NIHR Signal A review of restricting blood supply to a limb before heart surgery highlights the need for better evidence

Published on 18 January 2016

This review of trials looked at a procedure that restricts blood supply to a limb just before heart surgery, which might prepare the heart for reduced blood flow during surgery. The technique was tested alongside the use of inhaled or injected anaesthetic.

The review of 55 trials found the technique in combination with inhaled anaesthetic gave the best chance of survival compared to using an injected anaesthetic, not restricting blood supply before surgery or both.

The underlying trials were small and few made the direct comparison required and so the authors called for more research. Subsequent large trials have not found that restricting blood supply in this way is protective (please see ‘Large trial finds no benefit from restricting limb blood supply before heart surgery’). Notably, inhaled anaesthetic is usual practice in the UK and can be protective itself. Therefore the review’s findings should be seen in the context of the more recent contrary evidence and taken together these are unlikely to change practice.

A review of restricting blood supply to a limb before heart surgery highlights the need for better evidence

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Why was this study needed?

In one year (2012-13) there were around 34,000 open heart operations in the UK and the risk of dying in hospital afterwards was about 3 in every 100. Improvements in survival are crucial to patients and better care could also save the NHS money. The researchers wanted to know whether using inhaled or intravenous anaesthetic gave the best chance of survival after heart surgery. They also wanted to know whether using a pressure cuff to restrict blood supply to a limb for short periods before surgery (remote ischaemic preconditioning) could help prepare the heart for the reduced circulation that happens during open heart surgery. Previous small, single centre trials had found that using inhaled anaesthetic and restricting blood supply in this way could be beneficial when used separately, so the researchers were interested in whether benefits increased when the two approaches where used together.

What did this study do?

This review identified 55 randomised controlled trials, involving 6,921 patients. Most trials compared:

  • inhaled anaesthetic to intravenous anaesthetic,
  • inhaled anaesthetic with restriction of limb blood supply to inhaled anaesthetic alone, or
  • intravenous anaesthetic with restriction of limb blood supply to an intravenous anaesthetic alone.

Few trials directly compared combinations of restriction/no restriction and anaesthetic options. To get around this the researchers used a statistical method called network analysis. This estimates how well the interventions work relative to each other through an indirect comparison across trials.

The review followed guideline standards for conducting high-quality systematic reviews. However, our confidence in the findings is reduced because the review did not include any data from trials published after November 2013. Information was lacking about characteristics of the trial participants or types of operation and most of the deaths occurred in one trial.

What did it find?

  • Restricting limb blood supply and inhaled anaesthetic was the best combination tested. It lowered the risk of dying following heart surgery by 85% when compared with intravenous anaesthetic only (odds ratio [OR] 0.15, 95% credible interval [CrI] 0.04 to 0.55) and by 81% when compared with remote conditioning with intravenous anaesthetic (OR 0.19, 95% CrI 0.04 to 0.94).These are wide intervals and reduce confidence in the estimate of this effect.
  • Restricting limb blood supply and inhaled anaesthetic saved the equivalent of 14 lives per thousand people compared with inhaled anaesthetic only. The death rate was 0.7% using the best combination compared with 2.1% using inhaled anaesthetic only (OR 1.80, 95% CrI 0.82 to 3.92) 15 studies.
  • Using inhaled anaesthetic saved the equivalent of 10 lives per thousand people compared with intravenous anaesthetic. The death rate was 1.4% with inhaled compared to 2.4% using intravenous anaesthetic only (OR 0.56, 95% CrI 0.36 to 0.88) 36 studies,
  • Most of the included trials were single-centre studies with single blinding, which could introduce a risk of bias into the results.

What does current guidance say on this issue?

We did not identify any UK guidance on whether inhaled or intravenous anaesthetic is safer for cardiac surgery. Neither is there national guidance on the use of restricting limb blood supply and its impact on heart surgery survival.

What are the implications?

