat OHS patients did not show clinical benefits over those achieved with a fixed bi-level mode [41]. Moreover, VtPS mode has not directly been assessed in OHS during AHRF. Limited studies have assessed the predictors of NIV failure in OHS patients with acute respiratory failure. Lemyze et al. demonstrated in a prospective study (n = 76) that severe pneumonia and multiple organ failure predict early NIV failure in morbidly obese patients with acute respiratory failure [42]. The same study reported that more than half of the patients experienced a delayed response to NIV, with persistence of hypercapnic acidemia during the first 6 h 42[ ]. Once the patient is stable, it is recommended to perform a sleep study for patients with OHS to choose the right ventilatory mode and pressure needed to eliminate the obstructive respiratory events and hypoventilation. All patients with OHS will 24 NIV in Type 2 (Hypercapnic) Acute Respiratory Failure 235

Obese patient with AHRF

No contra-indications to NIV

Start Bi-level PAP

EPAP IPAP o Start with 4-6 cmH2O o Start with 8-10 cmH2O o Build-up pressure up by o Build-up pressure up by 1-2 cm H2O to eliminate: 1-2 cm H2O until: Snoring Steady SpO2>88% Witnessed apneas To achieve good alveolar Paradoxical breathing ventilation IPAP is kept Intermittent hypoxemia 8-10 cm H2O above EPAP

Monitor the following Vital signs, level of consciousness, respiratory pattern, SpO2, minute ventilation, blood gases (after 1 hr)

Add oxygen, if the patient continues to desaturate (<88%) despite delivering high positive airway pressure

Consider intubation if the NIV trail fails

Fig. 24.1 A proposed algorithm for the NIV management of OHS patients with AHRF eventually need NIV use at home. Studies that followed OHS patients with AHRF after discharge indicated higher mortality in patients who refused PAP therapy [33, 40]. Several studies have reported that good compliance with domiciliary NIV results in improvement in gas exchange, daytime sleepiness, quality of life, and number of hospitalizations in patients with OHS [43].

Conclusion Obesity represents a global epidemic, and obese patients are at a higher risk for developing AHRF. Practitioners should recognize that morbidly obese patients with sleep hypoventilation, daytime hypercapnia, and pulmonary hypertension have an increased risk of AHRF. NIV is currently an accepted therapeutic 236 S.O. Qasrawi and A.S. BaHammam

strategy in several disorders that can be complicated by respiratory failure and in particular AHRF. The use of NIV in obese patients with AHRF helps to prevent further deterioration and avert the need for IMV. When NIV is implemented, clear treatment goals should be defined, and a plan of care should document escalation measures in the event of failure of NIV. Although NIV is considered now as a great progress in managing respiratory failure, it should not delay intubation and IMV in those patients who fail to respond to NIV or in whom NIV is not indicated.

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Ali A. El Solh

25.1 Background

With the rise in prevalence of obesity worldwide, clinical providers are encounter- ing an increasing number of critically ill obese patients requiring intensive care. The management of these patients poses significant challenges in the settings of respiratory failure or artificial ventilation. Observational studies of this population have uniformly described prolonged periods of ventilatory support and length of stay in intensive care units [1–3]. Mechanical ventilation requires specific ventilatory settings due to the mechanical and physiologic alterations dictated by body habitus. Conventional respiratory function tests have unvaryingly showed a reduction in functional residual capacity due to the effect of abdominal contents on the diaphragm [4]. The buildup of adipose tissue in the anterior abdominal wall and in the intra-abdominal visceral tissue hinders diaphragmatic movement, diminishes basal lung expansion during inspiration, and with the closure of peripheral lung units causes ventilation–perfusion abnormalities. These alterations are further aggravated in the reclined or Trendelenburg position. Respiratory muscle strength is compromised as the load of the extra adipose tissue poses undue burden on muscle activity [5]. The combined effect of these changes is a tendency for hypoxemia at rest and rapid desaturation under condition of apnea. The care of these patients is further complicated by the observation that up to 30% of patients with morbid obesity have obesity hypoventilation syndrome manifested by CO2 retention, pulmonary

A.A. El Solh, M.D., M.P.H. The Veterans Affairs Western New York Healthcare System, 3495 Bailey Avenue, Medical Research, Bldg. 20 (151) VISN02, Buffalo, NY 14215-1199, USA Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health Professions, Buffalo, NY, USA e-mail: [email protected]

© Springer International Publishing AG 2018 239 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_25 240 A.A. El Solh hypertension, and biventricular failure [6]. As a result, morbid obesity is associated with extended weaning periods and an additional threat in the form of ventilator- associated events. Determining readiness for liberation from mechanical ventilation is of considerable clinical relevance for obese patients. Commonly used predictors for weaning and successful liberation from mechanical ventilation have not shown to be reliable parameters. This may be due to differences in the pathophysiology of weaning and extubation readiness. While weaning failure underlines the imbalance between respiratory capacity and load [7], extubation failure is impacted by extrinsic factors. Hence, decisions regarding timing of extubation are based on thorough assessment of respiratory and non-respiratory parameters. Prior to extubation, the usual criteria should be met, including hemodynamic stability, satisfactory oxygen-carrying capacity, normothermia, adequate respiratory rate and tidal volume, good oxygen saturation, and a conscious, alert patient who is able to clear secretions, protect the airway, and maintain airway patency. While there is no definitive evidence that the frequency of reintubation in severely obese patients mechanical ventilation for >48 h is different from non-obese patients, the adverse impact on outcome from failure to be liberated successfully from mechanical ventilation necessitates that accurate prediction of extubation is potentially important. The outcome for patients who tolerate extubation is generally favorable, with hospital mortality rates below 10–15% [8, 9]. In contrast, the mortality rate associated with extubation failure ranges from 2.5 to 10 times that are experienced by successfully extubated patients [10, 11]. The worse prognosis has been attributed to complications related to the act of reintubation itself, to the rise of unfavorable events in the interval between extubation and reintubation, and to the fact that reintubation is a surrogate for a poor prognosis. With these facts in mind, the process used to make extubation decisions in obese critically ill needs to be reliable, especially regarding the identification of patients at high risk for extubation failure.

25.2 Causes of Post-extubation Failure

The causes for post-extubation failure in obese patients are multifactorial in nature (Table 25.1). The vast majority of patients do so because of an imbalance between respiratory muscle capacity and the load placed on the respiratory system [12, 13]. High airway resistance (bronchospasm and excessive airway secretions) [14] and low respiratory system compliance (stiff chest wall, stiff lungs, consolidated alveoli) [15] contribute to the increased work of breathing and lead to unsuccessful liberation from mechanical ventilation. This pathophysiologic mechanism is amplified by the coexistence of obstructive sleep apnea (OSA) in patients with severe obesity. Patients with OSA have relatively narrow airways and require disproportionate activation of pharyngeal muscles during wakefulness to maintain patency [16]. Activation is driven by a combination of influences including the wakeful state itself, ventilatory drive, and reflex activation initiated by upper airway mechanoreceptors that respond to intraluminal negative pressure developed during inspiration. If the patient is obtunded from residual sedatives or anxiolytics or lingering systemic disease, there is reduced drive to the upper airway muscles from all these sources. 25 Prevention of Post-extubation Failure in Critically Ill Obese Patient 241

Table 25.1 Risk factors for extubation failure in obese patients Risk factor Pre-extubation test Increased secretions • A sawtooth pattern on the flow volume curve • Frequency of suctioning (every 2 h or less) Poor cough strength • Placing a white card at 1–2 cm from the end of endotracheal tube. Any wetness on the card is classified as a positive test • A peak expiratory flow (PEF) rate during a cough of <35 L/min Upper airway • Cuff-leak test edema • Visual assessment via indirect laryngoscopy Vocal cord paralysis • Cuff-leak test Respiratory failure • Noninvasive positive pressure ventilation Cardiac failure • Diuresis and/or vasodilator therapy Neurologic • Correction of metabolic derangements impairment • Noise control • Restoration of sleep cycle

25.2.1 Secretions and Cough

In the absence of other causes of airway obstruction, upper airway patency relies on the ability to maintain the airway clear of secretions, owing to a balance between cough strength and amount and thickness of respiratory secretions irrespective of body weight. Cough strength has been found to be a more reliable predictor of extubation outcome than the amount of endotracheal secretions. One study showed that patients who were unable to cough on command or who had a peak expiratory flow (PEF) rate during a cough of <35 L/min had a relative risk of 6.9 for extubation failure, while another showed that if PEF during a cough was ≤60 L/min, the relative risk for extubation failure was 4.8 [17, 18]. Patients with PEF ≤60 L/min are five times more likely to require reintubation [19]. Another simpler method of assessing cough is holding a white index card held 1–2 cm from the end of the endotracheal tube. Inability to moisten the card after 3–4 cough attempts is associated with three times more likelihood of failing extubation [20]. Similarly, patients with moderate or abundant secretions are more than eight times as likely to have unsuccessful extubation as those with no or small amounts of secretions. Specifically, patients requiring endotracheal suctioning every 2 h or less are 16 times as likely to experience unsuccessful extubation as patients suctioned less frequently [20].

25.2.2 Post-extubation Upper Airway Obstruction

Obese patients are particularly at higher risk for post-extubation stridor [2] secondary to anatomic features such as short neck, large tongue, excessive palatal and pharyngeal soft tissue, and restricted ability to open the mouth that predispose these patients to mechanical trauma of the larynx during intubation [21, 22]. Some of risk factors associated with early onset laryngeal edema include very large tube size, excessive endotracheal tube mobility, aggressive suctioning, or high cuff pressure. Those requiring extended mechanical ventilation exhibit similar lesions 242 A.A. El Solh

Table 25.2. Measurement of the cuff leak volume in mechanically ventilated patients • Before performing the cuff leak test, first suction endotracheal and oral secretions and set the ventilator in the assist control mode • With the cuff inflated, record displayed inspiratory and expiratory tidal volumes to see whether these are similar. Record cuff pressure • Deflate the cuff • Directly record the expiratory tidal volume over the next six breathing cycles as the expiratory tidal volume will reach a plateau value after a few cycles • Average the three lowest values • The difference between the inspiratory tidal volume (measured before the cuff was deflated) and the averaged expiratory tidal volume is the cuff leak volume with mucosal ulcerations developing 36 h post insertion of endotracheal tube. However, laryngeal edema can develop as early as 6 h post intubation [23]. When upper airway obstruction occurs, it is typically manifested within 5–30 min after extubation [24]. The gold standard for determination of laryngeal edema is direct laryngoscopy of the airway prior to extubation. Unfortunately, this is not possible prior to extubation due to the endotracheal tube which is well below this area. Due to this fact, the cuff leak test has been advocated as a test for the determination of possible laryngeal edema (Table 25.2). It’s a simple test that involves placing the obese patient on a set tidal volume by setting the mechanical ventilator on assist control mode. After the endotracheal tube has been thoroughly suctioned, the cuff is deflated. The expiratory volumes are measured over the course of several breaths after the patient has ceased coughing. The expiratory volumes are subtracted from the inspiratory volumes, and this is defined as “the cuff leak volume.” Miller and Cole were the first to attempt to correlate the volume of leak with the possibility of post-extubation stridor [25]. A cuff leak volume <110 mL predicted a significant risk of post-extubation failure. Other studies have used similar or higher threshold values of cuff leak volume. Using a receiver operator characteristic curve analysis to find out the best threshold, Jaber and colleagues [26] considered a true positive test as a leak <130 mL or <12% of inspired VT together with post-extubation stridor, while De Bast and coworkers [23] used a threshold of 15.5%. The absence of a cuff leak alone is an imperfect predictor of post-extubation stridor. The cuff leak predicts post-extubation stridor with a sensitivity of 15–85% and a specificity of 72–99% [25–27]. Although these studies did not consistently specify the BMI of patients who participated in the trials, the noninvasive nature of the test may still prove of utility in this population pending validation of the data in obese patients. With the widespread use of ultrasonographic imaging in the management of critically ill patients, noninvasive examination of the vocal cords and the larynx is more accessible. Using ultrasonography, the air column width (ACW), which is defined as the width of the acoustic shadow present at the level of the vocal cords, was introduced as a tool to predict outcome of extubation. If the ACW is measured before and after endotracheal cuff deflation, the air column width difference (ACWD) can be calculated. Using real-time laryngeal ultrasonography, two studies 25 Prevention of Post-extubation Failure in Critically Ill Obese Patient 243

[28, 29] showed that a lower air column width during balloon deflation was a good predictor of post-extubation stridor. However, these results could not be consistently replicated [30]. Because of the small sample size and the limited number of events with post-extubation laryngeal edema, the utility of this intervention remains questionable, and its applicability in obese patients has not been tested. Eliminating possible risk factors of post-laryngeal extubation may decrease the incidence of post-extubation failure. It is recommended that an adequate-sized endotracheal tube should be selected. In contrast to prevailing views, obese patients do not have larger airways [31]. Generally accepted maximum endotracheal tube sizes are 7.0 mm for women and 8.0 mm for men. Once the underlying causes for respiratory failure have resolved, the endotracheal tube should be withdrawn as soon as possible since the duration of intubation in patients with post-extubation stridor (PES) is longer compared with patients without PES. However, there is no data on a definitive cutoff length of intubation where by the risk for PES in obese patients is increased. Management of post-extubation laryngeal edema involves reestablishing a patent airway and adequate oxygenation and relieving the distress. Though not examined specifically in obese patients, corticosteroids have been investigated in several trials in the prevention of laryngeal edema. Initial studies failed to show a beneficial effect of corticosteroids on post-extubation laryngeal edema [32, 33]. In more recent studies, corticosteroids were shown to decrease the incidence of post-laryngeal edema by more than 50% [24, 34, 35] via downregulating the inflammatory response and decreasing capillary permeability [36]. However, the effectiveness of glucocorti- coids in post-extubation laryngeal edema has yet to be confirmed in randomized controlled trials because data on the most effective dose has not been determined. That said, an argument can be made for a dosage of methylprednisolone 20–40 mg, or dexamethasone 5 mg could be initiated 24 h before planned extubation and continued for 24–48 h after extubation [35, 37]. Epinephrine nebulization is another potentially effective therapy. Epinephrine acts through local stimulation of α-adrenergic receptors on vascular smooth muscle cells, thereby causing vasoconstriction and decreased blood flow, which diminishes edema formation. There is no consensus about the potentially effective dosage of epinephrine nebulization in obese patients. A dose of 1 mg epinephrine in 5 mL normal saline has proved successful in some cases of upper airway obstruction in adults [38]. Rebound edema is known to occur and close observation is essential. Evidence for benefit of noninvasive positive pressure ventilation (NIPPV) in laryngeal edema is lacking overall, and in the absence of any well-designed controlled trials, the clinical application of NIPPV in obese patients with laryngeal edema is not recommended.

25.2.3 Unplanned Extubation

Unplanned extubation rates range from 5 to 15%, and reintubation rates after unplanned extubation vary between 35 and 75% [39]. There is no evidence hitherto 244 A.A. El Solh to suggest that obese patients are at higher risk of unplanned extubation. Further, there is no consensus on strategies for the prevention of this event [40, 41]. The majority of studies available on this topic provide a risk assessment of the factors associated with unplanned extubations. Understanding these factors is crucial for identifying patients at risk and for developing interventions to reduce the frequency of this complication. Among these, severe agitation is a long time recognized risk factor for self-extubation. In a retrospective case-controlled study, Tung et al. observed that ICU patients who self-extubated were more than twice as likely as controls to be agitated [42]. Various physical restraints have been used to prevent patients from removing their endotracheal tubes. However, the use of physical restraints to address agitation or for any other reason requires careful evaluation, because the use of physical restraint increases the risk for unplanned extubation by 3.11 times, and the risk increases to 12.44 times if a nosocomial infection is also present [43]. For patients who still require mechanical ventilation, the role of sedatives in preventing unplanned extubation remains unclear. Studies have shown that more than half of patients were receiving a sedative at the time of unplanned extubation [44, 45] suggesting that inadequate sedation may be partly to blame for prema- ture extubation. A prospective study by Balon [46] demonstrated that IV boluses of morphine sulfate, diazepam, midazolam, lorazepam, and haloperidol given “as needed” were found to increase the incidence of unplanned extubations. Two other studies associated the use of benzodiazepines with an increased occurrence of these events [42, 47]. A paradoxical excitatory effect is thought to be responsible for this association; however, the dose and schedule of administration of these sedatives were not defined in these studies. Because self-extubation tends to recur, constant vigilance by the ICU staff is necessary. Proper positioning of the tip of the endotracheal tube 4–5 cm above the carina reduce the risk of inadvertent self-extubation such as during positioning, transport, or extension of the head and neck. Additionally, failure to identify patients ready for liberation from ventilatory support is an important element contributing to increased self-extubation incidence. Formal weaning protocols may reduce the incidence of unplanned extubations, although self-extubation may still occur because of the usually low sedation level during weaning [48]. Other aspects such as nurse workload and standardization of procedures (the method of securing the endotracheal tube and the use of hand restraints) have been reported to be useful in reducing the accidental removal of the orotracheal tube [49, 50]. Several measures can be adopted to minimize unplanned extubations and its consequences in intubated obese patients: (1) more comprehensive approach to agitated patients that include pain control and appropriate sedation; (2) verification of the correct position of the endotracheal tube daily in patients who are orally intubated; (3) strong attachment of the tracheal tube, particularly in orally intubated patients; and (4) daily evaluation for liberation from mechanical ventilation. In one study, the implementation of a care bundle consisting of educational courses, standardization of selected procedures such as tracheal tube fixation, tube suctioning, patient hygiene and transport, identification of high-risk patients, and standardization of sedation practices resulted in reducing the incidence of unplanned extubation from 2.9 to 0.6 per 100 intubation days [51]. 25 Prevention of Post-extubation Failure in Critically Ill Obese Patient 245

25.2.4 Other Causes

Other reasons for extubation failure in obese patients include unrecognized myocardial ischemia and congestive heart failure. Both obesity and OSA have been associated with impairment in left ventricular function [52]. Abrupt removal of mechanical ventilation and reinstitution of spontaneous ventilation typically increases the pressure gradient for venous return. As a result, right ventricular dilation shifts the interventricular septum toward the left ventricle, impede left ventricular filling, and decrease subsequent cardiac output. In addition, right ventricular dilation may augment right ventricular intrachamber pressure and influence the pressure gradient for coronary blood flow. These responses are even greater in obese individuals who exhibit increased breathing work because of the significantly greater change in intrathoracic pressure necessary to produce gas flow into the lungs. In a study of 74 patients who required reintubation within 72 h of extubation, congestive heart failure was the reason for extubation failure in 23% of the patients [22]. Increase in B-type natriuretic peptide levels during spontaneous breathing trial was found to predict weaning failure from cardiac origin [53]. Reestablishing euvolemia through diuresis and/or the addition of vasodilator therapy may obviate or diminish the risk of extubation failure in these patients with reduced cardiac reserve. Another condition that may contribute to extubation failure in critically obese patients is delirium. Delirium remains unrecognized in as many as 66–84% of ICU patients experiencing this complication. Delirium promotes extubation failure through alteration of consciousness, agitation and subsequent sedation, aspiration, and noncompliance to treatments including NIV (42). Risk factors can be classified into three groups: (1) host factors, (2) the acute illness itself, and (3) iatrogenic or environmental factors. Psychoactive drugs are the leading cause for delirium. Benzodiazepines, narcotics, phenothiazines, and other antipsychotic medications are associated with a 3–11 times increased relative risk [54], and the rate of adding psychoactive medications increases the risk of delirium by 4–10 times. Prevention and management of delirium should be instituted ahead of weaning trial to avoid extubation failure. Many prevention strategies have been studied, including sedation protocols (such as alternative sedatives) and non-pharmacological management such as creating an ICU environment with less noise and more natural light, reinstituting the sleep/wake cycle (e.g., eye masks and earplugs at night), and early mobilization [55–57]. Medications should be used only after addressing all modifiable risk factors such as correction of electrolytes abnormalities, treating underlying infections, and normalizing gas exchanges.

