Jean-Christophe M. Richard

Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

CONTEXT The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated. OBJECTIVE To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI. DESIGN, SETTING, AND PATIENTS A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005. INTERVENTION Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H(2)O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O (increased recruitment strategy; n = 385). MAIN OUTCOME MEASURES The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure-free days at 28 days. RESULTS The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure-free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements. CONCLUSIONS A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00188058.

High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure

BACKGROUND Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis.

RATIONALE Many patients with severe acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1) infection receive extracorporeal membrane oxygenation (ECMO) as a rescue therapy. OBJECTIVES To analyze factors associated with death in ECMO-treated patients and the influence of ECMO on intensive care unit (ICU) mortality. METHODS Data from patients admitted for H1N1-associated ARDS to French ICUs were prospectively collected from 2009 to 2011 through the national REVA registry. We analyzed factors associated with in-ICU death in ECMO recipients, and the potential benefit of ECMO using a propensity score-matched (1:1) cohort analysis. MEASUREMENTS AND MAIN RESULTS A total of 123 patients received ECMO. By multivariate analysis, increasing values of age, lactate, and plateau pressure under ECMO were associated with death. Of 103 patients receiving ECMO during the first week of mechanical ventilation, 52 could be matched to non-ECMO patients of comparable severity, using a one-to-one matching and using control subjects only once. Mortality did not differ between the two matched cohorts (odds ratio, 1.48; 95% confidence interval, 0.68-3.23; P = 0.32). Interestingly, the 51 ECMO patients who could not be matched were younger, had lower Pa(o(2))/Fi(o(2)) ratio, had higher plateau pressure, but also had a lower ICU mortality rate than the 52 matched ECMO patients (22% vs. 50%; P < 0.01). CONCLUSIONS Under ECMO, an ultraprotective ventilation strategy minimizing plateau pressure may be required to improve outcome. When patients with severe influenza A(H1N1)-related ARDS treated with ECMO were compared with conventionally treated patients, no difference in mortality rates existed. The unmatched, severely hypoxemic, and younger ECMO-treated patients had, however, a lower mortality.

Early Corticosteroids in Severe Influenza A/H1N1 Pneumonia and Acute Respiratory Distress Syndrome

RATIONALE Despite their controversial role, corticosteroids are often administered to patients with adult respiratory distress syndrome (ARDS) secondary to viral pneumonia. OBJECTIVES To analyze the impact of corticosteroid therapy on outcomes of patients having ARDS associated with influenza A/H1N1 pneumonia. METHODS Patients from the French registry of critically ill patients with influenza A/H1N1v 2009 infection were selected if fulfilling criteria for ARDS, excluding patients having other indication for corticosteroids, or decompensated underlying disease as the primary cause for intensive care unit admission. Survival to hospital discharge was analyzed using Cox regression, accounting for the time to administration of steroids, and after adjustment on the propensity for receiving steroid therapy. MEASUREMENTS AND MAIN RESULTS Of 208 patients with ARDS, 83 (39.9%) received corticosteroids (median initial dose of 270 mg equivalent hydrocortisone per day for a median of 11 d). Steroid therapy was associated with death, both in crude analysis (33.7 vs. 16.8%; hazard ratio, 2.4; 95% CI, 1.3-4.3; P = 0.004) and after propensity score-adjusted analysis (adjusted hazard ratio, 2.82; 95% CI, 1.5-5.4; P = 0.002), controlling for an admission severity Simplified Acute Physiology Score, version 3, greater than 50, initial administration of vasopressors, and immunodepression. Early therapy (≤ 3 d of mechanical ventilation) appeared more strongly associated with mortality than late administration. Patients receiving steroids had more acquired pneumonia and a trend to a longer duration of ventilation. CONCLUSIONS Our study provides no evidence of a beneficial effect of corticosteroids in patients with ARDS secondary to influenza pneumonia, but suggests that very early corticosteroid therapy may be harmful.

