Update in Management of Severe Hypoxemic Respiratory Failure

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Update in Management of Severe Hypoxemic Respiratory Failure

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Dharani Kumari Narendra, MD, FCCP; Dean R. Hess, PhD, RRT; Curtis N. Sessler, MD, FCCP; Habtamu M. Belete, MD;

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Kalpalatha K. Guntupalli, Master FCCP; Felix Khusid, RRT, ACCS, RRT-NPS, RPFT, FCCP; Charles Mark Carpati, MD; Q2 Q3

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Mark Elton Astiz, MD; and Suhail Raoof, MD, FCCP

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Mortality related to severe-moderate and severe ARDS remains high. We searched the litera-

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ture to update this topic. We defined severe hypoxemic respiratory failure as PaO2/FIO2 <

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150 mm Hg (ie, severe-moderate and severe ARDS). For these patients, we support setting the

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ventilator to a tidal volume of 4 to 8 mL/kg predicted body weight (PBW), with plateau pressure

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(Pplat) # 30 cm H2O, and initial positive end-expiratory pressure (PEEP) of 10 to 12 cm H2O. To

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promote alveolar recruitment, we propose increasing PEEP in increments of 2 to 3 cm provided

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that Pplat remains # 30 cm H2O and driving pressure does not increase. A fluid-restricted

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strategy is recommended, and nonrespiratory causes of hypoxemia should be considered.

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For patients who remain hypoxemic after PEEP optimization, neuromuscular blockade and

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prone positioning should be considered. Profound refractory hypoxemia (PaO2/FIO2 <

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80 mm Hg) after PEEP titration is an indication to consider extracorporeal life support. This may

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necessitate early transfer to a center with expertise in these techniques. Inhaled vasodilators

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and nontraditional ventilator modes may improve oxygenation, but evidence for improved

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outcomes is weak.

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KEY WORDS: acute hypoxemic respiratory failure; ARDS; nonventilatory strategies in ARDS; prone positioning in ARDS; ventilatory strategies in ARDS

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ARDS, a life-threatening condition, is an important cause of acute hypoxemic respiratory failure and accounts for approximately 10% of ICU admissions and 25% of patients who require mechanical ventilation.1 Currently, there is controversy about the management of severely

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hypoxemic patients, both in the selection of rescue strategies and the sequence in which they are used. To provide greater clarity in the management of such patients, we conducted a PubMed search (severe hypoxemic respiratory failure, prevention of ARDS, ventilator management, recruitment

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APRV = airway pressure release ventilation; DP = driving pressure; ECMO = extracorporeal membrane oxygenation; HFOV = high-frequency oscillatory ventilation; HFPV = high-frequency percussive ventilation; NIV = noninvasive ventilation; NMBA = neuromuscular blocking agent; PBW = predicted body weight; PEEP = positive end-expiratory pressure; PP = prone positioning; Pplat = plateau pressure; P-SILI = patient self-inflicted lung injury; RCT = randomized controlled trial; RHC = right heart catheterization; RV = right ventricular; VV ECMO = venovenous extracorporeal membrane oxygenation AFFILIATIONS: From the Pulmonary Critical Care and Sleep Section (Dr Narendra), and the Section of Pulmonary, Critical Care, and Sleep Medicine (Dr Guntupalli), Department of Medicine, Baylor College of Medicine, Houston, TX; Massachusetts General Hospital and Harvard Medical School (Dr Hess), Boston, MA; the Division of Pulmonary ABBREVIATIONS:

Diseases and Critical Care Medicine (Dr Sessler), Virginia Commonwealth University Health System, Richmond, VA; Lenox Hill and Northwell Hofstra School of Medicine (Dr Belete), New York; the Respiratory Therapy and Pulmonary Physiology Center (Dr Khusid), New York Presbyterian Brooklyn Methodist Hospital, Brooklyn; the Surgical ICU (Dr Carpati), the Departments of Internal Medicine and Critical Care Medicine (Dr Astiz), and the Department of Pulmonary Medicine (Dr Raoof), Lenox Hill Hospital, and Hofstra Northwell School of Medicine, New York, NY. CORRESPONDENCE TO: Suhail Raoof, MD, FCCP, 2178 Kirby Lane, Muttontown, New York, NY 11791; e-mail: [email protected] Copyright Ó 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: http://dx.doi.org/10.1016/j.chest.2017.06.039

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maneuver, ECMO, prone positioning, neuromuscular blocking agents, inhaled prostaglandins, nitric oxide, nutrition, and ARDS), limited to the past 6 years to provide an update for our previously published papers.2,3 This search was supplemented by appropriate cross-references and our individual familiarity with the topic. Through this narrative review, we aim to provide a concise overview of the definition, diagnosis, recognition, prevention, and treatment of severe hypoxemic respiratory failure.

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Definition of Severe Hypoxemic Respiratory Failure The Berlin definition incorporates the timing and origin of pulmonary edema and categorizes severity based on the degree of hypoxemia with a minimum positive endexpiratory pressure (PEEP) of 5 cm H2O.4 Severe ARDS is defined as a PaO2/FIO2 # 100 mm Hg, and moderate ARDS is defined as a PaO2/FIO2 of 100 to 200 mm Hg.2 Several recent studies5,6 have focused on patients with ARDS in whom the PaO2/FIO2 is < 150 mm Hg (severemoderate and severe ARDS) as the population most likely to respond to interventions such as prone positioning (PP) and neuromuscular blockade. Consistent with these trials and for the purpose of this review, we define severe hypoxemic respiratory failure as a PaO2/FIO2 of < 150 mm Hg.

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Impact of Severe ARDS Increased ventilator days, length of ICU stay, and mortality as high as 52% have been reported in severe ARDS.4 Among patients with ARDS, the prevalence of severe hypoxemic respiratory failure (PaO2/FIO2 < 100 mm Hg) is about 23%, with a 46% mortality.7 Conversely, many patients with mild ARDS go unrecognized and therefore fail to receive appropriate lung-protective ventilation.7 In such cases, ventilatorinduced lung injury may perpetuate lung damage.

