Key messages
• We found that performing short periods of limb blood flow obstruction by inflating a blood pressure cuff before surgery (remote ischaemic preconditioning, RIPC) probably does not reduce deaths, organ injury, duration of hospital stay, or operating time in people undergoing vascular surgery (e.g. a treatment method to repair narrowing or swelling of an artery).
• Larger, well-designed studies with patient-centred outcomes, such as quality of life, are needed to better estimate the benefits and potential harms of RIPC for people undergoing vascular surgery.
What is remote ischaemic preconditioning?
As the population ages, more people will experience vascular disease or artery disease, narrowing due to the build-up of fatty deposits or balloon-like bulging of arteries. As an essential treatment strategy for severe artery disease, vascular surgery removes the deposits or repairs the bulge, but this carries an increased risk of death and complications. The high risk of surgery is mainly due to the obstruction and subsequent restoring of blood flow involved in the vascular surgery procedure, also known as 'ischaemia-reperfusion injury'. Several approaches have been used to reduce the surgery risk, but have obtained limited effect.
The temporary blockage (by a few minutes) of blood flow to an organ can reduce injury in that organ (local ischaemic preconditioning) but may also reduce damage in other organs (remote ischaemic preconditioning, RIPC). Generally, RIPC is performed by frequently inflating and deflating using a blood pressure cuff placed on the upper arm or leg. As a safe and easy method, the effect of RIPC has been proven to prevent organ damage for heart surgery in animal studies.
What did we want to find out?
We wanted to find out whether RIPC versus no RIPC can reduce death and organ injury in people undergoing vascular surgery, and if it may cause any harm.
What did we do?
We searched for studies that looked at RIPC in people undergoing vascular surgery. We included studies with a randomised design (where people are randomly assigned to one of two or more treatment groups) that compared RIPC with no RIPC. We compared and summarised the results of the included studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 14 studies including 1295 people from the UK, Ireland, Estonia, Spain, China, the USA, Singapore, and New Zealand. The average age ranged from 65 to 76 years. The majority of the participants (84%) were men. The overall methodological quality of the studies was acceptable.
In people undergoing vascular surgery, compared to no RIPC:
• RIPC probably leads to little or no difference in death (10 studies, 965 people), heart attack (11 studies, 1001 people), kidney injury (12 studies, 1054 people), and stroke (4 studies, 392 people), and may lead to little or no difference in limb loss (3 studies, 322 people); and
• RIPC probably leads to little or no difference in hospital stay (7 studies, 569 people) and operating time (10 studies, 803 people).
What are the limitations of the evidence?
Our confidence in our findings is only moderate due to concerns about the following factors: firstly, the evidence was based on a few cases such as for death and limb loss, and some studies were small; secondly, the studies used different methods to detect outcomes such as kidney injury; and finally, for some results, such as heart attack, some of the studies conducted in the area have not made their results public yet, preventing an objective picture of all the available evidence (publication bias). The results of further research may differ from the results of this review, which means our conclusions could change as more research is reported.
How up-to-date is this evidence?
This review updates a previous Cochrane Review. The evidence is current to 1 April 2022.
Overall, compared with no RIPC, RIPC probably leads to little or no difference in perioperative mortality, myocardial infarction, renal impairment, stroke, hospital stay, and operating time, and may lead to little or no difference in limb loss in people undergoing elective major vascular and endovascular surgery. Adequately powered and designed randomised studies are needed, focusing in particular on the clinical endpoints and patient-centred outcomes.
Despite advances in perioperative care, elective major vascular surgical procedures still carry a significant risk of morbidity and mortality. Remote ischaemic preconditioning (RIPC) is the temporary blocking of blood flow to vascular beds remote from those targeted by surgery. It has the potential to provide local tissue protection from further prolonged periods of ischaemia. However, the efficacy and safety of RIPC in people undergoing major vascular surgery remain unknown. This is an update of a review published in 2011.
To assess the benefits and harms of RIPC versus no RIPC in people undergoing elective major vascular and endovascular surgery.
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov to 1 April 2022.
We included all randomised controlled trials that evaluated the role of RIPC in reducing perioperative mortality and morbidities in people undergoing elective major vascular or endovascular surgery.
We collected data on the characteristics of the trial, methodological quality, and the remote ischaemic preconditioning stimulus used. Our primary outcome was perioperative mortality, and secondary outcomes included myocardial infarction, renal impairment, stroke, hospital stay, limb loss, and operating time or total anaesthetic time. We analysed the data using random-effects models. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) based on an intention-to-treat analysis. In addition, we used GRADE to assess the certainty of the evidence for each outcome.
We included 14 trials which randomised a total of 1295 participants (age range: 64.5 to 76 years; 84% male; study periods ranged from 2003 to 2019). In general, the included studies were at low to unclear risk of bias for most risk of bias domains. The certainty of evidence of main outcomes was moderate due to imprecision of results, moderate heterogeneity, or possible publication bias.
We found that RIPC made no clear difference in perioperative mortality compared with no RIPC (RR 1.41, 95% CI 0.59 to 3.40; I2 = 0%; 10 studies, 965 participants; moderate-certainty evidence). Similarly, we found no clear difference between the two groups for myocardial infarction (RR 0.82, 95% CI 0.49 to 1.40; I2 = 7%; 11 studies, 1001 participants; moderate-certainty evidence), renal impairment (RR 1.07, 95% CI 0.62 to 1.86; I2 = 40%; 12 studies, 1054 participants; moderate-certainty evidence), stroke (RR 0.33, 95% CI 0.04 to 3.15; I2 = 0%; 4 studies, 392 participants; moderate-certainty evidence), limb loss (RR 0.74, 95% CI 0.05 to 10.61; I2 = 32%; 3 studies, 322 participants; low-certainty evidence), hospital stay (MD −0.94 day, 95% CI −1.95 to 0.07; I2 = 17%; 7 studies, 569 participants; moderate-certainty evidence), and operating time or total anaesthetic time (MD 5.76 minutes, 95% CI −3.25 to 14.76; I2 = 44%; 10 studies, 803 participants; moderate-certainty evidence).