Association of active mobilisation variables with adverse events and mortality in patients requiring mechanical ventilation in the intensive care unit: a systematic review and meta-analysis

Background Mobilisation during critical illness is now included in multiple clinical practice guidelines. However, a large, randomised trial and systematic review have recently identified an increased probability of adverse events and mortality in patients who received early active mobilisation in the intensive care unit (ICU). We aimed to determine the effects of mobilisation compared with usual care on adverse events and mortality in an acute ICU setting. In subgroup analyses, we specifically aimed to investigate possible sources of harm, including the timing and duration of mobilisation achieved, ventilation status, and admission diagnosis. Methods In this systematic review with frequentist and Bayesian analyses, we searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, SPORTDiscus, SCOPUS, Web of Science, and PEDro electronic databases, as well as clinical trial registries (ICTRP and ClinicalTrials.gov), from inception to March 16, 2023, without language restrictions. Eligible studies were randomised controlled trials that examined active mobilisation compared with either no mobilisation or mobilisation commencing later, or at a lower frequency or intensity, in adults who were critically ill during or after a period of mechanical ventilation in an acute ICU setting. Two authors independently screened reports, extracted data, and assessed the risk of bias using the Cochrane risk-of-bias tool (version 1). The primary outcome was the number of adverse events that occurred during the implementation of mobilisation, with the effect of mobilisation on mortality being the secondary outcome. Risk ratios (RRs) with 95% CIs were calculated in R (version 4.0.3) using random-effects modelling, with Bayesian analysis completed to calculate the probability of treatment harm (ie, RR >1). Subgroup analyses were completed to investigate the association of various factors of mobilisation on adverse events and mortality: duration of mobilisation (longer [≥20 min per day] vs shorter [<20 min per day]), timing of commencement (early [≤72 h from ICU admission] vs late [>72 h from ICU admission]), ventilation status at commencement (all patients mechanically ventilated vs all patients extubated), and ICU admission diagnosis (surgical vs medical). This study was registered with PROSPERO, CRD42022369272. Findings After title and abstract screening of 14 440 studies and review of 466 full texts, 67 trials with 7004 participants met inclusion criteria, with 59 trials contributing to the meta-analysis. Of the 67 included studies, 15 (22%) did not mention adverse events and 13 (19%) reported no adverse events occurring across the trial period. Overall, we found no effect of mobilisation compared with usual care on the occurrence of adverse events (RR 1·09 [95% CI 0·69–1·74], p=0·71; I2 91%; 32 731 events, 20 studies; very low certainty), with a 2·96% occurrence rate (693 events in 23 395 intervention sessions; 25 studies). Mobilisation did not have any effect on mortality (RR 0·98 [95% CI 0·87–1·12], p=0·81; I2 0%; n=6218, 58 studies; moderate certainty). Subgroup analysis was hindered by the large amount of data that could not be allocated and analysed, making the results hypothesis generating only. Interpretation Implementation of mobilisation in the ICU was associated with a less than 3% chance of an adverse event occurring and was not found to increase adverse events or mortality overall, providing reassurance for clinicians about the safety of performing this intervention. Subgroup analyses did not clearly identify any specific variable of mobilisation implementation that increased harm. Funding None.