Ventilator-Induced Lung Injury: Classic and Novel Concepts

Bhushan H Katira

Introduction Classic Concept Heart-Lung Interactions Can Contribute to VILI Lung Deflation Injury Effort-Induced Lung Injury Summary

Ventilator-induced lung injury (VILI) is a central confounder to improving outcomes from use of positive-pressure ventilation in critical illness. Therefore, with increasing use of positive-pressure ventilation, awareness to prevent VILI has grown. Because VILI cannot be diagnosed at the bedside, its prevention can only be attained by identifying the clinical mechanisms of harm, such as high tidal volume, high plateau pressure, and so forth, which, in turn, are derived from decades of laboratory work. The practice of positive-pressure ventilation has undergone a significant change; most important in the past decade is the preference to use noninvasive ventilation. Although noninvasive ventilation prevents the complications of intubation, it has potential to cause harm, especially in patients with de novo respiratory failure. This review covers some of the classic and emerging concepts of VILI genesis and their role during noninvasive ventilation. Combined mod- ulation of these mechanisms could have a potential to impact outcomes. Key words: ventilator- induced lung injury; heart-lung interaction; lung deflation; effort-induced lung injury. [Respir Care 2019;64(6):629–637. © 2019 Daedalus Enterprises]

Introduction of delivering positive-pressure ventilation has significantly evolved with more sophistication and user friendliness.2 It Positive-pressure ventilation came into vogue with the is a life-saving therapy and, if instituted correctly, can alter 1950s polio outbreak1 and has become the very foundation outcomes in disease states, such as ARDS and asthma. It of critical care practice. Over the past 7 decades, the method can now be delivered without intubation, referred to as noninvasive ventilation (NIV), and has revolutionized the practice, especially in the field of long-term and/or home Dr Katira is affiliated with Translational Medicine, The Research Insti- use. tute, Hospital for Sick Children, Toronto, Ontario, Canada; Department However, despite being beneficial, positive-pressure of Critical Care Medicine, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and Interdepartmental Division of ventilation can harm the lungs in several ways and lead to Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada. what is called ventilator-induced lung injury (VILI). This was understood in the early days of mechanical ventila- Dr Katira presented a version of this paper at the 57th RESPIRATORY CARE tion, and the term respirator lung was used to identify lung Journal Conference, Noninvasive Respiratory Support in Adults, held June 14-15, 2018, in St Petersburg, Florida. injury on autopsy of patients exposed to positive-pressure ventilation during the polio epidemic.3 Over the past 5 de- Correspondence: Bhushan H Katira MBBS, Translational Medicine, The cades, VILI has been extensively studied and several mech- Research Institute, Hospital for Sick Children, 686 Bay St, Toronto, ON 4 M5G 0A4, Canada. E-mail: [email protected]. anisms of harm have been identified. It is important to understand VILI because it can confound outcomes, espe- DOI: 10.4187/respcare.07055 cially in the presence of significant lung disease of any

RESPIRATORY CARE • JUNE 2019 VOL 64 NO 6 629 VENTILATOR-INDUCED LUNG INJURY cause. This paper briefly described the origin of some of have an impact on VILI and, therefore, on outcomes in the classic concepts and the impact of their implementa- ARDS. In a recent study, Carteaux et al19 reported that the tion. It also discusses a few emerging concepts around use of exhaled VT during NIV (with an ICU ventilator VILI genesis: the contribution of hemodynamics and spon- circuit able to monitor exhaled volume) was an indepen- taneous breathing. dent risk factor for NIV failure when the predicted body Ͼ weight was 9.5 mL/kg. VT is usually not measured dur- Classic Concept ing NIV, and clinical response is inferred by reduction of

respiratory effort. A high effort would mean high VT, and As far back as the 1960s, by using several canine lung persistence of such high effort has been postulated to cause lobes, Faridy et al5 showed that increasing tidal volume patient’s self-inflicted lung injury.20 So, whether it is the