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Prevention of ARDS Strategies to prevent ARDS should be used whenever possible. The Lung Injury Prediction Score was developed to stratify patients at high risk for ARDS. Sepsis and pneumonia are two high-risk conditions that predispose to ARDS.8,9 The Checklist for Lung Injury Prediction8 was developed to allow earlier recognition of patients at high risk for the development of lung injury for the purpose of instituting early preventive measures. This includes restrictive blood transfusions, appropriate and timely antimicrobial agents, diligent perioperative

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care, adherence to lung-protective ventilation, aspiration precautions, and appropriate management of shock, pancreatitis, and trauma. The term patient self-inflicted lung injury (P-SILI) was recently introduced.10 In spontaneously breathing patients with a high respiratory drive, there may be large tidal volumes and potentially injurious transpulmonary pressure swings. This can occur with pressure control, pressure support, airway pressure release ventilation (APRV), and even with noninvasive ventilatory support. Due to pendelluft, a strong effort can induce intrapulmonary redistribution of gas, even before the start of inflation.11 Due to the potential for P-SILI, clinicians must be cognizant of adverse effects from excess spontaneous breathing in patients with moderate and severe ARDS and consider remedial measures such as sedation and paralysis.12

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Ventilatory Strategies

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Ventilator-Induced Lung Injury and Prevention

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For patients with severe hypoxemic respiratory failure, invasive ventilation is preferred over noninvasive ventilation (NIV), as poor outcomes have been reported in patients treated with NIV.13 Provided that the tenets of lung-protective ventilation are followed, usually volume-control or pressure-control ventilation can be used.14,15 Setting limits to tidal volume and to alveolar distending pressure should be routinely performed.16 Specifically, the tidal volume target should be 4 to 8 mL/ kg predicted body weight (PBW)17 and reduced to as low as 4 mL/kg PBW if plateau pressure (Pplat) targets are not achieved. Pplat should not exceed 30 cm H2O provided that chest wall effects are normal. When the chest wall exerts a collapsing effect on the lungs (eg, morbid obesity, abdominal hypertension, chest wall deformity), Pplat > 30 cm H2O might be safe provided that transpulmonary pressure is acceptable. Gattinoni et al18 proposed that transpulmonary pressure (stress) should not exceed 22 to 23 cm H2O. Given the inhomogeneity in the lungs of patients with ARDS and the magnifying effect of stress raisers, a conservative approach of limiting transpulmonary pressure to < 20 cm H2O seems reasonable. In the setting of elevated pleural pressure, esophageal manometry might be useful to establish a safe ventilating pressure. The authors of recently published evidence-based clinical practice guidelines recommend that patients with ARDS receive mechanical ventilation with strategies that limit tidal volumes (4-8 mL/kg PBW) and Pplat (< 30 cm H2O)

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(strong recommendation, moderate confidence in effect estimates).17 Since high tidal volumes might be an important determinant for the development of ARDS19 and because ARDS is frequently unrecognized,7 a reasonable recommendation is to limit volume and pressure in all mechanically ventilated patients. An emerging concept is that ventilator driving pressure (DP), the difference between Pplat and PEEP, may be correlated with outcome. Relative risk of death was > 1 when DP was more than 15 cm H2O in a secondary analysis of data from randomized controlled trials (RCTs).20 Although the simplicity of choosing ventilator settings based on DP makes it attractive, the concept should be confirmed21 in prospective clinical trials.

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Positive End-Expiratory Pressure

Optimizing PEEP is the first consideration in a patient with refractory hypoxemia due to diffuse parenchymal lung disease such as ARDS. Although individual RCTs did not find a mortality benefit for higher PEEP,22-24 each trial reported better oxygenation in the higher PEEP group. Using individual patient data from these three trials, Briel et al25 found that in subjects with moderate and severe ARDS, hospital mortality was 34% with higher PEEP and 39% with lower PEEP. In subjects with mild ARDS, hospital mortality was 27% with higher PEEP and 19% with lower PEEP. In another analysis of the same data used by Briel et al,25 Kasenda et al26 found that for patients with a PaO2/FIO2 of 100 to 150 mm Hg, higher PEEP was associated with lower hospital mortality, but the beneficial effect appeared to plateau for patients with severe ARDS. Patients with mild ARDS (PaO2/FIO2 > 200 mm Hg) did not benefit from higher PEEP, and it might be harmful. The results of these studies25,26 suggest that higher PEEP should be reserved for those with severe-moderate and severe ARDS. The authors of recently published evidence-based clinical practice guidelines suggest that patients with moderate or severe ARDS receive higher rather than lower levels of PEEP (conditional recommendation, moderate confidence in effect estimates).17 An important practical question is the necessary wait time after PEEP is changed to assess the response. Chiumello et al27 found that when performing a PEEP titration, changes in oxygenation after 5 min might be used to judge the direction of change (improving or worsening), but the full effect might take 60 min or longer. A variety of approaches have been suggested to determine appropriate PEEP for an individual patient

(Table 1).28 In a physiological crossover study of 51 patients with ARDS, Chiumello et al29 compared PEEP selection by lung mechanics (ExPress24 or stress index), Q10 esophageal manometry, and oxygenation (higher PEEP table of the Lung Open Ventilation Study,23 similar to the high PEEP table of the ARDS Network22). When patients were classified according to ARDS severity, the approach using the PEEP/FIO2 table was the only one that resulted in lower PEEP in mild and moderate ARDS compared with severe ARDS. We have previously argued that the benefit of PEEP in patients with refractory hypoxemia might depend on the Q11 potential for alveolar recruitment.2 Gattinoni et al33 suggest that similar PEEP is required in patients with higher and lower potential for recruitment and that PEEP selection methods based on PEEP/FIO2 tables were the only discriminating factors between patients with higher recruitability and those with lower recruitability. Gattinoni et al33 also recommend selecting PEEP according to the ARDS severity: 5 to 10 cm H2O with mild ARDS, 10 to 15 cm H2O with moderate ARDS, and 15 to 20 cm H2O with severe ARDS. Use of this approach or a PEEP/FIO2 table (Table 2) can be used for any patient with ARDS, regardless of expertise and available technology. Advanced methods such as stress index, esophageal manometry, ultrasonography, and electrical impedance tomography should be reserved for hospitals with the necessary equipment and expertise. The selection of PEEP is always a balance between recruitment and overdistention. Goligher et al34 reported that an increase in PaO2/FIO2 with an increase in PEEP (presumably the result of recruitment) was associated with lower mortality, whereas a decrease in PaO2/FIO2 after an increase in PEEP (presumably the result of overdistention) was associated with a higher mortality. Applying PEEP that results in a Pplat > 30 cm H2O or a DP > 15 cm H2O is not recommended. Applying an increase in PEEP that results in a decrease in DP

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TABLE 1

] Techniques Used to Determine Best

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PEEP28,30-32

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Gas exchange: oxygenation: PEEP/FIO2 tables, dead space

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Respiratory mechanics: compliance, driving pressure, pressure-volume curve, stress index, esophageal manometry.

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Imaging: electrical impedance tomography, ultrasonography, chest CT imaging

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PEEP ¼ positive end-expiratory pressure.