25.3 Noninvasive Positive Pressure Ventilation

Two randomized clinical trials failed to show benefit of NIPPV in avoiding reintubation in patients who have developed respiratory failure after extubation [58, 59]. The lack of benefit in these studies was attributed to the heterogeneous study 246 A.A. El Solh population and to the fact that NIPPV was instituted after the onset of respiratory failure (therapeutic NIPPV). More recent evidence revealed that in obese patients with acute respiratory failure, early extubation with immediate application of NIPPV has a positive impact on important outcomes, turning to advantage when compared with continuous invasive weaning [60, 61] (prophylactic NIPPV). By applying positive pressure ventilation, NIPPV can augment patient’s native efforts to overcome critical closing pressures and volumes. The resulting effect is a better match regional time constant variations leading the zero pressure to move to a more proximal point in the airway, hence minimizing atelectasis. Since obese patients are particularly susceptible to this phenomenon, El-Solh and colleagues [60] evaluated the application of NIPPV in critically ill morbidly obese patients during the first 48 h post extubation. Compared with conventional therapy, the institution of NIPPV resulted in 16% (95% confidence interval 2.9–29.3%) absolute risk reduction in the rate of respiratory failure. There was also significant difference in the intensive care unit and length of hospital stay in the NIPPV group. More importantly, hypercapnic patients showed a significant reduction in hospital mortality when NIPPV was applied early. It is necessary to stress that NIPPV must be applied immediately after extubation to avoid respiratory failure and consequent reintubation after elective extubation. Keenan and colleagues [59] showed that if NIPPV is administered to patients that develop respiratory distress after extubation, NIPPV will not be able to prevent reintubation. Whenever NIPPV is applied post extubation, the patient must be watched carefully. A critical issue related to the success of NIPPV is the setting of IPAP and EPAP levels according to each patient’s needs. IPAP should be adjusted for ventilation adequacy, whereas EPAP should be set for maintenance of airways and alveolar stability. When choosing the NIPPV interface in obese patients, great consideration should be given to minimizing unintentional leak which impairs NIPPV efficiency [62, 63] particularly during the first few hours of ventilation, when the patient is adapting to NIPPV, and during sleep, due to the loss of voluntary muscle control and decreased muscle tone. Interventions to reduce air leak include mask-support ring; ensuring proper interface type, size, and securing system; and optimizing patient comfort and efficiency with, for instance, hydrogel or foam seal, lip seal or mouth taping, and/or chin strap.

Conclusion The decision to extubate obese patients from mechanical ventilatory support is a complex clinical problem. Obese patients at risk of extubation failure may benefit from management with a weaning algorithm specifically tailored to minimize the risk for post-extubation respiratory failure and need for reintubation. Extubation failure has been shown to be associated with an increase in mortality related to reintubation and the complications that develop after reintubation. Immediate application of NIV appears to prevent post-extubation respiratory distress in obese patients at high risk of extubation failure. However, caution is warranted, because NIPPV appears to be ineffective for established post-extubation respiratory failure. 25 Prevention of Post-extubation Failure in Critically Ill Obese Patient 247

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26.1 Postoperative Respiratory Problems of Obese Patients

The risk of postoperative respiratory failure is especially greater if such patients are made to undergo long duration, high-risk surgical procedures like upper abdominal or thoracic surgeries [1]. General anaesthesia, by reducing the muscular tone, also adds to pump failure. Gas exchange failure results from reduction of phrenic output, disruption of muscle output and pain [2]. Other insults like sepsis, shock, ischaemia and reperfusion injury and blood transfusions worsen lung injury leading to worsening of gas exchange [2]. In the morbidly obese, absorption of CO2 during pneumoperitoneum can lead to an increase in PaCO2 levels; however, hypercarbia is commonly avoided with appropriate ventilatory changes. Absorption of CO2 also alters the acid-base balance and increase in CO2 excretion load [3]. The decrease in lung and chest wall compliance may increase the work of breathing in the postoperative period when patients resume spontaneous ventilation. In the first hours after surgery, there is a 20% decrease in tidal volume, paired with a 20% increase in respiratory rates and diaphragmatic dysfunction. This can persist for 1 week [4]. The resulting alveolar hypoventilation paired with atelectasis can contribute to the development of pneumonia. Pulmonary atelectasis is reported to develop in 85–90% of obese patients during the first minutes of anaesthesia and can persist for even 24 h after the end of the surgical procedure. Several factors (reduced FRC especially in the supine position, difficult to mobilize postoperatively and bed resting, disruption of respiratory

G. Fiorentino, M.D., F.C.C.P. (*) • A. Annunziata, M.D. UOC di Fisiopatologia e Riabilitazione Respiratoria, Monaldi Hospital Naples, Naples, Italy e-mail: [email protected]; [email protected] A.M. Esquinas, M.D., Ph.D., F.C.C.P. Intensive Care Unit and Non Invasive Ventilatory Unit, Hospital Morales Meseguer, Murcia, Spain

© Springer International Publishing AG 2018 251 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_26 252 G. Fiorentino et al. muscles as well as the reflex inhibition of the diaphragmatic excursion) contribute to the persistence of postoperative atelectasis in obese patients [5]. In the immediate postoperative period, the risk of airway obstruction is high due to the anatomical changes associated with obesity and possible residual anaesthesia, neuromuscular blockade or suboptimal or excessive analgesia. This risk is increased in the presence of obstructive apnoea syndrome (OSA) or hypopnoea syndrome. Drug effects are more marked after short procedures and are aggravated with increasing age. Especially upper airway muscle tone can be negatively affected by propofol [6]. Aspiration pneumonitis following regurgitation of gastric contents under general anaesthesia, although rare, occurring approximately 1 in every 3000 general anaesthetics, can result in devastating consequences. The mortality rate following aspiration of gastric contents is 1 in 71,000 general anaesthetics. Obese patients have typically been considered to have high-volume, low-pH gastric contents that may lead to increased risk of aspiration pneumonitis, although these findings have not been confirmed in more recent studies 7[ ].

26.2 Postoperative Respiratory Management of Obese Patients

Postoperative vigilance may be important, and the painful stimulus of blood gas collection may have altered postoperative wakefulness; fast-track scores are too crude for a detailed evaluation of postoperative consciousness [6]. Incentive spirometry, respiratory physiotherapy and targeted pulmonary toileting should be instituted in the immediate postoperative stage. Supplemental oxygen is only a symptomatic measure to prevent arterial desaturation. Pressurization of the airway (CPAP and NIV) reduces the work of breathing (enhancing compliance by increasing FRC, as well as inspiratory assistance) and the right ventricle afterload (by favouring left ventricular systole), and it also improves oxygenation (reducing atelectasis). Pressurization also keeps the upper airway open in patients with easy collapsibility (OSA) [8].

26.3 Role of Positive Airway Pressure in the Postoperative Period

26.3.1 Continuous Positive Airway Pressure (CPAP)

Continuous positive airway pressure (CPAP) therapy is often used in obese patients after extubation in the recovery room to improve recruitment of atelectatic lungs; maintaining patency of the upper airway improves oxygenation and reduces work of breathing [9]. The use of CPAP during preoxygenation at the beginning of a general anaesthetic and in the immediate postoperative period has been shown to improve respiratory mechanics and lung function during the hospital stay [9]. 26 NIV in the Obese Patient After Surgery 253

Pasquina et al. [10] reported that when CPAP was applied in patients who developed postoperative atelectasis (based on roentgenographic evidence) following cardiac surgeries, there was considerable improvement of atelectasis, as determined by radiological scores The settings chosen are usually titrated to upper airway patency and can be empirically set to a start value corresponding to what is used at home. Unfortunately, this technique is underutilized in PACU and is better tolerated by patients who are already using a CPAP machine at home [10]. Theoretical advantages of CPAP include promoting airway patency and preventing alveolar collapse, with a decrease in the FiO2 needed and a decrease in absorption atelectasis. Left ventricular afterload is also decreased, with an improvement in cardiac output [4].

26.3.2 Non-invasive Positive Pressure Ventilation (NIV)

The rationale for the use of NIV is to decrease the work of breathing by improving ventilation (increase CO2 removal) and to decrease the amount of atelectasis, with subsequent improvement of gas exchange, in attempt to avoid endotracheal intubation. Patient cooperation is crucial in order for this technique to be successful. NIV combines the use of pressure support ventilation (PSV) and positive end-expiratory pressures (PEEP). The use of end-expiratory pressure promotes upper airway patency, while the inspiratory component is useful to control central hypoventilation. Starting with low PEEP and then adding PSV can be helpful. The feasibility and safety of NIV use in the recovery room after various types of surgery have been demonstrated. One study showed a 16% absolute risk reduction in post-extubation acute respiratory failure with a reduced length of ICU stay by application of 48 h of NIV in the immediate postoperative stage for patients with a BMI above 35 kg/mq [11]. Although there are no clinical trials that have shown the effectiveness of NIV in the postoperative setting for the management of patients with established chronic respiratory failure, it is considered the standard of care [11–14]. Studies have also demonstrated that NIV is more effective if instituted as early as possible and in a continuous way, not in an intermittent approach [8]. The most important issue in this setting is to choose the best interface for the individual patient, even if that requires trying various types. Improved comfort is associated with adequate synchrony and increased success of NIV. NIV has been shown to significantly reduce pulmonary dysfunction following gastroplasty in obese patients and accelerates re- establishment of preoperative pulmonary function [15]. In morbidly obese patients undergoing abdominal surgeries, studies have clearly demonstrated the benefits of prophylactic use of NIV in the postoperative period [15]. Joris et al. [16] demonstrated that the application of bilevel positive airway pressure set at 12 and 4 cm PEEP significantly improved the peak expiratory flow rate, the forced vital capacity and the oxygen saturation on the first postoperative day. In these patients, the beneficial effects of NIV were attributed to an improvement in lung inflation, prevention of alveolar collapse and reduced inspiratory threshold load. 254 G. Fiorentino et al.

Together these data suggest that postoperative prophylactic use of NIV could improve outcome of morbidly obese patients. Its use is recommended in morbidly obese patients at high risk of postoperative pulmonary complications after thoracic or abdominal surgery. These include the more severely obese (BMI > 45), those with preexisting respiratory disease and those who remain hypoxaemic despite chest physiotherapy and low flow supplemental oxygen via a nasal cannula [16]. Aguilo et al. [17] investigated early effects of NIV after lung surgery in comparison with the conventional treatment. NIV improved arterial oxygenation after 1-h application, and this effect continued one more hour after the cessation of the ventilator support and carbon dioxide level, and physiological dead space did not change at that moment. The procedure was feasibly tolerable, and only one of the patients had considerable pleural air leak. Perrin et al. [18] applied prophylactic NIV in both preoperative and postoperative periods of the same patients and compared it to oxygen therapy. They tested whether NIV ensures a better gas exchange and pulmonary function on lung resection in patients with a forced expiratory volume lower than 70% of predicted. Gas exchange and spirometer values were better, and hospital stay was lower in NIV group [18]. Lefebvre et al. [19] reported that of the patients at risk for severe complications following lung resection surgeries, 16.3% eventually developed acute respiratory failure, which were both hypoxaemic and hypercapnic types. The overall success rate of NIV in this group was 85.3%; however, the mortality associated with NIV failure was 46.1%. In the same study, the presence of cardiac comorbidities and lack of initial response to NIV were found to be independently associated with NIV failure. Matte et al. [20] reported that when preventive NIV was used in 96 patients in the first 2 days after cardiac surgery, there was improved oxygenation and lower reduction of lung volumes. However, the incidence of atelectasis was similar (12–15%) to the non-NIV group. There have been only a few studies reporting the use of NIV for treatment of respiratory failure following cardiac surgeries. Olper et al. [21] studied 85 patients who received NIV for treatment of respiratory failure following cardiac surgery and reported that NIV was a safe and feasible solution for postoperative acute respiratory failure, even when applied after discharge from the ICU.

26.4 Mechanical Setting

NIV in the postoperative period should always be provided in appropriately monitored locations. It is important to explain the procedure to the patient and reassure the patient before initiating NIV. The patient must be propped up at least 30° and have received adequate analgesia. It is advisable to begin with low PS as it usually takes a few minutes for the patient to accommodate to the pressure applied and synchronize his breathing with that of the machine. Once the patient 26 NIV in the Obese Patient After Surgery 255 starts to feel comfortable and breathing begins to improve, it is easier to gradually increase the PS till there is improvement in symptoms, reduced respiratory rates and good synchrony. The end points of the PS applied must be always individualized. An arterial blood gas should be obtained by 1–2 h to verify clinical improvements. Normally, a sensible inspiratory trigger (1–2 L/min or 1–2 cm of

H2O) is applied, with moderate to maximal slope. EPAP levels of 4 cm and IPAP of 8 cm of H2O (4 cm above EPAP) are normally used at initiation. These may be gradually increased by increments of 1–2 cm till a maximum EPAP of 10 and

IPAP of 25 cm of H2O [22]. The end points of the PS applied must be always individualized. An arterial blood gas should be obtained by 1–2 h to verify clinical improvements. Pelosi et al. [23] demonstrated that the addition of PEEP at

10 cm H2O in morbidly obese patients increased elastance and improved oxygenation compared with nonobese subjects. If higher pressures are required, it may be necessary to change the interface and adjust mask fit. The expiratory trigger is generally fixed at 0.8–1 s or between 40 and 60% of the peak flow rate. The most appropriate tidal volume of the patient should be based on ideal and not actual body weight to avoid high peak and plateau airway pressures and barotrauma. Because of the reduced chest wall compliance of respiratory system in obesity, inflation pressures should be interpreted with caution with the initial target tidal volume calculated from the IBW and then adjusted according to gas exchange. The use of a low tidal volume and a high fraction of inspired oxygen in the obese population can lead to progressive formation of atelectasis, with secondary hypoxaemia and hypercapnia [24]. The goal for mechanical ventilation in this patient population should focus on the use of peak inspiratory pressures high enough to open collapsed lung regions and the use of PEEP to keep the alveoli open at the end of expiration [23]. It is important to carefully monitor these patients and recognize those who are not responding adequately. One may need to consider other factors like leaks in circuit, poor mask fit, inadequate trigger levels, etc., which may be readjusted for better results.

26.5 Interfaces

The most important factor to be taken into consideration while choosing the right mask is a good fit, patient comfort and mask tolerance. Tolerance of a tightly held facemask was previously rated identically before and after surgery. As the mask must be held tightly to avoid leaks and to maintain maximal FiO2, it seems important to reassure patients before and during preoxygenation of their ability to breathe with the facemask. While there is no evidence favouring the use of any one over the other, oronasal masks are more commonly used than others [25]. Holanda et al. [26] observed that while the full facemask avoided pain over the bridge of the nose and prevented air leaks around the eyes and mouth, they caused more oronasal dryness and claustrophobia. Kwok et al. [27] noted that in the dyspnoeic patient, nasal masks are less well tolerated than are oronasal masks. 256 G. Fiorentino et al.

26.6 Side Effects

Most of the patients were unfamiliar with long-term support for sleep apnoea, but this did not reduce tolerance. We did not find any significant cardiovascular depres- sant effects of NIV with respect to BP and heart rate. Gastric distension was greater after NIV, but the increase was modest. O2 administration with PEEP alone did not increase gastric air insufflation, suggesting that the pressure support component promoted gastric distension during NIV. Positive-pressure ventilation may increase gastric air content and hence may promote pulmonary aspiration during endotracheal intubation. There is a risk with an insufflation pressure of more than

20 cm H2O, which can be easily obtained using manual ventilation. There may be some concerns gastrointestinal increased anastomotic leakage in patients who receive NIV after gastrointestinal anastomoses, especially following upper gastrointestinal anastomosis, where use of NIV may be considered a relative contraindication [28]. However, several studies on the use of NIV in patients who had undergone procedures like oesophagectomies, digestive surgeries, gastrectomies and colosto- mies showing increased benefits and reduced morbidity with the use of NIV postoperatively have not reported any problems with suture integrity [28]. Gastric inflation pressures should be carefully monitored as the risk of anastomotic leakage seems to be more if very high insufflation pressures are applied (more than 25 cm H2O). NIV is contraindicated in case of upper GI surgery, where it could contribute to leaks at the anastomosis site. Increased secretions can cause an increased work of breathing and decrease the efficacy of NIV.

