Physiology of the Respiratory Drive in ICU Patients: Implications for Diagnosis and Treatment Annemijn H

Jonkman et al. Critical Care (2020) 24:104 https://doi.org/10.1186/s13054-020-2776-z REVIEW Open Access Physiology of the Respiratory Drive in ICU Patients: Implications for Diagnosis and Treatment Annemijn H. Jonkman1,2†, Heder J. de Vries1,2† and Leo M. A. Heunks1,2* Abstract This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http:// www.springer.com/series/8901. Introduction chapter is to discuss the (patho)physiology of respiratory The primary goal of the respiratory system is gas ex- drive, as relevant to critically ill ventilated patients. We change, especially the uptake of oxygen and elimination discuss the clinical consequences of high and low re- of carbon dioxide. The latter plays an important role in spiratory drive and evaluate techniques that can be used maintaining acid-base homeostasis. This requires tight to assess respiratory drive at the bedside. Finally, we control of ventilation by the respiratory centers in the propose optimal ranges for respiratory drive and breath- brain stem. The respiratory drive is the intensity of the ing effort, and discuss interventions that can be used to output of the respiratory centers, and determines the modulate a patient’s respiratory drive. mechanical output of the respiratory muscles (also known as breathing effort) [1, 2]. Detrimental respiratory drive is an important contribu- Definition of Respiratory Drive tor to inadequate mechanical output of the respiratory The term “respiratory drive” is frequently used, but is muscles, and may therefore contribute to the onset, dur- rarely precisely defined. It is important to stress that the ation, and recovery from acute respiratory failure. Studies activity of the respiratory centers cannot be measured in mechanically ventilated patients have demonstrated directly, and therefore the physiological consequences detrimental effects of both high and low breathing effort, are used to quantify respiratory drive. Most authors de- including patient self-inflicted lung injury (P-SILI), critical fine respiratory drive as the intensity of the output of illness-associated diaphragm weakness, hemodynamic the respiratory centers [3], using the amplitude of a compromise, and poor patient-ventilator interaction [3, 4]. physiological signal as a measure for intensity. Alterna- Strategies that prevent the detrimental effects of both high tively, we consider the respiratory centers to act as oscil- and low respiratory drive might therefore improve patient latory neuronal networks that generate rhythmic, wave- outcome [5]. like signals. The intensity of such a signal depends on Such strategies require a thorough understanding of several components, including the amplitude and fre- the physiology of respiratory drive. The aim of this quency of the signal. Accordingly, we propose a more precise but clinically useful definition of respiratory drive: the time integral of the neuronal network output * Correspondence: [email protected] †Annemijn H. Jonkman and Heder J. de Vries contributed equally to this of the respiratory centers, derived from estimates of work. breathing effort. As such, a high respiratory drive may 1Department of Intensive Care Medicine, Amsterdam UMC, Location VUmc, mean that the output of the respiratory centers has a Amsterdam, The Netherlands 2Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC, higher amplitude, a higher frequency, or both. Amsterdam, The Netherlands © Jonkman et al. 2020 Jonkman et al. Critical Care (2020) 24:104 Page 2 of 10 The respiratory drive directly determines breathing ef- expiratory flow. Post-inspiratory activity increases the fort when neuromuscular transmission and respiratory time before the respiratory system reaches end- muscle function are intact. We define breathing effort as expiratory lung volume. This can lead to a more laminar the mechanical output of the respiratory muscles, in- expiratory flow and might prevent alveolar collapse, cluding both the magnitude and the frequency of re- while also increasing the duration of gas exchange in the spiratory muscle contraction [1]. alveoli [2]. Post-inspiration is a common part of the breathing cycle in healthy subjects at rest, but disappears What Determines the Respiratory Drive? rapidly when respiratory demands increase, to favor fas- Neuroanatomy and Physiology of the Respiratory Control ter expiration [8] (Fig. 2). Centers The importance of the post-inspiratory phase in mech- The respiratory drive originates from clusters of inter- anically ventilated patients remains unclear, as the onset neurons (respiratory centers) located in the