|Year : 2006 | Volume
| Issue : 3 | Page : 145-151
Coronary artery bypass surgery: Does it lead to cognitive impairment?
D Vibha, J Kalita, R Agarwal, UK Misra
Department of Neurology, Sanjay Gandhi PGIMS, Lucknow, India
U K Misra
Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow - 226 014
Source of Support: None, Conflict of Interest: None
Coronary artery bypass grafting is an important treatment option for coronary artery disease. A wide variety of neurocognitive impairment ranging from stroke, postoperative delirium, depression and early and delayed impairment in memory and visuospatial functions has been reported. The results of the studies are variable because of various patient populations, associate comorbidity, timing of study and absence or type of controls. The reported causes of cognitive impairment are micro-emboli, hypo-perfusion, systemic inflammatory response syndrome, anesthesia, associated depression, genetic susceptibility and associated cardiovascular risk factor and MRI abnormalities. Further studies are needed to evaluate employing objective clinical and electrodiagnostic measures.
Keywords: Coronary artery bypass grafting, cognitive deficits, delirium memory, depression, visuo-spatial deficits
|How to cite this article:|
Vibha D, Kalita J, Agarwal R, Misra U K. Coronary artery bypass surgery: Does it lead to cognitive impairment?. Ann Indian Acad Neurol 2006;9:145-51
|How to cite this URL:|
Vibha D, Kalita J, Agarwal R, Misra U K. Coronary artery bypass surgery: Does it lead to cognitive impairment?. Ann Indian Acad Neurol [serial online] 2006 [cited 2015 Oct 10];9:145-51. Available from: http://www.annalsofian.org/text.asp?2006/9/3/145/27656
| Introduction|| |
Coronary artery bypass grafting (CABG) has become a standard method of treatment of significant coronary artery stenosis since 1967. About 800,000 patients world over undergo CABG every year, which reduces angina and stabilizes ventricular functions. With the improvement in surgical technique and anesthesia, CABG is now being offered to patients with more severe underlying disease and comorbidities that may further increase the risk of its complications.
The complications following CABG include stroke, postoperative delirium, cognitive impairment (memory loss, visuospatial deficits) and depression. The cognitive impairment can be short term or delayed. The studies of neuro-behavioural effects of CABG have a number of variables which influence the conclusions and these include different technique, variability of associated comorbidity (diabetes, hypertension, stroke, carotid artery disease), timing of study (too early studies may include the effect of drugs and anesthesia and too late may result in spontaneous recovery) and controls. In this review the effects of CABG on neuro-behavioural functions are presented.
Stroke is more frequently reported following CABG compared to other surgical procedures occurring in 0.8-3.2% individual undergoing CABG., Mortality in CABG patients with stroke is 20% whereas without it 2-4%. Stroke in CABG not only prolongs the suffering and ICU stay of patient but also increases the hospital cost. The risk of stroke in CABG patients is increased if the patient has the conventional risk factors for stroke such as hypertension, diabetes, peripheral vascular disease, previous cerebro-vascular disease and age. Multiplicity of risk factors further increases the risk of stroke.
The location of atherosclerotic plaque in ascending aorta can influence the surgical decisions and subsequent occurrence of stroke. Prospective evaluation has shown an incidence of stroke is 2.7% and mortality 22% in CABG patients. Epiaortic ultrasonography and transesophageal echo-cardiography are valuable in detecting and assessing severity of aortic atherosclerosis and cardiac source of embolus.
Postoperative delirium and encephalopathy
Postoperative delirium can occur following any major surgery. Its severity may ranges from intermittent delirium to permanent confusional state, stupor or coma. In a prospective study delirium was reported in 117 out of 13141 (9%) patients undergoing noncardiac surgery. The reported frequency of delirium in CABG is variable. In earlier studies it was as high as 10-28% but much lower rates have been reported in recent studies.,,, Delirious patients have higher incidence of major complications, longer hospitalization and higher rates of transfer to long-term rehabilitation facilities. In a study on 2711 CABG, the incidence of encephalopathy was 6.9% and these patients had longer hospital stay (15.2 days) and higher mortality (7.5%). The preoperative risk factors for encephalopathy were age, prior stroke, carotid bruit, hypertension and diabetes. Similar results were also reported in another study and was suggested that use of cardiopulmonary bypass is the only perioperative predictor of short and long term brain dysfunction following CABG.