Conclusion Standard perioperative medications (anaesthetics, sedatives, opioids and neuromuscular-blocking agents), interventions (patient positioning, mechanical ventilation and surgical trauma) and diseases (lung hyperinflation, obesity and obstructive sleep apnoea) have differential effects on the respiratory muscle. These effects on the upper airway dilators and respiratory pump muscles impair their coordination and function and can result in respiratory failure. Perioperative management strategies can help decrease the incidence of postoperative respiratory muscle dysfunction. In the past decade, the NIV has proven to be an effective alternative to invasive ventilation in the setting of moderate and severe acute postoperative respiratory failure. The use of NIV has not only reduced intubation rates with the attendant complications associated with mechanical ventilation but has also reduced morbidity, length of hospital stay and mortality in these patients. The effect lasted 24 h after discontinuation of NIV. Patient selection is necessary in order to establish clinically relevant improvements. This translates to huge benefits in costs of treatment too, especially in a country like ours where resources are limited and costs of therapy play a major role in deciding treatment options. Early initiation of short-term NIV during the postoperative promotes more rapid recovery of postoperative lung function and oxygenation in the obese. 26 NIV in the Obese Patient After Surgery 257

References

1. Branson RD. The scientific basis for the postoperative respiratory care. Respir Care. 2013;58:1974–84. 2. Levi D, Goodman ER, Patel M, Savransky Y. Critical care of the obese and bariatric surgical patient. Crit Care Clin. 2003;19(1):11–32. 3. Nguyen NT, Wolfe BM. The physiologic effects on pneumoperitoneum in the morbidly obese. Ann Surg. 2005;241(2):219–26. 4. Jaber S, Michelet P, Chanques G. Role of non-invasive ventilation (NIV) in the perioperative period. Best Pract Res Clin Anaesthesiol. 2010;24(2):253–65. 5. Eichenberger AS, Proietti S, Wicky S, Frascarolo P, Suter M, Spahn DR, et al. Morbid obesity and postoperative pulmonary atelectasis: an underestimated problem. Anesth Analg. 2002;95(6):1788–92. 6. American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Obstructive Sleep Apnea. Practice guidelines for the perioperative management of patients with obstructive sleep apnea. Anesthesiology. 2014;120(2):1–19. 7. Endler GC. The risk of anesthesia in obese patients. J Perinatol. 1990;10:175–9. 8. Queos C, Abelha F. Postoperative pulmonary complications and strategies to prevent them in the perioperative period: a review. Rev Soc Port Anestesiol. 2015;24(3):75–88. 9. Pedoto A. Lung physiology and obesity: anesthetic implications for thoracic procedures. Anesthesiol Res Pract. 2012;2012:154208. 10. Pasquina P, Merlani P, Granier JM, Ricou B. Continuous positive airway pressure versus noninvasive pressure support ventilation to treat atelectasis after cardiac surgery. Anesth Analg. 2004;99(4):1001–8. 11. Pérez de Llano LA, Golpe R, Ortiz Piquer M, et al. Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity- hypoventilation syndrome. Chest. 2005;128:587–94. 12. Carrillo A, Ferrer M, Gonzalez-Diaz G, et al. Noninvasive ventilation in acute hypercapnic respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:1279–85. 13. Priou P, Hamel JF, Person C, et al. Long-term outcome of noninvasive positive pressure ventilation for obesity hypoventilation syndrome. Chest. 2010;138:84–90. 14. Masa JF, Celli BR, Riesco JA, et al. The obesity hypoventilation syndrome can be treated with noninvasive mechanical ventilation. Chest. 2001;119:1102–7. 15. Martí-Valeri C, Sabaté A, Masdevall C, Dalmau A. Improvement of associated respiratory problems in morbidly obese patients after open Roux-en-Y gastric bypass. Obes Surg. 2007;17(8):1102–10. 16. Joris JL, Sottiaux TM, Chiche JD, Desaive CJ, Lamy ML. Effect of bi-level positive airway pressure (BiPAP) nasal ventilation on the postoperative pulmonary restrictive syndrome in obese patients undergoing gastroplasty. Chest. 1997;111:665–70. 17. Aguilo R, Togores B, Pons S, et al. Noninvasive ventilatory support a er lung resectional surgery. Chest. 1997;112:117–21. 18. Perrin C, Jullien V, Venissac N, Berthier F, Padovani B, Guillot F, et al. Prophylactic use of non-invasive ventilation in patients undergoing lung resectional surgery. Respir Med. 2007;101:1572–8. 19. Lefebvre A, Lorut C, Alifano M, Dermine H, Roche N, Gauzit R, Regnard JF, Huchon G, Rabbat A. Noninvasive ventilation for acute respiratory failure after lung resection: an observational study. Intensive Care Med. 2009;35(4):663–70. 20. Matte P, Jacquet M, Vandyck M, Goenen M. Effects of conventional physiotherapy, continuous positive airway pressure and non-invasive ventilatory support with bilevel positive airway pressure after coronary artery bypass grafting. Acta Anaesthesiol Scand. 2000;44:75–81. 21. Olper L, Cabrini L, Landoni G, Rossodivita A, Nobile L, Monti G, et al. Non-invasive ventilation after cardiac surgery outside the intensive care unit. Minerva Anestesiol. 2010;76:1–6. 258 G. Fiorentino et al.

22. Mathai AS. Non-invasive ventilation in the postoperative period: is there a role? Indian J Anaesth. 2011;55(4):325–33. 23. Pelosi P, Gregoretti C. Perioperative management of obese patients. Best Pract Res Clin Anaesthesiol. 2010;24(2):211–25. 24. Marik P, Varon J. The obese patient in the ICU. Chest. 1998;113:492–8. 25. Delay JM, Sebbane M, Jung B, Nocca D, Verzilli D, Pouzeratte Y, Kamel ME, Fabre JM, Eledjam JJ, Jaber S. The effectiveness of noninvasive positive pressure ventilation to enhance preoxygenation in morbidly obese patients: a randomized controlled study. Anesth Analg. 2008;107(5):1707–13. 26. Holanda MA, Reis RC, Winkeler GF, Fortaleza SC, Lima JW, Pereira ED. Influence of total face, facial and nasal masks on short-term adverse effects during noninvasive ventilation. J Bras Pneumol. 2009;35(2):164–73. 27. Kwok H, McCormack J, Cece R, Houtchens J, Hill NS. Controlled trial of oronasal versus nasal mask ventilation in the treatment of acute respiratory failure. Crit Care Med. 2003;31(2):468–73. 28. Huerta S, DeShields S, Shpiner R, et al. Safety and efficacy of postoperative continuous positive airway pressure to prevent pulmonary complications after Roux-en-Y gastric bypass. J Gastrointest Surg. 2002;6:354–8. Determinants of NIV Success or Failure 27 Antonello Nicolini, Ines Maria Grazia Piroddi, Cornelius Barlascini, Gianluca Ferraioli, and Paolo Banfi

Patients who are likely to benefit from noninvasive ventilation (NIV) need to be identified early [1, 2]. Failure to do so often results in increased morbidity and mortality as well as inappropriate use of limited resources [2]. Before starting NIV, it is crucial to identify good candidates [1]. The best way to do this is to look for predictors of failure [3]. The absence of the essential qualifica- tions of alertness and ability to follow instructions excludes many patients. Hypotension, pneumothorax, gastric insufflation, vomiting, and risk of aspiration must be evaluated. The risk of NIV failure determines the intensity of monitoring needed [3]. Moreover, knowing the factors affecting the likelihood of success of NIV may help to decide also the duration of NIV trial. One approach to determining the need for monitoring is to assess the patient’s risk of NIV failure [4]. Some of these are simple bedside assessments, such as ease of arousability, agitation, cough integrity, and respiratory rate. Other methods require simple laboratory tests, such as determination of arterial blood gas. Other methods require proven evaluation protocols: Acute Physiology and Chronic Health Evaluation (APACHE) II or Simplified Acute Physiology Score (SAPS) II. When a quick decision is required, reliance on simple bedside observations and rapidly obtained laboratory values such as pH is best choice [4, 5].

A. Nicolini (*) • I.M.G. Piroddi Respiratory Diseases Unit, Hospital of Sestri Levante, Sestri Levaente, Italy e-mail: [email protected] C. Barlascini Hygiene and Health Medicine Unit, Hospital of Sestri Levante, Sestri Levaente, Italy G. Ferraioli Emergency and Internal Medicine Unit, Hospital of Lavagna, Lavagna, Italy P. Banfi Pulmonology Department, Don Gnocchi Foundation IRCSS, Milan, Italy

© Springer International Publishing AG 2018 259 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_27 260 A. Nicolini et al.

The risk of NIV failure determines the level of monitoring required. A patient with multiple risk factors for NIV failure should be in a closely monitored setting such as an ICU or step-down respiratory unit. Three critical moments identify NIV failure: (1) immediate failure (within minutes to <1 h), (2) early failure (1–48 h), and (3) late failure (after 48 h) [6–8].

27.1 Immediate NIV Failure

Immediate NIV failure refers to failure within 60 min [9]. Predictors of failure in this period have never been systematically analyzed. A weak cough reflex leading to inefficient clearance of excessive secretions from airways is a common cause of immediate NIV failure. The inability to spontaneously remove secretions is considered a contraindication to NIV, e.g., patients with impaired consciousness and depressed cough reflex. Hypercapnic encephalopathy syndrome (HES) is often considered a cause of immediate NIV failure because of poor compliance due to confusion and/or agitation. It is a relative contraindication because of the increased risk of aspiration [3, 8, 9]. The risk of aspiration has been shown to be minimized by the rapid improvement of neurological status. Patient tolerance has been shown to be critical for NIV success, especially in the first few minutes while the patient adapts to this “new mode” of breathing 10[ ].

27.2 Early NIV Failure

Nearly 65% of NIV failures occur within 1–48 h of NIV use. This time interval has received more attention in assessments of NIV failure than any other. Several investigators have tried to assess the best predictors of NIV failure. Confalonieri et al. found that subjects likely to fail NIV had more severe respiratory acidosis and a lower level of consciousness, were older and more hypoxemic, and had a higher respiratory rate on presentation [4]. Clinical signs that are only equivocal on presentation become more definitively predictive of failure if they persist after 2 h of NIV. It is important to assess clinical trajectory after 1–2 h of initiation of NIV to identify response. However, even on presentation, subjects who have a pH < 7.25, an APACHE II score >29, and a Glasgow coma score <11 have failure rates ranging from 64 to 82%. Patients with excessive respiratory secretions or without improvement after 60 min of NIV have high risk of failure [4, 11].

27.3 Late NIV Failure

Late NIV failure (after 48 h) is an event occurring after an initial good response to NIV. It is more likely in subjects who, at the time of admission, showed functional limitations evaluated using a score correlated to home activities of daily living (ADL), the number of comorbidities, a lower pH at baseline, and the underlying cause of acute respiratory failure (ARF), e.g., pneumonia [6, 8, 12]. 27 Determinants of NIV Success or Failure 261

27.4 Obesity Hypoventilation Syndrome

Obesity hypoventilation syndrome (OHS) is defined as a combination of obesity 2 (BMI > 30 kg/m ), daytime hypercapnia, PaCO2 < 45 mmHg, and sleep-disordered breathing during sleep [13, 14]. OHS is a chronic disease associated with respiratory and cardio-metabolic impairments leading to a decrease in activities of daily life and social involvement as well as a higher risk of hospitalization and death. About more than 30% of patients are diagnosed when hospitalized for acute on chronic respiratory failure [1, 7]. Patients with OHS often respond well to NIV. The pathophysiology of OHS results from complex interactions between various sleep breathing disorders (obstructive sleep apnea, REM sleep hypoventilation), increased work of breathing due to a decreased thoracoabdominal compliance, and altered ventilatory drive [15]. These mechanisms can be successfully corrected by NIV. Patients with OHS can be treated in an acute care setting with better results than other diseases such as COPD. NIV reduces the respiratory load, increases minute volume for a given breathing effort, and provides ventilation during central apneic events [16]. Only a few studies have investigated NIV success or failure in OHS patients [1, 7, 16]. Several observations have emerged from these works: (a) In OHS NIV rarely failed in reversing ARF. (b) Obese patients who exhibited early NIV failure had a high severity score and a low HCO3 level at admission and were likely to have hypoxemic ARF caused by pneumonia. (c) Factors associated with a successful response to NIV included high paCO2 at admission and a diagnosis of idiopathic hypercapnic decompensation of OHS. (d) More than half of hypercapnic patients with decompensated OHS exhibited a delayed response to NIV with late NIV failure.

The authors concluded that in obese patients with ARF, both pH and paCO2 may not accurately predict patient response to NIV, especially in the first hours of NIV treatment [7]. The decreased responsiveness in hypoxic and hypercapnic ventilatory drive that characterizes this last category may explain why they need more time than expected to correct respiratory acidosis compared to all other patients [1, 7]. No ventilatory mode has been shown to lead to better outcome than others [17– 20]. Numerous modes have been implemented: continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], pressure support ventilation [PSV], pressure control ventilation [PCV], Bilevel Positive Airway Pressure [BiPAP] spontaneous-timed [ST] with AVAPS [average volume-assured pressure support], and airway pressure release ventilation [APRV] [7, 14, 16, 21–24]. The setting of ventilator is very important because the delay in the reduction of

PaCO2 may be due to:

1. Inadequate level of inspiratory (IPAP) or expiratory (EPAP) pressure: in obese

patients, IPAP should range from 12 to 30 H2O or greater and EPAP from 8 to 12 cm H2O. 2. Inadequate duration of NIV: the obese patients as previously explained require longer NIV therapy than non-obese patients especially during the night; their 262 A. Nicolini et al.

apneas or hypoventilation worsen during hours of sleep. These findings suggest that NIV setting needs to be titrated more aggressively in OHS than other syndromes when acute illness precipitates respiratory decompensation (especially pneumonia) [7, 21].

Although few studies are available concerning morbidly obese patients with decompensation of OHS, they suggest that these patients have similar mortality and intubation rates compared to non-obese patients. OHS patients require more aggressive NIV settings and a longer time to reduce paCO2 levels below 50 mmHg and more frequently have late NIV failure. The best ventilatory strategy is to treat each patient as unique using flexibility and vigilance.

References

1. Gursel G, Aydodgu M, Tasyurek S, Gulbas G, Ozkaya S, Nazik S, et al. Factors associated with noninvasive ventilation response in the first day of therapy in patients with hypercapnic respiratory failure. Annals Thor Med. 2012;7(2):92–7. 2. Ciledag A, Kaya A, Akdogan BB, Kabalak PA, Onen ZP. Early use of noninvasive mechanical ventilation in patients with acute hypercapnic respiratory failure in respiratory ward: a prospective study. Arch Bronconeumol. 2010;46(10):538–42. 3. Pacilli AM, Nava S, et al. Determinants of noninvasive ventilation outcomes during an episode of acute hypercapnic respiratory failure in chronic obstructive pulmonary disease: the effects of comorbidities and causes of respiratory failure. Bio Med Res Int. 2014;2014:9. 4. Confalonieri M, Garuti G, Cattaruzza S, et al. A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J. 2005;25:348–55. 5. Kaya A, Ciledag A, Cayli I, Onen ZP, Sen E, Gulbay B. Associated factors with non-invasive ventilation failure in acute hypercapnic respiratory failure. Tuberkuloz ve Tor Dergisi. 2010;58(2):128–34. 6. Moretti M, Cilione C, Marchioni A, Tampieri A, Fracchia C, Nava S. Incidence and causes of non-invasive mechanical ventilation failure after initial success. Thorax. 2000;55:819–25. 7. Lemyze M, Taufour P, Duhamel A, Temine J, Nigeon O, Vangrunderbeeck N, et al. Determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure. PLoS One. 2014;9(5):e97563. 8. Ozyilman E, Ugurlu AO, Nava S. Timing of noninvasive ventilation failure: causes, risk factors, and potential remedies. BMC Pulm Med. 2014;14:19. 9. BTS/ICS Guidelines for the management of acute hypercapnic respiratory failure in adults. Thorax 2016;71:suppl 1–44. 10. Bello G, De Pascale G, Antonelli M. Noninvasive ventilation: practical advice. Curr Opin Crit Care. 2013;19:1–8. 11. Berg KM, Clardy P, Donnino MW. Noninvasive ventilation for acute respiratory failure: a review of the literature and current guidelines. Int Emerg Med. 2012;7:539–45. 12. Carratu’ P, Bonfitto P, Dragonieri S, Schettini F, Clemente R, Di Gioia G, et al. Early and late failure of noninvasive ventilation in chronic obstructive pulmonary disease with acute exacerbation. Eur J Clin Invest. 2005;35:404–9. 13. Pépin JL, Borel JC, Janssens JP. Obesity hypoventilation syndrome: an underdiagnosed and undertreated condition. Am J Respir Crit Care Med. 2012;186(12):1205–7. 14. Mokhlesi B. Obesity hypoventilation syndrome: a state of the art review. Respir Care. 2010;55:1347–62. 15. Piroddi IMG, Karamichali S, Barlascini S, Nicolini A. Obesity and breathing related sleep disorders: concise clinical review. SMJ Pulm Med. 2015;1:1002. 27 Determinants of NIV Success or Failure 263

