Extracorporeal Membrane Oxygenation For Acute Respiratory Distress Syndrome Research Articles

Efficacy of proning in acute respiratory distress syndrome on extracorporeal membrane oxygenation.

ObjectivesProning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, although few data exist evaluating the safety and feasibility of proning patients with ARDS on extracorporeal membrane oxygenation (ECMO).MethodsA single-institution retrospective review of all patients with ARDS placed on ECMO between March 1 and May 31, 2020, was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation, and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO.ResultsIn total, 30 patients were placed on ECMO for ARDS, with 12 patients (40%) proned while on ECMO. A total of 83 proning episodes occurred, with a median of 7 per patient (interquartile range, 3-9). No ECMO cannula-associated bleeding, cannula displacement, or endotracheal tune dislodgements occurred (0%). Oropharyngeal bleeding occurred twice (50%). Four patients were proned with chest tubes in place, and none had complications (0%). Lung compliance improved after proning in 70 events (84%), from a mean of 15.4 mL/mm Hg preproning to 20.6 mL/mm Hg postproning (P < .0001). Sweep requirement decreased in 36 events (43%). Oxygenation improved in 63 events (76%), from a mean partial pressure of oxygen of 86 preproning to 103 postproning (P < .0001). Mean ECMO flow was unchanged.ConclusionsProning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

Impact of Invasive Fungal Diseases on Survival under Veno-Venous Extracorporeal Membrane Oxygenation for ARDS.

Objective: To assess the incidence and significance of invasive fungal diseases (IFD) during veno-venous (VV) ECMO support for acute respiratory distress syndrome (ARDS). Methods: Retrospective analysis from January 2013 to April 2021 of all ECMO cases for ARDS at a German University Hospital. In patients with IFD (IFD patients), type of IFD, time of IFD, choice of antifungal agent, duration, and success of therapy were investigated. For comparison, patients without IFD (non-IFD patients) were selected by propensity score matching using treatment-independent variables (age, gender, height, weight, and the Sequential Organ Failure Assessment (SOFA) score at ICU admission). Demographics, hospital and ICU length of stay, duration of ECMO therapy, days on mechanical ventilation, prognostic scores (Charlson Comorbidity Index (CCI), Therapeutic Intervention Scoring System (TISS), and length of survival were assessed. Results: A total of 646 patients received ECMO, 368 patients received VV ECMO. The incidence of IFD on VV ECMO was 5.98%, with 5.43% for Candida bloodstream infections (CBSI) and 0.54% for invasive aspergillosis (IA). In IFD patients, in-hospital mortality was 81.8% versus 40.9% in non-IFD patients. The hazard ratio for death was 2.5 (CI 1.1–5.4; p: 0.023) with IFD. Conclusions: In patients on VV ECMO for ARDS, about one in 17 contracts an IFD, with a detrimental impact on prognosis. Further studies are needed to address challenges in the diagnosis and treatment of IFD in this population.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Association of COVID-19 with Intracranial Hemorrhage during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A 10-Year Retrospective Observational Study.

Extracorporeal membrane oxygenation (ECMO) is potentially lifesaving for patients with acute respiratory distress syndrome (ARDS) but may be accompanied by serious adverse events, including intracranial hemorrhage (ICRH). We hypothesized that ICRH occurs more frequently in patients with COVID-19 than in patients with ARDS of other etiologies. We performed a single-center retrospective analysis of adult patients treated with venovenous (vv-) ECMO for ARDS between January 2011 and April 2021. Patients were included if they had received a cranial computed tomography (cCT) scan during vv-ECMO support or within 72 h after ECMO removal. Cox regression analysis was used to identify factors associated with ICRH. During the study period, we identified 204 patients with vv-ECMO for ARDS, for whom a cCT scan was available. We observed ICRH in 35.4% (n = 17/48) of patients with COVID-19 and in 16.7% (n = 26/156) of patients with ARDS attributable to factors other than COVID-19. COVID-19 (HR: 2.945; 95%; CI: 1.079–8.038; p = 0.035) and carboxyhemoglobin (HR: 0.330; 95%; CI: 0.135–0.806; p = 0.015) were associated with ICRH during vv-ECMO. In patients receiving vv-ECMO, the incidence of ICRH is doubled in patients with COVID-19 compared to patients suffering from ARDS attributable to other causes. More studies on the association between COVID-19 and ICRH during vv-ECMO are urgently needed to identify risk patterns and targets for potential therapeutic interventions.

