Department of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA UK
E-mail: Peter.Alston{at}ed.ac.uk
Symptomatic benefit aside, coronary artery bypass grafting (CABG) surgery has prognostic advantages. Every day around the world, and despite the inexorable rise in the use of angioplasty, many thousands of patients still have patterns of coronary artery disease that require them to undergo CABG surgery to improve their longevity. However, this success of CABG surgery continues to be marred by a number of serious complications, in particular brain damage.
The most overt manifestation of brain damage is stroke, which fortunately, given its impact on quality of life, occurs infrequently, in 3% of patients.1 If looked for prospectively, more subtle neurological deficits occur far more frequently, in
20% of patients.2 3 Cognitive decrements are another manifestation; 1926% of patients undergoing conventional CABG surgery will experience permanent decrements and the incidence increases with increasing age.35 These decrements are important as they affect memory, concentration and attention. Therefore brain damage following CABG surgery has several manifestations, some of which occur more frequently and most of which have important implications to patients. Pejoratively, pump head is the populist term commonly used by those who work in the area to describe such brain damage, and in particular cognitive impairment, after heart surgery using cardiopulmonary bypass (CPB).6
A survey of the causes of brain damage associated with CABG and other forms of heart surgery is beyond the scope of this editorial, but this has been reviewed recently by Ahonen and Salmenpera.7 Whilst it is probable that the causes of brain damage are multifactorial, in this editorial cerebral hypoperfusion and embolism will be considered as the most likely culprits.
Historical background
Cardiopulmonary bypass, which was first successfully used on May 6, 1953 by J. H. Gibbon to enable surgical closure of an atrial septal defect,8 has been the keystone that has enabled CABG surgery to be undertaken safely since the 1960s.9 However, many of the adverse effects of conventional on-pump CABG surgery, including brain damage, have been attributed to the process of CPB. In the belief that it results in less adverse events, surgeons are increasingly using techniques of CABG surgery that avoid CPB known as beating heart or off-pump coronary artery bypass (OPCAB) surgery.6 Most of the support for this contention comes from casecontrol studies and there is a dearth of robust evidence from randomized controlled trials of sufficient statistical power. At present, the highest level of evidence that is available from a meta-analysis of these studies indicates that rates of perioperative myocardial infarction, reoperation for bleeding, renal failure and mortality are indeed all lower after OPCAB than after on-pump CABG surgery.10
OPCAB and stroke
OPCAB involves much less surgical manipulation of the aorta, as aortic cannulation and cross-clamping are eliminated and side-clamping is reduced, particularly if only arterial conduits, such as the internal mammary artery, which avoid proximal anastomosis to the aorta are used. Given that macroembolism in the form of debris shed from atheromatous plaques in the ascending aorta during surgical manipulation is a probable cause of stroke, a lower incidence of stroke would be an expected benefit of OPCAB. The findings of two recent meta-analyses suggest that OPCAB does reduce the incidence of stroke, albeit at the possible cost of a higher re-intervention rate and overall mortality.10 11 However, this cannot be regarded as top-grade evidence because data from observational as well as randomized controlled studies were included.
OPCAB and cognition
If the cause of brain damage is the same as that of stroke, OPCAB should result in fewer cognitive decrements. However, it is more likely that cognitive decrements are related to micro- rather than macroemboli.12 Again, the origin is probably atheromatous debris shed during manipulation of the ascending aorta, although there may be other forms including fat and gas emboli. Transcranial Doppler ultrasound has clearly shown that embolic signal counts are lower with OPCAB.13 If this measure is meaningful, it should translate into improved cognitive outcome. Indeed, Zamvar and colleagues, in a tightly controlled study with one surgeon in one centre, found OPCAB to reduce the incidence of cognitive decline at 10 weeks postoperatively from 40% to 10%.14 However, this stark finding was in contrast to two earlier studies that found no difference in cognitive outcome between on- and off-pump CABG.15 16 Because of the small population size in all these studies, it is possible that these contradictory findings may be the result of types 1 and 2 statistical errors.