16. Carrillo A, Ferrer M, Gonzalez-Diaz G, Lopez-Martinez A, Llamas N, Alcazar M, et al. Noninvasive ventilation in acute hypercapnic respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:1279–85. 17. Esquinas AM. Obesity hypoventilation syndrome and acute hypercapnia and role of noninvasive positive-pressure ventilation: a call of caution to intensivists for selecting the best strategy. Minerva Anestesiol. 2011;77(1):4–5. 18. Esquinas AM, Bahamman AS. The emergent malignant obesity hypoventilation syndrome: a new critical care syndrome. J Intensive Care Med. 2012;28(3):198–9. 19. Hess DR. Noninvasive ventilation for acute respiratory failure. Respir Care. 2013;58(6):950–69. 20. Nava S. Behind a mask: tricks, pitfalls and prejudices for noninvasive ventilation. Respir Care. 2013;58(8):1367–76. 21. Gursel G, Aydogdu M, Gulbas G, Ozkaya S, Tasyurek S, Yildirim F. The influence of severe obesity on non-invasive ventilation (NIV) strategies and responses in patients with acute hypercapnic respiratory failure attacks in the ICU. Minerva Anestesiol. 2011;77:17–25. 22. Marik PE, Desai H. Characteristics of patients with the “malignant obesity hypoventilation syndrome” admitted to an ICU. J Intens Care. 2013;28(2):124–30. 23. Marek PE. The malignant obesity hypoventilation syndrome (MOHS). Obes Rev. 2012;13(10):902–9. 24. BaHamamam A,Al-Jawder SE. Managing acute respiratory decompensation in the morbidly obese. Respirol 2012;17:759–71. Chronic Ventilation in Obese Patients 28 Jean Christian Borel, Jean-Paul Janssens, Renaud Tamisier, Olivier Contal, Dan Adler, and Jean-Louis Pépin

28.1 Introduction

Obesity is defined by a body mass index (BMI) of ≥30 kg/m2.The general increase in prevalence of obesity is a major challenge facing governments and health-care systems worldwide [1]. The prevalence of severe obesity (class III), defined as a BMI ≥40 kg/m2, is increasing at a much faster rate than other classes of obesity [2]. Obesity is associated with an increased rate of death from cardiovascular diseases and a higher cancer incidence [3] and also has a major impact on respiratory health. Morbid obesity is one of the main causes for severe hypercapnic respiratory failure requiring ICU admission [4–6]. Obesity-related respiratory impairment is complex, involving thoraco-pulmonary mechanic abnormalities, central respiratory control alterations, and sleep breathing disorders. Obstructive sleep apnea syndrome (OSAS) is commonly associated with obesity [7]. However, beyond OSAS, obesity hypoventilation syndrome (OHS) is a specific entity defined as a combination of 2 obesity (BMI ≥ 30 kg/m ), daytime hypercapnia (PaCO2 ≥ 45 mmHg), and

J.C. Borel (*) HP2 Laboratory, INSERM U1042, University Grenoble Alps, Grenoble, France EFCR Laboratory, Grenoble Alps University Hospital, Grenoble, France AGIR à dom. Association, 36 bd du Vieux Chêne, 38240 Meylan, France e-mail: [email protected] J.-P. Janssens • D. Adler Division of Pulmonary Diseases, Geneva University Hospital, Geneva, Switzerland R. Tamisier • J.-L. Pépin HP2 Laboratory, INSERM U1042, University Grenoble Alps, Grenoble, France EFCR Laboratory, Grenoble Alps University Hospital, Grenoble, France O. Contal Haute Ecole de Santé de Vaud, HESAV, Lausanne, Switzerland

© Springer International Publishing AG 2018 265 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_28 266 J.C. Borel et al. sleep-disordered breathing after ruling out other disorders that may cause alveolar hypoventilation. Although this condition remains often underdiagnosed [4, 5, 8], patients with OHS are characterized by a higher morbidity-mortality than eucapnic obese patients. OHS has become the primary cause for long-term home noninvasive mechanical ventilation [9]. In this chapter, we will discuss (1) the main pathophysiological mechanisms leading to obesity-related chronic respiratory failure and their implications for treatment decision, (2) the need to improve early diagnosis in these patients, and (3) treatment modalities, mainly use of long-term noninvasive positive airway pressure therapies. We will finally discuss the importance of screening for comorbidities and the need to offer combined treatment strategies including weight loss strategies as well as changes in lifestyle habits and rehabilitation programs to improve long-term outcomes.

28.2 Physiopathology of Obesity-Related Chronic Respiratory Failure

Hypoventilation is defined by an inadequate alveolar ventilation for a given metabolic activity and production of CO2 (VCO2) resulting in hypoxemia and hypercapnia. In obese patients, hypoventilation results from the conjunction/combination of several factors which interact to overwhelm the compensatory mechanisms of CO2 homeostasis.

28.2.1 Respiratory Mechanics

A decrease in pulmonary volumes (vital capacity, total lung capacity, functional residual capacity (FRC), and expiratory reserve volume (ERV)) has been reported as a determinant of hypoventilation in obese patients [10–15]. This restrictive ventilatory defect, mainly related to fat deposits [16, 17], is also associated with decreases in chest wall compliance, expiratory flow limitation [18, 19], and intrinsic positive end-expiratory pressure [20]. This contributes to an increase in total work of breathing. The reduced expiratory reserve volume may lead to abnormalities in distribution of ventilation (ventilation/perfusion mismatches) and therefore of gas exchanges [21]. The central fat distribution (intrathoracic and abdominal) phenotype is a strong determinant of lung volume restriction [22, 23]. It may also be a cause of the development of chronic hypoventilation [24]. Although there is a correlation between inspiratory muscle strength and the development of hypoventilation, hypercapnic obese patients are usually able to temporarily correct hypoventilation with voluntary breathing [12]. Additionally, during spontaneous breathing [25], transdiaphragmatic pressures are preserved compared to eucapnic patients [25, 26]. This suggests that muscle function may be slightly impaired but, mainly, respiratory muscles cannot cope with the overload imposed on the respiratory system. 28 Chronic Ventilation in Obese Patients 267

28.2.2 Sleep Breathing Disorders

Most patients with obesity and chronic respiratory failure suffer from severe OSAS [27, 28]. OSAS is multifactorial, but fat deposits surrounding upper airways, reduced lung volume [29], and fluid overload shifting from the legs to the neck in recumbent position [30] contribute to obstructive events during sleep. The severity of OSAS is a key component in the development of hypoventilation [31] and, more specifically, occurrence of prolonged apneas/hypopneas [32] and insufficient post-event ventilatory compensation [33] (Fig. 28.1). Apart from OSAS, periods of central hypoventilation during sleep, characterized by a sustained reduction in ventilation associated with reduced respiratory drive [34, 35], are encountered in obese patients. These periods are more pronounced during REM sleep [34] (Fig. 28.2). Their repetitive occurrence and severity induce renal bicarbonate retention which may not be fully cleared during waking hours, leading to a gradual depression of respiratory drive and daytime hypoventilation [35–37].

5 minutes epoch

SpO2

THO

ABD

THERM

FLOW

PTT

HYPN

CO2 excretion ) Blunted ventilatory responses

CO Metabolic 2 CO2 Load Insufficient post-event Load production ventilatory compensation CO2 (mL/breath

Time Diurnal Hypoventilation

Fig. 28.1 (a) Polysomnographic pattern of obstructive sleep apnea syndrome. SpO2 Oxygen blood saturation, THO thoracic movements, ABD abdominal movements, THERM bucconasal thermistor, FLOW nasal pressure, EOG electrooculogram, ECG electrocardiogram, PTT pulse transit time (an indirect measure of respiratory effort). (b) Schematic representation of insufficient post-event ventilatory compensation (From Borel et al. Respirology 2012; 17: 601–610) 268 J.C. Borel et al.

5 minute epoch : sustained reduction in airflow amplitude during REM sleep

A2-C3 Arousal EOG THER FLOW THO ABD SpO 2 ECG

W REM S1 S2 S3 Hypnogram S4 REM

SpO 2, % ↓ SpO 2 ↑ PtCO 2 PtCO 2, mmHg

Overnight

Fig. 28.2 Polysomnographic pattern of REM sleep hypoventilation. (a) 5 min epoch. A2-C3

Electroencephalogram, SpO2 oxygen blood saturation, THO thoracic movements, ABD abdominal movements, THERM bucconasal thermistor, FLOW nasal pressure, EOG electrooculogram, ECG electrocardiogram. (b) Overnight hypnogram (see the increase in PtCO2 during REM sleep) (From Borel et al. Respirology 2012; 17: 601–610)

These distinct pathophysiological phenotypes are clinically relevant for identifying OHS subtypes responding to different PAP modalities. This has been recently demonstrated in clinical trials specifically dedicated to OHS with prominent OSAS or REM hypoventilation, respectively [27, 38].

28.3 Improving Early Diagnosis in Patients with Obesity- Related Chronic Respiratory Failure

In a stable state, the clinical presentation of OHS patients differs slightly from eucapnic obese patients referred to the sleep laboratory for suspicion of sleep- related breathing disorders. OHS patients are more likely to have class III obesity, to complain of severe sleepiness, and to exhibit multi-morbid conditions [39, 40]. However, a third of obese patients with chronic respiratory failure are diagnosed during an episode of acute respiratory failure [41–43]. This emphasizes the under- diagnosis of these patients before the end stage of the disease, hence the necessity for early identification [8]. An increase in venous bicarbonate concentration

[HCO3-v] has recently been proposed as a simple biomarker for identifying OHS −1 patients. A threshold of [HCO3-v] > 27 mMol L has been shown to be highly sensitive for the identification of OHS patients [13]. Furthermore, the presence of a 28 Chronic Ventilation in Obese Patients 269

Table 28.1 Staging of hypoventilation in obesity 0 At risk BMI > 30 kg m−2 OSA No hypercapnia I Obesity- BMI > 30 kg m−2 OSA/ Intermittent hypercapnia associated sleep hypoventilation during sleep, full recovery

hypoventilation during sleep during sleep (PaCO2 or PtcCO2 morning~evening) II Obesity- BMI > 30 kg m−2 OSA/ Serum bicarbonate associated sleep hypoventilation <27 mmol L−1 when awake, hypoventilation during sleep intermittent hypercapnia

during sleep (PaCO2 or PtcCO2 morning > evening) −2 −1 III Obesity BMI > 30 kg m OSA/ Serum HCO3 ≥27 mmol L hypoventilation hypoventilation when awake, HCO3 during sleep increased during day Sustained hypercapnia

(PaCO2 > 45 mmHg while awake) IV Obesity BMI > 30 kg m−2 OSA/ Sustained hypercapnia hypoventilation hypoventilation while awake, syndrome during sleep cardiometabolic comorbidities From [45]; Randerath W et al. Eur Respir J. 2016

raised base excess without diurnal hypercapnia could represent an early stage of obesity-related hypoventilation [44]. This concept of a gradual spectrum in obesity- related hypoventilation, recently included in a European Respiratory Society Task Force statement (Table 28.1) [45], could have important implications for the early identification and management of OHS patients: indeed, a treatment initiated earlier may have more impact than at the end stage of OHS with established comorbidities.

28.4 Treatment Modalities in Patients with Obesity-Related Chronic Respiratory Failure

28.4.1 Positive Airway Pressure Therapies

Positive airway pressure therapies (CPAP or NIV) represent the cornerstone of treatment for sleep breathing disorders. As previously described, most patients with obesity-related chronic respiratory failure suffer from severe OSAS: in these patients, CPAP efficiently reverses diurnal hypoventilation 27[ , 46, 47] and improves sleep parameters and clinical symptoms [27] when followed 2–3 months. Piper et al. [47] showed that failure of CPAP to normalize nocturnal gas exchanges (i.e., persistent oxygen desaturation during CPAP titration) does not preclude its efficacy after 3 months. NIV has also been envisaged as first-line therapy to treat sleep breathing disorders [48], raising the question of the optimal treatment between 270 J.C. Borel et al.

CPAP and NIV. Although no long-term studies have demonstrated whether NIV is more beneficial than CPAP on outcomes such as cardiovascular events, hospitalization, or mortality, three randomized controlled trials have compared the efficacy of these two modalities over 2–3 months [27, 47, 49]. Neither study has demonstrated the superiority of one modality to another with respect to daytime PaCO2 or rate of treatment failure (defined as hospital admission, persistent or worsening ventilatory failure, or nonadherence). NIV may have a more favorable impact than CPAP on health-related quality of life [27] and functional [27] or psychomotor criteria [47]; however, these results should be interpreted with caution since issued from exploratory analyses (secondary outcomes) in the studies. Moreover, two of these three trials [38, 47] did not include patients with less severe forms of OSAS [27] or with severe continuous and non-apneic oxygen desaturation under CPAP [47] who are more likely to respond to NIV [38]. In clinical practice (Fig. 28.3), in patients with obesity-related chronic respiratory failure and severe OSAS, an initial CPAP trial conducted for a duration of 2–4 weeks is recommended [50]. An assessment of CPAP efficacy should at least include nocturnal oximetry, ideally completed by transcutaneous PCO2, and respiratory polygraphy or polysomnography [51]. In case of persisting sleep-related hypoventilation despite adequate CPAP therapy, shifting to NIV is justified.

Patient with Obesity-related Hypoventilation

Severe OSAS (AHI ≥30 events/hour)

Yes No

CPAP trial for 2 to 4 weeks Non-Invasive with assessment of CPAP efficacy Ventilation Poly(somno)graphy+ PtcCO2

Persistant hypoventilation despite adequate CPAP therapy? Yes

Continue treatment with CPAP

Fig. 28.3 Proposed algorithm for choosing the appropriate PAP therapy in patients with obesity- related hypoventilation. NIV Noninvasive ventilation, AHI apnea and hypopnea index, and CPAP continuous positive airway pressure 28 Chronic Ventilation in Obese Patients 271

According to the AASM rules for scoring respiratory events in sleep, hypoventilation is scored when (1) arterial PCO2 is > 55 mmHg for ≥ 10 min or (2) there is an increase in arterial PCO2 ≥ 10 mmHg (in comparison to an awake supine value) to a value exceeding 50 mmHg for ≥ 10 min [52]. Finally, clinicians should be aware that auto-CPAP modes have not been designed to detect and report hypoventilation. Therefore, analysis of residual events based on built-in software of auto-CPAP devices may be falsely reassuring in spite of persistent hypoventilation and oxygen desaturation, particularly during REM sleep [53]. In the particular phenotype of obese patients who are mostly hypoventilators without severe obstructive sleep apnea and in patients with failure of a CPAP trial, NIV is the most common modality of treatment to control sleep breathing disorders [38]. NIV is more expensive and more complex to set up than CPAP, with a large range of ventilatory modes which require knowledge and experience in choice of appropriate modes and titration procedure.

28.4.2 Selecting the Mode of NIV and Titration Procedures

Currently NIV is mainly applied by bilevel positive airways pressure (BiPAP) with three main modes [9]: (1) the spontaneous mode “S” in which each pressurization by the ventilator is triggered and cycled by the patient; (2) the spontaneous/timed “S/T” mode in which, if the patient fails to trigger the ventilator, a pressurization within a given time frame is automatically delivered based on a backup respiratory rate; and (3) the timed mode “T” in which the NIV device delivers pressurizations at a preset respiratory rate, during a preset inspiratory time. Although there is a lack of data comparing these different modes on long- term outcome, the S/T mode is generally admitted as the most appropriate for these patients [27, 38, 41, 43, 54]. The spontaneous mode may promote central sleep apnea [55] and ineffective efforts (for triggering the ventilator) rendering it less effective than the S/T mode. In the S/T mode, a sufficient expiratory positive airway pressure (EPAP) should be set to prevent upper airway obstruction. Inspiratory positive airway pressure (IPAP) should be increased until abolition of hypoventilation. Table 28.2 reports the main settings applied in the most recent RCT published in the field. Under NIV, and particularly in S/T mode, asynchronies between patient and ventilator may occur. Patient-ventilator asynchronies can have a negative impact on sleep quality or correction of hypoventilation [56, 57]. This justifies a systematic overnight monitoring under NIV with the aim of adjusting ventilator settings and interface to suppress abnormal residual events [51, 58]. Manufacturers have developed other types of ventilatory modes such as volume- assured pressure support (VAPS) [59, 60] and auto-titrating noninvasive ventilation [61, 62]. By automatically adapting EPAP, IPAP, or backup respiratory rate (according to each specific algorithm), these modes have in theory the ability to provide appropriate ventilation during the different phases of sleep and body positions. Although two studies [59, 60] have reported greater improvements in nocturnal 272 J.C. Borel et al.

Table 28.2 NIV settings applied in patients with OHS according to the recent published RCTs EPAP IPAP Backup Ventilatory mean (SD), respiratory rate,

Reference mode cmH2O mean (SD), cmH2O mean (SD) Piper et al. S 10 (2) 16 (2) – [47] CPAP 14 (3) – – Borel et al. S/T 11 (2) 18 (3) 13 (2) [48] Murphy S/T 10 (2) 25 (3) 14 (1) et al. [63] S/T with 9 (1) Set IPAP = EPAP + [4 – 30] 14 (1) VAPS mean Vte = 657 (96) mL Masa et al. S/T with 7.8a Set IPAP = [18–22] 14a [27] VAPS Mean IPAP = 20 CPAP 11a Masa et al. S/T with 7.1a 18.2a 15a [38] VAPS Howard S/T 11.9 (2.3) 19.3 (2.8) 15 (2.7) et al. [49] CPAP 15.2 (2.8) S Spontaneous, S/T spontaneous/timed, VAPS volume-assured pressure support aSD non available hypoventilation using VAPS mode, the largest RCT prospectively comparing VAPS ventilation to classical S/T mode did not find any difference in terms of correction of PaCO2 or health-related quality of life after 3 months of treatment [63]. Regarding auto-titrating noninvasive ventilation, two RCTs including clinical and medico- economic outcomes are currently ongoing in patients with OHS (NCT01757444; NCT02342899). The clinical relevance of these specific modes (volume-assured pressure support and auto-titrating NIV) has thus yet to be clarified [64].