Quality of life and functional status of patients treated with venovenous extracorporeal membrane oxygenation at 6 months.

Quality of life (QoL) outcomes of patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) have been conflicting. This study reports on QoL outcomes for a broad group of ARDS patients managed with up-to-date treatment modalities. We prospectively recruited patients at a quaternary hospital in the United Kingdom from 2013 to 2015 who were treated with ECMO for ARDS. We evaluated their pulmonary function and QoL at 6-months after admission using three QoL instruments: EuroQoL 5D (EQ-5), HADS, and PTSS-14. Forty-three patients included in the analysis had near-normal pulmonary function at 6 months. HADS showed moderate-to-severe anxiety and depression in 32% and 11% of patients, respectively. PTSS-14 showed 29% had signs of post-traumatic stress disorder. EQ-5D showed that 67% of patients had difficulty returning to usual activities, 74% suffered some pain, none reported severe problems and 77% were able to return to work. No clinical or demographic variables were associated with poor 6-month QoL. Patients with ARDS treated with ECMO generally had good QoL outcomes, similar to outcomes reported for patients managed without ECMO. With respect to QoL, VV-EMCO represents a valid treatment modality for patients with refractory ARDS.

Physical Therapy and Sedation While on Extracorporeal Membrane Oxygenation for COVID-19–Associated Acute Respiratory Distress Syndrome

ObjectivesThis study aimed to determine whether patients on extracorporeal membrane oxygenation (ECMO) with coronavirus disease 2019 (COVID-19) achieved lower rates of physical therapy participation and required more sedation than those on ECMO without COVID-19.DesignRetrospective, observational, matched-cohort study.SettingBicenter academic quaternary medical centers.ParticipantsAll adults on ECMO for severe COVID-19-associated acute respiratory distress syndrome (ARDS) during 2020 and matched (matched 1:1 based on age ± 15 years and medical center) adults on ECMO for ARDS not associated with COVID-19.InterventionsObservational only.Measurements and Main ResultsMeasurements were collected retrospectively during the first 20 days of ECMO support and included daily levels of physical therapy activity, number of daily sedation infusions and doses, and level of sedation and agitation (Richmond Agitation and Sedation Score). During the first 20 days of ECMO support, the 22 patients who were on ECMO for COVID-19–associated ARDS achieved a similar proportion of days with active physical therapy participation while on ECMO compared to matched patients on ECMO for non-COVID-19 ARDS (22.5% v 7.5%, respectively; p value 0.43), a similar proportion of days with Richmond Agitation and Sedation Score ≥-2 while on ECMO (47.5% v 27.5%, respectively; p value 0.065), and a similar proportion of days with chemical paralysis while on ECMO (8.4% v 18.0%, respectively; p value 0.35).ConclusionsThe results of this matched cohort study supported that sedation requirements were not dramatically greater and did not significantly limit early physical therapy for patients who had COVID-19–associated ARDS and were on venovenous extracorporeal membrane oxygenation (VV-ECMO) versus those without COVID-19–associated ARDS who were on VV-ECMO.

Revisiting extracorporeal membrane oxygenation for ARDS in burns: A case series and review of the literature