Preoperative evaluation of individual risk factors may contribute to appropriate postoperative management, reduced incidence of delirium and improved surgical outcome.
Advances in anesthesia and surgical techniques have lead to the assumption that postoperative cognitive impairment is less common now than in the past. The benefit of such advances may have been offset by inclusion of older patients with more risk factors. The measurement of postoperative cognitive decline would also depend to some extent on the evaluation technique, timing of examination and statistical method employed. The cognitive changes may arise from more than one etiological mechanism. Hence the tests should encompass all cognitive domains. If the test battery does not include frontal (planning or abstraction) or parietal (spatial or constructional) abilities, abnormalities in those areas are likely to be missed.
The preoperative baseline performance of patients on cognitive tests may show a wide variability; some performing at the expected age and education adjusted levels and others performing at significantly below the expected levels. This variability has been attributed to emotional stress before surgery in some studies; but more recent studies have suggested that a subset of patients for CABG may be cognitively impaired before surgery. A cognitive decline in CABG patients who are already impaired at baseline thus may be underestimated. On the other hand, chronic cerebrovascular disease itself might be associated with mild cognitive impairment, which could improve following CABG. Several methods have been used to measure post CABG cognitive change.
The outcome measure is typically defined as a decline in performance on cognitive tests by 1 SD or more on atleast two tests. This approach is useful for cognitive changes especially in intervention studies such as reduction in the number of microemboli. An alternative is to assess specific cognitive domains such as memory, language that helps in understanding the pathophysiology of post CABG cognitive changes. Domain specific approach helps in differentiating post CABG changes from Alzheimer's disease or primary dementia because middle cerebral arterial territory is especially susceptible to microemboli.
Short-term cognitive changes
In the first few weeks after the surgery, memory and visuo-spatial impairment are the most common complaints. The results of cognitive tests can be confounded by pain, sedation and other medications. Cognitive studies carried out within days or weeks after surgery therefore have revealed a wide range of short-term cognitive decline ranging from 33 to 83%., Some of the discrepancy can be attributed to the differences in test materials diversity in age and comorbidities in the sample. Most of the studies on cognitive impairment following CABG lack controls; presence of cognitive impairment in such groups does not prove it to be due to CABG as it could as well be found following any other major surgery.
In a comparison of 1218 noncardiac postoperative patients with control (no surgery); cognitive dysfunction was found in 26% patients at 1 week and in 10% at 3 months after surgery compared to 3.4-2.8% of controls respectively. Comparison of CABG with hip or knee replacement patients at 1 week and 6 months revealed similar incidence of cognitive impairment. Similar frequencies of cognitive decline in patients undergoing major vascular or thoracic surgery and CABG have been reported., Three recent studies have evaluated cognitive outcome 1-12 weeks after surgery. About sixtyseven CABG patients examined before surgery and at day 6 and 9 after surgery were compared with hospital inpatients with peripheral neuropathy. CABG patients had a transient decline in neuropsychological performance at day 3, which gradually returned to baseline by day 9. Comparison of cognitive function of 57 patients undergoing CABG and 55 controls revealed lower baseline cognitive performance in CABG group, which did not decline at follow up. These findings suggest that some of the short-term cognitive changes after CABG may be nonspecific and may also be seen following other major surgical procedures.
