This generally well-conducted review concluded that the evidence supported noninvasive ventilation for patients with acute cardiogenic pulmonary oedema, despite contradictory evidence from a recent large trial. Continuous positive airway pressure reduced mortality most in patients with oedema secondary to acute myocardial ischaemia or infarction. These conclusions are likely to be reliable, but concerns about trial quality should be considered.

To assess the effect of noninvasive ventilation on clinical outcomes in patients with acute cardiogenic pulmonary oedema.

PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles from 1966 to December 2009. Conference proceedings of three relevant bodies and reference lists of identified articles and meta-analyses were also searched. No language restrictions were used.

Parallel-design randomised controlled trials (RCTs) that compared continuous positive airway pressure (CPAP), bi-level ventilation, or both with standard therapy (oxygen by facemask, diuretics, nitrates, and other supportive care) or with each other, in patients aged at least 18 years with acute cardiogenic pulmonary oedema, were eligible for inclusion. Trials had to report all-cause in-hospital mortality, the need for new intubation, and the incidence of new myocardial infarction (MI).

Most of the patients in the included RCTs were mature (aged 51 to 92 years) and approximately half were male. CPAP pressures ranged from 20 to 25cm of H₂O and bi-level ventilation inspiratory pressures ranged from 8 to 20cm of H₂O, with expiratory pressures ranging from 3 to 10cm of H₂O.

Two reviewers independently assessed the studies for inclusion in the review and differences were resolved through discussion or by consultation with a third reviewer.

Two reviewers independently assessed the trials for validity using the 11-item PEDro scale. Differences were resolved through consensus or by consultation with a third reviewer.

Two reviewers independently extracted data on the patient characteristics and primary and secondary outcomes for the calculation of relative risks and 95% confidence intervals, and for meta-regression. Differences between reviewers were resolved through consensus or by consultation with a third reviewer.

A Mantel-Haenszel random-effects meta-analysis was used to calculate a pooled relative risk and 95% confidence interval. A random-effects meta-regression was used to investigate the impact of patient characteristics and control group rates of mortality and intubation on the treatment effect. Statistical heterogeneity between trials was assessed using the Cochran Q and the I² statistics. Sensitivity analyses based on quality criteria were conducted and secondary Bayesian meta-analyses were conducted. Publication bias was assessed by a visual inspection of the funnel plots and by the Begg-Mazumdar rank correlation method.

Thirty-one RCTs (2,887 patients) were included in the review; 10 compared CPAP with standard therapy, five compared bi-level ventilation with standard therapy, 11 compared bi-level ventilation with continuous positive airway pressure (CPAP), and five assessed all three therapies. All trials were randomised, 18 reported allocation concealment, 26 used an intention-to-treat analysis, 29 had similar baseline characteristics, 28 had drop-out rates below 15%, and only one was double-blind.

CPAP versus standard therapy (15 RCTs): Mortality was lower with CPAP than with standard therapy (RR 0.64, 95% CI 0.44 to 0.92; 13 trials) as was the need for intubation (RR 0.44, 95% CI 0.32 to 0.60; 15 trials), but there was no statistically significant difference in the incidence of new MI (four trials).

Bi-level ventilation versus standard therapy (10 RCTs): Bi-level ventilation reduced the need for intubation compared with standard therapy (RR 0.54, 95% CI 0.33 to 0.86; nine trials), but there were no statistically significant differences in mortality and incidence of new MI (six trials).

CPAP versus bi-level ventilation (16 RCTs): There were no statistically significant differences between the treatments on any of the outcomes assessed.

Meta-regression indicated that the benefit of CPAP was greater in trials in which the acute cardiogenic pulmonary oedema was caused by myocardial ischaemia or infarction in a higher proportion of patients. The relative risk was 0.43 (95% CI 0.17 to 1.07) where 50% of patients had ischaemia or MI compared with a relative risk of 0.92 (95% CI 0.76 to 1.10) where 10% had ischaemia or MI. The results of subgroup and sensitivity analyses were also reported. Publication bias was not ruled out by the inspection of funnel plots and was indicated by the Begg-Mazumdar test, but only for the analysis of mortality, when comparing CPAP with standard therapy (p=0.002).

The evidence supported the use of noninvasive ventilation for patients with acute cardiogenic pulmonary oedema, despite contradictory evidence from a recent large trial. CPAP was most effective in reducing mortality for patients with acute cardiogenic pulmonary oedema secondary to acute myocardial ischaemia or infarction.

The review question and the inclusion criteria were clear. The authors searched three relevant databases and other sources, without language restriction, which reduces the risk of bias and publication bias was assessed. The authors used methods designed to reduce bias and error at all stages of the review process and an appropriate method was used to assess the validity of the included trials, which subsequently informed the synthesis. The meta-analyses and the assessment of heterogeneity were appropriate, but the results of the heterogeneity assessment were not reported.

The authors' conclusions reflected the results of this generally well-conducted review, and are likely to be reliable, but they noted that there were some concerns with trial quality that might affect their conclusions.

Practice: The authors did not state any implications for practice.

Research: The authors noted that firm conclusions would depend on the findings of two ongoing trials and other future trials.

No funding received.

Correction: noninvasive ventilation in acute cardiogenic pulmonary edema. Annals of Internal Medicine. 2010;153(1):67. [Online journal has been updated.]

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.