Restricting blood supply remotely using a pressure cuff is simple and cheap and inhaled anaesthesia is usual practice in the UK. However, the results should be interpreted with some caution because most of the deaths occurred in one study and there were few direct comparisons of different approaches. Also, the credibility intervals were wide suggesting that a direct comparison with even more participants might be of value. The authors call for further studies: these have now been conducted with two recent, large, trials now concluding that the procedure does not bring benefits for patients undergoing planned heart surgery. Cardiac surgery is a specialty with an abundance of good data, and where surgeons carefully monitor the outcomes of their surgery. Mortality rates in the UK are generally lower than rates reported in these trials. It is likely that an uncertain review result such as this will mean that the procedure would only be introduced if better evidence of a useful effect was identified.

Bibliography

Guidelines for the Provision of Anaesthetic Services 2015. London: Royal College of Anaesthetists; 2015.

Hausenloy D, Candilio L, Ariti C, et al. Remote ischemic preconditioning and outcomes of cardiac surgery. N Eng J of Med. 2015;373(15):1408-17.

Meybohm P, Bein B, Brosteanu O, et al. A multicenter trial of remote ischemic preconditioning for heart surgery. N Eng J Med. 2015: 373(15):1397-1407.

Service specifications for cardiac surgery. London: NHS England, 2015.

Zaugg M, Lucchinetti E. Remote ischemic preconditioning in cardiac surgery – ineffective and risky? N Eng J Med. 2015: 373(15):1470-1472.

Why was this study needed?

In one year (2012-13) there were around 34,000 open heart operations in the UK and the risk of dying in hospital afterwards was about 3 in every 100. Improvements in survival are crucial to patients and better care could also save the NHS money. The researchers wanted to know whether using inhaled or intravenous anaesthetic gave the best chance of survival after heart surgery. They also wanted to know whether using a pressure cuff to restrict blood supply to a limb for short periods before surgery (remote ischaemic preconditioning) could help prepare the heart for the reduced circulation that happens during open heart surgery. Previous small, single centre trials had found that using inhaled anaesthetic and restricting blood supply in this way could be beneficial when used separately, so the researchers were interested in whether benefits increased when the two approaches where used together.

What did this study do?

This review identified 55 randomised controlled trials, involving 6,921 patients. Most trials compared:

  • inhaled anaesthetic to intravenous anaesthetic,
  • inhaled anaesthetic with restriction of limb blood supply to inhaled anaesthetic alone, or
  • intravenous anaesthetic with restriction of limb blood supply to an intravenous anaesthetic alone.

Few trials directly compared combinations of restriction/no restriction and anaesthetic options. To get around this the researchers used a statistical method called network analysis. This estimates how well the interventions work relative to each other through an indirect comparison across trials.

The review followed guideline standards for conducting high-quality systematic reviews. However, our confidence in the findings is reduced because the review did not include any data from trials published after November 2013. Information was lacking about characteristics of the trial participants or types of operation and most of the deaths occurred in one trial.

What did it find?

  • Restricting limb blood supply and inhaled anaesthetic was the best combination tested. It lowered the risk of dying following heart surgery by 85% when compared with intravenous anaesthetic only (odds ratio [OR] 0.15, 95% credible interval [CrI] 0.04 to 0.55) and by 81% when compared with remote conditioning with intravenous anaesthetic (OR 0.19, 95% CrI 0.04 to 0.94).These are wide intervals and reduce confidence in the estimate of this effect.
  • Restricting limb blood supply and inhaled anaesthetic saved the equivalent of 14 lives per thousand people compared with inhaled anaesthetic only. The death rate was 0.7% using the best combination compared with 2.1% using inhaled anaesthetic only (OR 1.80, 95% CrI 0.82 to 3.92) 15 studies.
  • Using inhaled anaesthetic saved the equivalent of 10 lives per thousand people compared with intravenous anaesthetic. The death rate was 1.4% with inhaled compared to 2.4% using intravenous anaesthetic only (OR 0.56, 95% CrI 0.36 to 0.88) 36 studies,
  • Most of the included trials were single-centre studies with single blinding, which could introduce a risk of bias into the results.

What does current guidance say on this issue?

We did not identify any UK guidance on whether inhaled or intravenous anaesthetic is safer for cardiac surgery. Neither is there national guidance on the use of restricting limb blood supply and its impact on heart surgery survival.

What are the implications?