Long-term cognitive impairment
The long-term cognitive complaints are more subtle such as difficulty in following directions, playing chess or calculation. Only a few studies have followed up the changes beyond 6 months. There have been reports of persistent cognitive symptoms and in some instances delayed cognitive decline.,, Follow-up study revealed that some cognitive deficits such as constructional apraxia may even worsen from 1 month to 1 year. Preliminary analysis of 5-year data suggests that long-term deficits may persist and reflect damage or continuing damage of posterior parietal cortex (watershed area), which is primarily vulnerable to hypoperfusion.
A prospective study of 261 patients undergoing CABG revealed cognitive decline in 53% at discharge, which decreased to 24% at 6 months. 172 patients (66%) were followed up at 5 year and 42% of them performed below their baseline performance on a global measure of cognition. Another prospective study on 172 evaluated before and after CABG followed up for 5 years revealed significant cognitive decline in most cognitive domains between 1 and 5 years. Comparison of baseline performance with 5 years performance showed decline of two cognitive domains- psychomotor and visuo-construction. A study of 52 patients with CABG who had an uncomplicated peri-operative period, after a median follow-up of 55 months, no patient showed a decline in neuropsychological test compared to baseline. The unique feature of this study was control of postoperative vascular risk factors such as smoking, hypertension, cholesterol and blood sugar. Another prospective neuropsychological evaluation of CABG patients revealed decline in overall neuropsychological performance, followed by improvement at 8 weeks and then decline at 5 years. The greatest decline was in motor and psychomotor speed but verbal memory and learning were spared. Cognitive decline was related to number of emboli during surgery, degree of decline at the time of discharge, degree of recovery between discharge and follow-up testing between 6 and 8 weeks.
Comparison of cognitive functions in CABG and angioplasty revealed that there was no difference in long-term cognitive functions between the two groups. This study however did not include any measure to assess visuoconstruction or visual memory, which have been found to be involved by some investigators.,,
In a twin control design, the postoperative cognitive performance of 232 CABG patients stratified across 3 age categories was compared with their twins who did not have CABG. The CABG patients who had their surgery at relatively early age (63-70 year) had better cognitive performance 1-2 year after surgery than their twins who had not undergone CABG. There seems to be some evidence that mild cognitive decline does occur between baseline and 5 years follow-up. The decline is mainly in domains of motor and psychomotor speed with no significant decline in memory. This pattern is consistent with subcortical involvement as would be expected if late decline were related to underlying white matter small vessel disease.
In a recent non-randomized study, four groups of patients were evaluated; CABG 140 (off pump coronary surgery 72 patients), nonsurgical cardiac control, coronary artery disease (CAD) patients managed without surgery (99 patients) and heart healthy control (69 patients). The subjects were evaluated at baseline, 3 months and 12 months for eight cognitive domains, global cognitive score, depressive and subjective symptoms were analyzed. At baseline CAD patients had lower performance than healthy controls in several cognitive domains by 3 months. All groups had improved from 3 to 12 months. There were minimal intrasubject changes for all groups. This study highlights the need for appropriate controls for interpreting longitudinal changes in cognitive performance after CABG.
| Causes of Cognitive Impairment|| |
Short term cognitive changes
a) Microemboli: Transcranial Doppler studies have demonstrated that showers of micro-emboli occur during surgery especially during clamping or unclamping of aorta. The emboli are variable in size and composed of air, debris of lipid, silicon and aluminum derived from cardiopulmonary circuit and its tubing. Some studies have revealed a weak association between emboli and short-term cognitive outcome, but not in others.,Studies using diffusion weighted MRI have shown new ischemic lesions on post operative MRI which are consistent with showers of emboli but their relation to neuropsychological function remain unclear.,,
b) Hypoperfusion: Many patients undergoing CABG have hypertension. The mean arterial BP during cardiopulmonary bypass is quite low (<50 mm Hg). The previously hypertensive patients thus undergo temporary or fluctuating hypotension. Prolonged period of hypotension during CABG may result in risk of ischemic brain injury. The degree and duration of hypotension that can be tolerated is not clear. Older patients and those with comorbid conditions such as diabetes may be at greater risk because of alteration in auto-regulation of cerebral blood flow. Decreased blood flow during surgery may result in decreased washout of embolic material from brain and the watershed area of brain is particularly vulnerable.