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TABLE 2

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] Tables Used to Set combinations of Fio2 and PEEP to Achieve an Spo2 of 88% to 95%a

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See Table 1 legend for expansion of abbreviations. a The lower PEEP table might be used for mild ARDS, whereas the higher PEEP table might be used for moderate and severe ARDS. Adapted with permission from Brower et al.22

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suggests recruitment. However, applying an increase in PEEP that results in an increase in DP suggests that overdistention has occurred, and PEEP should be decreased to the previous level. The exception is the patient with abnormal chest wall mechanics (eg, obesity, abdominal hypertension) in whom PEEP is necessary to counterbalance the collapsing effect of the chest wall. In this setting, esophageal manometry is recommended to estimate transpulmonary pressure.28,32

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Recruitment Maneuvers

A recruitment maneuver is a transient increase in transpulmonary pressure to promote the reopening of collapsed alveoli, thereby improving gas exchange and the distribution of volume in the lungs.28,35 Approaches include the following: 1. Sustained high-pressure inflation using pressures of 30 to 40 cm H2O for 30-40 s (eg, 40 cm H2O for 40 s) 2. A stepwise increase in PEEP with a constant DP (eg, 15 cm H2O) or a fixed tidal volume (eg, 4-6 mL/kg PBW) Keenan et al36 and Marini37 suggest that stepwise recruitment maneuvers are more effective for lung recruitment than abrupt applications of high peak pressure, with less adverse hemodynamic effects (Fig 1). Suzumura et al38 conducted a meta-analysis of 10 RCTs assessing the effect of recruitment maneuvers on mortality and reported a risk ratio (RR) of 0.84 (95% CI, 0.74-0.95) favoring recruitment. In a Cochrane review,39 data from five trials showed a lower ICU mortality (RR, 0.83; 95% CI, 0.72-0.97; P ¼ .02) but no difference in 28-day mortality (RR, 0.86; 95% CI, 0.74-1.01; P ¼ .06). The analysis found no differences in barotrauma. In both these meta-analyses, the authors commented that the results were contaminated by cointerventions in patients receiving recruitment maneuvers. The authors of recently

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published evidence-based clinical practice guidelines suggest that patients with ARDS receive recruitment maneuvers (conditional recommendation, low to moderate confidence in the effect estimates).17

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An approach to setting PEEP is to perform a recruitment maneuver followed by a decremental PEEP titration (open lung approach).40,41 Decremental PEEP titration is performed by setting the PEEP to 20 to 25 cm H2O, and then decreasing it in 2 to 3 cm H2O steps every 4 to 5 min. PEEP is maintained at the level that maintains oxygenation and respiratory system compliance.

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High-Frequency Oscillatory Ventilation

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HFOV delivers very low tidal volume (1-2 mL/kg) at high frequencies (3-15 Hz/min). Enthusiasm for HFOV was dampened after two RCTs failed to show a survival benefit.46,47 The authors of a Cochrane review48 suggested that HFOV does not reduce hospital and 30-day mortality in patients with ARDS, and thus these findings do not

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Nontraditional ventilator modes used in the setting of severe hypoxemic respiratory failure include highfrequency oscillatory ventilation (HFOV), highfrequency percussive ventilation (HFPV), and APRV. The technical features of these modes have been described elsewhere.2,42-44 Each mode can result in improved oxygenation, and each has passionate advocates, but none of these modes has received widespread acceptance, most likely due to limited highlevel evidence supporting improved outcomes. It is important to appreciate that ventilator approaches resulting in better gas exchange might not result in better survival. In a pivotal ARDS Network study,45 for example, subjects in the low-tidal-volume group had worse gas exchange but better survival, indicating that oxygenation may be a flawed surrogate for outcome.

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Nonconventional Ventilator Modes

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FIO2: 0.6 VT: 0.3 L ΔP: 10 cm H2O SpO2: 96%

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FIO2: 1 VT: 0.3 L ΔP: 15 cm H2O SpO2: 79%

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FIO2: 1 VT: 0.23 L SpO2: 96% FIO2: 1 FIO2: 1 VT: 0.25 L VT: 0.25 L SpO2: 96% FIO2: 1 SpO2: 80% FIO2: 1 VT: 0.27 L VT: 0.27 L FIO2: 0.6 SpO2: 98% VT: 0.3 L SpO2: 79% FIO2: 1 VT: 0.3 L ΔP: 12 cm H2O FIO2: 0.6 VT: 0.32 L SpO2: 79% SpO2: 96% ΔP: 10 cm H2O SpO2: 95%

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Stepwise Recruitment Maneuver

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Figure 1 – Examples of stepwise recruitment maneuvers with decremental PEEP titration for constant tidal volume (left) and constant driving pressure (right). DP ¼ driving pressure; PEEP ¼ positive end-expiratory pressure; Pplat ¼ plateau pressure; SpO2 ¼ oxygen saturation measured by pulse oximetry; VT ¼ tidal volume.

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support the use of HFOV as a first-line strategy in patients undergoing mechanical ventilation for ARDS. The authors of recently published evidence-based clinical practice guidelines recommend that HFOV not be used routinely in patients with moderate or severe ARDS (strong recommendation, moderate to high confidence in effect estimates).17A recent meta-analysis49 reported that HFOV was harmful in patients with moderate ARDS, whereas it showed possible benefit in patients with severe hypoxemia. Meade et al state that HFOV might be considered in patients with severe ARDS who remain hypoxemic after optimizing conventional lung-protective ventilation or when approaches such as PP and extracorporeal membrane oxygenation (ECMO) are either contraindicated or unavailable.

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High-Frequency Percussive Ventilation

HFPV consists of pneumatically powered, pressurelimited, time-cycled, and flow-interrupted breaths with biphasic percussions. It generates minibursts or pulses of subtidal volume, resulting in the production of intrapulmonary percussive waves. Percussive breaths are purported to facilitate clearance of respiratory secretions, facilitate lung recruitment, and reduce the need for sedation.50

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In observational studies, HFPV has been reported to improve oxygenation for patients with hypoxemic respiratory failure.51-54 One study reported less time on ECMO when HFPV was combined with ECMO.55 Chung et al56 conducted a single-center RCT comparing HFPV

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with low-tidal-volume ventilation in patients who were admitted to a burn ICU with respiratory failure. Patients receiving HFPV had higher oxygenation compared with low tidal volume; however, this did not translate to more ventilator-free days or reduction in mortality.

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Airway Pressure Release Ventilation

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APRV is a mode of mechanical ventilation that uses two levels of positive airway pressure: (Phigh) and (Plow). The APRV intermittently switches between two levels of CPAP while allowing the patient to breathe spontaneously throughout both cycles. APRV has been shown to improve oxygenation in observational studies, but few RCTs have been conducted.57,58 In a secondary analysis of an observational study in 349 ICUs in 23 countries, Gonzalez et al59 could not demonstrate any improvement in outcomes with APRV compared with conventional ventilation. In an RCT, Varpula et al60 compared APRV and synchronized intermittent mandatory ventilation with pressure support; they did not find significant differences in clinically relevant outcomes. In an RCT comparing APRV with conventional low-tidal-volume ventilation, Maxwell et al61 reported no difference in mortality and trends for subjects receiving APRV to have increased ventilator days, ICU length of stay, and VAP. Of concern in the study by Maxwell et al and another by Maung and Kaplan62 is the fact that APRV may increase ventilator days in trauma patients. This raises the possibility that APRV could potentiate lung injury. Specifically, spontaneous breathing during the application of high pressures can result in alveolar overdistention; similarly, low pressures during the release phase might result in collapse of alveoli with low compliance (producing opening/closing injury).58 Further, APRV is routinely associated with generation of tidal volumes in excess of 6 mL/kg PBW. The brief exhalation time (often < 0.6 s) virtually guarantees the presence of intrinsic PEEP, which is difficult to measure and control. Controversy will continue to surround APRV in the setting of hypoxemic respiratory failure until a multicenter RCT with an appropriately designed control group is able to assess patient-related outcomes.