Patient-Ventilator Asynchrony During Noninvasive Ventilation: A Bench and Clinical Study

BACKGROUND Different kinds of ventilators are available to perform noninvasive ventilation (NIV) in ICUs. Which type allows the best patient-ventilator synchrony is unknown. The objective was to compare patient-ventilator synchrony during NIV between ICU, transport—both with and without the NIV algorithm engaged—and dedicated NIV ventilators. METHODS First, a bench model simulating spontaneous breathing efforts was used to assess the respective impact of inspiratory and expiratory leaks on cycling and triggering functions in 19 ventilators. Second, a clinical study evaluated the incidence of patient-ventilator asynchronies in 15 patients during three randomized, consecutive, 20-min periods of NIV using an ICU ventilator with and without its NIV algorithm engaged and a dedicated NIV ventilator. Patient-ventilator asynchrony was assessed using flow, airway pressure, and respiratory muscles surface electromyogram recordings. RESULTS On the bench, frequent auto-triggering and delayed cycling occurred in the presence of leaks using ICU and transport ventilators. NIV algorithms unevenly minimized these asynchronies, whereas no asynchrony was observed with the dedicated NIV ventilators in all except one. These results were reproduced during the clinical study: The asynchrony index was significantly lower with a dedicated NIV ventilator than with ICU ventilators without or with their NIV algorithm engaged (0.5% [0.4%-1.2%] vs 3.7% [1.4%-10.3%] and 2.0% [1.5%-6.6%], P < .01), especially because of less auto-triggering. CONCLUSIONS Dedicated NIV ventilators allow better patient-ventilator synchrony than ICU and transport ventilators, even with their NIV algorithm. However, the NIV algorithm improves, at least slightly and with a wide variation among ventilators, triggering and/or cycling off synchronization.

The Decision to Extubate in the Intensive Care Unit

The day of extubation is a critical time during an intensive care unit (ICU) stay. Extubation is usually decided after a weaning readiness test involving spontaneous breathing on a T-piece or low levels of ventilatory assist. Extubation failure occurs in 10 to 20% of patients and is associated with extremely poor outcomes, including high mortality rates of 25 to 50%. There is some evidence that extubation failure can directly worsen patient outcomes independently of underlying illness severity. Understanding the pathophysiology of weaning tests is essential given their central role in extubation decisions, yet few studies have investigated this point. Because extubation failure is relatively uncommon, randomized controlled trials on weaning are underpowered to address this issue. Moreover, most studies evaluated patients at low risk for extubation failure, whose reintubation rates were about 10 to 15%, whereas several studies identified high-risk patients with extubation failure rates exceeding 25 or 30%. Strategies for identifying patients at high risk for extubation failure are essential to improve the management of weaning and extubation. Two preventive measures may prove beneficial, although their exact role needs confirmation: one is noninvasive ventilation after extubation in high-risk or hypercapnic patients, and the other is steroid administration several hours before extubation. These measures might help to prevent postextubation respiratory distress in selected patient subgroups.

A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease.

Objective:To assess the effect of a helium-oxygen mixture on intubation rate and clinical outcomes during noninvasive ventilation in acute exacerbation of chronic obstructive pulmonary disease. Design:Multicenter, prospective, randomized, controlled trial. Setting:Seven intensive care units. Patients:A total of 204 patients with known or suspected chronic obstructive pulmonary disease and acute dyspnea, Paco2> 45 mm Hg and two among the following factors: pH <7.35, Paco2 <50 mm Hg, respiratory rate >25/min. Interventions:Noninvasive ventilation randomly applied with or without helium (inspired oxygen fraction 0.35) via a face mask. Measurements and Main Results:Duration and complications of NIV and mechanical ventilation, endotracheal intubation, discharge from intensive care unit and hospital, mortality at day 28, adverse and serious adverse events were recorded. Follow-up lasted until 28 days since enrollment. Intubation rate did not significantly differ between groups (24.5% vs. 30.4% with or without helium, p = .35). No difference was observed in terms of improvement of arterial blood gases, dyspnea, and respiratory rate between groups. Duration of noninvasive ventilation, length of stay, 28-day mortality, complications and adverse events were similar, although serious adverse events tended to be lower with helium (10.8% vs. 19.6%, p = .08). Conclusions:Despite small trends favoring helium, this study did not show a statistical superiority of using helium during NIV to decrease the intubation rate in acute exacerbation of chronic obstructive pulmonary disease.

Alveolar recruitment in pulmonary and extrapulmonary acute respiratory distress syndrome: comparison using pressure-volume curve or static compliance.

