Remote ischemic preconditioning (RIPC) did not reduce myocardial injury or other postoperative conditions among adult patients undergoing noncardiac surgery, according to results from the PRINCE trial published in Circulation.

In the multinational, double-blind trial, Massimiliano Greco, MD, et al., randomized 1,213 patients to either RIPC (n=599) or sham-RIPC (n=614). Participants were eligible if they were over 50 years of age and were undergoing intermediate or high-risk noncardiac surgical procedures under propofol-free general anesthesia.

Most were smokers or former smokers, had an American Society of Anesthesiologists score ≥3 and suffered from hypertension. The most common surgical types were abdominal and intrathoracic surgeries (34%); 44% were high risk.

RIPC was performed in three 10-minute cycles – a five-minute ischemic cycle using a blood-pressure cuff inflated to 200 mm Hg followed by five minutes of reperfusion. During sham-RIPC, the release valve was left open. The procedure was performed on an upper limb in most patients (85%) and the remainder on a lower limb.

Results showed there was no significant difference between groups for the primary endpoint of postoperative rate of myocardial injury as determined by an increase in troponin levels above the highest 99th percentile of reference values within three days post procedure.

Myocardial injury occurred in 215 (38%) of patients in the RIPC group vs. 223 (37%) in the sham-RIPC group (relative risk [RR] 1.02; p=0.84). Subgroup analysis revealed a higher rate of myocardial injury in patients receiving RIPC to the lower limb.

There were no significant differences in secondary outcomes, including myocardial infarction, stroke, acute kidney injury, need for intensive care unit, length of hospital stay and 30-day all-cause mortality.

RIPC was associated with a greater incidence of limb petechiae (1.7% vs. 0.2%; RR 10.20; 95% CI 1.31-79.44) and hospital readmissions within 30 days (6.0% vs. 3.5%; RR, 1.74).

"In contrast to previous findings, the PRINCE trial provides robust evidence of the absence of beneficial effects of RIPC on biochemical and clinical outcomes in high- and intermediate-risk noncardiac surgery patients," write the authors, adding that the results could clear up discrepancies between smaller and larger randomized control trials (RCTs) that "can be attributed to local biases in single-center RCT, lack of blinding and the low-fragility index of small studies and meta-analyses."