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

Abstract

BackgroundNebulised 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.MethodsWe 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.ResultsTwo 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; I2 = 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.ConclusionsWe 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.Systematic review registrationThe International Prospective Register of Systematic Reviews (PROSPERO), no. CRD442015016047.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-015-0142-z) contains supplementary material, which is available to authorized users.

Progression of Cystic Fibrosis Lung Disease from Childhood to Adulthood: Neutrophils, Neutrophil Extracellular Trap (NET) Formation, and NET Degradation

“…Deoxyribonuclease (DNase) digests polymerized DNA; hence, it reduces mucus viscosity and promotes mucus clearance in the CF airways. Therefore, the use of aerosolized recombinant human DNase I (dornase alfa) is an attractive approach to alleviate DNA-related mucus viscosity in patients with CF [197]. One caveat; however, is the inhibition of the enzyme by globular actin.…”

How Should Aerosols Be Delivered During Invasive Mechanical Ventilation?

“…A systematic review with meta-analysis found only 2 trials comparing nebulized dornase alfa with placebo, no therapy, or hypertonic saline. 168 The evidence was of low quality and did not report any benefit or harm from use of nebulized dornase alfa in critically ill patients. Mucoactive agents may have a role in preventing lung collapse and hypoxemia in ventilated patients with thick inspissated secretions who are refractory to other forms of treatment.…”

Should We Nebulize Hypertonic Saline Prophylactically in Our Pediatric Intubated Patients?

“…14,15,18 Nevertheless, the most recent meta-analysis evaluating the therapeutic and prophylactic nebulization of mucoactive agents in adult critically ill patients found very low quantity and quality of evidence to support their use. 14 Little evidence exists of their prophylactic use in the pediatric critical care setting to decrease the duration of mechanically ventilation, and no prospective blinded studies in children undergoing mechanical ventilation have been reported.…”

“…Despite some obvious limitations of the study by Shein et al 15 , their results are consistent with a few trials where nebulized hypertonic saline did not significantly improve any of the clinical outcomes measured. 14,18,19 The evidence supporting the prophylactic use of nebulized hypertonic saline for patients undergoing mechanical ventilation as a mucoactive agent and its impact on clinical outcomes is lacking. This study invites clinicians to take a closer look at the potential prophylactic role of mucoactive agents to improve mucociliary clearance and possibly impact important clinical outcomes, such as ventilator length of stay.…”