1 Department of Anaesthesia, The Royal Brompton Hospital, London SW3 6NP, UK E-mail: j.gothard{at}rbh.nthames.nhs.uk
It is widely accepted that the use of cardiopulmonary bypass for cardiac surgery is associated with significant morbidity, in particular that secondary to activation of the inflammatory and coagulation systems. It is therefore surprising that almost a decade after the establishment of equipment and surgical techniques enabling coronary artery surgery to be routinely performed without cardiopulmonary bypass, evidence to demonstrate its superiority in all but high-risk patient populations remains controversial. This may, in part, be because the techniques involved are technically demanding with a substantial learning curve. In addition, it is likely that the physiological and pathological processes occurring during coronary artery surgery, whether with cardiopulmonary bypass or without, are more complex than has been previously thought. Many of the trials published relating to off-pump cardiac surgery (OPCAB) are case series, often compared with historical controls, and are therefore subject to the criticism that bias in patient selection is likely. Large-scale, multi-centre, randomized clinical trials remain lacking. The debate therefore continues as to whether cardiac surgery performed without cardiopulmonary bypass results in less morbidity and mortality than that performed with cardiopulmonary bypass. The comprehensive review of the physiology and anaesthetic management of OPCAB surgery published by Chassot and colleagues1 in this edition of the British Journal of Anaesthesia is therefore a welcome addition to the literature on this topic. These authors also examine some of the remaining surgical issues relating to OPCAB surgery and, laudably, categorize their literature references from Level I to Level V evidence. Interestingly, although the authors have been relatively selective, only 23% of their quoted references reach the Level I criteria of prospective, randomized, and blinded trials with clear cut results. Even some of these Level I studies are underpowered, as acknowledged by the authors.2
Chassot and colleagues discuss the lack of clear benefit in terms of a reduction in clinically significant neurological injury associated with OPCAB surgery. Although some studies have suggested that patients undergoing OPCAB surgery may demonstrate a lower postoperative incidence of cognitive dysfunction, this benefit is not sustained in the medium to long term, however,3 and is not a universal finding.4 Intuitively, the risk of stroke should be less in OPCAB surgery, as cardiopulmonary bypass is associated with significantly higher levels of both particulate and gaseous emboli. Indeed, it has been demonstrated by Watters and colleagues5 that the embolic load, as evidenced by transcranial Doppler, is decreased in multi-vessel OPCAB surgery by some 20-fold. So why is there not a correspondingly dramatic reduction in neurocognitive dysfunction and stroke? This may be partly explained by the fact that transcranial Doppler does not allow the differentiation between gaseous and particulate emboli. It is possible that the gaseous emboli prevalent during cardiopulmonary bypass, pose less of a risk of clinically significant neurological injury than the particulate matter released on manipulation of the aorta. The latter of course occurs during both on bypass and off bypass surgery; although in off bypass surgery, the aorta is not subjected to cannulation, cross clamping, and cardioplegic administration. There is also known to be a significant decline in cognitive function after non-cardiac surgery, which suggests that anaesthesia and/or surgical trauma itself may be a cause of cerebral injury.6
The neurocognitive dysfunction seen may indeed be related to aortic manipulation, in particular the removal of the side-biting clamp following anastomosis of the grafts to the aorta releasing a particulate embolic shower. In multi-vessel OPCAB surgery, injury may also be a result of the distortion of the mitral and tricuspid annuli during exposure of the posterior and lateral cardiac walls.7 This results in reduced systemic arterial pressure, impaired cerebral venous drainage and inadequate cerebral perfusion in the presence of probable cerebrovascular disease. Clearly, it is difficult for the anaesthetist to influence the cerebral venous drainage in the presence of physical obstruction to venous return; however, it is possible to maintain the cerebral perfusion pressure during these periods of dislocation of the heart with judicious use of vasoactive drugs and inotropic support. The use of the Trendelenburg position also restores the arterial pressure in these circumstances, but at the expense of increasing central venous hypertension and impaired cerebral venous drainage.
