Pooled Efficacy and Exploration of Effect Modifiers of Exercise Prehabilitation: A Systematic Review and Meta-regression Analysis of Randomized Controlled Trials

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BACKGROUND: Low certainty evidence supports exercise prehabilitation's efficacy in reducing complications and length of stay in specific populations. Identification of procedural, participant, and program characteristics associated with greater prehabilitation efficacy is required to optimize effective application of prehabilitation programs. Our objectives were to (1) estimate the pooled efficacy of all approaches to exercise prehabilitation across all procedures, participants, and programs in reducing postoperative complications and length of stay, and (2) identify program, participant, and procedural characteristics associated with greater efficacy of exercise prehabilitation. METHODS: A peer-reviewed search strategy was applied to Ovid Medline, Embase, CINAHL, PsycINFO, Web of Science, and the Cochrane CENTRAL Register of Controlled Trials (inception to March 1, 2022, and updated on October 25, 2023, and April 10, 2024). Randomized controlled trials addressing a population of adults (≥18 years) undergoing major elective surgery where participants were allocated to an exercise prehabilitation intervention were included. A multistage review of 6675 citations and 1220 full texts was completed independently in duplicate using DistillerSR. Data were pooled using random effects pairwise meta-analyses and meta-regression. Certainty of evidence and credibility of effect modifiers were evaluated. Critical outcomes were postoperative length of stay and the incidence of postoperative complications. Effect modifiers and hypotheses were identified a priori and published in the study's registered protocol (CRD42023487683). RESULTS: Across 99 included trials (n = 8222), pooled data suggested that exercise prehabilitation likely reduces complication rates (odds ratio [OR] = 0.54; 95% confidence interval [CI], 0.44-0.67; P < .01; I2 = 45%; moderate certainty) and length of stay (mean difference = -0.90 days; 95% CI, -1.23 to -0.58; P < .01; I2 = 78%; low certainty). Inspiratory muscle training was the only significant effect modifier for greater efficacy of exercise prehabilitation in reducing both complications (OR = 0.65; 95% CI, 0.44-0.97; low certainty) and length of stay (MD = -1.04; 95% CI, -1.75 to -0.32; low certainty). No other prespecified procedural, participant, or program factors were consistent or credible effect modifiers. CONCLUSIONS: Exercise prehabilitation may reduce complications and LoS; however, well-reported multicenter trials synthesized using individual participant data are required to identify procedural, participant, and program factors associated with optimal exercise prehabilitation efficacy.

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