28.5 Long-Term Follow-Up of Patients with Obesity-Related Chronic Respiratory Failure: The Need to Screen Comorbidities and to Propose Multimodal Therapeutic Strategies

Uncontrolled studies have consistently reported a lower mortality rate in patients with obesity-related chronic respiratory failure treated with long-term NIV [43, 54, 65] compared to untreated patients [8, 14, 66]. However, mortality rate of these patients remains substantially higher than that of patients with simple obstructive sleep apnea [42]. Cardiovascular [41] and metabolic comorbidities [42] remain the major determinant of mortality in these patients treated by NIV. Thus, NIV should be combined with other modalities of treatment to further improve these risk factors. Interventional studies designed to allow weight loss in obese patients have shown that weight loss achieved either by bariatric surgery [67] or by lifestyle intervention [68] was associated with improvements in sleep-related breathing disorders and diurnal hypoventilation [69–72]. 28 Chronic Ventilation in Obese Patients 273

Increasing physical activity in patients with obesity-related respiratory failure is likely to be an essential lever for improving outcomes. However, these patients often have a very limited social activity and lack motivation regarding rehabilitation programs [73]. The implementation of NIV could be an appropriate time to initiate a rehabilitation program since nocturnal NIV itself may increase exercise tolerance [74]; in that way, a trial aimed at comparing the effect of an exercise and nutrition program in addition to NIV versus NIV alone is currently ongoing (https://clinicaltri- als.gov/ct2/show/NCT01483716). Modalities of exercise training in this population require further studies. For instance, in patients who hypoventilate during exercise, NIV during exercise training may increase performance and efficacy of training [75]. Combining respiratory muscle training with a low-calorie diet and a physical activity program may improve dyspnea and exercise capacity more than physical activity and diet alone [76]. Finally, home-based neuromuscular electrical stimulation might help morbidly obese patients to return to at least a minimal level of physical activity.

Conclusion Positive airway pressure therapies (CPAP and/or NIV) are the cornerstone treatment of patients with obesity-related chronic respiratory failure. In the absence of long-term studies showing which ventilator mode is most effective, the choice of nocturnal CPAP or NIV should be based on obtaining the best control of underlying sleep-related respiratory abnormalities. However, nocturnal pressure therapies cannot be considered as the only strategy: (1) there is a need to identify as early as possible patients at risk of developing obesity-related chronic hypoventilation and (2) to implement multimodal therapeutic approaches before the occurrence of less reversible comorbidities and unfavorable outcomes.

Conflicts of Interest: Jean Christian Borel is employed by AGIR à dom, a nonprofit home care provider. The other authors have no conflict of interest in relation to this chapter.

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67. Ashrafian H, Toma T, Rowland SP, Harling L, Tan A, Efthimiou E, et al. Bariatric surgery or non-surgical weight loss for obstructive sleep apnoea? A systematic review and comparison of meta-analyses. Obes Surg. 2015;25(7):1239–50. 68. Mitchell LJ, Davidson ZE, Bonham M, O'Driscoll DM, Hamilton GS, Truby H. Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta- analysis. Sleep Med. 2014;15(10):1173–83. 69. Boone KA, Cullen JJ, Mason EE, Scott DH, Doherty C, Maher JW. Impact of vertical banded gastroplasty on respiratory insufficiency of severe obesity. Obes Surg. 1996;6(6):454–8. 70. Lumachi F, Marzano B, Fanti G, Basso SM, Mazza F, Chiara GB. Hypoxemia and hypoventilation syndrome improvement after laparoscopic bariatric surgery in patients with morbid obesity. In Vivo. 2010;24(3):329–31. 71. Marti-Valeri C, Sabate A, Masdevall C, Dalmau A. Improvement of associated respiratory problems in morbidly obese patients after open Roux-en-Y gastric bypass. Obes Surg. 2007;17(8):1102–10. 72. Sugerman HJ, Fairman RP, Sood RK, Engle K, Wolfe L, Kellum JM. Long-term effects of gastric surgery for treating respiratory insufficiency of obesity. Am J Clin Nutr. 1992;55(2):597S–601S. 73. Jordan KE, Ali M, Shneerson JM. Attitudes of patients towards a hospital-based rehabilitation service for obesity hypoventilation syndrome. Thorax. 2009;64(11):1007. 74. Holland AE, Wadell K, Spruit MA. How to adapt the pulmonary rehabilitation pro- gramme to patients with chronic respiratory disease other than COPD. Eur Respir Rev. 2013;22(130):577–86. 75. Dreher M, Kabitz HJ, Burgardt V, Walterspacher S, Windisch W. Proportional assist ventilation improves exercise capacity in patients with obesity. Respiration. 2010;80(2):106–11. 76. Villiot-Danger JC, Villiot-Danger E, Borel JC, Pepin JL, Wuyam B, Verges S. Respiratory muscle endurance training in obese patients. Int J Obes (Lond). 2011;35(5):692–9. Part V How to Support Nutritionally the Critically Ill Obese Patient Nutritional Support in the Critically Ill Obese Ventilated Patient 29

Kasuen Mauldin and Janine W. Berta

29.1 Introduction

About 25–30% of patients admitted to an intensive care unit (ICU) are obese per body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) greater than or equal to 30.0 kg/m2, and these patients have a higher risk of having malnutrition in the ICU setting [1, 2]. Obesity is a chronic condition that is often characterized by low-grade systemic inflammation and associated with metabolic alterations that result in glucose intolerance, altered fuel utilization, and greater potential for loss of lean body mass [2, 3]. Critical illness is characterized by catabolic stress, indicating greater nutritional needs, especially protein, in critically ill obese patients [2, 3]. Critically ill obese patients requiring mechanical ventilation tend to have greater complications, such as acute respiratory distress syndrome and acute renal failure, during the course of ventilation [4]. This group of patients is also at risk for missed or delayed detection of malnutrition, which can result in increased hospital morbidity and longer lengths of stays [1, 2]. In the ICU setting, chronic disease-related malnutrition such as sarcopenic obesity, defined as loss of muscle mass with reduced physical function in the context of excess body fat, is of concern, and timely, tailored nutrition support can improve clinical outcomes [1, 3].

K. Mauldin, Ph.D., R.D. (*) • J.W. Berta, M.S., R.D., C.N.S.C. Department of Nutrition, Food Science, and Packaging, San José State University, San José, CA, USA Department of Clinical Nutrition, Stanford Health Care, Palo Alto, CA, USA e-mail: [email protected]; [email protected]

© Springer International Publishing AG 2018 281 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_29 282 K. Mauldin and J.W. Berta

29.2 Discussion and Analysis

In nutrition assessment of the critically ill obese patient, current guidelines recommend clinician focus on evidence of comorbidities that can make clinical management more difficult. Factors that put the obese ICU patient at highest risk are the presence of central adiposity, metabolic syndrome (evaluated by blood pressure and serum glucose, triglyceride, and cholesterol concentrations), and sarcopenia [2]. A nutrition-focused physical assessment of critically ill obese patients can help detect central adiposity, sarcopenic obesity, and malnutrition in obese mechanically ventilated patients and help guide nutrition interventions. Emerging methods such as computed tomography (CT) and ultrasound scans have been used to assess body composition or the analysis of lean versus fat mass, especially in the abdominal region. CT can identify low muscle volume and poor muscle quality, but it does require expensive equipment and exposure to radiation, and very obese patients may be difficult to analyze 5[ ]. Ultrasound scans can be conducted at bedside, with low patient burden, to measure muscle thickness, but recommendations for use in practice have yet to be established [6]. Other body composition analysis methods, such as bioelectrical impedance analysis, dual-energy X-ray absorptiometry, dilution techniques with isotopic water, air displacement plethysmography, and underwater weighing, are not appropriate or feasible in this patient population [3]. If possible, measuring waist circumference, as a proxy for central adiposity, may be more relevant to clinical outcomes than just calculating BMI [2]. The guidelines for assessing energy and protein needs in critically ill obese individuals have undergone several revisions within the past decade. Current guidelines are still based primarily on expert consensus and low-grade evidence. Further revisions to predictive equations can be expected as this body of evidence continues to evolve. Indirect calorimetry (IC) is heralded as the gold standard for measuring energy needs. There are several indications for indirect calorimetry (see Table 29.1). Particularly, obese critically ill patients may benefit from IC as predictive equations for this population are problematic. However, use of IC remains low, 0.8% of available cases [7]. Cost and lack of trained staff to conduct the measurement remain major barriers to implementation of this technology in clinical practice. When IC is available, the American Society for Parenteral and Enteral Nutrition (ASPEN) and Society of Critical Care Medicine (SCCM) recommend targeting enteral nutrition (EN) support at 65–70% of measured energy needs in order to promote steady weight loss [2]. As energy needs change with clinical condition progression, the IC measurement should be repeated as regularly as is feasible. Predictive equations for critically ill obese patients are designed to provide hypocaloric, high-protein nutritional regimens with the goal of steady weight loss and positive nitrogen balance. Hypocaloric feeding should be used with caution in patients who have renal or hepatic function impairment. When IC is not available, ASPEN and SCCM recommend targeting nutrition support regimens at 11–14 kcal/kg actual body weight for BMI between 30 and 50 kg/m2 and 22–25 kcal/kg ideal body weight for BMI > 50 kg/m2 (Table 29.2) with concurrent 29 Nutritional Support in the Critically Ill Obese Ventilated Patient 283

Table 29.1 Indications and contraindications for IC measurement [8] Contraindications or reasons to delay Indications for IC measurement IC measurement

• Acute or chronic respiratory syndrome • FiO2 greater than 60% • Large or open wounds • Acute changes in ventilation • Trauma within 1–2 h of the study • Multi-organ failure • Excessive moisture in the circuit • Post-op transplant • Inhaled nitric oxide or anesthetic • Sepsis, SIRS gas delivery • Use of sedation or paralytics • Patient instability • Malnutrition with altered body composition – Hemodynamics – Obesity – Body temperature – Underweight – Agitation – Ascites – PEEP > 16 cm H2O – Peripheral edema – Painful procedure within the – Limb amputation hour prior to the study • Failure to respond to nutrition support based on – General anesthesia 6–8 h predictive equations before study is completed • Evaluation of whether under/overfeeding is contributing to metabolic or respiratory distress – Hemodialysis 3–4 h before the study is completed – Nursing care cannot be avoided during the study • Leak in system > 1 L/min

Table 29.2 Weight-based BMI range Equation to estimate daily energy requirement equations for estimating 30–50 kg/m2 11–14 kcal/kg actual body weight energy requirements for > 50 kg/m2 22–25 kcal/kg ideal body weight various BMI ranges [2]

Table 29.3 Weight-based BMI range Equation to estimate daily protein requirement equations for estimating 30–40 kg/m2 2.0 g protein/kg ideal body weight protein requirements for 40 kg/m2 Up to 2.5 g protein/kg ideal body weight various BMI ranges [2] ≥ protein provision in a range from 2.0 g/kg ideal body weight for BMI 30–40 kg/m2 up to 2.5 g/kg ideal body weight for BMI ≥ 40 kg/m2 (Table 29.3) [2]. Early enteral feeding is a well-established practice in critical care. ASPEN and SCCM recommend initiating EN within 24–48 h in critically ill patients who are unable to maintain volitional intake, provided that the patient is hemodynamically stable. In the presence of a functional gastrointestinal tract, EN is always preferred as it provides many physiologic and cost benefits over parenteral nutrition (PN) [2]. Until recently, meeting the correct ratio of energy and protein for patients on hypocaloric, high-protein feeds required the addition of protein modulars, as the ratio of calories to protein in most standard enteral formulas was designed for the normal-weight patient population. Within the past 5 years, two formulas have been developed for use in the critically ill obese population, Peptamen Bariatric (Nestle) and Vital High Protein (Abbott). Both feature an energy-to-protein ratio 284 K. Mauldin and J.W. Berta that meets the needs of most patients with a BMI between 30 and 40 kg/m2 without the use of additional protein modulars. Both of these formulas are peptide- based, which may not be necessary for critically ill patients; however, the practicality of providing a ready to hang formula as opposed to a standard formula with additional protein modulars often outweighs the lack of indication for a peptide-based formula [2]. Standard practice for any hospitalized patient receiving EN therapy includes monitoring of energy and protein provision, fluid status, weight, stooling patterns, electrolytes, glycemic control, and micronutrients for long-term nutrition support patients. Obese critically ill patients are predisposed to metabolic derangements and should be closely monitored for hyperglycemia, hyperlipidemia, fluid overload, and hepatic fat accumulation [2]. Adequacy of protein provision can be monitored via nitrogen balance studies, provided that confounding losses from large wounds or drains are absent or quantifiable. Appropriate energy provision can be confirmed with repeat IC measurements. Patients who have undergone bariatric surgery are at risk for malabsorption and micronutrient deficiencies. These patients require lifelong daily micronutrient supplementation at twice the standard dose and routine biochemical monitoring of vitamin and mineral levels [9]. Bariatric and standard enteral formulas contain insufficient levels of vitamins and minerals to meet these increased needs. Additional supplementation via the parenteral route would not require an increase from the standard dose, as the gastrointestinal tract is bypassed, and therefore, malabsorption is not a concern. Initial enteral access is often achieved through a temporary nasoenteric feeding tube. If a patient requires enteral feeding for longer than 4 weeks, long-term surgical or endoscopic access should be considered. Selection of the device (gastrostomy, jejunostomy, gastrostomy-jejunostomy) and method of placement should meet the individualized needs of the patient [9]. Patients who have undergone a Roux-en-Y gastric bypass may tolerate gastrostomy placement into the remnant stomach without risk of aspiration. Jejunostomy tubes may be more appropriate for patients who have had a sleeve gastrectomy; however, gastric feeding has been reported successfully. Special consideration must be taken to properly secure the enteral access device, as dislodgement is an increased risk in patients with a large pannus [9]. EN is the preferred method of nutrition support, but there are certain conditions, such as gastrointestinal ischemia, intestinal obstruction, intractable vomiting and/or diarrhea, paralytic ileus, and any other situations where gastrointestinal rest is desired and where enteral feeding may not be possible [9]. In this case, PN may be initiated but only if PN support is planned for greater than 7 days. In general, a percutaneously inserted central venous catheter is placed into the superior vena cava to provide parenteral nutrition. The components of PN include water, electrolytes, vitamins, trace minerals, and energy-yielding macronutrients in the form of dextrose, amino acids, and fat emulsion [9]. All patients receiving PN should be monitored daily for potential catheter-related infections, hepatobiliary complications (steatosis and/or cholestasis), fluid overload, hypercapnia, hyperglycemia, and/or 29 Nutritional Support in the Critically Ill Obese Ventilated Patient 285 hypertriglyceridemia [2, 9]. Attention should also be paid to the rate of PN advance- ment, weight changes (not masked by fluid shifts), and nutrition adequacy. The target blood glucose range for critically ill patients is 140–180 mg/dL, and to prevent hyperglycemia, the carbohydrate (dextrose) content of PN should not exceed 7 g per kg body weight per day [9]. In addition, to prevent hypertriglyceridemia and associated complications (possibly pancreatitis, immunosuppression, and altered pulmonary function), the lipid content of PN should not exceed 1.0 g per kg body weight per day [10]. If serum triglyceride levels exceed 400 mg/dL but not greater than 500 mg/dL, then intravenous fat emulsion should be dosed at the minimum amount required to prevent essential fatty acid deficiency (typically 250 mL 20% lipid given once to twice per week) [10]. If serum triglyceride levels exceed 500 mg/dL, daily fat emulsion should be discontinued until triglyceride levels are below 500 mg/dL [10]. The electrolyte and micronutrient levels in parenteral solutions should be adjusted based on laboratory values checked per hospital protocols [9]. Given the benefits of EN over PN, repeated efforts should be made to transition the critically ill obese patient to enteral feeding when clinically feasible. During the transition, the amount of calories delivered by both EN and PN should not exceed total target estimated needs. As tolerance to EN improves, the amount of PN calories should be decreased and eventually discontinued when EN therapy exceeds 60% of target calorie requirements [2]. Of concern in critically ill obese mechanically ventilated patients is obesity hypoventilation syndrome, characterized by low blood oxygen (pO2 < 75 mmHg) and high blood CO2 (pCO2 > 45 mmHg) levels, and about 10–20% of patients with obesity are presumed to have this condition [4]. In patients with respiratory failure, who may be prone to CO2 retention, current guidelines stress the importance of avoiding overfeeding (i.e., nutrition support energy provision exceeds energy requirements) due to the risk of hypercapnia [2]. Overfeeding promotes lipogenesis, a metabolic process that produces significant CO2. Also of concern in this population is fluid overload, as extreme obesity tends to increase circulating blood volume and possible cardiovascular alterations that can impair fluid balance [4]. It is also recommended that energy-dense EN formulas (providing 1.5–2 kcal/mL) be considered for patients with acute respiratory failure, especially if they are in a state of volume overload and require fluid restriction 2[ ]. Lastly, current guidelines also recommend serum phosphate levels be monitored when nutrition support (EN or PN) is initiated in the ICU patient with pulmonary failure. Hypophosphatemia may contribute to respiratory muscle weakness, so close monitoring and prompt reple- tion are needed to optimize respiratory function in ventilated patients [2].

Conclusion Critically ill obese mechanically ventilated patients are at risk for chronic disease-related malnutrition and metabolic alterations. When providing nutrition care to this population, proper evaluation and documentation of nutrition assessment factors of concern will help guide the nutrition intervention. The goal of nutrition support for this population is to provide high-protein, hypocaloric 286 K. Mauldin and J.W. Berta

feeding, preferably via enteral access, in an effort to preserve lean body mass, promote lipolysis, and minimize the metabolic complications of overfeeding.

29.3 Key Recommendations

1. In nutrition assessment, evaluate for and document central adiposity, metabolic syndrome, and sarcopenia. 2. Use indirect calorimetry to assess energy needs. If indirect calorimetry is unavail- able, use suggested weight-based equations based on BMI range. 3. Enteral nutrition is preferred over parenteral nutrition support. 4. Nutrition support regimen should not exceed 65–70% of target energy needs as measured by indirect calorimetry. 5. Nutrition support regimen should provide high protein in a range from 2.0 g protein per kg ideal body weight per day for patients with BMI of 30–40 kg/m2 up to 2.5 g protein per kg ideal body weight per day for patients with BMI greater or equal to 40 kg/m2.