Restricting blood supply remotely using a pressure cuff is simple and cheap and inhaled anaesthesia is usual practice in the UK. However, the results should be interpreted with some caution because most of the deaths occurred in one study and there were few direct comparisons of different approaches. Also, the credibility intervals were wide suggesting that a direct comparison with even more participants might be of value. The authors call for further studies: these have now been conducted with two recent, large, trials now concluding that the procedure does not bring benefits for patients undergoing planned heart surgery. Cardiac surgery is a specialty with an abundance of good data, and where surgeons carefully monitor the outcomes of their surgery. Mortality rates in the UK are generally lower than rates reported in these trials. It is likely that an uncertain review result such as this will mean that the procedure would only be introduced if better evidence of a useful effect was identified.

Bibliography

Guidelines for the Provision of Anaesthetic Services 2015. London: Royal College of Anaesthetists; 2015.

Hausenloy D, Candilio L, Ariti C, et al. Remote ischemic preconditioning and outcomes of cardiac surgery. N Eng J of Med. 2015;373(15):1408-17.

Meybohm P, Bein B, Brosteanu O, et al. A multicenter trial of remote ischemic preconditioning for heart surgery. N Eng J Med. 2015: 373(15):1397-1407.

Service specifications for cardiac surgery. London: NHS England, 2015.

Zaugg M, Lucchinetti E. Remote ischemic preconditioning in cardiac surgery – ineffective and risky? N Eng J Med. 2015: 373(15):1470-1472.

Additive Effect on Survival of Anaesthetic Cardiac Protection and Remote Ischemic Preconditioning in Cardiac Surgery: A Bayesian Network Meta-Analysis of Randomized Trials

Published on 1 August 2015

Zangrillo, A.,Musu, M.,Greco, T.,Di Prima, A. L.,Matteazzi, A.,Testa, V.,Nardelli, P.,Febres, D.,Monaco, F.,Calabro, M. G.,Ma, J.,Finco, G.,Landoni, G.

PLoS One Volume 10 , 2015

INTRODUCTION: Cardioprotective properties of volatile agents and of remote ischemic preconditioning have survival effects in patients undergoing cardiac surgery. We performed a Bayesian network meta-analysis to confirm the beneficial effects of these strategies on survival in cardiac surgery, to evaluate which is the best strategy and if these strategies have additive or competitive effects. METHODS: Pertinent studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register (updated November 2013). A Bayesian network meta-analysis was performed. Four groups of patients were compared: total intravenous anesthesia (with or without remote ischemic preconditioning) and an anesthesia plan including volatile agents (with or without remote ischemic preconditioning). Mortality was the main investigated outcome. RESULTS: We identified 55 randomized trials published between 1991 and 2013 and including 6,921 patients undergoing cardiac surgery. The use of volatile agents (posterior mean of odds ratio = 0.50, 95% CrI 0.28-0.91) and the combination of volatile agents with remote preconditioning (posterior mean of odds ratio = 0.15, 95% CrI 0.04-0.55) were associated with a reduction in mortality when compared to total intravenous anesthesia. Posterior distribution of the probability of each treatment to be the best one, showed that the association of volatile anesthetic and remote ischemic preconditioning is the best treatment to improve short- and long-term survival after cardiac surgery, suggesting an additive effect of these two strategies. CONCLUSIONS: In patients undergoing cardiac surgery, the use of volatile anesthetics and the combination of volatile agents with remote preconditioning reduce mortality when compared to TIVA and have additive effects. It is necessary to confirm these results with large, multicenter, randomized, double-blinded trials comparing these different strategies in cardiac and non-cardiac surgery, to establish which volatile agent is more protective than the others and how to best apply remote ischemic preconditioning.

During heart surgery blood flow to the heart is temporarily reduced and the lack of oxygen can cause damage to tissues. Restricting blood flow to a limb before surgery (remote ischaemic preconditioning) aims to lessen this damage by preparing the heart for interrupted circulation. It is thought that substances are released by the preconditioning that protect the heart. It involves repeated short-term artificial reduction of blood flow to the limbs. This can be done simply and cheaply using a pressure cuff or tourniquet, for example.