The anaesthetic management during off-pump cardiac surgery is certainly an interesting challenge. There are probably few areas in which we work as anaesthetists where the choice of an anaesthetic technique, and its execution, play such a significant role in determining the outcome. As Chassot suggests,1 effective communication and team working between the anaesthetist and surgeon is essential, as is knowledge of the pattern of disease from the preoperative angiogram. Central to the role of the anaesthetist during OPCAB surgery is the management of potentially severe acute haemodynamic instability, or the more insidious combination of impaired venous return and low cardiac output. It is also essential to minimize the extent and time course of myocardial ischaemia. This can be achieved, to some extent, by surgical technique, with careful positioning of the heart and the use of coronary artery shunts. The ischaemic preconditioning effects of volatile anaesthetic agents and opioids may also have an important role to play in this area in the future.8
Halogenated volatile anaesthetic agents have been shown to protect rat myocytes from ischaemic damage in a dose dependent way. This is achieved by enhancing the opening of the myocyte mitochondrial adenosine triphosphate sensitive potassium channel (mitoKATP channel), and to a lesser extent the sarcolemmal adenosine triphosphate sensitive potassium channel (sarcKATP channel) to effect ischaemic preconditioning.9 The opening of the channel produces cytoprotection by decreasing cytosolic and mitochondrial calcium overload. Maximum benefit with isoflurane and sevoflurane in vitro appears to occur in the region of 12 MAC. Importantly, increasing the concentration further does not appear to confer additional benefit and concentrations as low as 0.25 MAC have been shown to have an effect.10
It is probable that the threshold concentration required to produce ischaemic preconditioning is specific for each volatile agent. Interestingly, sulphonylureas (e.g. glibenclamide) and theophylline block KATP channels in a non-specific fashion and have been shown to abolish the ischaemic preconditioning effects of isoflurane on human atrial trabeculae. Conversely, nicorandil (an ATP sensitive K channel agonist) appears to lower the threshold for ischaemic preconditioning and may provide a useful future adjunct to volatile anaesthesia. Clinical studies are presently limited but perhaps support a cardio-protective role for isoflurane and sevoflurane in patients undergoing coronary revascularization with cardiopulmonary bypass, further randomized controlled clinical trials are clearly required.1113 Halogenated anaesthetics, such as isoflurane, may also prove to be the agents of choice for OPCAB surgery, especially as anaesthetic-induced ischaemic preconditioning may affect a variety of other tissues in addition to the heart. Myocardial protection by anaesthetic agents has been the subject of an authoritative review by Kato and Foëx.8 These authors emphasize that whilst the i.v. agent propofol does not have a preconditioning effect, it may also act directly to mitigate ischaemia during the critical phase of reperfusion by reducing free radicals, Ca2+ influx, and neutrophil activity. It is not clear how effective this mechanism is at therapeutic drug concentrations and one early clinical study did not demonstrate a clinical benefit from these properties.14
It is probable that many exciting advances in OPCAB surgery and its anaesthetic management are just around the corner. Without well-designed, large-scale, randomized clinical trials it will be difficult to assess their merit objectively. In addition, the contribution of anaesthetic data to national surgical audit databases would provide a further useful source of information in the future.
On the basis of the current evidence, it appears that in younger patients with moderate aortic and cerebral atheromatous disease OPCAB surgery is safe and cost effective, but the benefits are modest.2 Cardiopulmonary bypass in these low-risk groups is also associated with very low morbidity and mortality and, indeed, this technology continues to improve. Problems arise, however, when a severely diseased aorta is manipulated, cannulated and cross-clamped with the subsequent need for strategies of myocardial protection. Thus, the benefits of OPCAB surgery in terms of improved morbidity and mortality has only become apparent in small studies (mainly Level III evidence, i.e. non-controlled, non-randomized) in the more elderly high-risk patient populations with significant co-morbidity.1518 It is particularly important in this group of high-risk patients, that the surgical approach and the associated anaesthetic technique continue to be investigated in a scientific manner and carefully refined in order to continue to improve outcome.
References
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