(VT) and lowering PEEP resulted in lower lung volume for ventilator that delivers the high VT or the patient who the same transpulmonary pressure. They concluded that breathes it in, the resultant effect is propagation of lung high VT and low PEEP resulted in higher surface forces. It injury (Table 1). is known today that high surface forces (as caused by As demonstrated by Webb and Tierney,7 PEEP was surfactant depletion) lead to collapse and inflammation (ie, protective for pulmonary edema and, hence, an integral VILI). Thereafter, in 1970, Mead et al6 demonstrated a part of lung-protective ventilation. In most disease states, wide range of shear strain distribution in a model of het- PEEP can be set according to an oxygenation response. erogeneous lung disease, which thus provided a mechan- However, in heterogenous lung disease, such as ARDS, ical basis of VILI. Later in 1974, Webb and Tierney7 determining the optimal PEEP is challenging because low published the first in vivo study of VILI. They showed that PEEP can cause atelectasis and high PEEP can cause over- healthy rats ventilated with peak airway pressures of inflation. Despite several physiologic studies that demon-

45 cm H2O and no PEEP died from florid (and hemor- strate the benefits of optimal PEEP as well as its determi- rhagic) pulmonary edema within 20–30 min; whereas add- nation, most randomized control trials of high versus low 21 ing a PEEP of 10 cm H2O while keeping the same peak PEEP failed to show any benefit in patients with ARDS. airway pressure caused minimum or no lung injury.7 Vas- This is particularly because of the inability to recognize cular interdependence (high hydrostatic pressure) was pos- recruitability of lungs. The clinical application of lung- tulated as the cause of pulmonary edema. 7 This was a key protective strategies continues to evolve and so does the paper in the field and inspired much research. understanding of VILI. This is particularly important be- In the early 1980s, key papers demonstrated that high cause the mortality in ARDS has plateaued over past

VT ventilation caused pulmonary edema by increasing mi- 2 decades. crovascular permeability, which led to protein and water 8,9 leak as well as inflammation. Limiting VT while keeping Heart-Lung Interactions Can Contribute to VILI the airway pressure similar protected the lung, which thus separated barotrauma from volutrauma.10,11 These evolv- In a recent paper, Katira et al22 repeated the classic work ing concepts led to the principle of lung-protective strat- by Webb and Tierney7 and studied hemodynamics by us- egies and paved the path for clinical studies by Hick- ing echocardiography, right and left ventricular pressures. ling et al12,13 who showed, in 2 different observational The original work demonstrated that healthy rats, when papers in the early 1990s, that limiting VT to achieve ventilated with high inflation pressures without PEEP, re- “permissive hypercapnia” improved the predicted mor- sulted in fatal pulmonary edema.7 This was demonstrated tality in subjects with acute respiratory failure. An in- again in our study,22 and florid pulmonary edema prompted teresting concept of biotrauma was postulated by Slutsky the likelihood of a hemodynamic mechanism. Two impor- and colleagues, who, initially, in preclinical models, tant patterns of heart-lung interactions were observed: 14-16 followed by clinical study, showed that high VT ventilation led to expression of inflammatory mediators 1. During each respiratory cycle (peak inspiratory pres- and neutrophil recruitment (biological consequence of sure, 45 cm H2O, PEEP 0 cm H2O), the pulmonary biophysical factors). This, they thought, could contrib- blood flow was completely obliterated during inspira- ute toward multiple organ dysfunction, a frequent com- tion and exaggerated during expiration. Combined re- plication in critical illness. sults from echocardiography and right ventricular pres- Eventually, a randomized control trial by Amato et al,17 sure measurements indicated that, during inspiration, in the late 1990s, and ARDSnet,18 in 2000, demonstrated the right ventricular cavity was completely obliterated significant mortality benefit by reducing VT in subjects due to mechanical compression from the inflating lung. with ARDS during invasive ventilation. However, over the During expiration, the right heart was overfilled, with past decade, NIV was being increasingly used for de novo resultant high pulmonary blood flow. The pulmonary respiratory failure. Although it avoids intubation, it may vascular bed, therefore, had a high flow–no flow–high

