Relative efficacy of prehabilitation interventions and their components: systematic review with network and component network meta-analyses of randomised controlled trials

OBJECTIVE: To estimate the relative efficacy of individual and combinations of prehabilitation components (exercise, nutrition, cognitive, and psychosocial) on critical outcomes of postoperative complications, length of stay, health related quality of life, and physical recovery for adults who have received surgery. DESIGN: Systematic review with network and component network meta-analyses of randomised controlled trials. DATA SOURCES: Medline, Embase, PsycINFO, CINAHL, Cochrane Library, and Web of Science were initially searched 1 March 2022, and updated on 25 October 2023. Certainty in findings were assessed using the Confidence in Network Meta-Analysis (CINeMA) approach. MAIN OUTCOME MEASURES: To compare treatments and to compare individual components informed by partnership with patients, clinicians, researchers, and health system leaders using an integrated knowledge translation framework. Eligible studies were any randomised controlled trial including adults preparing for major surgery who were allocated to prehabilitation interventions or usual care, and where critical outcomes were reported. RESULTS: 186 unique randomised controlled trials with 15 684 participants were included. When comparing treatments using random-effects network meta-analysis, isolated exercise (odds ratio 0.50 (95% confidence interval (CI) 0.39 to 0.64); very low certainty of evidence), isolated nutritional (0.62 (0.50 to 0.77); very low certainty of evidence), and combined exercise, nutrition, plus psychosocial (0.64 (0.45 to 0.92); very low certainty of evidence) prehabilitation were most likely to reduce complications compared with usual care. Combined exercise and psychosocial (-2.44 days (95% CI -3.85 to -1.04); very low certainty of evidence), combined exercise and nutrition (-1.22 days (-2.54 to 0.10); moderate certainty of evidence), isolated exercise (-0.93 days (-1.27 to -0.58); very low certainty of evidence), and isolated nutritional prehabilitation (-0.99 days (-1.49 to -0.48); very low certainty of evidence) were most likely to decrease length of stay. Combined exercise, nutrition, plus psychosocial prehabilitation was most likely to improve health related quality of life (mean difference on Short Form-36 physical component scale 3.48 (95% CI 0.82 to 6.14); very low certainty of evidence) and physical recovery (mean difference in meters on the six min walk test 43.43 (95% CI 5.96 to 80.91); very low certainty of evidence).When comparing individual components using component network meta-analysis, exercise and nutrition were the individual components most likely to improve all critical outcomes. The certainty of evidence for all comparisons across all outcomes was generally low to very low due to trial level risk of bias and imprecision; however, results for exercise and nutritional prehabilitation were robust with exclusion of high risk of bias trials. CONCLUSIONS: Consistent and potentially meaningful effect estimates suggest that exercise prehabilitation, nutritional prehabilitation, and multicomponent interventions including exercise may benefit adults preparing for surgery and could be considered in clinical care. However, multicentre trials that are appropriately powered for high priority outcomes and that have a low risk of bias are required to have greater certainty in prehabilitation's efficacy. REGISTRATION: International prospective registry of systematic reviews CRD42023353710.