References

1. Mauldin K, O’Leary-Kelley C. New guidelines for assessment of malnutrition in adults: obese critically ill patients. Crit Care Nurse. 2015;35(4):24–30. 2. McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient—Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN). JPEN J Parenter Enteral Nutr. 2016;40(2):159–211. 3. Gallagher D, DeLegge M. Body composition (sarcopenia) in obese patients implications for care in the intensive care unit. JPEN J Parenter Enteral Nutr. 2011;35(5 suppl):21S–8S. 4. Dickerson RN. Management of the obese patient. In: Seres DS, Van Way CW, editors. Nutrition support for the critically ill. Cham: Humana Press; 2016. p. 173–93. 5. Beebe ML, Peterson SJ. Use of computed tomography scans to assess body composition. Support Line. 2015;37(3):9–15. 6. McGhee B, Roosevelt H. Application of ultrasonography for measuring change in lean body mass in acute care. Support Line. 2015;37(3):3–5. 7. Singer P, Singer J. Clinical guide for the use of metabolic carts: indirect calorimetry—no longer the orphan of energy estimation. Nutr Clin Pract. 2015;31:30–8. 8. Siobal MS, Baltz JE. Determining nutritional requirements. In: A guide to the nutritional assessment and treatment of the critically ill patient. Irving: American Association for Respiratory Care; 2013. p. 31–3. 9. Isom KA, Andromalos L, Ariagno M, et al. Nutrition and metabolic support recommendations for the bariatric patient. Nutr Clin Pract. 2014;29:718–39. 10. Mueller CM, Kovacevich DS, McClave SA, et al. The ASPEN adult nutrition support core curriculum. Silver Spring: American Society for Parenteral and Enteral Nutrition; 2012. Long-Term Outcomes After Mechanical Ventilation 30

Rose Franco and Rahul Nanchal

30.1 Introduction

Twenty-five years ago, the standard measure for outcomes after critical illness was the 28-day all-cause mortality. Long-term outcomes were a nascent field of investigation; the first organized report of 1-year outcomes after acute respiratory distress syndrome (ARDS) was published in the year 2003 [1]. In the past decade, the expanding arma- mentarium of therapies for critical illness and refinements in understanding its pathophysiology have led to improved survival rates but have created an increasing number of survivors that suffer from the long-term sequelae of critical illness. Manifestations of these long-term outcomes span a constellation of physical, cognitive, and mental domains and are collectively termed post-intensive care syndrome (PICS). Caregivers of survivors may be overwhelmed with this drastic life-changing event and can become affected with mood disorders, a phenomenon known as PICS-Family (PICS-F) [2, 3]. Close to two million hospitalizations each year in the USA alone are for acute respiratory failure, and approximately half require invasive mechanical ventilation [4]. Although steady improvements have been observed in short-term mortality rates, likely secondary to advances in general ICU supportive care, survivors remain at heightened risk for late mortality and morbidity. Survivors of acute respiratory distress syndrome (ARDS) typically have prolonged ICU stays and have been the most extensively studied group. However, recent additional studies on other at risk groups of patients such the elderly, survivors of sepsis and those requiring prolonged mechanical ventilation not ARDS related have slowly emerged. This chapter will review the physical, neurologic, and neurocognitive outcomes for survivors of critical illness and touch on the impact on caregivers. We will examine predictors of poor

R. Franco, M.D. • R. Nanchal, M.D., M.S. (*) Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA e-mail: [email protected]

© Springer International Publishing AG 2018 287 A.M. Esquinas, M. Lemyze (eds.), Mechanical Ventilation in the Critically Ill Obese Patient, https://doi.org/10.1007/978-3-319-49253-7_30 288 R. Franco and R. Nanchal long-term outcomes (patient characteristics, burden of comorbidities, and ICU practice patterns). Lastly we will review the current state of research into interventions that might change the outcomes and quality of life for patients and their families.

30.2 Impact on Health-Related Quality of Life

Health-related quality of life (HRQOL) measures have emerged as important patient-centric metrics of recovery post critical illness. HRQOL is a multidimen- sional concept that includes domains pertinent to physical, mental, emotional, neurocognitive, and social functioning. These domains are determined through the administration of questionnaires and comparison with published normative data. The Medical Outcomes Study 36-Item Short Form Health Survey, Standard Form (SF-36) is the most commonly used tool to measures HRQOL is survivors of critical illness. SF-36 comprises 36 items and measures both physical and mental health. The first report that prospectively evaluated the link between pulmonary dysfunction and functional disability in ARDS survivors was published by McHugh et al., who noted that scores for the Sickness Impact Profile (a crude quality of life measure) significantly improved 3 months post extubation but appeared to plateau thereafter up to 1 year. They also found that only a small proportion of the decreased physical functioning could be attributed to pulmonary dysfunction [5]. Weinert et al. used SF-36 in a small cohort of acute lung injury survivors 6–41 months post hospitalization to evaluate HRQOL [6]. They reported decrements in all domains compared to the general population with significantly more impairment in social functioning and mental health domains than those with chronic medical disorders. Several investigators across continents have subsequently demonstrated reduced HRQOL in survivors of critical illness; most cohorts received mechanical ventilation while hospitalized [7–11]. Although there appears to be a long-term cost to an acute episode of severe critical illness, other factors such as age, pre-illness functional status, chronic organ dysfunctions, and physiological reserve likely play an important role in determining post-illness trajectory of health and quality of life [12–15]. HRQOL comparisons of ARDS survivors to patients with chronic respiratory illnesses such as cystic fibrosis have suggested global physical functioning rather than pulmonary dysfunction as the etiology of decreased scores [16]. The lingering physical, emotional, cognitive, and social impacts of critical illness are key factors leading to reduced quality of life. Common physical manifestations of critical illness-related sequela include heterotopic ossifications, alopecia, tracheal stenosis, ischemic digits, striae, hearing loss, neuropathy, and muscle atrophy leading to weakness, frozen joints, and contractures. Equally important aspects of reduced HRQOL are mental health issues and neurocognitive impairment. These brain impairments may be slow to recover and more importantly lead to residual permanent disability [17–20]. Prolonged mechanical ventilation is a significant risk for post critical illness physical impairment and mortality [8, 21, 22]. The major factor affecting HRQOL in the initial months after critical illness requiring prolonged mechanical ventilation appears to be diminished physical capacity as a consequence of ICU-acquired weakness. Longer-term 30 Long-Term Outcomes After Mechanical Ventilation 289 studies of functional outcomes demonstrate that survivors even after 5 years have not returned to their normal predicted level of functioning and continue to experience new or persistent physical and neuropsychological impairments [19]. A 5-year cohort study of survivors of critical illness reported by Cuthbertson et al. found that during the 5 years after survivorship, the cumulative quality-adjusted life years remained significantly lower than that expected for the general population and suggested, based on these findings, survivors of critical illness be considered to have a lifelong diagnosis of critical illness associated with ICU admission with subsequent associated excess mortality, morbidity, and the requirement for ongoing health-care support [23]. Survivorship from critical illness may result in frequent physician visits, assistance with cares, and even continuous skilled nursing care. This creates additional health-care-associated costs that are on par with that seen with chronic disease states [19, 23, 24]. Lone et al. studied over 5500 survivors of acute illness and over 5 years after initial hospital discharge compared those requiring ICU care to those who did not. At 5 years, the ICU cohort had higher mortality, used more hospital resources, and had 51% higher mean 5-year hospital costs [25]. Excess resource use and mortality was greatest for younger patients without significant comorbidity 26[ ]. Additional collateral costs, financial due to lost income and reductions in HRQOL for both survivors and their caregivers, are likely underreported and frequently under-recognized by the health professionals caring for them [27–31]. Thus, our understanding of HRQOL post ICU has progressed beyond simple correlations of pulmonary function to quality of life to novel risk factors and the spectrum of long-term functional and neurocognitive limitations that lead to subsequent increased costs and health-care utilization. Subsequent sections in this chapter detail physical, neurocognitive, and caregiver burdens of survivorship from critical illness.

30.3 Physical Manifestations

Physical limitations are common after critical illness. Some are permanent. See Table 30.1.

30.3.1 Pulmonary Function

ARDS survivors are the best-studied cohort of mechanically ventilated patients in terms of subsequent pulmonary function and outcomes. Most studies report good pulmonary recovery with normal or near normal function achieved by 6 months to 1 year after the acute episode [1, 19]. Pulmonary function tests often demonstrate mild restriction or obstruction with an associated decreased diffusion capacity [32, 33]. When mild pulmonary function abnormalities are present beyond 1 year following the acute illness, they are associated with decreased HRQOL and in some studies are likely to remain permanent [9]. However, this mild degree of pulmonary dysfunction does not explain functional impairments in survivors [34]. In fact most survivors do not attribute their reduced quality of life and physical compromise to 290 R. Franco and R. Nanchal

Table 30.1 Complications Physical of critical illness. Weakness due to critical illness neuropathy/myopathy Contractures/frozen joints Ischemic digits Residual renal impairment Post-inflammatory pulmonary fibrosis/bronchiectasis Ventilator dependence Tracheal stenosis Scars (cosmesis) Alopecia Heterotopic ossifications Striae Hearing loss Taste changes Cognitive Attention deficits Executive function impairments Worsening dementia Psychological Depression Anxiety Post-traumatic stress disorder Addiction (narcotics/sedatives) Financial Uncovered/underinsured cost of care acute care and rehab care for first year Lost income disabled from occupation Delay in income disability support from all work Cost of additional home assistance or in home skilled nursing care Ongoing therapy costs Assist devices (ventilator, bed, canes, etc.) Family loss of income (caregiver) breathing difficulties 19[ , 35]. Lung imaging studies of ARDS survivors demonstrate reticular patterns, pulmonary fibrosis, and other parenchymal changes such as interlobular septal thickening which are more pronounced in the nondependent lung regions. These imaging abnormalities persist even at 5 years post ARDS; however, they are minor and constitute less than 10% of the lung parenchyma [36–38].

30.3.2 Neuromuscular Dysfunction

Weakness associated with critical illness (or ICU-acquired weakness (ICU-AW)) was recognized as one of the major sources of morbidity and mortality even as long ago as the late 1800s by Sir William Osler [39]. Studies have demonstrated that 30 Long-Term Outcomes After Mechanical Ventilation 291 muscle weakness develops even within the first hours after mechanical ventilation is initiated [40]. ICU-AW is a significant morbidity affecting up to one third of critically ill and may exceed 50% of those with ARDS and multi-organ failure [41]. Bolton et al. in 1984 reported on five ventilator-dependent patients who by electrophysiologic testing demonstrated a primary axonopathy which manifested as a mixed sensorimotor neuropathy [42]. An extensive meta-analysis of 24 studies utilizing all available testing (electromyogram, nerve conduction studies, and/or muscle and nerve histology) of 1421 critically ill patients found that 46% of patients demonstrated critical illness neuromyopathy [43]. ICU-AW is a major factor inhibiting the ability to liberate patients from mechanical ventilation and when present is associated with prolonged mechanical ventilation, longer ICU and hospital stays, and higher overall health-related costs as well as increased risk of death. It is also a key driver of long-term functional limitations experienced by survivors [44–48]. An international working recently proposed a simple and clinically relevant clas- sification system that uses basic clinical evaluations and bedside testing. It catego- rizes ICU-AW as a broad diagnosis of exclusion. The basic tenets include onset of diffuse, symmetrical generalized weakness during critical illness, ventilator dependence, and bedside muscle testing that demonstrates weakness (Medical Research Council or MRC Score) [49]. They further defined, critical illness polyneuropathy as ICU-AW in conjunction with electrophysiologic testing consistent with a sensorimotor axonal polyneuropathy. Finally they proposed using the term critical illness myopathy for those with ICU-AW and electromyographic or muscle biopsy proven myopathic features; presence of both muscle and nerve dysfunction was classified as critical illness myoneuropathy [50].

30.3.3 Etiology of Critical Illness Polyneuropathy and Myopathy

Table 30.2 lists factors that contribute to the development of critical illness- associated polyneuropathy and myopathy. Many investigators have reported a strong association of sepsis and systemic inflammatory response syndrome with the development critical illness polyneuropathy and myopathy [49]. Microcirculatory changes may create relative ischemia of the tissue and result in axonal injury and degeneration [51].

Table 30.2 Sources of Sepsis/SIRS critical illness Glucose metabolism derangement polyneuropathy and Medications myopathy Corticosteroids Neuromuscular blockers Synergistic effects with other medications Inactivity/disuse atrophy Catabolism Channelopathy 292 R. Franco and R. Nanchal

Elevated glucose levels can negatively impact mitochondrial function and therefore contribute to oxidative stress and cell death [52]. Hyperglycemia, in both surgical and medical critical illness, has been associated with ICU-acquired weakness. Van Den Berghe et al. demonstrated a significant reduction in the number of patients with neurophysiologic testing confirmed critical illness polyneuropathy with tight glycemic control [53–55]. However, in a large well-designed randomized trial, aggressive glucose control was shown to increase the risk of death in critically ill patients; therefore, intensive insulin therapy solely for the purpose of preventing critical illness polyneuropathy is not recommended [56].

30.3.4 Medications in Critical Illness Linked to Neuromuscular Dysfunction

It is difficult to replicate the true risk associated with specific drugs and drug-drug interactions likely because of confounding influence of other conditions such as renal replacement therapy, nutritional deficiencies, liver dysfunction, and medications that either directly or indirectly affect muscle and nerve function like amino- glycosides and vasopressors in those with systemic inflammatory response syndrome and severe sepsis. In animal models, administration of corticosteroids can produce selective muscle atrophy, particularly of fast-twitch fibers 57[ ]. Critical illness myopathy is a non- necrotizing diffuse process with fatty degeneration of the muscle fibers, fiber atrophy, and fibrosis [58]. In studies of the critically ill, where a muscle biopsy was used as the gold standard, the incidence is reported anywhere from 48 to 96% [59]. These lesions have also been linked to corticosteroids and paralytic exposure [58]. Thick- filament myopathy is a selective loss of myosin filaments seen with exposure to corticosteroid or paralytic agents and immobility [60]. Acute necrotizing myopathy microscopically characterized by extensive myonecrosis with vacuolization and phagocytosis of muscle fibers has also been linked to use of corticosteroids and paralytic agents and multisystem organ dysfunction [61]. In an ARDS study with ongoing evaluations over 1 year, the investigators reported that those patients who received systemic corticosteroids were more likely to have an associated decrease in 6 min walk distance at 3 months and diminished proximal weakness of the shoulder and hip girdle regions [1]. In a randomized study of corticosteroids for persistent ARDS, there was no improvement in 60-day mortality, but there were cases of neuromyopathy reported only in treatment arm receiving methylprednisolone [62]. Neuromuscular blockers, given to help with ventilator synchrony in ARDS, were traditionally considered a source of acquired neuromuscular weakness, but a well- designed prospective trial by Papazian et al. found that there was no added risk above that created by the etiology of the ARDS [63]. Further, the arm receiving neuromuscular blockade had significantly better survival thought to be related to attenuation of ventilator-induced lung injury (VILI) through enhanced patient- ventilator synchrony. The combined exposure to neuromuscular blockers with 30 Long-Term Outcomes After Mechanical Ventilation 293 systemic corticosteroids does appear to result in higher likelihood of residual neuromuscular weakness. Behbehani et al. found a threefold increase in the risk for significant weakness in patents with status asthmaticus who received treatment with both paralytics and systemic corticosteroids (10% vs. 30% for those receiving both agents) [64].

30.3.5 Role of Immobility and Other Factors

Factors that contribute to the development of myopathy in critical illness include inactivity, catabolism, inflammation, and derangement of membrane excitability. Lack of movement in the critically ill patient stimulates protein loss from the muscle beds. The role of nutrition in reducing the muscle loss and myopathy remains in question. Animal models suggest that rather than the nutritional status being a major factor, it is in fact the disuse of the muscle group that has the most deleterious impact [65]. Critical illness particularly sepsis rapidly induces a catabolic state with skeletal muscle wasting. Depressed protein synthesis and elevation of protein breakdown relative to protein synthesis resulting in a net catabolic state resulting in early skeletal muscle wasting in critically ill patients were demonstrated in an elegant study by Puthucheary et al. [66]. These findings were more severe in patients with multiple organ failure as compared to single organ failure. Other measures demonstrating a net catabolic state such as urinary nitrogen loss, low protein, and gluta- mine and DNA levels in muscle biopsies and upregulation of calpain and ubiquitin proteolytic pathways as well as increased apoptosis have been documented [67]. Acquired channelopathy may also be a significant contributor to the pathology of myopathy in critical illness. Allen et al. reported on acquired sodium channel dysfunction resulting in alteration in muscle-fiber excitability [68]. An important facet of failure to wean from mechanical ventilation and myopathy is diaphragmatic dysfunction related to mechanical ventilation and critical illness. The diaphragm is exquisitely susceptible to rest and the effects of sepsis on its function [69, 70]. Within hours of initiation of controlled ventilation, there is objective evidence of muscle breakdown and atrophy of the muscle [71, 72]. Preserving diaphragm function through selection of spontaneous ventilation modes would seem to intuitively counteract these effects; yet to date no study has shown this as a tangible reality.

30.3.6 Additional Physical Morbidities

Entrapment Neuropathy: The Toronto ARDS Outcomes study reported 6% prevalence of peroneal and ulnar nerve palsy. The presence of these complicates rehabilitation and prolongs time to recovery [1].. Heterotopic Ossification: Deposition of para-articular ectopic bone has been reported in the setting of trauma, burns, pancreatitis, and ARDS. Development of this condition is associated with paralysis and prolonged immobilization. In the 294 R. Franco and R. Nanchal

Toronto ARDS Outcomes Study, the prevalence was 5% [1]. This condition while remediable with surgical intervention, if left undetected/treated, can also hamper patients’ recovery. Cosmesis/Scars: The physical transformative nature of critical illness which may include scars from laparotomy, burns, striae from volume overload, tracheostomy, and central line scars have been reported by survivors to contribute to social isola- tion and sexual dysfunction [1].