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Table 1. Mechanisms of VILI During PPV in Patients With De Novo Respiratory Failure

Management During Invasive Mechanisms of VILI PPV Parameter Management During NIV Ventilation

Volutrauma High VT Lowering VT If VT continues to be high, then abort NIV and intubate early

Biotrauma High VT and low PEEP Lower VT and optimize PEEP If VT continues to be high, then abort NIV and intubate early

Adverse heart-lung interaction High VT and low PEEP Lower VT and optimize PEEP If VT continues to be high, then abort NIV and intubate early Lung deflation injury Abrupt disconnections Avoid open suction slow Avoid multiple and abrupt removals lowering of PEEP of the NIV interface* Effort-induced lung injury High diaphragmatic effort Sedation, paralysis, treat acidosis, Judicious sedation, optimize EPAP, adequate recruitment, prone treat acidosis positioning, avoid double If high effort persists, then abort triggering NIV and intubate early

Various mechanisms are involved in VILI genesis and are incited by a specific PPV parameter; physiologically, these mechanisms can affect lungs during invasive and NIV alike, however, the management may slightly differ, as shown here. * This mechanism needs further confirmation. VILI ϭ ventilator-induced lung injury PPV ϭ positive-pressure ventilation VT ϭ tidal volume NIV ϭ noninvasive ventilation EPAP ϭ expiratory positive airway pressure

flow state. Such a pattern was consistent with vascular Lung Deflation Injury shearing, which was known to cause endothelial injury (capillary stress failure). Endothelial injury would fa- In yet another study, Katira et al discovered a new mech- cilitate microvascular leakage of protein and water into anism of potential harm during mechanical ventilation.23 the alveoli, which results in high permeability pulmo- Because it is associated with abrupt release of airway pres- nary edema. sure, we termed it lung deflation injury.23 In multiple se- 2. Over the course of the experiment (20 min) right heart ries of experiments that used healthy in vivo rats, abrupt failure developed and right ventricular volume increased, removal of PEEP after sustained inflation was associated which shifted the interventricular septum into the left with poor lung compliance, poor oxygenation, increased ventricle. This resulted in increased left ventricular end- lung water, and inflammation. The primary injury was to diastolic pressure (back pressure for pulmonary capil- the endothelium along with alveolar edema. Given the laries), which facilitated edema formation. sudden development of edema, a hemodynamic mecha- nism was postulated. Results from echocardiography, right and left ventricular pressures indicated 2 possible hemo- Together these 2 observations indicated that high VT dynamic forces that contribute to lung injury: ventilation (as in the original and classic paper7) is accom- panied with adverse heart lung interactions, which result in 1. With sustained inflation, the cardiac output reduces but injurious degrees of hemodynamic forces that contribute the systemic vascular resistance increases to maintain to VILI genesis. These observations are important because blood pressure. With abrupt deflation, the cardiac out- they indicate cardiovascular targets in addition to respira- put abruptly increases, however, the systemic vascular tory targets to achieve lung protection Table 1. resistance does not relax as quickly. As a result, the In the context of NIV, vascular flows are likely to de- filled left ventricle now ejects a large volume of blood pend on 2 issues. First, the effort of breathing, which against heavy resistance and causes a left ventricular– would determine the VT. If the VT is high, then the vas- afterload mismatch. This leads to increased left ventric- cular flow will undergo significant changes with each breath ular filling pressure (left ventricular end-diastolic pres- (eg, in patients with asthma). If the effort and therefore the sure) and, therefore, a high back pressure in the

VT, are reduced with NIV support, then the vascular flows pulmonary capillaries. The left ventricular end-diastolic may not be harmful. Second, diaphragm tone is main- pressure in these animals was high enough to have caused tained in NIV and may act as PEEP, which thus protects endothelial injury. against heavy vascular flows, provided that the effort and 2. Another hemodynamic force that contributes to injury

