Journal of Invasive Cardiology

One of the main reasons for this difference might have been the high proportion of smaller studies with strongly positive results in our analysis, which might have over-estimated the effect of RIPC. However, the patients included in the study by Rahman et al⁴² used more beta-blockers than in other studies, and even if isoflurane was avoided, many subjects received enflurane or sevoflurane, which are all known to prevent myocardial injury in cardiac surgery.^66-68 Because of these issues, a reasonable conclusion cannot be drawn, yet we believe that a large multicenter trial is required to evaluate the effectiveness of RIPC for on-pump CABG after controlling the aforementioned factors. Based on the current available evidence, the role of RIPC on patients undergoing off-pump CABG cannot be determined due to an insufficient number of trials.^43,57

We also tried to compare different protocols of RIPC. In theory, the larger the mass undergoing ischemia, the stronger the protection provided. Most of the trials used cuff inflation around the upper arm for 2-4 sequential periods of 5 minutes followed by a similar period of reperfusion, but in the subgroup of patients undergoing AAA repair, clamping of the iliac arteries was used. Only 1 study (Ali et al⁶¹) using iliac clamping reported data on cardiac biomarkers and excluding it during the sensitivity analysis did not change the conclusions. Similarly, when we ran our analysis for the estimation of serum creatinine after excluding trials that deployed iliac artery clamping,^61-63 the results did not change significantly (data not shown). However, at this point, no conclusion can be made on the protocol for RIPC, because few patients have used clamping of the iliac artery and because no trial has compared both protocols directly.

The studies evaluating the role of RIPC were primarily powered to detect differences in cardiac and renal biomarkers. While some clinical outcomes were reported, this was done on a secondary basis. Our meta-analysis is the first to provide evidence for reducing the incidence of perioperative myocardial infarction. This is in contrast to prior studies that have failed to demonstrate any benefit on postoperative inotropic requirements,^42,45,55 cardiac hemodynamics,^42,51 and length of postoperative critical care stay⁶⁷ (54.2 ± 40.7 hours for RIPC vs 39.5 ± 25.7 hours for control group; P=.3).⁵⁰ These findings should be considered cautiously favorable, as it could be argued that it is inappropriate to pool the clinical outcomes reported by these proof-of-concept studies. However, these trials comprise the only available source of clinical outcome data from cohorts randomized to RIPC or standard interventions.