IntroductionRecent reports on the use of extracorporeal membrane oxygenation (ECMO) in critically ill burn patients with Acute Respiratory Distress Syndrome (ARDS) recommended against the use of ECMO. The authors cited the high mortality rates associated with the use of ECMO in these patients with no appreciable benefit. Accumulating evidence from referral centers suggests improved survival in patients with ARDS receiving ECMO. We report our recent experience treating patients with severe ARDS with ECMO in a burn intensive care unit. MethodsThis is a case series of consecutive patients placed on ECMO at our burn center from the initiation of our program in September 2012 to September 2017. We included only adult patients who had been placed on ECMO with burn injury, TEN, or inhalation injury and severe ARDS. ResultsFourteen patients with burn injury, inhalation injury or TEN were placed on ECMO from the initiation of the ECMO program to September 1st 2017. The average total body surface area burned in the 11 patients with burn injury was 27% (range 0.25–76%). The cause of ARDS in these patients included inhalation injury, airway trauma and bacterial pneumonia. Four patients had an inhalation injury and 1 patient had a grade 3 inhalation injury but no burn injury.In the majority of cases, prone positioning and use of neuromuscular blockade was also used in an attempt to improve oxygenation and patient synchrony with mechanical ventilation. The average time on ECMO was 276h (range 63–539h). Ten of the 14 patients survived to decanulation from ECMO (71%) and eight of 14 patients (57%) survived to hospital discharge. ConclusionsTo our knowledge, this is the lowest mortality rate reported to date in burn patients with ARDS place on ECMO. ECMO is a viable therapy that can be utilized successfully as a rescue modality when conventional interventions are unsuccessful.

The Use of GMP-Produced Bone Marrow-Derived Stem Cells in Combination with Extracorporeal Membrane Oxygenation in ARDS: An Animal Model

Acute respiratory distress syndrome (ARDS) is the result of a wide variety of disorders, which can be associated with different clinical disorders or systemic diseases directly affecting the lungs. Currently, the only existing therapy is limited to supportive care. In a 6 hour pilot study, we analyzed the use of the combination of both stem cell and extracorporeal membrane oxygenation (ECMO) strategies to prevent or treat severe lung injury. A total of 11 sheep were used. Five sheep received Escherichia coli endotoxin as a control group (group 1). Three sheep that received E. coli endotoxin were treated with veno-venous ECMO support in group 2. In group 3, 3 sheep received a dose of clinical grade good manufacturing practice (GMP)-produced MultiPotent Adult Progenitor cells (MAPC) intratracheally after the end of the infusion of E. coli endotoxin, followed by ECMO support. The respiratory parameters by means of blood gas results, measurements of lung injury, inflammatory responses, and integrity of the alveolar capillary barrier after the infusion of these cells were analyzed. Our data suggest that the combination of ECMO and stem cell therapy showed better histopathologic changes with less inflammation. We believe that the combination of stem cells with the ECMO treatment may be useful in future studies investigating the diagnosis, treatment, and prevention of ARDS.

Venovenous extracorporeal membrane oxygenation for ARDS: outcome analysis of a Croatian referral center for respiratory ECMO.

The use of venovenous extracorporeal membrane oxygenation (VV-ECMO) as arescue therapy in severe acute respiratory distress syndrome (ARDS) has become well established; however, the affirmation of evidence on VV-ECMO application and the analysis of patient outcomes after VV-ECMO treatment for ARDS continues. The aim of the study is to identify variables that affected the outcome of patients treated with VV-ECMO for severe ARDS outside amajor ECMO center. The study included adult patients with severe ARDS treated with ECMO at atertiary care hospital in Zagreb, Croatia between October 2009 and July 2014. Patients were recruited from aprospective database. The study enrolled 40 patients, 20 of whom had H1N1-induced ARDS. The hospital mortality was 38%. The difference in mortality and long-term outcome in H1N1-induced ARDS as compared to non-H1N1-induced ARDS was not significant. Variables associated with mortality included immunosuppression, shock at time of admission, acute renal failure, occurrence of heparin-induced thrombocytopenia antibodies, nosocomial sepsis and duration of ECMO. The results of our study indicate that ECMO use in severe ARDS is feasible with low mortality and identify or assert the variables associated with adverse outcomes.

Management of refractory hypoxemia during venovenous extracorporeal membrane oxygenation for ARDS.