VT improve Table 1. formation is the high forward pulmonary blood flow,

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which results in an acute rise in forward capillary pres- changes in pleural pressure). Under normal conditions, sure to the point of causing capillary injury. spontaneous effort induces a uniform change in pleural pressure throughout inspiration, which results in a uni- form change in transpulmonary pressure. However, with Together, these altered hemodynamic forces result in injured lungs, the spontaneous effort results in higher capillary stress failure, microvascular leak, and inflamma- and earlier negative pleural pressure in the dependent tion. Inflation forces in the alveoli have been extensively regions compared with non-dependent regions (lower 24-26 studied and are causative for VILI. However, this study and later). This results in air moving from non-depen- illustrated that lung deflation can be associated with in- dent regions to dependent in the early phase of inspi- jury; this is important because abrupt deflation may hap- ration. The distention that results from such pendelluft pen many times during mechanical ventilation, especially could result in significant tidal recruitment of dependent with suctioning and transport. In addition, several studies regions and worsen an existing lung injury.35 21 of lung inflation were negative ; there could be a potential 3. Spontaneous effort generates negative pleural pressure, contribution of deflation injury to those negative or equiv- which results in overall negative intrathoracic pressure. ocal outcomes. Although it is too early to say whether This increases venous return and lung perfusion, which deflation injury occurs in the clinical situation, there is a causes high intravascular pressure. This coupled with concern, especially in patients with ARDS, about addi- negative pleural pressure leads to high transvascular tional injury during suction and tube disconnections. This pressure (pressure inside the vessel – pressure outside may be true of NIV too if the expiratory positive airway the vessel [ie, pleural pressure]).36 During volume-cy- pressure is high. cled ventilation, spontaneous effort results in lowering of airway pressure and in increasing transvascular pres- Effort-Induced Lung Injury sure, which thus causes a propensity toward edema for- mation.37 Early paralysis in patients with ARDS has been shown 4. Spontaneous effort can also induce patient-ventilator to improve lung function and mortality.27-29 Results of a asynchrony, with some evidence toward worsening mor- multi-center randomized control trial showed less baro- tality. Especially in a condition of double38 or reverse 39 trauma and better survival in subjects with neuromuscular triggering the delivered VT, and the transpulmonary blockade.27 Similarly, in subjects with severe sepsis, mor- pressure can be higher and, despite lung-protective strat- tality was lower with paralysis.30 As opposed to that, a egies, may worsen lung injury and outcomes. post hoc analysis of the large observational study to un- derstand the global impact of severe acute respiratory fail- ure (LUNG SAFE) study31 demonstrated that subjects with Beneficial effects of spontaneous breathing, spontane- severe ARDS did worse with NIV.32 A single-center ran- ous effort, if not excessive, maintains diaphragm muscle domized control trial of airway pressure release ventila- tone and function.40 Muscle paralysis induces diaphragm tion, which allows more spontaneous breathing versus con- dysfunction, which results in difficult weaning.41 It also ventional ventilation, in pediatric subjects with ARDS increases right ventricular preload and may reduce right demonstrated higher mortality with airway pressure re- ventricular afterload, which results in overall better lung lease ventilation.33 Together, results of these studies indi- perfusion. This, in the setting pulmonary hypertension or cate an injurious contribution of spontaneous breathing mild lung injury, may be beneficial to improve ventilation- during mechanical ventilation, especially in patients with perfusion (V˙ /Q˙ ) match. In the presence of mild injury and acute lung injury. well-recruited lungs, spontaneous effort reduces further Several mechanisms of harm were discerned: injury and, by improving ventilation to dependent areas (well-perfused areas), improves V˙ /Q˙ match.42,43 1. Spontaneous breathing on the ventilator decreases pleu- Therefore, at the bedside, a judicious approach toward ral pressure and increases transpulmonary pressure, and, assessing spontaneous effort can help minimize injury to therefore, for the same mechanical properties of the improve outcomes. To facilitate this, regular use of esoph- 34 lung, it increases VT. During pressure-targeted venti- ageal manometry to measure the occurrence and strength lation, this increases the chances of barotrauma without of spontaneous effort is recommended. Good sedation and necessarily changing the plateau pressure. Under con- analgesia can significantly reduce heavy effort, and neu- ditions of lung injury, these changes can be signifi- romuscular blockade would completely abolish it. In ad- cantly detrimental. dition, adequate recruitment flattens the diaphragm, 2. Spontaneous effort in conditions of lung injury induces changes the force-length relationship, and reduces the a phenomenon of pendelluft (ie, exchange of gas from degree of effort. The same can be true of using the non-dependent to dependent areas due to differential prone position during mechanical ventilation. Correc-