brain stem and duration of inspiratory and expiratory flow depend (Fig. 1)[2]. These centers receive continuous informa- predominantly on the interplay between ventilator set- tion from sources sensitive to chemical, mechanical, be- tings (e.g., cycle criteria, breathing frequency, ventilator havioral, and emotional stimuli. The respiratory centers mode) and the respiratory mechanics of the patient. integrate this information and generate a neural signal. Additionally, the endotracheal tube bypasses the actions The amplitude of this signal determines the mechanical of the upper airway muscles. Experimental data in pig- output of the respiratory muscles (and thus tidal vol- lets suggest that post-inspiratory activity of the dia- ume). The frequency and timing of the neural pattern phragm prevents atelectasis and possibly cyclic alveolar relates to the breathing frequency and the duration of recruitment [9], although studies in patients weaning the different phases of the breathing cycle. Three phases from the ventilator did not find clear evidence for post- can be distinguished in the human breathing cycle: in- inspiratory activity [10]. Clearly, this field requires fur- spiration, post-inspiration, and expiration (Fig. 2). Each ther research. phase is predominately controlled by a specific respiratory center (Fig. 1)[2]. Expiration Expiration is generally a passive event during tidal Inspiration breathing. The elastic recoil pressure of the lungs and Inspiration is an active process that requires neural acti- chest wall will drive expiratory flow until the lung and vation and subsequent contraction (and energy expend- chest wall recoil pressures are in equilibrium at func- iture) of the inspiratory muscles. The pre-Bötzinger tional residual capacity, or at the level of positive end- complex, a group of interneurons positioned between expiratory pressure (PEEP) in mechanically ventilated the ventral respiratory group and the Bötzinger complex patients. In passive conditions, expiratory flow depends in the brain stem (Fig. 1), is the main control center of solely on the time-constant (i.e., the product of compli- inspiration [2]. The output from the pre-Bötzinger com- ance and resistance) of the respiratory system. The ex- plex increases gradually during inspiration and rapidly piratory muscles are recruited with high metabolic declines when expiration commences. Axons of the pre- demands, low inspiratory muscle capacity, increased Bötzinger complex project to premotor and motor neu- end-expiratory lung volume, and/or increased expiratory rons that drive the inspiratory muscles and the muscles resistance [11]. of the upper airways. The pre-Bötzinger complex has The lateral parafacial nucleus controls the expiratory multiple connections to the other respiratory centers, phase of breathing. An increased respiratory drive leads which is thought to ensure a smooth transition between to late-expiratory bursts, and consequent recruitment of the different breathing phases and to prevent concomi- the expiratory muscles (extensively reviewed in reference tant activation of opposing muscle groups [6]. [11]). Several inhibitory connections exist between the inspiratory pre-Bötzinger complex and the expiratory Post-inspiration lateral parafacial nucleus, which prevent concomitant ac- The aptly named post-inspiratory complex controls the tivation of inspiratory and expiratory muscle groups transitional phase between inspiration and expiration by (Fig. 1)[2, 6]. reducing expiratory flow. This is achieved by gradually reducing the excitation (and thus contraction) of the in- Feedback to the Respiratory Control Centers spiratory muscles, which leads to active lengthening (i.e., Central Chemoreceptors eccentric contractions) of the diaphragm [2, 7]. Add- The most important chemoreceptors in the central ner- itionally, the post-inspiratory center controls the upper vous system are positioned on the ventral surface of the airway muscles. Contraction of the upper airway muscles medulla and near the ventral parafacial nucleus (also re- increases expiratory flow resistance, effectively reducing ferred to as the retrotrapezoid nucleus). These receptors Jonkman et al. Critical Care (2020) 24:104 Page 3 of 10 Fig. 1 Schematic representation of the anatomy and physiology of respiratory drive. The respiratory centers are located in the medulla and the pons and consist of groups of interneurons that receive information from sources sensitive to chemical, mechanical, behavioral, and emotional stimuli. Important central chemoreceptors are located near the ventral parafacial nucleus (pFV) and are sensitive to direct changes in pH of the cerebrospinal

Load more