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Nonventilatory Strategies

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Neuromuscular Blockade

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Neuromuscular blocking agents (NMBAs) are frequently used in the management of patients with ARDS who have severe hypoxemia. In the Large Observational Study to

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Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study,7 neuromuscular blockade was used in about 22% of patients, including about 38% of patients with a PaO2/FIO2 < 100 mm Hg. A common indication for NMBAs is hypoxemia in a patient who exhibits poor ventilator synchrony despite deep sedation. Improvement in oxygenation has been demonstrated in placebo-controlled RCTs.6,63-65 Perhaps more important, there is evidence that routine use of NMBAs for patients with severe ARDS likely improves outcomes. In a meta-analysis of three placebocontrolled RCTs, patients with ARDS and a PaO2/FIO2 < 150 mm Hg who were randomized to continuous infusion of cisatracurium had lower ICU mortality (31% vs 45%; RR, 0.71; 95% CI, 0.55-0.90), lower 28-day mortality (23% vs 34%; RR, 0.68; 95% CI, 0.51-0.92), more ventilator-free days (6.8 vs 5.2 days; P ¼ .02), and less barotrauma (4.0% vs 9.6%; RR, 0.45; 95% CI, 0.22-0.92).65 Several caveats are worth considering when interpreting these results,66 particularly those from the largest RCT by Papazian et al.6 First, although patients with PaO2/FIO2 < 150 were enrolled in this RCT, post hoc analysis demonstrated that the mortality benefit was limited to patients with PaO2/FIO2 < 120 at baseline. Second, the average PEEP administered was lower than in nearly all other modern-era ARDS clinical trials and might influence patient selection and generalizability. Third, > 50% of patients randomized to receive placebo infusion received as-needed doses of NMBA. Fourth, all RCTs used cisatracurium for NMBA and were conducted or led (or both) by the same group of investigators, potentially limiting generalizability until more data are available. The mechanism for improvement in outcomes associated with NMBA is subject to speculation.67 In an observational study, Beitler et al68 reported that neuromuscular blockade prevented breath-stacking asynchrony, ensuring the provision of the intended lung-protective strategy. Forel et al63 demonstrated that patients with ARDS who were randomized to receive cisatracurium had decreasing levels of proinflammatory cytokines in BAL fluid and in serum, suggesting that NMBAs might reduce ventilator-induced biotrauma. Other potential mechanisms for the effects of cisatracurium include reduced oxygen consumption, improved ventilation-perfusion relationships, prevention of the pendelluft effect,11 and a direct antiinflammatory effect of the agent.

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Despite concerns about prolonged weakness after neuromuscular blockade, objective evidence of excessive

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weakness has not been demonstrated. Using the Medical Research Council’s muscle power scale on day 28 and at ICU discharge, the scores were identical for patients randomized to cisatracurium and those randomized to placebo.7 It is possible that the excellent safety profile of cisatracurium does not extend to steroid nucleus NMBAs such as vecuronium, which may produce a higher incidence of prolonged neuromuscular blockade or muscle weakness, or both, particularly among patients with renal or hepatic failure, or both.66 In its recently published guidelines for sustained neuromuscular blockade, the Society of Critical Care Medicine69 made a weak recommendation that an NMBA be administered by continuous IV infusion early in the course of ARDS for patients with a PaO2/FIO2 < 150. Since all the RCTs were conducted using cisatracurium, the recommendation for use of an NMBA in ARDS is limited to cisatracurium. A multicenter RCT is now under way in the United States to re-evaluate the hypothesis that neuromuscular blockade with cisatracurium improves outcomes in severe ARDS (ClinicalTrials.gov: NCT02509078).

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Prone Positioning

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The physiological rationale for PP in ARDS has been established (Table 3), making this therapy appealing.70,71 Following several negative RCTs,5,72 Guerin et al5 reported benefit with PP in severe ARDS in a multicenter RCT. In this study, there was a significant mortality benefit for PP (16% absolute risk reduction, 51% relative risk reduction with number needed to treat of six). Subjects with a PaO2/FIO2 # 150, an FIO2 $ 0.6, and PEEP $ 5 cm H2O were enrolled.

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A criticism of this study is that the PEEP levels were relatively low when subjects were enrolled; on average,

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TABLE 3

] Potential Physiological Benefits for Prone Positioning77

More homogeneous pleural pressure Dorsal lung is better perfused and aerated, thereby decreasing intrapulmonary shunting Improving ventilation-perfusion matching

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Improved lung recruitment

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Less ventilator-induced lung injury

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Decreased release of proinflammatory cytokines

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Improves PaO2 and decreases PaCO2 and Pplat by recruitment, which helps to preserve pulmonary circulation and improve RV dysfunction

713 714 715

Pplat ¼ plateau pressure; RV ¼ right ventricular.

only 10 cm H2O. Beitler et al73 observed that in three RCTS of PP, the postintervention PEEP was not more than 5 cm H2O in 17% of subjects and not more than 10 cm H2O in 66% of subjects. Postintervention PEEP would have been nearly twice the set PEEP had a highPEEP strategy been used. We advocate performing adequate PEEP titration before PP is instituted. PP has been shown to improve PaO2 and decrease PaCO2 and Pplat by recruitment, which helps to preserve pulmonary circulation and improve right ventricular (RV) dysfunction.74 The results of several recent meta-analyses recommended the use of PP in severely hypoxemic patients. Beitler et al75 concluded that PP was associated with significantly reduced mortality from ARDS in the low-tidal-volume era and that the substantial heterogeneity across studies can be explained by differences in tidal volume. Sud et al76 also concluded that the use of PP during mechanical ventilation improves survival in patients with ARDS who receive protective lung ventilation. The authors of recently published evidence-based clinical practice guidelines recommend that patients with severe ARDS receive PP for more than 12 hours per day (strong recommendation, moderate to high confidence in effect estimates).17 Use of PP requires commitment from the clinical staff caring for the patient, including physicians, nurses, and respiratory therapists. The key aspects of successful implementation of PP are listed in Table 4.77 It is important to note that a specialty bed is not required; although it might reduce staff burden, it will add expense.

716 717 718 719 720 721 722 723 724 725 726 727 728 729 730 731 732 733 734 735 736 737 738 739 740 741 742 743 744 745 746 747 748 749 750 751 752 753

TABLE 4

] Important Aspects for Successful

754

Implementation of Prone Positioning77

755

Early application of prone positioning when severe hypoxemia persists after initial stabilization

756

Duration of prone positioning more than 12 h/d

758

Strict adherence to lung-protective ventilation (tidal volume 6 mL/kg PBW and Pplat < 30 cm H2O).