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tion of acidosis and extracorporeal removal of CO2 can 2. MacIntyre N. Design features of modern mechanical ventilators. facilitate reduction of spontaneous effort. Detection and Clin Chest Med 2016;37(4):607-613. avoidance of patient-ventilator asynchrony with proper 3. Slutsky AS. History of mechanical ventilation. From Vesalius to ventilator-induced lung injury. Am J Respir Crit Care Med 2015; selection of mode and ventilators settings may help re- 191(10):1106-1115. duce effort-related change in lung inflation.44 These 4. Tremblay LN, Slutsky AS. Ventilator-induced lung injury: from the physiologic mechanisms of effort-induced injury or ben- bench to the bedside. Intensive Care Med 2006;32(1):24-33. efit are likely common between invasive ventilation and 5. Faridy EE, Permutt S, Riley RL. Effect of ventilation on surface NIV and, hence, principles to prevent harm and enhance forces in excised dogs’ lungs. J Appl Physiol 1966;21(5):1453-1462. 6. Mead J, Takishima T, Leith D. Stress distribution in lungs: a model benefit would be similar, certainly, with the exception of pulmonary elasticity. J Appl Physiol 1970;28(5):596-608. of deep sedation, paralysis, and use of extracorporeal 7. Webb HH, Tierney DF. Experimental pulmonary edema due to in- membrane oxygenation. termittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis Summary 1974;110(5):556-565. 8. Parker JC, Townsley MI, Rippe B, Taylor AE, Thigpen J. Increased Classically, VILI has been recognized as the result of microvascular permeability in dog lungs due to high peak airway high airway forces (high plateau pressure and V ) and pressures. J Appl Physiol Respir Environ Exerc Physiol: 1984;57(6): T 1809-1816. modulation of this is now recommended during ventilation 9. Dreyfuss D, Basset G, Soler P, Saumon G. Intermittent positive- for patients with ARDS. Changes in vascular forces (es- pressure hyperventilation with high inflation pressures produces pul- pecially vascular shearing) from adverse heart-lung inter- monary microvascular injury in rats. Am Rev Respir Dis 1985;132(4): actions can synergize with airway forces to augment lung 880-884. injury. Abrupt disconnections can be a potential contrib- 10. Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure utor toward harm; however, more data are needed to con- pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir firm this. Also, heavy spontaneous effort in the presence Dis 1988;137(5):1159-1164. of severe lung injury can significantly worsen outcomes, 11. Hernandez LA, Peevy KJ, Moise AA, Parker JC. Chest wall restric- and, hence, modulation of this is most desirable. There are tion limits high airway pressure-induced lung injury in young rab- risks associated with the delivery of NIV in patients who bits. J Appl Physiol (1985) 1989;66(5):2364-2368. are hypoxemic, particularly those with ARDS. However, 12. Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hyper- its use to treat patients with ARDS is surprising high glob- capnia in severe adult respiratory distress syndrome. Intenive Care ally. The previously mentioned the large observational Med 1990;16(6):372-377. study reported regular use of NIV for ARDS and worse 13. Hickling KG, Walsh J, Henderson S, Jackson R. Low mortality rate outcomes related to the severity of ARDS.31,32 In these in adult respiratory distress syndrome using low-volume, pressure- patients, as discussed, it makes physiologic sense that the limited ventilation with permissive hypercapnia: a prospective study. 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Discussion Katira: I don’t have an answer be- and that we need to identify which cause this was in normal rats that were patient we should worry about. Davies: Thank you, Bhushan. I have paralyzed.1 So the lung might be sud- a question or maybe a comment. You denly deflated or there may be more Davies: I do think we need to keep mentioned that the abrupt disconnec- vascular injury. Although this phe- in mind that abruptly removing them tion or removal of pressure in NIV nomenon has yet to be recognized in may come with deleterious conse- can have a deleterious effect. In many patients and may be different for awake quences. instances, we encourage patients to patients because the diaphragmatic take the mask off to eat or for aero- tone may not allow complete lung col- Strickland: To your point, John [Da- solized medication delivery. I wonder lapse (in other words, FRC may be vies], maybe what we need to con- if we are doing them a disservice by maintained). This work certainly indi- sider is not just removing NIV at a doing that? cates that there is a cause for worry point for whatever care we need to

