And now I get to be disappointed about remote ischemic preconditioning

Months ago, I got really excited about remote ischemic preconditioning:

The gist of it is that with cardiac surgery, there’s a significant risk of developing acute kidney injury. Up to 30% of patients wind up with it, and there’s not much we can do about it. But there’s a growing belief that “remote ischemic preconditioning” might help. What they do is fool the body into being concerned that ischemia, or periods of no oxygen, are coming. The theory is that this gets the tricked tissues to release certain factors that warn the rest of the body (ie kidneys) to slow down and prepare for badness. Then, when the cardiac surgery comes, the kidneys are better prepared for a hit.

Basically, doctors place a blood pressure cuff on the upper arm. Then they inflate it to at least 200 mm Hg (which is high) for five minutes. Then they deflate it for five minutes. They do this three times in a row. Then they go ahead and operate normally. There had been some small RCTs on this, but they were conflicting, so this was the first major multicenter trial.

The study I was referencing showed that remote ischemic preconditioning significantly reduced acute kidney injury. A new, and much larger, study in the NEJM disagrees. “A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery“:

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains.

METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90.

RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed.

CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery.

1400 patients. Nice sham placebo. Good choice of outcomes. No differences whatsoever. I would love for someone to tell me why I shouldn’t be saddenned by this. the one thing that was different was that the first study focused on acute kidney injury, which is based on serum creatinine and urine output, so they looked at slightly different things. I feel like that’s more of a process measure, and this new trial focused more on outcomes.

Regardless, unless I hear a good argument, I’m much less excited about remote ischemic preconditioning than I used to be,


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