Venovenous extracorporeal membrane oxygenation (VV ECMO) in acute respiratory distress syndrome (ARDS) is currently a widely used therapeutic strategy. However, patients are often still hypoxemic despite complete ECMO support. The major determinants of peripheral oxygen saturation (SpO2) during VV ECMO are pump flow, degree of recirculation, patient's systemic venous return and its oxygen saturation, hemoglobin concentration and residual lung function. Current guidelines state that the support can be considered adequate when the patient's SpO2 is equal or greater than 80%, but a possible objection could be that such a value of O2-tension may be too low and may worsen the patient's prognosis. Moving from the pathophysiology of hypoxemia during VV ECMO, this review focuses on recirculation of blood and on the possible strategies to minimize it, on the pharmacologic modulation of intrapulmonary shunt and on the questions related to management of ECMO flow and the risks and benefits of permissive hypoxemic states. Transfusional strategy during VV ECMO, administration of neuromuscular blocking agents and sedatives, therapeutic hypothermia, and prone positioning is also reviewed. The potential advantages of β-blockers are discussed. Finally, transition from VV ECMO to venoarterial ECMO (VA ECMO) or a hybrid configuration is also examined.

Extracorporeal membrane oxygenation treatment for H1N1-induced acute respiratory distress syndrome (ARDS): results of the Croatian Referral Center for Respiratory ECMO.

Extracorporeal membrane oxygenation (ECMO) has been effective in the treatment of H1N1-induced ARDS across the globe. However, the evidence supporting the use of ECMO in ARDS is still being collected. The intention of this study was to add a piece of puzzle to the growing body of evidence on the use of ECMO in ARDS patients. The study included adult patients with H1N1-induced ARDS treated with ECMO at the University Hospital for Infectious Diseases in Zagreb, Croatia between October 2009 and December 2013. 17 patients with H1N1-induced ARDS treated with ECMO were included in the study. The patient cohort of the study was young with a median age of 43 years (range 23-74). The hospital mortality was 35%. Possible variables associated with mortality were analyzed and only hemolysis was found to be significant. Our results confirm the usefulness of ECMO treatment in patients with H1N1-induced ARDS.

Update in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by permeability pulmonary edema and refractory hypoxemia. Recently, the new definition of ARDS has been published, and this definition suggested severity-oriented respiratory treatment by introducing three levels of severity according to PaO2/FiO2 and positive end-expiratory pressure. Lung-protective ventilation is still the key of better outcome in ARDS. Through randomized trials, short-term use of neuromuscular blockade at initial stage of mechanical ventilation, prone ventilation in severe ARDS, and extracorporeal membrane oxygenation in ARDS with influenza pneumonia showed beneficial efficacy. However, ARDS mortality still remains high. Therefore, early recognition of ARDS modified risk factors and the avoidance of aggravating factors during the patient's hospital stay can help decrease its development. In addition, efficient antifibrotic strategies in late-stage ARDS should be developed to improve the outcome.

Veno-venous ECMO in ARDS after post-traumatic pneumonectomy

Dear Editor, Post-traumatic pneumonectomy is rare, but burdened by high mortality (50–80 %) and high morbidity, with a complication rate of [85 %, most commonly pneumonia and respiratory failure [1]. Life-threatening acute respiratory distress syndrome (ARDS) can develop, and the worst outcome is associated with right pneumonectomy [2]. Extracorporeal membrane oxygenation (ECMO) is a rescue option in ARDS that allows for protective mechanical ventilation and potentially less ventilator-induced damage [3]. In the past, trauma cases requiring anticoagulation for ECMO implantation posed a clinical dilemma that has now been partially overcome with the advent of latest generation devices. We report a case of multifactorial ARDS (pneumonia, polytransfusion, and fluid overload) after right pneumonectomy due to blunt chest trauma in which the patient was non-responsive to protective ventilation and conventional therapy [4]. The patient survived with early implantation and 29 days of ECMO support. A 25-year-old male (170 cm, 61 kg) was admitted to another facility with major blunt thoracic trauma causing right hemothorax, right main bronchial disruption, left pneumothorax, and pneumomediastinum. Surgical treatment consisted of right pneumonectomy, left chest drainage, and tracheostomy. Despite lung-protective ventilation, the patient developed ARDS, with hypoxic–hypercapnic respiratory failure [partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) 40 at 36 h]. A PaO2/ FiO2 ratio of\100 with a FiO2 of 1.0 for more than 6 h indicates that a patient has a [80 % risk of death (Extracorporeal Life Support Organization guidelines) (Fig. 1). The referring center requested a consultation, and despite the recent trauma and surgery, we decided to start the patient on veno-venous ECMO (VV-ECMO) which achieved stabilization and allowed the patient to be safely transported about 200 km by helicopter to our institute. Vessel cannulation [18 Fr return (jugular) and 24 Fr drainage (femoral)] was performed after the administration of a heparin bolus (80 IU/kg). VVECMO support (miniaturized tip-totip heparin-coated circuit; Cardiohelp System; Maquet, Rastatt, Germany) was initiated, with the initial goal of achieving a blood flow of about 4 l/ min (3,000 rpm and 2 l/min of sweep gas flow) in order to provide maximal oxygenation support, but avoid iatrogenic alkalosis. Protective mechanical ventilation for transport was a FiO2 of 40 %, peak inspiratory pressure (PIP) of 20 cm H2O, positive end-expiratory pressure (PEEP) of 10 cm H2O, and respiratory rate (RR) of 10 breaths/min (Oxylog 3000 Plus; Draeger, Menlo Park, CA). On arrival at our institute, after a few hours of ECMO, gas exchange parameters were adequate (pH 7.34, PaO2 116 mmHg, PaCO2 58 mmHg). Microbiological screening revealed colonization by Acinetobacter baumannii (multi-drug resistant), which was confirmed by the swab test and bronchoalveolar lavage. Continuous heparin infusion was initiated to maintain an activated partial thromboplastin time of 40–50 s, and an