634 RESPIRATORY CARE • JUNE 2019 VOL 64 NO 6 VENTILATOR-INDUCED LUNG INJURY give or for relief from the face mask APRV.3 Part of the problem was high modynamics were not even reported. or whatever, but, maybe as Frat et al2 spontaneous effort during APRV in We know that circulatory death (from suggested to start doing some sequen- addition to airway pressure release, right heart failure) is a strong predic- tial HFNC so that we can still provide both of which I have presented today tor of mortality in ARDS. some of the responses that we were and concerning. Mortality was a sur- getting with the NIV while also still rogate of ventilator-induced lung in- Hill: I appreciate all of your caveats; giving the patients’ face a break and jury in this study. clearly what you’re working on is giving them the chance to do some something we can’t translate into the other activities and provide whatever * Hess: Back to your point, John. I clinical setting yet for the number of care is needed and to potentially avoid wonder if it’s a matter of what type of reasons you’ve given. But we’ve made this phenomenon. patient we are treating with NIV. I a lot of comments about NIV and hy- can imagine that, in a patient with poxemic respiratory failure, and some Kacmarek: In your rat studies, you COPD exacerbation, those removals of the observations you’ve made may showed it going from 12 to 0. How of the mask periodically might be less be relevant to how we use it. You much of a change, and do you have to injurious than in a patient with hypox- pointed out the LUNGSAFE study,4 go all the way to 0, for the effect to be emic respiratory failure or cardiogenic which did raise a lot of concerns about seen? If I’m on 20 of PEEP and I go pulmonary edema to whom we’re pro- to 8, do I see the same response as if viding NIV. I don’t know if there are using NIV in severe ARDS, and, I go from 12 to 0? any data about that. But your data are frankly, guidelines have not recom- primarily for animals with acute lung mended that we use NIV in that set- Katira: In rats, you don’t. Leaving injury, it’s not a model of COPD ex- ting. The most recent ATS/ERS guide- some end-expiratory pressure is pro- acerbation. line6 made no recommendation. It tective, but these are rat studies. The wasn’t a contraindication, some peo- effect that we showed was from 12 to Katira: These experiments were in ple have misinterpreted it as that, but 0; we need further study to appreciate normal rats; they were neither a model we just didn’t have enough data to this phenomenon. It would be very pre- of COPD nor a model of lung injury. make a recommendation one way or mature for me to say, “OK take these However, in pilot studies of pre-in- the other. But, having said that, we’re numbers and translate them to bed- jured lung conditions, we observed using NIV quite often in patients with side.” that APRV exacerbates lung injury, ARDS. Results of our studies showed and, thus, your point is well taken that rates of the use of NIV as the initial Kacmarek: So, at this point in time, it might be much more important in ventilator mode in some 40% of pa- we really don’t have a good handle on patients with hypoxemic respiratory tients admitted to hospitals with pneu- those types of injuries. failure. We also know from the monia,7 especially elderly patients 4 LUNGSAFE study subgroup analysis when there’s a reluctance to intubate. Katira: Yes, just appreciating that that NIV was injurious in severe One question I have for you is, given this phenomenon is happening in rats ARDS; the outcomes were worse com- the reality of the situation, what can very consistently and might be hap- pared with those with mild ARDS. So you say about the relevance of your pening in some patients. We just need there is reason to believe that, in a observations to how we’re using NIV to be mindful. But I don’t know ex- subgroup of patients, especially in se- in hypoxemic respiratory failure to- actly what pressures or limits. vere ARDS and significant hypoxemic day. Clearly, we use a gentler approach respiratory failure, doing NIV early than the one you’re illustrating; we Nishimura: When we use airway might be bad for a couple of reasons. pressure release ventilation (APRV), Most important, I think is self-induced certainly don’t go abruptly to 0 PEEP is it harmful? lung injury; but, apart from that, even with NIV. If you’re intubated and you’re bypassing upper-airway mech- high VT, independent of distribution, Katira: There was a recent study in might be injurious. Also, the hemody- anisms that maintain a “physiologic pediatric ARDS from India of sub- namic effects are really less appreci- PEEP,” you could theoretically go to jects with acute lung injury (which was ated. Except for the HFOV trial,5 in 0 or even a negative PEEP, but we moderate-to-severe ARDS).3 They which there was significant hypoten- don’t do that. So what is the clinical randomized subjects to APRV versus sion, in most high PEEP studies, he- relevance of your observation? normal low VT, high PEEP ventila- tion.3 Mortality doubled with APRV; Katira: Difficult question. it was 28% with low VT and adequate * Dean R Hess PhD RRT FAARC, Managing lung recruitment and was 56% with Editor, RESPIRATORY CARE. Hill: Of course.