To determine the true effects on cognition, van Dijk and colleagues17 undertook a sufficiently powered randomized multicentre study of 248 patients in The Netherlands. They found that whilst patients undergoing OPCAB fared better at 3 months than those done on-pump, there was no difference in cognition between groups at 12 months following surgery.17 In their discussion, the authors provided a number of reasons why there were not clear and sustained cognitive benefits associated with OPCAB. However, in a related study published in this journal, Diephuis and colleagues18 provide another possible explanation for why OPCAB did not result in greater and more sustained cognitive benefits.
Cerebral hypoperfusion
Using jugular bulb oxyhaemoglobin oxygen desaturation ( <50%) as their definition, Diephuis and colleagues18 have clearly demonstrated that, contrary to popular wisdom, patients undergoing OPCAB experience far more cerebral hypoperfusion than when conventional CABG surgery with CPB is used. Whilst 39% of the patients undergoing OPCAB surgery experienced one or more episodes of
<50%, only 27% of patients who had CABG surgery with CPB had an episode of
<50%, which after statistical adjustment gave an odds ratio of 0.42 (95% CI: 0.21, 0.84). This is a remarkable finding, as conventional on-pump CABG surgery itself has been associated with multiple and prolonged periods of
<50%.5 19
<50% during conventional on-pump CABG surgery is largely related to hypocapnoea.20 Although Diephuis and colleagues18 did not correct for arterial carbon dioxide tension in their analysis, the levels were comparable between groups and so are unlikely to account for much of the between-group differences in
<50%. The explanation most likely lies in the profound dislocation of the heart that is required to access the various coronary arteries for anastomoses, particularly those lying on the posterior surface of the heart. Indeed, Diephuis and colleagues18 found episodes of
<50% during anastomoses of the right, circumflex and left coronary arteries in 94%, 75% and 45% of patients, respectively. Dislocation of the heart can cause major decreases in stroke volume and mean arterial pressure, and therefore cerebral hypoperfusion is a very plausible finding.21 22 It may be that any benefit accrued in reducing cerebral microembolic load by using OPCAB surgery is offset by the occurrence of more cerebral hypoperfusion.
Limitations of <50%
Caution is required when equating estimates of cerebral hypoperfusion in the setting of cardiac surgery with adverse cerebral outcome. Cognitive assessments were undertaken by van Dijk and colleagues.17 However, Diephuis and colleagues18 rightly chose not to present any relationship between <50% and cognitive outcome as the use of CPB was not the only difference between the groups. Importantly, as they decided on a pragmatic approach to anaesthesia, there were major differences in anaesthetic technique which would have confounded any association that might have been found. Croughwell and colleagues19 have found an association between
<50% during rewarming on CPB and cognitive decrement or neurological outcome. However, Robson and colleagues5 could not find any association between neurological outcome and
<50% either during CPB or in the postoperative period, when it occurs for far longer periods. Therefore all that glitters is not gold, as the association between
<50% and cognitive decrement remains unclear.
It is worth noting that van Dijk and colleagues17 found that patients who underwent CABG surgery with CPB had significantly less improvement in their cognitive assessment at 3 months postoperatively than those who had OPCAB surgery. Improvement is an expected finding that results from the learning effect associated with repeated application of cognitive tests, and less improvement indicates impairment in the on-pump group. It may be that any detrimental effect of hypoperfusion during OPCAB is adequately compensated by increased cerebral extraction of oxygen.5 If so, this benefit of OPCAB is, curiously, not sustained at 12 months when there was no difference in cognitive abilities. This suggests that there are causes other than cerebral hypoperfusion involved in long-term cognitive deficits associated with CABG surgery undertaken on- or off-pump.
Conclusion
When considering neurological outcome from CABG surgery, pumphead is probably a justifiable populist description as OPCAB is associated with a lower incidence of stroke than conventional on-pump CABG surgery. However, its use is not justified when considering cognitive outcome from CABG surgery as the case against CPB remains not proven.
References
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