What is new in extracorporeal membrane oxygenation for ARDS in adults?

The use of extracorporeal membrane oxygenation (ECMO) in severe acute respiratory distress syndrome (ARDS) has increased considerably over the last several years, attributable to advances in extracorporeal technology, renewed interest, and accumulating evidence. Yet the role of ECMO in severe ARDS is still being defined. Looking ahead, the future of ECMO for ARDS may potentially involve an expanding role.

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome in Adults

Despite advances in treatment, acute respiratory distress syndrome (ARDS) remains a common cause of respiratory failure requiring ventilatory support and is associated with significantly high rates of morbidity and mortality. To date, the only treatment shown to increase survival rate in patients with ARDS is the use of supportive mechanical ventilation using low tidal volumes. Extracorporeal membrane oxygenation (ECMO) is a therapy that has been used in severe cases of ARDS when patients fail to improve with traditional management. Recent literature shows varying mortality rates for the use of ECMO for ARDS; however, the literature suggests that transfer of patients to an ECMO center for treatment using specific criteria and indications may improve outcomes. Further research is needed regarding the timing of the initiation of ECMO, standardization of therapy, and which type of ECMO reduces morbidity and mortality rates in patients with ARDS.

Outcomes of Long-Term Veno-Venous Extracorporeal Membrane Oxygenation Support for Acute Respiratory Distress Syndrome

Purpose Given substantial advances in veno-venous extracorporeal membrane oxygenation (ECMO) technology, long-term support is increasingly feasible. Although the benefits of short-term ECMO as a bridge to recovery in acute respiratory distress syndrome (ARDS) are well described in the literature, the outcomes of patients requiring long-term support remain unclear. Methods and Materials Patients requiring ECMO for ARDS between January 2009 and November 2012 were retrospectively reviewed and analyzed separately for those requiring short-term and long-term ECMO support (≥3 weeks). Demographics, ECMO variables and outcomes of patient bridged to recovery or transplantation were assessed. Results 57 patients with ARDS were placed on ECMO during that time period with 11 patients requiring long-term ECMO support (59±51 days). Recovery was the goal in all patients. In the long-term support group, pre-ECMO mechanical ventilation was conventional PC or PRVC (N=4), APRV (N=5), or HFO (N=2). The mean pre-ECMO FiO2 was 0.93±0.13 with mean pH, PaO2, and PaCO2 of 7.3±0.1, 69±26 mmHg, 63±21 mmHg, respectively. Pre-ECMO Murray Scores were 3.7±0.4 and 3.82±0.29 (p=NS) in the long-term and short-term groups, respectively. 8 (73%) long-term support patients were successfully bridged to recovery and 1 patient was bridged to transplantation after a refractory course. 25 (52%) short-term support patients and 8 (73%) long-term support patients survived to 30-days or hospital discharge. In the long-term support group, 4 of the 8 surviving patients had mid-term follow-up available; with 100% surviving, returned to home, and with normal functional status at 1 year. Conclusions Previously, long-term ECMO support has not been thought to be associated with favorable outcomes. This study, however, may provide support for the efficacy of ECMO for patients even requiring support greater than 3 weeks as a bridge to recovery or transplantation.