Background:Alveolar recruitment in response to positive end-expiratory pressure (PEEP) may differ between pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS), and alveolar recruitment values may differ when measured by pressure-volume curve compared with static compliance. Methods:The authors compared PEEP-induced alveolar recruitment in 71 consecutive patients identified in a database. Patients were classified as having pulmonary, extrapulmonary, or mixed/uncertain ARDS. Pressure-volume curves with and without PEEP were available for all patients, and pressure-volume curves with two PEEP levels were available for 44 patients. Static compliance was calculated as tidal volume divided by pressure change for tidal volumes of 400 and 700 ml. Recruited volume was measured at an elastic pressure of 15 cm H2O. Results:Volume recruited by PEEP (10 ± 3 cm H2O) was 223 ± 111 ml in the pulmonary ARDS group (29 patients), 206 ± 164 ml in the extrapulmonary group (16 patients), and 242 ± 176 ml in the mixed/uncertain group (26 patients) (P = 0.75). At high PEEP (14 ± 2 cmH2O, 44 patients), recruited volumes were also similar (P = 0.60). With static compliance, recruitment was markedly underestimated and was dependent on tidal volume (226 ± 148 ml using pressure-volume curve, 95 ± 185 ml for a tidal volume of 400 ml, and 23 ± 169 ml for 700 ml; P < 0.001). Conclusion:In a large sample of patients, classification of ARDS was uncertain in more than one third of patients, and alveolar recruitment was similar in pulmonary and extrapulmonary ARDS. PEEP levels should not be determined based on cause of ARDS.

Long-term Outcomes of Pandemic 2009 Influenza A(H1N1)-Associated Severe ARDS

BACKGROUND No data on long-term outcomes of survivors of 2009 influenza A(H1N1) (A[H1N1])-associated ARDS are available. The objective of this study was to compare the 1-year outcomes of survivors of A(H1N1)-associated ARDS, according to use or no use of extracorporeal lung assist (ECLA), using its need as an ARDS severity surrogate. METHODS Survivors of ARDS (12 with ECLA use vs 25 without, corresponding to 75% and 54% of the eligible patients for each group, respectively) selected from the Réseau Européen de Ventilation Artificielle (REVA) registry had previously been healthy, with only pregnancy and/or moderate obesity (BMI ≤ 35 kg/m²) as known risk factors for A(H1N1) infection. Lung function and morphology, health-related quality of life (HRQoL), and psychologic impairment were evaluated. RESULTS At 1 year post-ICU discharge for the ECLA and no-ECLA groups, respectively, 50% and 40% reported significant exertion dyspnea, 83% and 64% had returned to work, and 75% and 64% had decreased diffusion capacity across the blood-gas barrier, despite their near-normal and similar lung function test results. For both groups, exercise test results showed diminished but comparable exercise capacities, with similar alveolar-arterial oxygen gradients at peak exercise, and CT scans showed minor abnormal findings. HRQoL assessed by the 36-Item Short-Form Health Survey was poorer for both groups than for a sex- and age-matched general population group, but without between-group differences. ECLA and no-ECLA group patients, respectively, had symptoms of anxiety (50% and 56%) and depression (28% and 28%) and were at risk for posttraumatic stress disorder (41% and 44%). CONCLUSIONS One year post-ICU discharge, a majority of survivors of A(H1N1)-associated ARDS had minor lung disabilities with diminished diffusion capacities across the blood-gas barrier, and most had psychologic impairment and poorer HRQoL than a sex- and age-matched general population group. ECLA and no-ECLA group patients had comparable outcomes. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01271842; URL: www.clinicaltrials.gov

Epidemiology of Weaning Outcome according to a New Definition. The WIND Study

Rationale: The weaning process concerns all patients receiving mechanical ventilation. A previous classification into simple, prolonged, and difficult weaning ignored weaning failure and presupposed the use of spontaneous breathing trials. Objectives: To describe the weaning process, defined as starting with any attempt at separation from mechanical ventilation and its prognosis, according to a new operational classification working for all patients under ventilation. Methods: This was a multinational prospective multicenter observational study over 3 months of all patients receiving mechanical ventilation in 36 intensive care units, with daily collection of ventilation and weaning modalities. Pragmatic definitions of separation attempt and weaning success allowed us to allocate patients in four groups. Measurements and Main Results: A total of 2,729 patients were enrolled. Although half of them could not be classified using the previous definition, 99% entered the groups on the basis of our new definition as follows: 24% never started a weaning process, 57% had a weaning process of less than 24 hours (group 1), 10% had a difficult weaning of more than 1 day and less than 1 week (group 2), and 9% had a prolonged weaning duration of 1 week or more (group 3). Duration of ventilation, intensive care unit stay, and mortality (6, 17, and 29% for the three groups, respectively) all significantly increased from one group to the next. The unadjusted risk of dying was 19% after the first separation attempt and increased to 37% after 10 days. Conclusions: A new classification allows us to categorize all weaning situations. Every additional day without a weaning success after the first separation attempt increases the risk of dying.