760

Judicious use of neuromuscular blocking agents and sedation

762

Experienced and specially trained medical staff who are familiar with prone positioning

764

757 759 761 763 765

Optimization of PEEP for alveolar recruitment

766

Discontinuation of prone positioning when oxygenation is improved (Pao2/Fio2 $ 150 with a PEEP # 10 cm H2O, Fio2 # 0 .6 for at least 4 h in supine position)

767 768

PBW ¼ predicted body weight. See Table 1 and 3 legends for expansion of other abbreviations.

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771 772 773 774 775 776 777 778 779 780

Potential complications of PP include endotracheal tube obstruction and dislodgement and pressure ulcer formation on dependent areas such as the face, chest, and knees.77 Absolute contraindications for PP are spinal instability and unmonitored elevated intracranial pressure. Relative contraindications include open abdomen, late pregnancy, severe hemodynamic instability, unstable fractures, and absolute need for vascular access.

781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 811

Extracorporeal Membrane Oxygenation

ECMO, also called extracorporeal life support, can play an important role in the management of severe hypoxemic respiratory failure. For patients with respiratory failure, venovenous (VV) ECMO is used. This is often accomplished using a single dual-lumen catheter inserted through the internal jugular vein.78 ECMO is restricted to centers that have established expertise, as a higher volume of cases is associated with lower in-hospital mortality for adults.79 In the LUNG SAFE study, about 3% of invasively ventilated patients with ARDS received ECMO, including almost 7% with severe ARDS.7 The increased interest in ECMO80 may be related to successful application during recent influenza pandemics and recent clinical trial results. A multicenter prospective trial reported improved outcomes among patients with ARDS transferred to a single ECMO center compared with continuation of conventional management at regional hospitals (63% vs 47% 6-month disability-free survival).81 Interestingly, only 68 of the 90 patients referred to the ECMO center underwent ECMO, as many of the remaining patients improved with other interventions after transfer, obviating the need for ECMO. This supports the potential value of transferring patients with severe hypoxemic respiratory failure to a center with

specialized expertise, including ECMO. The duration of mechanical ventilation and ICU and hospital length of stay were longer when ECMO was used than with conventional management alone. In a recent multicenter retrospective analysis of patients with severe ARDS, those who received early VV ECMO had lower odds of ICU and hospital death but longer ICU and hospital length of stay.82 The authors of recently published evidence-based clinical practice guidelines state that additional evidence is necessary to make a definitive recommendation for or against the use of ECMO in patients with severe ARDS.17 ECMO is indicated when there is compromise to gas exchange that is refractory to optimal mechanical ventilation and medical therapy, threatens survival, and is reversible. Indications, contraindications, and complications are listed in Table 5.83,84 ECMO provides potentially lifesaving support of gas exchange and allows lung rest by reducing the intensity of mechanical ventilation. High DP during ECMO is associated with worse outcomes.85 Due to the risks and complexity of management that requires specialty center expertise, VV ECMO for ARDS is generally considered after conventional management has been optimized. However, there are benefits associated with early transfer to an ECMO center. Use of objective scoring systems that incorporate the degree of impairment of oxygenation and early response to conventional therapy, estimates of dead space ventilation, and other factors can help identify the appropriate candidate for transfer or initiation (or both) of ECMO.83 Managing ECMO effectively requires an experienced team. A challenge is weaning the patient from ECMO, which is as much art as science. It is important to consider that gas exchange using ECMO occurs at the membrane lung and that the patient’s arterial

826 827 828 829 830 831 832 833 834 835 836 837 838 839 840 841 842 843 844 845 846 847 848 849 850 851 852 853 854 855 856 857 858 859 860 861 862 863 864 865 866

812

867

813

868

814

TABLE 5

] Indications, Contraindications, and Adverse Effects of ECMO

815

Indications

816

Profound hypoxemia (PaO2/FIO2 < 80) on invasive ventilation with appropriate tidal volume and PEEP persisting for > 3-6 h of optimized mechanical ventilation Severe uncompensated hypercapnia with acidemia (pH < 7.15) despite appropriate ventilation persisting for > 3-6 h of optimized mechanical ventilation

817 818 819 820 821 822 823 824 825

869

Contraindications Mechanical ventilation > 7 d CNS catastrophe Irreversible condition in an individual who is not a lung transplant candidate Absolute contraindications for anticoagulation Multiple organ failure Age > 70 y

870

Adverse Effects

871

Infection Bleeding (surgical site, cannulation site, pulmonary site, GI tract, intracranial site) Clotting (at oxygenator, circuit) Hemolysis Disseminated intravascular coagulation Oxygenation failure

872 873 874 875 876 877 878 879 880

ECMO ¼ extracorporeal membrane oxygenation. See Table 1 legend for expansion of other abbreviations.

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881

936

Pao2/Fio2 < 150

882 883

937 938

884

939

885

940

Tidal Volume 4-6 mL/kg PBW Pplat < 30 cm H2O

886

941

887

942

888

943

Initial PEEP 10-12 cm H2O Increase PEEP by 2-3 cm H2O steps; stop with hypotension, desaturation, increased driving pressure, or Pplat > 30 cm H2O. Consider recruitment maneuver and decremental PEEP titration.

889 890

944 945

891

946

892

947

893

948

Pao2/Fio2 > 150

894 895 896

yes

949 950 951

no

897

952

Consider nonrespiratory causes (eg, PFO) Fluid restriction and diuresis as necessary

898 899

953 954

900

955

901

956

no

902 903

Pao2/Fio2 > 150

904

yes

Daily attempt to decrease PEEP by 2-3 cm H2O

957 958 959

no

905

Consider transfer to ECMO facility

906

960

Neuromuscular blockade

961

907

962

908

963

no

909 910

Pao2/Fio2 > 150

yes

964

Discontinue neuromuscular blockade at 48 h

965

911

966

no

912 913

967 968

Prone positioning

914

969

915 917 918 919 920 921

970

no

print & web 4C=FPO

916

ECMO

Pao2/Fio2 > 150

yes

971

Daily attempt to discontinue prone positioning

972 973 974

no

975

Consider inhaled vasodilators Consider nontraditional ventilator modes (note low level evidence to support these strategies)

922

976 977

923

978

924

979

925

980

no

926 927 928 929 930 931

Pao2/Fio2 > 150

yes

981 982

Figure 2 – A suggested approach to severe hypoxemic respiratory failure based on our view of the available evidence. The dashed lines represent lessfavored alternative approaches. This approach is intended to be reasonable, not rigid. Experienced clinicians might select different priorities, and this approach might be superseded as new evidence becomes available. ECMO ¼ extracorporeal membrane oxygenation; PBW ¼ predicted body weight; PFO ¼ xxx. See Figure 1 legend for expansion of other abbreviations.