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Katira: The practice of NIV is more HFNC works better in many patients personalized medicine. There may be of a spillover effect to all patient than NIV. It’s a tolerance of the pro- some patients even in severe ARDS groups, and we have to identify when cess and the overall patient response. who would clearly tolerate, and we it should be beneficial and when it But because we’ve all seen patients should go ahead, and there may be may not. From what I can conclude who are struggling with NIV, we’re some with COPD who would not tol- and the insights from all of these stud- all at fault for not interacting and erate it. Therefore, what we need to ies is at least in severe ARDS, say changing the approach to ventilating understand is if there are ways that we P /F of Ͻ 100 or 150 mm Hg, I them sooner. I can guarantee you that can measure returning V during NIV aO2 IO2 T would be de-recommending it unless if we walked around any hospital, (very high, say 10 mL VT can be in- more prospective trials show benefits. we’d find a few patients who should jurious) and the diaphragmatic activ- What we know is the acceptable time be intubated who are being main- ity, for example, by ultrasound (again for NIV, whether it should be for 24– tained either on NIV or HFNC but if very high can be detrimental), so 48 h, or 36 h, or 7 d (like some sub- are working their butt off and are in that we can titrate the ventilation time jects in LUNGSAFE),4 which I think severe ARDS, and nobody wants to and method (NIV versus invasive). is a bit too far. I don’t know the real accept that because their P is nor- Recognizing an injurious pattern of O2 target, but, I would say that, in severe mal. ventilation early is very important. ARDS, I would de-recommend NIV What time and how much time, it’s and recommend invasive ventilation, Hill: Clearly intolerance of the face very difficult to say at this stage. paralyze for the first 3 or 4 d, put mask has been a major impediment to them prone, and get their lungs sort- the success of NIV. Whether that’s ed; then exercise their diaphragm ad- the whole explanation for the differ- REFERENCES equately and get them off the vent. In ent responses to the helmet and the 1. Katira BH, Engelberts D, Otulakowski G, severe ARDS, I would like to intu- face mask, I’m not sure, but it’s part Giesinger RE, Yoshida T, Post M, et al. bate. of it, and synchrony is a big deal as Abrupt deflation after sustained inflation well. causes lung injury. Am J Respir Crit Care Hill: I think my question is a ques- Med 2018;198(9):1165-1176. 2. Frat JP, Brugiere B, Ragot S, Chatellier tion without a clear answer, but I asked Scott: First of all, excellent presen- D, Veinstein A, Goudet V, et al. Sequen- you to speculate. There are a couple tation. I wanted to ask a question about tial application of oxygen therapy via of other observations in the literature time, thinking about those of us in the high-flow nasal cannula and noninvasive that raise even more questions. One is emergency department who use NIV ventilation in acute respiratory failure: an the study by Patel et al8 which com- for acute cardiogenic pulmonary observational study. Respir Care 2015; 60(2):170-178. pared helmet versus standard face edema. Is NIV lung injury a product 3. Lalgudi Ganesan S, Jayashree M, Chandra mask where the intubation rate was of time? What relationship does time Singhi