Remote Ischemic Preconditioning and Survival in Noncardiac Surgery: An Updated Meta-analysis of Randomized Trials.

BACKGROUND

Remote ischemic preconditioning (RIPC) demonstrated potential benefits in terms of organ protection in preclinical and several clinical settings. This systematic review of randomized controlled trials (RCTs) evaluates the association of RIPC with mortality and other relevant clinical outcomes in patients undergoing noncardiac surgery.

METHODS

We conducted a systematic review and meta-analysis of RCTs assessing the effects of RIPC in adult patients undergoing noncardiac surgery. A comprehensive search was performed in PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and in proceedings from major congresses up to June 2025. Eligible studies compared RIPC with either standard care or a sham intervention. The primary outcome was all-cause mortality, assessed at the longest follow-up available. Exploratory outcomes included stroke, length of hospital stay, kidney and cardiac function. The risk of bias for each included RCT was assessed using the Cochrane risk-of-bias tool for randomized trials version 2. Rare binary outcomes were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs) estimated via random-effects generalized linear mixed models (GLMMs). Non-rare binary outcomes were analyzed using risk ratios (RRs) with 95% CIs via Mantel-Haenszel random-effects models.

RESULTS

We included 79 RCTs involving 9340 patients, predominantly single-center in design, with abdominal surgery (25 studies) being the most prevalent clinical setting. RIPC was primarily obtained by inflating a blood pressure cuff on upper limbs. RIPC was not associated with a statistically significant reduction in mortality compared to control in the overall population (OR = 0.79; 95% CI, 0.51-1.24; P = .30), but was associated with a significant reduction in mortality in the subgroup of patients receiving it before anesthesia induction (OR = 0.37; 95% CI, 0.17-0.81; P = .013). Exploratory findings suggested a reduction in stroke rate (OR = 0.41; 95% CI, 0.22-0.78; P = .006), length of hospital stay (mean difference = -0.84 days; P < .001), and peak postoperative serum neutrophil gelatinase-associated lipocalin (NGAL; mean difference = -10.27; P = .008) in RIPC patients. The strength of the data reported in the included studies may have been partially limited by the presence of different clinical conditions that could have either diminished or enhanced the effects of RIPC.

CONCLUSIONS

RIPC was not associated with a significant reduction in mortality in the noncardiac surgical population, except for the subgroup of patients who received RIPC before anesthesia induction. However, RIPC showed beneficial effects on biomarkers of renal damage, stroke rate, and length of hospital stay. Our results support further investigation of RIPC specifically when applied before the induction of anesthesia.