Ferguson, Niall D.

Abstract Rationale By minimizing tidal lung strain and maintaining alveolar recruitment, high-frequency oscillatory ventilation (HFOV) may protect against ventilator-induced lung injury. Objectives To summarize the current evidence in support of the use of HFOV in adult patients with acute respiratory distress syndrome. Methods We conducted a systematic review and meta-analysis of randomized trials comparing mortality rates with the use of HFOV versus conventional mechanical ventilation for adult patients with acute respiratory distress syndrome. Eligible trials were identified from previously published systematic reviews and an updated literature search. Data on 28-day mortality, oxygenation, adverse events, and use of rescue therapies were collected; effects were pooled using random effects models weighted by inverse variance. Strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology. Results Six trials were eligible for inclusion (total n = 1,715 patients). Four trials mandated lung-protective ventilation in the control group and one trial applied a higher positive end-expiratory pressure (PEEP) ventilation strategy in the control group. None of the trials were judged to be at high risk of bias, though all were unblinded. In trials that did not systematically employ any cointerventions with HFOV and that targeted low tidal volumes in the patients randomized to conventional ventilation (primary analysis), HFOV had no significant effect on mortality (three trials; risk ratio [RR], 1.14; 95% confidence interval [CI], 0.88 to 1.48; evidence grade = high). Pooled analysis of all six trials also did not suggest a significant mortality reduction (RR, 0.94; 95% CI, 0.71 to 1.24; evidence grade = low). The single trial that employed a conventional ventilation strategy with both lower tidal volumes and higher PEEP as control reported higher mortality in patients receiving HFOV (RR, 1.41; 95% CI, 1.12 to 1.79). HFOV was not associated with improved oxygenation after 24 hours (five trials; mean increase of 10 mm Hg; 95% CI, −16 to 37 mm Hg). Rates of barotrauma were not different between HFOV and conventional ventilation, although significant benefit or harm could not be excluded (RR, 1.15; 95% CI, 0.61 to 2.17). Conclusions Published randomized trials suggest that HFOV is not associated with a mortality benefit, and may even be harmful in comparison to ventilation with low tidal volumes and higher levels of PEEP.

Abstract Rationale In patients with acute respiratory distress syndrome (ARDS), lung recruitment maneuvers (LRMs) may prevent ventilator-induced lung injury and improve survival. Objectives To summarize the current evidence in support of the use of LRMs in adult patients with ARDS and to inform the recently published American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline on mechanical ventilation in ARDS. Methods We conducted a systematic review and meta-analysis of randomized trials comparing mechanical ventilation strategies with and without LRMs. Eligible trials were identified from among previously published systematic reviews and an updated literature search. Data on 28-day mortality, oxygenation, adverse events, and use of rescue therapy were collected, and results were pooled using random effects models weighted by inverse variance. Strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Results We screened 430 citations and previous systematic reviews and found six trials eligible for inclusion (n = 1,423 patients in total). The type of LRM varied widely between trials, and five of the trials involved a cointervention with a higher positive end-expiratory pressure (PEEP) ventilation strategy. Risk of bias was deemed high in one trial. In the primary analysis, the only trial without a cointervention showed that LRMs were associated with reduced mortality (one trial; risk ratio [RR], 0.62; 95% confidence interval [CI], 0.39–0.98; evidence grade = low). Meta-analysis of all six trials also suggested a significant mortality reduction (six trials; RR, 0.81; 95% CI, 0.69–0.95; evidence grade = moderate), and the use of a higher PEEP cointervention did not significantly modify the mortality effect (P = 0.27 for heterogeneity). LRMs were also associated with improved oxygenation after 24 hours (six trials; mean increase, 52 mm Hg; 95% CI, 23–81 mm Hg) and less frequent requirement for rescue therapy (three trials; RR, 0.65; 95% CI, 0.45–0.94). LRMs were not associated with an increased rate of barotrauma (four trials; RR, 0.84; 95% CI, 0.46–1.55). The rate of hemodynamic compromise was not significantly increased with LRMs (three trials; RR, 1.30; 95% CI, 0.92–1.78). Conclusions Randomized trials suggest that LRMs in combination with a higher PEEP ventilation strategy reduce mortality, but confidence in this finding is limited. Further trials are required to confirm benefit from LRMs in adults with ARDS.

Abstract Rationale Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. Objectives To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful. Methods The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. Measurements and Main Results Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159–1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg. Conclusions NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg. Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).