932 933 934 935

983 984 985 Q18

986 987

oxygenation is the result of mixing the ECMO blood with the native venous blood. The arterial blood oxygen content will be dependent on the oxygen content and

flow (proportion of cardiac output) of ECMO blood mixed with the venous return blood oxygen content and flow.86

988 989 990

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ECMO and PP

992

Limited evidence exists on the combination of ECMO and PP. Most are retrospective studies and underpowered clinical trials. Kredel et al87 showed that the combination of VV-ECMO and PP improved both oxygenation and respiratory compliance without any serious adverse events. Kimmoun et al88 noted that improvement in oxygenation was marked when PP was applied after 7 days of VV-ECMO, with a marked decrease in Pplat in patients having difficulty reducing Pplat on ECMO alone.

993 994 995 996 997 998 999 1000 1001 1002 1003 1004

Miscellaneous Therapies

1005 1006

Fluid Restriction

1007

The 2006 Fluid and Catheter Treatment Trial (FACTT) trial89 showed that aiming for central venous pressure < 4 mm Hg and pulmonary artery occlusion pressure < 8 mm Hg with aggressive fluid restriction and diuretics in ARDS improves lung function and increases ventilator- and ICU-free days without increasing nonpulmonary organ failure. There was no mortality benefit seen in this trial. Fluid management with a simplified conservative protocol in ARDS (FACTT lite) yielded similar results.90

1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 1018

Inhaled Vasodilators (Prostaglandins and Nitric Oxide)

1019 1020 1021 1022 1023 1024 1025 1026 1027 1028 1029

Q14

Selective pulmonary vasodilators improve oxygenation and lower pulmonary hypertension but have not been shown to improve mortality. Of concern is the potential for renal dysfunction and methemoglobinemia when inhaled nitric oxide is used.91 Inhaled prostaglandin can result in hypotension.92 Although they should not be used routinely, inhaled vasodilators might be used as a bridge to other therapy such as ECMO.

1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045

Additional Considerations It is important to point out that there are other important conditions frequently associated with ARDS that may compound the degree of hypoxemia or complicate its management. For example, almost 20% of patients with severe ARDS may have a patent foramen ovale.93 If hypoxemic respiratory failure is not responding to the ventilatory and nonventilatory strategies outlined further on, it behooves the treating clinician to look for this entity and consider a contrast study using agitated saline with transthoracic or transesophageal echocardiography.93,94 Another entity that is occasionally encountered and is potentially treatable is acute cor pulmonale or acute RV

10 Contemporary Reviews in Critical Care Medicine

1046

dysfunction. It may be seen in up to 25% of patients with severe ARDS95 and is associated with an increase in RV afterload.95 RV dysfunction may develop even when the pulmonary artery pressures remain unchanged. Although right heart catheterization (RHC) was initially used to diagnose acute RV dysfunction, echocardiographic imaging (transthoracic or transesophageal) has supplanted RHC and become standard of care. Echocardiographic findings include the ratio of right ventricular end-diastolic area over LV enddiastolic area > 0.6 with septal akinesis (D-sign). A RV protective approach74 includes limiting Pplat to < 27 cm H2O and DP to < 17 cm H2O, limiting PaCO2 to < 60 mm Hg, titrating PEEP according to RV function, and using PP in these patients.

1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062

Finally, we would like to point out that for patients who do not respond to initial treatment of severe hypoxemic respiratory failure, consideration should be given to transfer to a unit with expertise in caring for such patients and where therapies such as ECMO are available. Kahn et al96 reported that mechanical ventilation of patients in a hospital with a high case volume was associated with reduced mortality and that regionalization of intensive care might improve survival for patients receiving mechanical ventilation.97

1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075

Conclusions

1076

A suggested approach to the management of severe hypoxemic respiratory failure is shown in Figure 2. The initial approach should be lung-protective ventilation, with a tidal volume 4 to 6 mL/kg PBW and adequate PEEP titration. For patients who remain hypoxemic after PEEP titration, NMBAs and PP should be used. For patients who remain severely hypoxemic after these strategies, ECMO should be considered. Inhaled vasodilators and nontraditional ventilator modes might be considered, despite low-level evidence to support their use.

1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089

Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST the following: D. R. H. is associated Philips Respironics, Ventec Life Systems, Jones and Bartlett, McGraw-Hill, UpToDate, American Board of Internal Medicine, and Daedalus Enterprises. None declared (D. K. N., D. R. H., C. N. S., H. M. B., K. K. G., F. K., C. M. C., M. E. A., S. R.).

Q15 Q16

1090 1091 1092 1093 1094 1095 1096

References 1. Clark BJ, Moss M. The acute respiratory distress syndrome: dialing in the evidence? JAMA. 2016;315(8):759-761. 2. Esan A, Hess DR, Raoof S, George L, Sessler CN. Severe hypoxemic respiratory failure: part 1—ventilatory strategies. Chest. 2010;137(5): 1203-1216.

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3. Raoof S, Goulet K, Esan A, Hess DR, Sessler CN. Severe hypoxemic respiratory failure: part 2—nonventilatory strategies. Chest. 2010;137(6):1437-1448.

end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299(6):637-645.

4. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23): 2526-2533.

24. Mercat A, Richard JC, Vielle B, et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299(6):646-655.

5. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23): 2159-2168. 6. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107-1116. 7. Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788-800. 8. Beitler JR, Schoenfeld DA, Thompson BT. Preventing ARDS: progress, promise, and pitfalls. Chest. 2014;146(4):1102-1113. 9. Soto GJ, Kor DJ, Park PK, et al. Lung injury prediction score in hospitalized patients at risk of acute respiratory distress syndrome. Crit Care Med. 2016;44(12):2182-2191.

25. Briel M, Meade M, Mercat A, et al. Higher vs lower positive endexpiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303(9):865-873. 26. Kasenda B, Sauerbrei W, Royston P, et al. Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS. BMJ Open. 2016;6(9):e011148. 27. Chiumello D, Coppola S, Froio S, et al. Time to reach a new steady state after changes of positive end expiratory pressure. Intensive Care Med. 2013;39(8):1377-1385. 28. Hess DR. Recruitment maneuvers and PEEP titration. Respir Care. 2015;60(11):1688-1704.

10. Brochard L, Slutsky A, Pesenti A. Mechanical ventilation to minimize progression of lung injury in acute respiratory failure. Am J Respir Crit Care Med. 2017;195(4):438-442.

29. Chiumello D, Cressoni M, Carlesso E, et al. Bedside selection of positive end-expiratory pressure in mild, moderate, and severe acute respiratory distress syndrome. Crit Care Med. 2014;42(2):252-264.

11. Yoshida T, Torsani V, Gomes S, et al. Spontaneous effort causes occult pendelluft during mechanical ventilation. Am J Respir Crit Care Med. 2013;188(12):1420-1427.

30. Hess DR. Approaches to conventional mechanical ventilation of the patient with acute respiratory distress syndrome. Respir Care. 2011;56(10):1555-1572.

12. Yoshida T, Uchiyama A, Matsuura N, Mashimo T, Fujino Y. The comparison of spontaneous breathing and muscle paralysis in two different severities of experimental lung injury. Crit Care Med. 2013;41(2):536-545.

