Nebulised dornase alfa versus placebo or hypertonic saline in adult critically ill patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

Nebulised dornase alfa is used off-label in critically ill patients. We aimed to assess the benefits and harms of nebulised dornase alfa versus placebo, no prophylaxis, or hypertonic saline on patient-important outcome measures in adult critically ill patients. We performed a systematic review with meta-analysis and trial sequential analysis (TSA) using the Cochrane Collaboration methodology. Eligible trials were randomised clinical trials comparing nebulised dornase alfa with placebo, no prophylaxis, or hypertonic saline. The predefined outcome measures were all-cause mortality, duration of mechanical ventilation, length of stay, and adverse events. Two reviewers independently assessed trials for inclusion, data extraction, and risk of bias. Risk ratios (RRs) with 95 % confidence intervals (CIs) were estimated by conventional cumulative meta-analysis, and the robustness of the primary estimate was assessed by TSA. Two trials (n = 63) were included; both were judged to have high risk of bias. There was no statistically significant difference in mortality (random effects model RR (95 % CI) 0.73 (0.09-5.77); P = 0.24; I (2) = 30 %). TSA could not be conducted because less than 1 % of the required information size had been accrued. None of the two trials reported adequate and detailed data on any of the secondary outcome measures. We found very low quantity and quality of evidence for use of nebulised dornase alfa in adult critically ill patients in this systematic review with meta-analysis. The International Prospective Register of Systematic Reviews (PROSPERO), no. CRD442015016047.