Extracorporeal Membrane Oxygenation for ARDS in Adults

A 41-year-old woman presents with severe community-acquired pneumococcal pneumonia. Chest radiography reveals diffuse bilateral infiltrates, and hypoxemic respiratory failure develops despite appropriate antibiotic therapy. She is intubated and mechanical ventilation is initiated with a volume- and pressure-limited approach for the acute respiratory distress syndrome (ARDS). Over the ensuing 24 hours, her partial pressure of arterial oxygen (Pao2) decreases to 40 mm Hg, despite ventilatory support with a fraction of inspired oxygen (Fio2) of 1.0 and a positive end-expiratory pressure (PEEP) of 20 cm of water. She is placed in the prone position and a neuromuscular blocking agent is administered, without improvement in her Pao2. An intensive care specialist recommends the initiation of extracorporeal membrane oxygenation (ECMO).

Critical Care Medicine

Critical Care Medicine

ECMO in ARDS: a long‐term follow‐up study regarding pulmonary morphology and function and health‐related quality of life

A high survival rate can be achieved in patients with severe acute respiratory distress syndrome (ARDS) using extracorporeal membrane oxygenation (ECMO). The technique and the costs are, however, debated and follow-up studies in survivors are few. The aim of this study was to evaluate long-term pulmonary health after ECMO and severe ARDS. Twenty-one long-term survivors of severe ARDS and ECMO were studied in a follow-up program including high-resolution computed tomography (HRCT) of the lungs, extensive pulmonary function tests, pulmonary scintigraphy and the pulmonary disease-specific St George's Respiratory Questionnaire (SGRQ). The majority of patients had residual lung parenchymal changes on HRCT suggestive of fibrosis, but the extension of morphologic abnormalities was limited and without the typical anterior localization presumed to indicate ventilator-associated lung injury. Pulmonary function tests revealed good restitution with mean values in the lower normal range, while T(1/2) for outwash of inhaled isotope was abnormal in all patients consistent with subclinical obstructivity. Most patients had reduced health-related quality of life (HRQoL), according to the SGRQ, but were stating less respiratory symptoms than conventionally treated ARDS patients in previous studies. The majority were integrated in normal work. The majority of ECMO-treated ARDS patients have good physical and social functioning. However, lung parenchymal changes on HRCT suggestive of fibrosis and minor pulmonary function abnormalities remain common and can be detected more than 1 year after ECMO. Furthermore, most patients experience a reduction in HRQoL due to the pulmonary sequelae.

Extracorporeal lung assist: more than kicking a dead horse?

Up to now, the history of extracorporeal lung support has been a tale of great expectations and even greater disappointments. In 1972, Hill et al. 1 published the first case report on the use of extracorporeal membrane oxygenation (ECMO) in a young patient who suffered from acute respiratory distress syndrome (ARDS) after trauma. At that time, mortality rates from ARDS were extremely high and thus this report was embraced with great enthusiasm. However, only 2 yrs later reality caught up when the results of a randomised controlled trial using ECMO in ARDS were published showing mortality rates of >90% in both treatment arms 2. Despite these sobering results, several groups of investigators continued to work on extracorporeal devices. Gattinoni and co-workers 3, 4 were the first to introduce the use of extracorporeal CO2 removal to support protective ventilation strategies, now with survival rates of ∼50% among patients with ARDS. However, once again a randomised controlled trial failed to show a survival benefit in ARDS patients treated with extracorporeal CO2 removal 5 although the survival rates (33% in the extracorporeal group versus 42% in the conventional ventilation group) were now substantially better than in the 1970s. The reasons for the failure to demonstrate a survival benefit with extracorporeal lung support were certainly manifold. The study by Morris et al. 5 included only 40 patients and was gravely underpowered (for comparison, the ARDS Network trial on low tidal volumes recruited >800 patients before a survival difference of 22% became statistically significant 6). More importantly, the …