31. Hess DR. Ventilatory strategies in severe acute respiratory failure. Semin Respir Crit Care Med. 2014;35(4):418-430.

13. Bellani G, Laffey JG, Pham T, et al. Noninvasive ventilation of patients with acute respiratory distress syndrome. insights from the LUNG SAFE study. Am J Respir Crit Care Med. 2017;195(1):67-77.

33. Gattinoni L, Carlesso E, Cressoni M. Selecting the ‘right’ positive end-expiratory pressure level. Curr Opin Crit Care. 2015;21(1):50-57.

14. Rittayamai N, Katsios CM, Beloncle F, Friedrich JO, Mancebo J, Brochard L. Pressure-controlled vs volume-controlled ventilation in acute respiratory failure: a physiology-based narrative and systematic review. Chest. 2015;148(2):340-355. 15. Chacko B, Peter JV, Tharyan P, John G, Jeyaseelan L. Pressurecontrolled versus volume-controlled ventilation for acute respiratory failure due to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Cochrane Database Syst Rev. 2015;1:CD008807. 16. Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18): 1301-1308. 17. Fan E, Del Sorbo L, Goligher EC, et al. An official American Thoracic Society/European Society of Intensive Care Medicine/ Society of Critical Care Medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;195(9): 1253-1263. 18. Gattinoni L, Carlesso E, Caironi P. Stress and strain within the lung. Curr Opin Crit Care. 2012;18(1):42-47.

32. Hess DR. Respiratory mechanics in mechanically ventilated patients. Respir Care. 2014;59(11):1773-1794.

34. Goligher EC, Kavanagh BP, Rubenfeld GD, et al. Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress trials. Am J Respir Crit Care Med. 2014;190(1): 70-76.

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35. Suzumura EA, Amato MB, Cavalcanti AB. Understanding recruitment maneuvers. Intensive Care Med. 2016;42(5):908-911.

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36. Keenan JC, Formenti P, Marini JJ. Lung recruitment in acute respiratory distress syndrome: what is the best strategy? Curr Opin Crit Care. 2014;20(1):63-68.

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37. Marini JJ. Recruitment by sustained inflation: time for a change. Intensive Care Med. 2011;37(10):1572-1574.

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38. Suzumura EA, Figueiro M, Normilio-Silva K, et al. Effects of alveolar recruitment maneuvers on clinical outcomes in patients with acute respiratory distress syndrome: a systematic review and metaanalysis. Intensive Care Med. 2014;40(9):1227-1240.

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39. Hodgson C, Goligher EC, Young ME, et al. Recruitment manoeuvres for adults with acute respiratory distress syndrome receiving mechanical ventilation. Cochrane Database Syst Rev. 2016;11: CD006667. 40. Borges JB, Okamoto VN, Matos GF, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;174(3):268-278.

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19. Neto AS, Simonis FD, Barbas CS, et al. Lung-protective ventilation with low tidal volumes and the occurrence of pulmonary complications in patients without acute respiratory distress syndrome: a systematic review and individual patient data analysis. Crit Care Med. 2015;43(10):2155-2163.

41. Kacmarek RM, Villar J, Sulemanji D, et al. Open lung approach for the acute respiratory distress syndrome: a pilot, randomized controlled trial. Crit Care Med. 2016;44(1):32-42.

20. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755.

42. Habashi NM. Other approaches to open-lung ventilation: airway pressure release ventilation. Crit Care Med. 2005;33(3 suppl): S228-S240.

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21. Loring SH, Malhotra A. Driving pressure and respiratory mechanics in ARDS. N Engl J Med. 2015;372(8):776-777.

43. Hess D, Mason S, Branson R. High-frequency ventilation design and equipment issues. Respir Care Clin N Am. 2001;7(4):577-598.

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22. Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;351(4):327-336.

44. Lucangelo U, Fontanesi L, Antonaglia V, et al. High frequency percussive ventilation (HFPV). Principles and technique. Minerva Anestesiol. 2003;69(11):841-848, 848-851.

1208

23. Meade MO, Cook DJ, Guyatt GH, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive

45. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress

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syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-1308.

66. Sessler CN. Counterpoint: should paralytic agents be routinely used in severe ARDS? No. Chest. 2013;144(5):1442-1445.

1266

46. Ferguson ND, Cook DJ, Guyatt GH, et al. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med. 2013;368(9):795-805.

67. Slutsky AS. Neuromuscular blocking agents in ARDS. N Engl J Med. 2010;363(12):1176-1180.

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47. Young D. High-frequency oscillation for ARDS. N Engl J Med. 2013;368(23):2234. 48. Sud S, Sud M, Friedrich JO, et al. High-frequency oscillatory ventilation versus conventional ventilation for acute respiratory distress syndrome. Cochrane Database Syst Rev. 2016;4:CD004085. 49. Meade MO, Young D, Hanna S, et al. Severity of hypoxemia and effect of high frequency oscillatory ventilation in ARDS [published online ahead of print February 28, 2017]. Am J Respir Crit Care Med. http://dx.doi.org/10.1164/rccm.201609-1938OC. 50. Salim A, Martin M. High-frequency percussive ventilation. Crit Care Med. 2005;33(3 suppl):S241-S245. 51. Eastman A, Holland D, Higgins J, et al. High-frequency percussive ventilation improves oxygenation in trauma patients with acute respiratory distress syndrome: a retrospective review. Am J Surg. 2006;192(2):191-195.

68. Beitler JR, Sands SA, Loring SH, et al. Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria. Intensive Care Med. 2016;42(9): 1427-1436. 69. Murray MJ, DeBlock H, Erstad B, et al. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med. 2016;44(11):2079-2103.

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70. Gattinoni L, Taccone P, Carlesso E, Marini JJ. Prone position in acute respiratory distress syndrome. Rationale, indications, and limits. Am J Respir Crit Care Med. 2013;188(11):1286-1293.

1276

71. Guerin C, Baboi L, Richard JC. Mechanisms of the effects of prone positioning in acute respiratory distress syndrome. Intensive Care Med. 2014;40(11):1634-1642.

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72. Taccone P, Pesenti A, Latini R, et al. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2009;302(18):1977-1984.

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52. Lucangelo U, Zin WA, Fontanesi L, et al. Early short-term application of high-frequency percussive ventilation improves gas exchange in hypoxemic patients. Respiration. 2012;84(5):369-376.

73. Beitler JR, Guerin C, Ayzac L, et al. PEEP titration during prone positioning for acute respiratory distress syndrome. Crit Care. 2015;19:436.

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53. Paulsen SM, Killyon GW, Barillo DJ. High-frequency percussive ventilation as a salvage modality in adult respiratory distress syndrome: a preliminary study. Am Surg. 2002;68(10):852-856; discussion 856.

74. Paternot A, Repesse X, Vieillard-Baron A. Rationale and description of right ventricle-protective ventilation in ARDS. Respir Care. 2016;61(10):1391-1396.

