Anaesthetic Drugs and Survival in Cardiac Surgery
Anaesthetic Drugs and Survival in Cardiac Surgery
Background. Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival.
Methods. We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012).
Results. We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33–0.81, P-value for effect=0.004, number needed to treat 74, I=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14–0.64) and desflurane (OR=0.43, 95% credible interval 0.21–0.82) were individually associated with a reduction in mortality when compared with TIVA.
Conclusions. Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.
Every year more than 200 million patients worldwide undergo major surgery and are exposed to significant morbidity and mortality. A recent international consensus conference identified only 12 drugs, techniques, or strategies associated with a reduction in perioperative mortality, and the only anaesthetic drugs included in this short list were volatile agents.
Volatile agents have documented pharmacological but non-anaesthetic properties conferring cardiac protection and influencing perioperative and long-term clinically relevant outcomes, probably because of favourable transcriptional changes in protective and anti-protective proteins. The mechanism of action is related, but not limited, to the modulation of cytosolic calcium concentration through the potassium mitochondrial channels.
Five studies suggested that the beneficial effect of volatile agents (desflurane, isoflurane, and sevoflurane) might translate into reduced mortality rate when compared with total i.v. anaesthesia (TIVA) in cardiac surgery. Even if no randomized study or meta-analysis of randomized studies in favour of TIVA exists, it should be acknowledged that several meta-analysis performed in cardiac surgery and one large randomized trial performed in non-cardiac surgery did not confirm the beneficial effects of volatile anaesthetics on clinically relevant outcomes. Perhaps this is why TIVA is still commonly used in cardiac surgery.
A network meta-analysis is a statistical technique for comparison of different treatments that were never directly compared in head-to-head trials. On the basis of statistical inference, it is possible to establish which treatment is superior, reaching, through indirect comparison, reliable conclusions otherwise impossible to achieve. The primary objective of this study was therefore to determine whether anaesthetic techniques (TIVA vs volatile-based anaesthesia) confer a survival advantage for patients undergoing cardiac surgery. A secondary aim was to explore whether a particular volatile (desflurane, isoflurane, or sevoflurane) or TIVA (propofol) agent is associated with improved survival.
Abstract and Introduction
Abstract
Background. Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival.
Methods. We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012).
Results. We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33–0.81, P-value for effect=0.004, number needed to treat 74, I=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14–0.64) and desflurane (OR=0.43, 95% credible interval 0.21–0.82) were individually associated with a reduction in mortality when compared with TIVA.
Conclusions. Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.
Introduction
Every year more than 200 million patients worldwide undergo major surgery and are exposed to significant morbidity and mortality. A recent international consensus conference identified only 12 drugs, techniques, or strategies associated with a reduction in perioperative mortality, and the only anaesthetic drugs included in this short list were volatile agents.
Volatile agents have documented pharmacological but non-anaesthetic properties conferring cardiac protection and influencing perioperative and long-term clinically relevant outcomes, probably because of favourable transcriptional changes in protective and anti-protective proteins. The mechanism of action is related, but not limited, to the modulation of cytosolic calcium concentration through the potassium mitochondrial channels.
Five studies suggested that the beneficial effect of volatile agents (desflurane, isoflurane, and sevoflurane) might translate into reduced mortality rate when compared with total i.v. anaesthesia (TIVA) in cardiac surgery. Even if no randomized study or meta-analysis of randomized studies in favour of TIVA exists, it should be acknowledged that several meta-analysis performed in cardiac surgery and one large randomized trial performed in non-cardiac surgery did not confirm the beneficial effects of volatile anaesthetics on clinically relevant outcomes. Perhaps this is why TIVA is still commonly used in cardiac surgery.
A network meta-analysis is a statistical technique for comparison of different treatments that were never directly compared in head-to-head trials. On the basis of statistical inference, it is possible to establish which treatment is superior, reaching, through indirect comparison, reliable conclusions otherwise impossible to achieve. The primary objective of this study was therefore to determine whether anaesthetic techniques (TIVA vs volatile-based anaesthesia) confer a survival advantage for patients undergoing cardiac surgery. A secondary aim was to explore whether a particular volatile (desflurane, isoflurane, or sevoflurane) or TIVA (propofol) agent is associated with improved survival.
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