30.4 Neurocognitive and Psychiatric Manifestations

Hopkins et al. in 1999 in an ARDS cohort first reported cognitive impairment in 30% of patients at 1 year [73]. Longer-term studies suggest that some of this may be permanent with some reporting deficits out to 6 years after the acute illness 74[ ]. While initial improvements can occur within the first 6–12 months, many continue to have significant chronic impairments years after discharge 75[ ]. A prospective study of long-term effects after ICU care involving mechanical ventilated patients who prior to their illness did not have known cognitive impairments demonstrated neurocognitive impairment in 11 of 34 (32%) patients that persisted for at least 6 months after illness. The areas with most involvement were the psychomotor speed, visual and working memory, verbal fluency, and visuo-construction 76[ , 77]. The etiology of cognitive impairment in critical illness is complex. Many factors such as hypoxemia, hypotension, delirium, glucose dysregulation, medication effects of sedatives and hypnotics, and the direct effects of sepsis and systemic inflammatory response can potentially serve as the source or contributor to brain injury and cognitive impairments in critical illness. See Table 30.3.

Hypoxemia: Hopkins et al. found mean oxygen saturation (Spo2) and the extent of hypoxemia correlated significantly with neurocognitive dysfunction 73[ ]. Hypoxemia has been associated with cortical atrophy and ventricular enlargement (suggesting neuronal loss) [78]. Hypotension: The contribution of low blood pressure is less clear. A mean blood pressure <50 mmHg and memory impairment at hospital discharge has been reported. Others have reported only a modestly correlated impairment with duration of hypotension and this does not persist beyond 1 year of follow-up [79]. Delirium: Delirium affects 60–80% of ventilated patients and may go unrecognized when there is not systematic screening [80]. Delirium has emerged as a strong risk factor for ICU and hospital length of stay and increased cost as well as long- term neurocognitive impairment and death [20, 81–84].

Table 30.3 Sources of Hypoxemia cognitive impairment Hypotension Sepsis/SIRS Delirium Glucose dysregulation Sedatives/analgesics 30 Long-Term Outcomes After Mechanical Ventilation 295

Glucose Dysregulation: Blood glucose dysregulation and neurocognitive function have been found to have an important association. In a study of ARDS survivors, the presence of moderate hyperglycemia while in ICU was associated with poorer neurocognitive outcomes [85]. Hypoglycemia was also associated with three times the risk for depression in patient with ARDS [86]. Sedatives/Analgesics: The study of impact of agents including sedatives, narcotics, and anesthetics on long-term neurocognitive function has not provided strong evidence of causality. There may be some populations that are more at risk such as the elderly and those with prior neurocognitive impairment [87, 88]. In a prospective controlled trial of mechanically ventilated patients, there were no differences seen in long-term cognitive outcomes when daily sedation interruptions were instituted [89]. Systemic Inflammatory Response Syndrome and Sepsis: The brain is at risk from both the direct deleterious effects on the microcirculation from the cytokines (IL 1 and IL 6) as well as the direct effects on neuronal function that these cytokines may have. Animal models have demonstrated excess levels of these cytokines in the pre- frontal and hippocampal areas and impact on learning and memory. Long-term outcomes study of sepsis survivors demonstrates impairments that persist years after hospital discharge [90–92]. The cumulative effect of these insults may result in brain damage and combined with the psychological reaction to the stresses of critical illness, medications, pain, altered sensory inputs, and an unfamiliar environment may contribute to development of neuropsychiatric sequelae. The impact of critical illness and neurocognitive decline in the elderly is an area of study that could provide significant insight for providers and patients and their families when grappling with the questions of critical illness care and the after care. A longitudinal study in older adults without premorbid neurocognitive impairments or dementia using objective measures of neurocognitive function demonstrated that those requiring acute care or critical illness hospitalization had a greater decline in neurocognitive function and new incident dementia compared to those who were not hospitalized [93]. Iwashyna et al. used the Health and Retirement Study (HRS) database to study over 1100 older Americans 7 years prior to and 8 years after critical illness. They found that severe sepsis was three times more likely to result in moderate to severe cognitive impairments that would add substantial health and social costs for the care of the aged. The cognitive impairments were a key factor in the inability to continue to live independently [18]. Psychiatric disorders are common among survivors of critical illness. Depression and anxiety in survivors range in prevalence from 10 to 58% [94]. In a systematic review of psychiatric morbidity related to ARDS survivors in 2008 [95], Davydow et al. reported a point prevalence of clinically significant depression ranging from 17% in a prospective study [96] to 43% in a retrospective study [6]. Age, sex, and severity of illness were not predictive of depression, but early post-ICU depressive symptoms were strongly predictive of reduction in quality of life and further depressive symptoms [26]. 296 R. Franco and R. Nanchal

In ARDS survivors the prevalence of depression is higher compared to that in the general critically ill population. Hopkins et al. found that the risk factors for depression included duration of mechanical ventilation, ICU length of stay, sedation, alcohol dependence, female gender, and younger age [97]. They also reported on predictors of ongoing anxiety at 1-year post ARDS finding more risk with a higher lung injury score and with a longer duration of mechanical ventilation. More recently focus has turned to recognizing the development of post-traumatic stress disorder (PTSD) in those surviving critical illness after the report in 1998 by Schelling et al. In this study of 80 survivors, 28% met criteria for diagnosis of PTSD up to 4 years after the acute illness [98]. PTSD usually develops following an event that triggers serious personal threat in which the subject experiences helplessness and intense fear. The symptoms are grouped into three clusters: hyperarousal symptoms, intrusive recollections, and avoidance/numbing symptoms. In another study, Kapfhammer et al. found 44% of ICU survivors at discharge from hospital had PTSD, and 24% still had symptoms 8 or more years later and that pre-existing psychopathology, higher benzodiazepine use, memories of frightening/psychotic experiences in ICU, and the absence of any ICU memory were risk factors for post-ICU PTSD [99]. Disturbing dreams and persecutory delusions experienced as part of delirium are also important risks for long-term development of PTSD [100]. Factual memories do not protect survivors from )PTSD. Myhren et al. evaluated 194 survivors and found 27% had post-traumatic stress, and the predictors for PTSD were higher education, optimism, factual recall, and memory of pain [28]. Pre-existing psychiatric disease may predispose some to ICU-related PTSD). Patel et al. prospectively assessed 160 ICU survivors (a mix of veterans and civilians) over 1 year after acute illness. Pre-existing PTSD and depression were strong markers for ICU-related PTSD risk [101]. Interventions to prevent or reduce psychological sequelae are being investigated. Jones et al. in a randomized controlled trial reported that ICU diaries may reduce the incidence of PTSD. They reported only 5% of their intervention cohort had clinically significant PTSD compared to 13% of controls [102]. The greatest benefit came from those who experienced symptoms earlier.

30.5 Risk Factors for Poor Functional Outcomes After Critical Illness

The degree of functional impairment prior to the critical illness, the age of the patient, and the severity of the critical illness are all factors that have substantial impact on predicting long-term outcomes. See Table 30.4. Chelluri et al. reported on 817 patients who were studied for 1 year after requiring prolonged mechanical ventilation. Surviving to discharge was more likely if they had less comorbidity, lower severity of illness scores, and better functional status prior to critical illness. At 1 year follow-up, 57% still needed caregiver assistance [103]. 30 Long-Term Outcomes After Mechanical Ventilation 297

Table 30.4 Risk factors for Age poor functional outcomes Pre-event health and functional status Severity of the critical illness Length of ICU stay Duration of ventilator support

Iwashyna et al. reported that after critical illness, neurocognitive and physical decline persisted for at least 8 years after an episode of sepsis, and this impairment altered patients’ ability to live independently. In fact even at 8 years post event, the likelihood of significant cognitive impairment was fourfold higher (32%) than matched controls for the elderly [18]. Increased age by itself may not have as much of an impact on outcomes as suggested by some studies. There results on outcome of mortality are mixed. In a study of 484 patients, Khouli et al. reported that at 6 months post discharge, one third had died. Predictors of death at 6 months were number of days of physical health not good in the 30 days prior to admission, a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and chronic pulmonary disease. The oldest survivors had the worse health-related quality of life [15]. Unroe et al. studied 126 patients who required prolonged mechanical ventilation (more than 21 days of ventilator support). Older age and more comorbid conditions predicted the need for discharge to a post-acute care facility. This single-center cohort contained on average sicker people with most not working, retired or disabled at time of illness, and with two comorbid conditions on average. At 1 year only 11 people (9%) were without functional dependence. The mean cost of care per patient was 306, 135 US dollars (SD: 285,467), and the total cohort cost of care was 38.1 million, with 3.5 million per independently functioning survivor at 1 year [21]. For this same cohort at the time of placement of tracheostomy, Cox et al. assessed expectations from both physicians as well as surrogates for patients (often family). The cohort of 126 had only 11 (9%) who were alive and independently functioning at 1 year. The patient surrogates projected survival at 93% and functional status and quality of life at 71% and 83%, respectively. Physicians also overestimated survivorship at 43% but were more realistic on functional status and quality of life (6% and 4%). Yet only 26% of surrogates reported that the physicians had discussed what to expect for survival, general health, and caregiving needs [104].

30.6 Caregiver and Family Burden

Caregiver burden has been studied over the last several decades, and any summary chapter on the long-term outcomes after critical illness would fall woefully short without consideration of this area. There is a physical and psychological toll that begins as soon as their family member becomes critically ill. Bedside vigils followed by assuming almost all responsibility for medical and psychological care for new more complex needs are a burden that without assistance could cause complete 298 R. Franco and R. Nanchal collapse of their health and well-being as well as that of the family unit. PTSD symptoms are common with reports ranging from 13 to 56% [105]. A task force of the Society of Critical Care Medicine in 2010 that met to explore these issues for family and patients proposed the term post-intensive care syndrome-family (PICS-F) and recommended that active assessment for and initiation of interventions to improve outcomes begin during the hospital stay [2, 3]. Based on the current evidence, limitations in active communication and understanding during the hospitalization contribute to some of the ongoing stress and even development of PICS-F [106]. Interventions trialed with some benefit include structured communication and active involvement of the family with care decisions during hospitalization [107] to setting up after ICU care clinics to address both patient and family needs. Yet the best path forward is not entirely clear. A recent multicenter study of 286 critically ill patients using a nurse-led intensive follow-up versus usual care found no difference in long-term outcomes with the nurse-led program yet costing significantly more [108]. More than half of ICU survivors who needed prolonged mechanical ventilation still required assistance of a family caregiver 1 year after their critical illness. This caregiver status implies that the caregiver as well as the survivor has not returned to full-time work status and the family unit suffers financial stressors as well as psychological and physical stressors that come with the caregiver status. Griffiths et al. reported a negative impact on family income by 33% of all patients at 6 months and 28% at 12 months [109]. Among all patients receiving care, 26% reported requiring greater than 50 h a week. More than 70% of survivors of critical illness receive their care from family members and as such are not compensated and are likely not in a position where they can be relieved of their responsibilities regularly such as one does in an structured care facility. As a result the caregivers have higher risk for PTSD, emotional distress, depression, and anxiety [103, 104, 110].

30.7 Potential Strategies to Optimize Long-Term Outcomes

Appropriate rehabilitation post ICU stay requires attention. In systematic comparative studies on rehabilitative interventions in the post-ICU patients, ICU diaries had the best potential effectiveness in reducing PTSD for patients [111, 112]. While structured nurse-supervised post-ICU care may be more resource draining without clear benefits above usual care, a self-help manual with instructions for physical therapy improved 6-month outcomes in physical function [113]. Based on the neurocognitive and physical residual impairments of critical illness, the next wave of research should focus on interventions to change these outcomes. In fact, some of the currently accepted ICU practices may contribute to the burden for rehabilitation. Sedating and “resting” the patient during the initial period of critical illness very likely contribute to residual weakness at discharge. The lighting, the sounds of the ICU, and care staff may contribute to delirium and risk for psychiatric dysfunction. Some experts have commented that rehabilitation should begin when the patient is admitted to the ICU. Early mobilization of the 30 Long-Term Outcomes After Mechanical Ventilation 299 critical ill may have a significant protective effect in reducing critical illness morbidity related to weakness [114] especially when coupled with interruption in sedation, delirium [115, 116]. The weight of evidence in favor of early mobilization is such that the European Respiratory Society and European Society of Intensive Care Medicine Task Force on Physiotherapy for Critically Ill Patients advocate for mobilization and muscle training instituted early [117]. The use of paralytics, the role of steroids, the control of glucose levels, and the ever present risk/benefit role of sedatives and analgesics in preventing and controlling delirium are all areas of investigation. Ongoing collaborative multicenter interventional studies in critical illness designed to study how we can improve the outcomes stated above are the current priority for International Critical Care and Medical societies. As we learn more and more about the care choices made for the patient with critical illness, the model for best practices during the acute stay and the post-ICU care will undergo future trans- formation that will lead to improvements in quality of life for patients and their families as well as further improve the associated morbidity and mortality of surviving critical illness.

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A Acute respiratory failure (ARF), 139, 142, Abdominal compartment syndrome (ACS), 67, 143, 207, 208 68, 71, 72 Adiposity, 46 definitions, 65, 66 Adjuvants clinical features alpha-agonist, 115 hemodynamics, 67 gabapentinoids, 115 imaging, 68 ketamine, 114 laboratory, 68 magnesium, 115 physical examination, 67 Adult respiratory distress syndrome symptoms, 67 (ARDS), 153 consequences, 69 clinical data, 160 definitions, 66 Air column width (ACW), 242 diagnosis, 68, 69 Airway passage, 51 etiologies, 67 Airway pressure release ventilation (APRV) invasive mechanical ventilation advantages, 168 PEEP, 72 disadvantages, 168 plateau pressure, 72 fixed modes, 169 recruitment maneuvers, 72 in obese critical care patients, 168 tidal volume, 72 personalised modes, 169 ventilator mode, 71 pressure control ventilation, 168 management, 70 protective lung ventilation, 168 noninvasive ventilation, 71 sedation requirements, 168 obesity, 69 timing, 169 positioning, 72–73 treatment, 168 pulmonary physiology, 70 Airway resistance, 205 Absolute humidity, 217 Airway size, 152 Acetazolamide, 83 Alpha-agonist, 115 Acute exacerbations of COPD (AECOPD), Alveolar collapse, 52 230 Analgesia, 114, 115 Acute hypercapnic respiratory failure (AHRF) adjuvants asthma, 232 alpha-agonist, 115 causes of, 229, 230 gabapentinoids, 115 contraindications, 230, 231 ketamine, 114 COPD, 230, 232 magnesium, 115 extra-pulmonary restrictive lung diseases, central adverse effects, 110 233 central neuraxial blocks, 117 indications, 230, 231 flupirtine, 114 non-CF bronchiectasis, 233 intraoperative non-opioid analgesic OHS, 234, 235 regimen vs. fentanyl-based Acute necrotizing myopathy, 292 analgesia, 112

Analgesia (cont.) Cardiogenic shock, 61 intraperitoneal infusions, 117 Cardiovascular events (CVEs), 46, 47, 146 multimodal approach, 112 Central neuraxial blocks, 117 neurocognitive and psychiatric Central sleep apnea (CSA) manifestations, 295 respiratory drive, 83 NSAIDs, 113 treatment, 83 paracetamol, 113–114 Cephalad displacement, 141 peripheral blocks, 116–117 Chemical control of breathing, 4–6 peripheral mechanisms, 110 in eucapnic obesity postoperative complications, 109 chemosensitivity, 5 regional anesthesia, 116 compensatory mechanisms, 4 surgical site infusions, 117 external elastic loading, 4 Apnea-Hypopnea Index, 78 HOVR, 5 Apneic oxygenation, 103 with OSA, 6 Apnoeas, 152 without OSA, 4, 5 Apocynin, 159 in hypercapnic obesity, 6–8 Aspiration pneumonitis, 252 Chemosensitivity, 5–9 Assist control (AC), 201 Chest wall deformity, 233 Asthma, 232 Cheyne-Stokes breathing, 83 Atelectasis Chronic obstructive pulmonary disease causes, 51–52 (COPD), 153 definition, 51 Chronic respiratory failure (CRF), 207, 209 meta-analysis, 53 Comorbidities outcomes, 52 adiposity, 46 PEEP, 53 asthma, 47 predicted body weight formula, 53 cardiovascular events, 46, 47 prevention, 52 chronic kidney disease, 47 recruitment maneuvers, 53 chronic obstructive pulmonary disease, 47 tidal volume setting, 52 coronary artery disease, 47 treatment, 53 heart failure, 46 Atelectrauma, 153 hypertension, 46 Auto-titrating noninvasive ventilation, 271 left ventricular hypertrophy, 46 Average volume-assured pressure support microalbuminuria or proteinuria, 47 (AVAPS) mode, 81, 82, 169, 200 obesity hypoventilation syndrome, 47 obstructive and central sleep apnea, 47 percutaneous coronary intervention studies, B 44, 45, 47 Barotrauma, 146, 148 PICO strategy, 44 Bedside test, 159 Sao Paulo Epidemiologic Sleep Study, 47 Bi-level positive airway pressure Sleep Heart Health Study, 48 (BPAP/BiPAP), 81, 82, 154, 194, Wisconsin Sleep Cohort Study, 47 200, 201, 207 Congestive heart failure (CHF), see Heart devices, 202 failure OHS (see Obesity hypoventilation Continuous positive airway pressure (CPAP), syndrome (OHS)) 81, 82, 154, 194, 201, 252 respiratory mechanics and physiology, 207 treatment modality, with OSA, 207 Biotrauma, 153 Conventional oxygen therapy (COT)