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54. Velmahos GC, Chan LS, Tatevossian R, et al. High-frequency percussive ventilation improves oxygenation in patients with ARDS. Chest. 1999;116(2):440-446.

75. Beitler JR, Shaefi S, Montesi SB, et al. Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med. 2014;40(3): 332-341.

55. Michaels AJ, Hill JG, Long WB, et al. Adult refractory hypoxemic acute respiratory distress syndrome treated with extracorporeal membrane oxygenation: the role of a regional referral center. Am J Surg. 2013;205(5):492-498; discussion 498-499.

76. Sud S, Friedrich JO, Adhikari NK, et al. Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and metaanalysis. CMAJ. 2014;186(10):E381-E390.

56. Chung KK, Wolf SE, Renz EM, et al. High-frequency percussive ventilation and low-tidal-volume ventilation in burns: a randomized controlled trial. Crit Care Med. 2010;38(10):1970-1977.

77. Guerin C. Prone ventilation in acute respiratory distress syndrome. Eur Respir Rev. 2014;23(132):249-257.

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78. Berdajs D. Bicaval dual-lumen cannula for venovenous extracorporeal membrane oxygenation: AvalonÓ cannula in childhood disease. Perfusion. 2015;30(3):182-186.

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57. Facchin F, Fan E. Airway pressure release ventilation and highfrequency oscillatory ventilation: potential strategies to treat severe hypoxemia and prevent ventilator-induced lung injury. Respir Care. 2015;60(10):1509-1521. 58. Mireles-Cabodevila E, Kacmarek RM. Should airway pressure release ventilation be the primary mode in ARDS? Respir Care. 2016;61(6): 761-773. 59. Gonzalez M, Arroliga AC, Frutos-Vivar F, et al. Airway pressure release ventilation versus assist-control ventilation: a comparative propensity score and international cohort study. Intensive Care Med. 2010;36(5):817-827. 60. Varpula T, Valta P, Niemi R, Takkunen O, Hynynen M, Pettila VV. Airway pressure release ventilation as a primary ventilatory mode in acute respiratory distress syndrome. Acta Anaesthesiol Scand. 2004;48(6):722-731. 61. Maxwell RA, Green JM, Waldrop J, et al. A randomized prospective trial of airway pressure release ventilation and low-tidal-volume ventilation in adult trauma patients with acute respiratory failure. J Trauma. 2010;69(3):501-510; discussion 511. 62. Maung AA, Kaplan LJ. Airway pressure release ventilation in acute respiratory distress syndrome. Crit Care Clin. 2011;27(3):501-509. 63. Forel JM, Roch A, Marin V, et al. Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2006;34(11): 2749-2757. 64. Gainnier M, Roch A, Forel JM, et al. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit Care Med. 2004;32(1):113-119. 65. Neto AS, Pereira VG, Esposito DC, Damasceno MC, Schultz MJ. Neuromuscular blocking agents in patients with acute respiratory distress syndrome: a summary of the current evidence from three randomized controlled trials. Ann Intensive Care. 2012;2(1):33.

12 Contemporary Reviews in Critical Care Medicine

1288 1289 1290 1291 1292 1293 1295 1297

79. Barbaro RP, Odetola FO, Kidwell KM, et al. Association of hospitallevel volume of extracorporeal membrane oxygenation cases and mortality. Analysis of the extracorporeal life support organization registry. Am J Respir Crit Care Med. 2015;191(8):894-901.

1300

80. McCarthy FH, McDermott KM, Kini V, et al. Trends in U.S. extracorporeal membrane oxygenation use and outcomes: 20022012. Semin Thorac Cardiovasc Surg. 2015;27(2):81-88.

1302

1298 1299 1301

81. Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet. 2009;374(9698): 1351-1363. 82. Kanji HD, McCallum J, Norena M, et al. Early veno-venous extracorporeal membrane oxygenation is associated with lower mortality in patients who have severe hypoxemic respiratory failure: a retrospective multicenter cohort study. J Crit Care. 2016;33: 169-173.

1303 1304 1305 1306 1307 1308 1309 1310 1311

83. Bohman JK, Hyder JA, Iyer V, et al. Early prediction of extracorporeal membrane oxygenation eligibility for severe acute respiratory distress syndrome in adults. J Crit Care. 2016;33:125-131.

1312

84. Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011;365(20):1905-1914.

1314

85. Serpa Neto A, Schmidt M, Azevedo LC, et al. Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis: mechanical ventilation during ECMO. Intensive Care Med. 2016;42(11):1672-1684. 86. Bartlett RH. Physiology of gas exchange during ECMO for respiratory failure. J Intensive Care Med. 2017;32(4):243-248.

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87. Kredel M, Bischof L, Wurmb TE, Roewer N, Muellenbach RM. Combination of positioning therapy and venovenous extracorporeal membrane oxygenation in ARDS patients. Perfusion. 2014;29(2): 171-177.

1322 1323 1324

88. Kimmoun A, Guerci P, Bridey C, Ducrocq N, Vanhuyse F, Levy B. Prone positioning use to hasten veno-venous ECMO weaning in ARDS. Intensive Care Med. 2013;39(10):1877-1879.

1325 1326

89. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354(24):2564-2575.

1327 1328 1329

90. Grissom CK, Hirshberg EL, Dickerson JB, et al. Fluid management with a simplified conservative protocol for the acute respiratory distress syndrome*. Crit Care Med. 2015;43(2): 288-295.

1330 1331 1332 1333 1334 1335 1336

Q17

91. Gebistorf F, Karam O, Wetterslev J, Afshari A. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database Syst Rev. 2016;(6):CD002787. 92. Fuller BM, Mohr NM, Skrupky L, Fowler S, Kollef MH, Carpenter CR. The use of inhaled prostaglandins in patients with

ARDS: a systematic review and meta-analysis. Chest. 2015;147(6): 1510-1522.

1376 1377

93. Mekontso Dessap A, Boissier F, Leon R, et al. Prevalence and prognosis of shunting across patent foramen ovale during acute respiratory distress syndrome. Crit Care Med. 2010;38(9):1786-1792.

1378

94. Legras A, Caille A, Begot E, et al. Acute respiratory distress syndrome (ARDS)-associated acute cor pulmonale and patent foramen ovale: a multicenter noninvasive hemodynamic study. Crit Care. 2015;19:174.

1380

95. Biswas A. Right heart failure in acute respiratory distress syndrome: an unappreciated albeit a potential target for intervention in the management of the disease. Indian J Crit Care Med. 2015;19(10): 606-609.

1379 1381 1382 1383 1384 1385 1386

96. Kahn JM, Goss CH, Heagerty PJ, Kramer AA, O’Brien CR, Rubenfeld GD. Hospital volume and the outcomes of mechanical ventilation. N Engl J Med. 2006;355(1):41-50.

1388

97. Kahn JM, Linde-Zwirble WT, Wunsch H, et al. Potential value of regionalized intensive care for mechanically ventilated medical patients. Am J Respir Crit Care Med. 2008;177(3):285-291.

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