S, Bansal A. Airway pressure re- lowered from 62% with the face mask have on lung injury? I ask because lease ventilation in pediatric acute respira- compared with 18% for the helmet. some patients in the emergency de- tory distress syndrome: a randomized con- Different ventilators and settings were partment only require NIV support for trolled trial. Am J Respir Crit Care Med 2018;198(9):1199-1207. used for each interface, but it raised hours versus days as in the ICU. 4. Bellani G, Laffey JG, Pham T, Madotto F, the question of whether the interface Fan E, Brochard L, et al.; LUNG SAFE and settings make a big difference and Katira: Again, it’s very difficult to Investigators, ESICM Trials Group. Non- that may alter what you’re saying answer that question, at least for indi- invasive ventilation of patients with acute about how severe a patient’s condi- vidualized patients. If there’s a sense respiratory distress syndrome. Insights from the LUNG SAFE Study Am J Respir Crit tion must be before we say he or she that the effort is very strong despite Care Med 2017;195(1):67-77. is too sick for NIV. adequate support, then maybe this is a 5. Ferguson ND, Cook DJ, Guyatt GH, Mehta patient for whom you should now go S, Hand L, Austin P, et al.; OSCILLATE Kacmarek: I don’t think, Nick ahead, and if there’s a sense that ef- Trial Investigators, Canadian Critical [Hill], that it’s necessarily the device fort has reduced (eg, by ultrasound as- Care Trials Group. High-frequency oscil- lation in early acute respiratory distress that makes the difference; it’s the pa- sessment of diaphragm), then we could syndrome. N Engl J Med 2013;368(9): tient’s tolerance of the application. continue to use NIV. This is not based 795-805. You and I have both had the helmet on any prospective study or work but 6. Rochwerg B, Brochard L, Elliott MW, on, and I would clearly rather have just thinking if you want to do some- Hess DR, Hill NS, Nava S, et al.; Raoof the helmet on than a face mask thing to titrate ventilation based on S Members Of The Task Force. Official ERS/ATS clinical practice guidelines: strapped to my face. So it may be the patient effort. To say that all patients noninvasive ventilation for acute respira- ability of the patient to work with and should be Ն4 d or should all be Յ6h tory failure. Eur Respir J 2017;50(2). pii: tolerate the device, which is why sounds not applicable in the era of 1602426.

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7. Ozsancak Ugurlu A, Sidhom SS, Khoda- outcomes in patients with acute respiratory muscular blockers in early acute respira- bandeh A, Ieong M, Mohr C, Lin DY, et al. distress syndrome enrolled in a randomized tory distress syndrome. N Engl J Med 2010; Use and outcomes of noninvasive positive clinical trial of helmet versus facemask non- 363(12):1107-1116. pressure ventilation in acute care hospitals invasive ventilation. Crit Care Med 2018; 10. Katira BH, Giesinger RE, Engelberts D, in Massachusetts. Chest 2014;145(5):964- 46(7):1078-1084. Zabini D, Kornecki A, Otulakowski G, et 971. 9. Papazian L, Forel JM, Gacouin A, Penot- al. Adverse heart-lung interactions in ven- 8. Patel BK, Wolfe KS, MacKenzie EL, Salem Ragon C, Perrin G, Loundou A, et al; tilator-induced lung injury. Am J Respir D, Esbrook CL, Pawlik AJ, et al. One-year ACURASYS Study Investigators. Neuro- Crit Care Med 2017;196(11):1411-1421.

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