Extracorporeal life support for acute respiratory failure. A systematic review and metaanalysis

Abstract

Rationale: Extracorporeal life support (ECLS) for acute respiratory failure has increased as a result of technological advancements and promising results from recent studies as compared with historical trials.

Objectives: Systematically review the effect of ECLS compared with mechanical ventilation on mortality, length of stay, and adverse events in respiratory failure.

Methods: Data sources included were MEDLINE, EMBASE, and CENTRAL (through to October 2013). Any randomized controlled trial (RCT) or observational study comparing ECLS to mechanical ventilation in adults was used. Two authors independently abstracted the data. Our primary outcome was mortality. Secondary outcomes included intensive care unit length of stay, hospital length of stay, and adverse events. A sensitivity analysis was performed restricted to RCTs and quasi-RCTs, and a number of predefined subgroups were identified to explore heterogeneity.

Measurements and main results: Ten studies (four RCTs, six observational studies, 1,248 patients) were included. There was no significant difference in hospital mortality with ECLS as compared with mechanical ventilation (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.79-1.33; I(2) = 77%). When restricted to venovenous ECLS studies of randomized trials and quasi-randomized trials (three studies; 504 patients), there was a decrease in mortality with ECLS compared with mechanical ventilation (RR, 0.64; 95% CI, 0.51-0.79; I(2) = 15%). There were insufficient study-level data to evaluate most secondary outcomes. Bleeding was significantly greater in the ECLS group (RR, 11.44; 95% CI, 3.11-42.06; I(2) = 0%). In the H1N1 subgroup (three studies; 364 patients), ECLS was associated with significantly lower hospital mortality (RR, 0.62; 95% CI, 0.45-0.8; I(2) = 25%).

Conclusions: ECLS was not associated with a mortality benefit in patients with acute respiratory failure. However, a significant mortality benefit was seen when restricted to higher-quality studies of venovenous ECLS. Patients with H1N1-acute respiratory distress syndrome represent a subgroup that may benefit from ECLS. Future studies are needed to confirm the efficacy of ECLS as well as the optimal configuration, indications, and timing for adult patients with respiratory failure.

Keywords: adult; critical care; extracorporeal life support; intensive care units; respiratory distress syndrome; systematic review.

Figure 1.

In-hospital mortality. Forest plot showing pooled analysis of four randomized controlled trials and six observational studies comparing extracorporeal life support (ECLS) to conventional mechanical ventilation (MV). In this analysis the GenMatch data were used for Pham and Noah and the per-protocol analysis was used for Peek (see Figure E1 for REVA matching for Pham). Using a random effects model: risk ratio, 1.02; 95% confidence interval (CI), 0.79–1.33; I² = 77%; P = 0.87. Given the significant heterogeneity, refer to the sensitivity analysis performed (Figure 2).

Figure 2.

In-hospital mortality sensitivity analysis (randomized controlled trial, quasi-randomized controlled trial, and venovenous extracorporeal membrane oxygenation [VV ECMO] only). Forest plot showing pooled analysis of six higher-quality studies. In this analysis, the GenMatch data were used for Pham and Noah and the per-protocol analysis for Peek (see Figure E1 for REVA matching). Using a random effects model: risk ratio, 0.80; 95% confidence interval (CI), 0.61–1.04; I² = 68%; P = 0.09. The analysis was then further limited to studies in which the predominant ECLS modality was VV ECMO. Using a fixed effects model: risk ratio, 0.64; 95% CI, 0.51–0.79; I² = 15%; P < 0.0001.

Figure 3.

Subgroup analysis. Summary of the subgroups of interest and an assessment of interaction. The H1N1 subgroup demonstrated a significant mortality benefit from ECLS using a random effects model: risk ratio, 0.62; 95% confidence interval (CI), 0.45–0.84; I² = 25%; P = 0.002. LPV = lung-protective ventilation; PF = Pa_O2/Fi_O2 ratio; PNA = pneumonia.

Figure 4.

Adverse events. Pooled analysis using a fixed effects model for adverse events (bleeding, sepsis, and barotrauma). Of note, barotrauma reports were from studies before the lung-protective ventilation era. CI = confidence interval; ECLS = extracorporeal life support; MV = mechanical ventilation.