Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis

Abstract

PurposeAcute respiratory failure (ARF) is a common cause of admission to intensive care units (ICUs). Mucoactive agents are medications that promote mucus clearance and are frequently administered in patients with ARF, despite a lack of evidence to underpin clinical decision making. The aim of this systematic review was to determine if the use of mucoactive agents in patients with ARF improves clinical outcomes.MethodsWe searched electronic and grey literature (January 2020). Two reviewers independently screened, selected, extracted data and quality assessed studies. We included trials of adults receiving ventilatory support for ARF and involving at least one mucoactive agent compared with placebo or standard care. Outcomes included duration of mechanical ventilation. Meta-analysis was undertaken using random-effects modelling and certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation.ResultsThirteen randomised controlled trials were included (1712 patients), investigating four different mucoactive agents. Mucoactive agents showed no effect on duration of mechanical ventilation (seven trials, mean difference (MD) −1.34, 95% CI −2.97 to 0.29, I2=82%, very low certainty) or mortality, hospital stay and ventilator-free days. There was an effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, MD −3.22, 95% CI −5.49 to −0.96, I2=89%, very low certainty).ConclusionOur findings do not support the use of mucoactive agents in critically ill patients with ARF. The existing evidence is of low quality. High-quality randomised controlled trials are needed to determine the role of specific mucoactive agents in critically ill patients with ARF.PROSPERO registration numberCRD42018095408.

Use of mechanical insufflation exsufflation and manual techniques in an intubated adult with COVID‐19 positioned in prone—A case study

“…This rationale is echoed in a recent study exploring UK physiotherapy practice (Connolly et al., 2020 ). Despite high use, a recent systematic review and meta‐analysis does not support the use of mucoactive agents in critically ill patients with acute respiratory failure, however it is noted the existing evidence base is of low quality (Anand et al., 2020 ).…”

Mucus Clearance Strategies in Mechanically Ventilated Patients

“…Data from meta- analysis of 4 mucoactive agents (including NAC, hypertonic saline, heparin, and ambroxol) across 13 randomized control trials have shown no effect on the duration of mechanical ventilation or hospital stay, but the analysis demonstrated a small effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, 95% CI −5.49 to -0.96, I 2 = 89%) was appreciated ( Anand et al, 2020 ).…”

The Use of Aerosolized Medications in Adult Intensive Care Unit Patients: A Prospective, Multicenter, Observational, Cohort Study

“…(8) In mechanically ventilated patients, nebulized N-acetylcysteine was not more effective than normal saline nebulization in reducing the secretion thickness. (9) A recent meta-analysis (10) described four mucoactive agents (N-acetylcysteine, ambroxol, hypertonic saline, and heparin) showed that mucoactive agents did not affect the duration of mechanical ventilation or mortality, hospital stay, and ventilator-free days, but only reduced the length of stay at ICU with a very low certainty. Thus, high-quality, randomized, controlled trials are needed to determine the efficacy of inhaled mucus-regulating agents in critically ill patients.…”