Breathing pattern, 158 FiO2, dilution of, 216 inspired gases, humidification and heating, 217 C rational for, 216 Carbon monoxide diffusion capacity Coronary artery disease, 47 (DLCO), 206 Critical illness, 289–296 Cardiac chair position, 142 caregiver and family burden, 297, 298 Index 309

neurocognitive and psychiatric post-extubation laryngeal edema, 243 manifestations post-laryngeal extubation, 243 cognitive impairment, 294 receiver operator characteristic curve delirium, 294 analysis, 242 glucose dysregulation, 295 risk factors, 240, 241, 245 hypotension, 294 secretions and cough, 241 hypoxemia, 294 unplanned extubation, 243–244 psychiatric disorders, 295 upper airway obstruction, 242 PTSD, 296 Cyclical waxing, 83 sedatives/analgesics, 295 sepsis, 295 systemic inflammatory response D syndrome, 295 Decannulation process physical manifestations non-invasive ventilation, 188 acquired channelopathy, 293 percutaneous dilatational vs. surgical acute necrotizing myopathy, 292 tracheotomy, 188 complications, 289, 290 positioning, 188 corticosteroids, 292 spontaneous breathing, 187, 188 cosmesis/scars, 294 Delirium, 294 diaphragm, 293 prevention and management, 245 entrapment neuropathy, 293 psychoactive medications, 245 factors, 293 Dexmedetomidine, 110 heterotopic ossification, 293 neuromuscular blockers, 292 neuromuscular dysfunction, 290–291 E polyneuropathy and myopathy, 291 End-expiratory lung volumes (EELV), 29 pulmonary function, 289–290 Enteral nutrition (EN), 283 systemic corticosteroids, 292, 293 Entrapment neuropathy, 293 thick-filament myopathy, 292 Epinephrine nebulization, 243 risk factors, 296, 297 Eucapnic obesity, 4–6 strategy, 298, 299 chemical control of breathing Critically ill obese patient, 52, 239–245 chemosensitivity, 5 atelectasis compensatory mechanisms, 4 body weight formula prediction, 53 external elastic loading, 4 causes, 51–52 HCVR, 5 meta-analysis, 53 with OSA, 6 outcomes, 52 without OSA, 4–6 PEEP, 53 respiratory drive, 4 prevention, 52 Expiratory positive airway pressure (EPAP), recruitment maneuvers, 53 200, 207 tidal volume setting, 52 Expiratory reserve volume (ERV), 152 treatment, 53 Extracorporeal membrane oxygenation post-extubation failure (ECMO), 159 ACW, 242 Extraparenchymal restrictive respiratory clinical background, 239 disorders, 153 congestive heart failure, 245 Extra-pulmonary restrictive lung diseases, 233 cuff leak test, 242 delirium, 245 high airway resistance, 240 F low respiratory system compliance, 240 Fiberoptic bronchoscopy, 53 myocardial ischemia, 245 Flexible bronchoscopy, 53 NIPPV, 245 Flupirtine, 114

pathophysiologic mechanism, 240 Fraction of alveolar oxygen (FAO2), 100 PES, 243 Fraction of expired oxygen (FEO2), 101 310 Index

Fraction of inspired oxygen (FiO2), 196 PEEP, 219 Functional residual capacity (FRC), PIP, 219 146, 152 indications hypoxemic acute respiratory failure, 220 G post-extubation support, 221 Gabapentinoids, 115 postoperative period, 221 Gas exchange, 17, 29, 33, 34 preoxygenation, before endotracheal Gel masks, 194 intubation, 222 Glucose dysregulation, 295 in obese patients, 223 technical characteristics, 217, 218 High tidal volume, 146 H Humidification, 203, 217 Head-elevated laryngoscopy (HELP) Hybrid modes, 201 position, 140, 141 Hypertension, 46 Health and Retirement Study (HRS) Hypophosphatemia, 285 database, 295 Hypopnoea syndrome, 152, 252 Health-related quality of life (HRQOL) Hypotension, 294 ARDS vs. patients with chronic respiratory Hypoventilation, 266 illness, 288 Hypoxemia, 158, 159, 294 critical illness, 288 domains, 288 functional outcomes, 289 I physical manifestations, 288 ICU-acquired weakness (ICU-AW), 290 prolonged mechanical ventilation, 288 Indirect calorimetry (IC), 282, 283 recovery post critical illness, 288 Inspiratory positive airway pressure (IPAP), SF-36, 288 200, 202, 207 Sickness Impact Profile, 288 Intelligent volume-assured pressure support survivorship, 289 (iVPAPS), 200 Heart failure, 46 Intra-abdominal hypertension (IAH), 67, 68 cardiogenic shock, 61 clinical features definition, 57, 58 hemodynamics, 67 diagnosis, 58 imaging, 68 myocardial infarction, 61 laboratory, 68 obesity paradox, 60 physical examination, 67 pathophysiology, 58, 59 symptoms, 67 right ventricular functional and consequences, 69 morphologic alterations, 59 definitions, 65, 66 therapy, 60–61 diagnosis, 68, 69 weight loss, 61 etiologies, 67 Heart failure with preserved ejection fraction obesity, 69 (HFpEF), 58 pulmonary physiology, 70–71 Heart failure with reduced ejection fraction Intra- and postoperative respiratory (HFpEF), 58 complications, 145 Heat and moisture exchangers (HME, 203 Intraoperative ventilation Heated humidifiers (HH), 203 PEEP, 146, 147 Hemodynamics, 67 RM, 147, 148 Heterotopic ossification, 293 Intraperitoneal infusions, 117 High-flow nasal cannula (HFNC) oxygen Intrinsic positive end-expiratory pressure therapy, 219–222 (iPEEP), 151, 158 advantages, 223 Isothermic saturation, 217 dead space washout, 220

FiO2 dilution, 219 gas mixture, humidification and K heating, 219–220 Ketamine, 114 Index 311

L N Lateral decubitus position, 141 N-acetylcysteine, 159 Leptin, 8, 9 Neuromuscular blockers, 292 Lorrain-Smith effect, 159 Neuromuscular diseases (NMD), 233 Lungs Nocturnal breathing disorders, 59 atelectasis, 203 Nocturnal polysomnography, 79 elastance and resistance, 30 Non-CF bronchiectasis, 233 mechanics, 151 Non-communicable disease (NCD), 15 posterior and basal segments, 52 Noninvasive positive pressure ventilation recruitment, 147 (NIPPV), 155 volumes and functions, 18, 19, 29, 152 with acute hypercapnia failure, 169, 170 advantage, 170 APACHE II score, 170 M in laryngeal edema, 243 Magnesium, 115 obesity arm, 170 Masks post-extubation failure, 245 helmets, 194, 195 preoxygenation, 101–102 nasal, 194, 195 prolonged inspiratory time, 170 nasal pillows, 194 respiratory failure, 170 oral, 194 role, 169 oronasal, 194 spontaneous/time ventilatory mode, 169 total face, 194, 195 time-mode options, 169 Mechanical ventilation, 32–35, 139 Noninvasive ventilation (NIV), 194–196, airway management, 32 229–235 complication, 152 AHRF due to derecruitments, 153 asthma, 232 duration, 154, 155 causes of, 229, 230 effects, 159 contraindications, 230, 231 extubation and weaning period, 35 COPD, 230, 232 indications, tracheotomy, 36 extra-pulmonary restrictive lung liberating process, 154 diseases, 233 respiratory pathophysiological changes, indications, 230, 231 164 non-CF bronchiectasis, 233 ventilatory support OHS, 233–235 aspects, 32 atelectasis, 53 body positioning, 35 beneficial effects, 253 driving pressure, 32 bilevel positive airway pressure, 253 gas exchange, 33–34 close double-tube circuit, 196 ling protection, 32 CPAP, 252 lung protection, 32 dead space, 196 monitoring respiratory mechanics, decannulation, 188 33–34 early, 260 PEEP functions, 34 exercise training, 273 plateau pressure, 33 expensive and complex, 271 pleural pressure, 33 feasibility and safety, 253 Mechanoreceptors, 110 gas exchange and spirometer values, 254 Medical Outcomes Study 36-Item Short Form immediate, 260 Health Survey, 288 implementation, 273 Medroxyprogesterone, 83 interfaces, 255 Monitoring Respiratory Mechanics, late, 260 33–34 lung resection surgeries, 254 Morbidity obesity, 139, 140, 142, masks 151, 202 fitting, 196 Mucolytics, 54 helmets, 194, 195 Myocardial infarction, 61 nasal, 194, 195 312 Index

Noninvasive ventilation (NIV) (cont.) severe hypercapnic respiratory failure, 265 nasal pillows, 194 Obesity hypoventilation syndrome (OHS), oral, 194 151–155 oronasal, 194 AHRF, 234, 235 total face, 194, 195 ARF, 207–209 upper airway obstruction, 195–196 arterial blood gas, 79 mechanical setting, 254–255 causes, 78 OHS, 261–262 clinical evaluation, 79 open single-tube circuit, 196 vs. COPD, 171 oxygen supply and interface, 196–197 CRF, 207, 209–211 positive end-expiratory pressures, 253 definition, 77, 206, 261 postoperative prophylactic use, 254 definitive test, 79 postoperative respiratory failure, 251–252 duration, 171 postoperative respiratory management, 252 long-term management, 171 pressure support ventilation, 253 mechanisms, 261 prevention, 254 morbidity, 207 prophylactic, 254 mortality, 207 settings, 272 nocturnal polysomnography, 79 side effects, 256 organ system derangements, 80 sleep breathing disorders, 269 outcomes, 171 treatment modality, 271 pathophysiology, 78, 80, 207, 261 Non-pulmonary-associated alterations, 28–29 preoperative and postoperative Nonsteroidal anti-inflammatory drugs cardiopulmonary complications, 80 (NSAIDs), 113 prevalence, 206 Nutritional support, 282–285 pulmonary function test, 79 in critically ill obese patients risks, 80 body composition analysis methods, sleep disordered breathing, 23 282 symptoms, 79, 206 central adiposity, 282 ventilator modes, 261 computed tomography, 282 Obesity paradox, 60 energy and protein provision, 284 Obesity supine death syndrome, 139 energy requirement estimation, 283 Obesity-related chronic respiratory failure, energy-to-protein ratio, 283 266–272 enteral access device, 284 cardiovascular and metabolic enteral nutrition, 283, 284 comorbidities, 272 factors, 282 hypoventilation, staging of, 269 hypophosphatemia, 285 long-term follow up, 272–273 indirect calorimetry, 282, 283 morbidity, 151 lipogenesis, 285 physiopathology malnutrition, 282 OSAS, 267 metabolic process, 285 REM sleep, 267, 268 micronutrient supplementation, 284 respiratory mechanics, 266 overfeeding, 285 treatment modalities parenteral nutrition, 284, 285 NIV settings, 271, 272 peptide-based formula, 284 positive airway pressure therapies, 269, protein requirement estimation, 283 270 sarcopenic obesity, 282 spontaneous mode (S), 271 ultrasound scans, 282 timed mode, 271 titration procedure, 271 Obstructive sleep apnea syndrome (OSAS), O 151, 152, 154, 155, 252, 265, 267 Obesity daytime symptoms, 78 definition, 265 definition, 78 prevalence, 265 OSA-induced nocturnal hypoxemia, 80 Index 313

pathophysiology, 81 fat deposition, 100

preoperative and postoperative FEO2, 101 cardiopulmonary complications, 80 FRC, 100 prevalence, 78 general anesthesia, 104 risk factors, 80 increased oxygen consumption and sleep disordered breathing, 22 alterations, 100 Oxygenation, 159 intubation, 100 life-threatening complications, 100 noninvasive positive pressure ventilation, P 101 Paracetamol, 113 patient positioning, 104 Parenchymal restrictive respiratory disorders, respiratory system, 99 153 SAP, 100 Parenteral nutrition (PN), 284, 285 slow method, 101

Percutaneous dilational tracheostomy (PDT), SpO2, 101 182 Pressure-controlled ventilation (PCV) Peripheral blocks, 116 in critical care, 165

Peripheral oxygen saturation (SpO2), 101 theoretical advantage, 165 Permissive hypercapnia, 34 vs. VCV, 166 Pickwickian’ syndrome, 23 Pressure-controlled ventilation volume Population, intervention, comparator, and guaranteed (PCV-VG), 166 outcome (PICO) strategy, 44 Pressure-regulated controlled volume (PRCV), Positive airway pressure (PAP) therapies, 81, 166 83, 269–271 Pressure support ventilation (PSV), 167, 201, Positive end-expiratory pressure (PEEP), 146, 253 154, 159, 202, 253 Prone position, 141, 159, 174 HFNC, 219 Proportional assist ventilation (PAV), 201 Positive inspiratory pressure (PIP), HFNC, Psychiatric disorders, 295 219 Pulmonary atelectasis, 251 Post-extubation failure Pulmonary consequences ACW, 242 breathing work, 30, 31 clinical background, 239–240 gas exchange, 29 congestive heart failure, 245 lung elastance and resistance, 30 cuff leak test, 242 lung volume, 29 delirium, 245 respiratory efficiency, 30, 31 high airway resistance, 240 upper airway anatomy, 29 low respiratory system compliance, 240 Pulmonary function tests, 206 myocardial ischemia, 245 Pulmonary physiology, 70 NIPPV, 245 pathophysiologic mechanism, 240 PES, 243 R post-extubation laryngeal edema, 243 Ramped position, 140, 141 post-laryngeal extubation, 243 Real-time ultrasound guidance (RUSG), 184 receiver operator characteristic curve Recruitment-derecruitment phenomenon, 153 analysis, 242 Recruitment maneuvers (RM), 147, risk factors, 240, 241, 245 148, 172 secretions and cough, 241 ACS, 72 unplanned extubation, 243 atelectasis, 53 upper airway obstruction, 242 Refractory hypoxemia, 202 Post-extubation stridor (PES), 243 Regional anesthesia, 116 Post-traumatic stress disorder (PTSD), 296 REM sleep, 267 Preoxygenation Respiratory comorbidities, 52 apneic oxygenation, 103 Respiratory complications, 146 fast method, 101 Respiratory cycle, 153 314 Index

Respiratory mechanics, 266 prevalence, 78 background, 15 risk factor, 80 compliance, 18 treatments, 81 continuous positive airway pressure, 18 Sleep Heart Health Study, 48 functional residual capacity, 18 Sleep-disordered breathing, 152–154 gas exchange, 17 fat distribution, 21–22 human diaphragm, 16 leptin resistance, 22 lung volumes, 18, 19 obesity hypoventilation syndrome NCD, 15 (OHS), 23 pressure–volume curves, 18, 20 OSA, 22 respiratory muscle pump, 16, 17 weight gain, 22 Respiratory neural drive, 4 Sleep-related breathing disorders (SRBD), 59 Respiratory physiology, 154 Sniff position, 140 Respiratory physiotherapy, 146 Standard Form (SF-36), 288 Respiratory system compliance, 151, 152 STOP-BANG score, 81 Reverse Trendelenburg positiin, 173 Supine position, 139 Rigid bronchoscopy-guided tracheostomy, 183 Surgical tracheostomy, 182, 185 Systemic corticosteroids, 292, 293 Systemic inflammatory disorder, 152 S Systemic inflammatory response Safe apnea period (SAP), 100 syndrome, 295 Sao Paulo Epidemiologic Sleep Study, 47 Sedation, neurocognitive and psychiatric manifestations, 295 T Sepsis, 295 Thick-filament myopathy, 292 Sickness Impact Profile, 288 Total lung capacity (TLC), 151, 152 Sitting position, 142, 143 Total respiratory system compliance, 205 Sleep apnea, 59 Tracheostomy, 81, 82 Sleep breathing disorders, 77–81, 83 anatomic variations, 181 CSA complication rates, 182 respiratory drive, 83 contraindications, 180 treatment, 83 indications, 180 OHS optimal timing, 181 arterial blood gas, 79 patient’s anatomy and comorbidities, 181 causes, 78 PDT, 182, 183 clinical evaluation, 79 rigid bronchoscopy-guided tracheostomy, definition, 77 182–184 definitive test, 79 RUSG, 184 nocturnal polysomnography, 79 surgical, 182, 185 organ system derangements, 80 Transpulmonary pressure (TPP), 33, 153 pathophysiology, 78, 80 Trendelenburg position, 139, 140 preoperative and postoperative cardiopulmonary complications, 80 pulmonary function test, 79 U risks, 80 Upper airway anatomy, 29 symptoms, 79 OSA daytime symptoms, 78 V definition, 78 Ventilation modes, 147, 165, 166, 172, 173 nocturnal hypoxemia, 80 APRV, 168–169 pathophysiology, 81 NIPPV, 168–170 preoperative and postoperative oesophageal pressure-guided mechanical cardiopulmonary complications, 80 ventilation Index 315

optimum PEEP, 172 pressure support ventilation, 201 recruitment manoeuvres, 172–173 proportional assist ventilation, 201 respiratory failure, 172 respiratory rate, 202 in supine position, 172 reverse Trendelenburg position, 201 OHS, 169–171 sitting position, 201 open lung ventilation, 167 tidal volume, 202 PCV volume-controlled NIV, 202 in critical care, 165 Ventilator-induced lung injury (VILI) theoretical advantage, 165 characterization, 157–158 vs. VCV, 166 clinical data, 160 PCV-VG, 166 fatty deposition, 158 PRCV, 166 medical treatment, 159 proning, 174 respiratory mechanics, 158 PSV, 167 ventilation-perfusion mismatch, 158 reverse Trendelenburg position, 173 Ventilatory support VCV aspects, 32 vs. PCV, 166 body positioning, 35 target volume, 165 driving pressure, 32 Ventilation perfusion mismatch, 206 gas exchange, 33–34 Ventilation-perfusion ratio (shunt effect), 141 lung protection, 32 Ventilator, 201–203 PEEP functions, 34 assist-control mode, 200 plateau pressure, 33 hybrid mode, 200 pleural pressure, 33 ICU, 200 respiratory mechanics, 33–34 NIV modes, 200 Volume-assured pressure support (VAPS), 271 pressure-cycled, 200 Volume-controlled ventilation (VCV) settings vs. PCV, 166 assist control, 201 target volume, 165 BPAP, 201 Volutrauma, 157 continuous positive airway pressure, 201 humidification, 203 W hybrid modes, 201 Waning pattern, 83 low initial pressures, 202 Wisconsin Sleep Cohort Study, 47