Abstract: We screened 2686 citations and included two trials enrolling 95 participants and one cohort study enrolling 17 participants. We assessed one randomized controlled trial as being at unclear risk of bias, and the other at high risk of bias; we assessed the non-randomized study as being at high risk of bias. We were unable to pool data due to the small number of studies meeting our inclusion criteria and therefore present narrative results rather than meta-analyses. One trial of 75 participants reported that extubation success (defined as no need for reintubation within 48 hours) was higher in the mechanical insufflation-exsufflation (MI-E) group (82.9% versus 52.5%, P < 0.05) (risk ratio (RR) 1.58, 95% confidence interval (CI) 1.13 to 2.20, very low-quality evidence). No study reported weaning success or reintubation as distinct from extubation success. One trial reported a statistically significant reduction in mechanical ventilation duration favouring MI-E (mean difference -6.1 days, 95% CI -8.4 to -3.8, very low-quality evidence). One trial reported mortality, with no participant dying in either study group. Adverse events (reported by two trials) included one participant receiving the MI-E protocol experiencing haemodynamic compromise. Nine (22.5%) of the control group compared to two (6%) MI-E participants experienced secretion encumbrance with severe hypoxaemia requiring reintubation (RR 0.25, 95% CI 0.06 to 1.10). In the lung volume recruitment trial, one participant experienced an elevated blood pressure for more than 30 minutes. No participant experienced new-onset arrhythmias, heart rate increased by more than 25%, or a pneumothorax. For outcomes assessed using GRADE, we based our downgrading decisions on unclear risk of bias, inability to assess consistency or publication bias, and uncertainty about the estimate of effect due to the limited number of studies contributing outcome data. The overall quality of evidence on the efficacy of cough augmentation techniques for critically-ill people is very low. Cough augmentation techniques when used in mechanically-ventilated critically-ill people appear to result in few adverse events.

Plain-language summary: We found two randomized controlled trials (95 adult participants) and one non-randomized controlled study (17 children aged at least four weeks) conducted in Portugal, Canada, and the United States. We rated the two randomized trials as being of unclear quality and the non-randomized study as being low quality. The largest randomized trial (75 participants) found a 83% success rate for extubation with mechanically- and manually-assisted cough used in combination, compared with 53% in the control group (extubation success over 1½ times more likely) (very low-quality evidence). The time spent on a ventilator was six days less in people using mechanically- and manually-assisted cough (very low-quality evidence). No participants died in this trial. Complications were reported by the two randomized trials. One person receiving mechanically-assisted cough experienced a prolonged drop in blood pressure; another person receiving breathstacking and suctioning in addition to manually-assisted cough experienced a prolonged rise in blood pressure. In one trial, following removal of the breathing tube, more people in the group not receiving mechanically-assisted cough experienced secretion retention, a drop in oxygen levels, and needed the breathing tube to be reinserted (nine people compared with two, very low-quality evidence). The non-randomized study reported that the breathing tube could be removed in all of the six children in the group receiving interventions to assist with coughing. In this non-randomized study, death was only reported for children receiving a cough-promoting technique. One child died, but this was not thought to be related to the cough technique. This study did not report adverse events associated with assisted coughing. No included study evaluated a single cough-promoting technique in isolation. The two randomized trials combined manually-assisted cough with either mechanical assistance (MI-E) or breathstacking, and the non-randomized study used all three methods. Very low-quality evidence from single trial findings suggests that cough-promoting techniques might increase successful removal of the breathing tube and decrease the time spent on mechanical ventilation, while not causing harm. The limited participant numbers made it difficult to determine the likelihood of harms.