The efficacy and safety of leg cycle ergometry in critically ill adults: A systematic review and meta-analysis

Rationale: Survivors of critical illness may experience physical function deficits that persist for years following intensive care unit (ICU) discharge. In-bed cycle ergometry may facilitate early mobilization and decrease functional impairments following critical illness. Methods: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, REHABDATA, and PEDro from inception until 5/2018, supplemented with personal files. We included randomized (RCTs) and nonrandomized studies of critically ill adults, admitted to ICU for ≥24 hours, comparing cycling initiated in the ICU at any frequency, intensity and duration compared to control arms which did not receive cycling. Main outcomes of interest included physical function, quality of life (QoL), mechanical ventilation (MV) duration, mortality, and safety. We conducted independent duplicate screening of citations, data abstraction, and risk of bias (RoB) assessments. When possible, we performed pooled analyses with RCT data using a random effects model and provided relative risk (RR) for dichotomous outcomes and mean difference (MD) or standardized mean difference (SMD) for continuous outcomes, with 95% confidence intervals (CIs). We assessed quality of pooled outcome data using GRADE. Results: Of 5,028 citations, 9 RCTs and 2 observational studies proved eligible (n=699, cycling=354, control=345). Studies had low RoB for MV duration, mortality and safety outcomes, but we identified performance and attrition biases for measures of physical function and QoL. High imprecision and heterogeneity contributed to downgrading the quality of evidence for most outcomes. There was no difference in physical function at ICU discharge (SMD 0.00, 95% CI -0.20, 0.19; 3 RCTs; moderate-quality evidence) nor at hospital discharge (SMD 0.21, 95% CI -0.47, 0.89; 2 RCTs; very low-quality evidence) between cycling and control groups. Similarly, there was no difference in 6-month QOL (MD 11.75 points on SF- 36 physical function domain, 95% CI -4.39, 27.89; 2 RCTs; very low-quality evidence). MV duration (MD -0.18 days, 95% CI -1.49, 1.12; 6 RCTs; moderate-quality evidence), ICU mortality (RR 1.03, 95% CI 0.77, 1.37; 6 RCTs; moderate-quality evidence), and hospital mortality (RR 1.24, 95% CI 0.91, 1.69; 4 RCTs; moderate-quality evidence) were similar between groups. Lastly, there were 66 adverse events reported across 2,587 cycling sessions (2.6%; 8 studies; low-quality evidence). Conclusions: Cycling initiated in the ICU appears to be safe, but may not improve physical function, QoL, MV duration or mortality compared to control interventions. These RCT findings are limited by RoB, imprecision and inconsistency. There is a strong urgency for rigorous, well-designed RCTs to investigate the effect of cycling on patient-important outcomes. (Figure Presented).