c) Systemic inflammatory response syndrome (SIRS): Cardiopulmonary bypass is associated with SIRS, which may result in mild pulmonary dysfunction to temporary multi-organ failure., A causal relationship between SIRS and CNS dysfunction has also been suggested. However, in a study on 100 CABG patients; no significant association between levels of serum inflammatory markers and change in neuropsychological tests was found.
d) Anesthesia: General anesthesia per se can result in postoperative cognitive impairment in patients undergoing non-cardiac surgery. In a study on patient aged 40-60 year, 19% were found to have cognitive decline 7 days after surgery compared to only 4% in matched controls. By 3 months after surgery, cognitive decline was minimal and not different from control.
e) Depression: Depression is commonly reported after most cardiac surgeries with a frequency of upto 25%. Most of the studies however have not taken into account preoperative mood of the patient. Recent studies indicate newly acquired depression after CABG is uncommon and preoperative mood is the best predictor of postoperative depression., No association between depression and mood changes in cognitive performance has been reported. Preliminary data has revealed that newly acquired depression is associated with increasing mortality and poor cardiac outcome after CABG. Moreover depression is associated with poor outcome after myocardial infarction and fourfold increase in mortality in patients with depression. Whether recognition and treatment of depression would lead to better outcome after myocardial infarction or CABG is not known.
f) Genetic factors: The role of apolipoprotein E4, a known genetic marker for late ons et Alzhemer's disease was associated with cognitive decline in four out of nine cognitive measures 6 weeks after CABG. The investigators suggested the decline of cognitive function was due to a genetically determined deficit in maintenance and repair of neuronal functions., However, another study on neuropsychological evaluation before and 4-7 weeks after surgery did not find any relation between cognitive function and E4 allele status.
Long-term cognitive change
Most of the above-mentioned studies reporting late cognitive decline after CABG did not include a control group. It is therefore difficult to determine if the cognitive changes are caused by cardio-pulmonary bypass with general anesthesia 3 years earlier or caused by normal aging, development of Alzheimer's disease or other causes. The choice of appropriate control for CABG has been controversial. The presence of diabetes, hypertension and other cardiovascular risk factors has increased in the candidates for CABG. Therefore ideal controls should also include patients with similar frequency of risk factors for cerebrovascular disease. Neither duration nor the severity of these risk factors can be easily quantified and how these risk factors translate into cerebro-vascular disease is also unknown.
Cerebrovascular risk factors
Evidence from large epidemiological studies suggests that history of one or more risk factors for cerebrovascular disease may be associated with increased risk for cognitive decline even without cardiac surgery. History of hypertension and diabetes at baseline was associated with cognitive decline over 4-6 years follow up. According to some studies, diabetes also may be associated with accelerated cognitive decline at 4 years follow up. Poorer cognitive performance was reported in patients who had diabetes for longer period. Some evidence exists that patients who have both diabetes and hypertension have accelerated rate of cognitive decline late in life, however, long-term studies have revealed that cognitive performance of patients treated for diabetes and hypertension may not differ from that of control subjects without these risk factors., This would be consistent with the results of longitudinal follow up CABG studies, which suggested that strict control of cardiovascular risk factors during 5-year period after surgery may account for lack of cognitive decline. There is substantial epidemiological evidence of a predictive relation between duration and degree of vascular risk factor and possibility of cognitive decline in later part of life even in persons not undergoing CABG.
| Pre-existing MRI Abnormalities|| |
Silent brain infarctions are common in MRI of neurologically asymptomatic elderly people, which may be associated with cognitive decline or dementia. The specific neuropsychological implications of such lesions though variable, but both psychomotor and motor speed are typically slowed with such lesions. The effects of degree and duration of cerebrovascular risk factor on the brain in CABG candidates have been difficult because obtaining preoperative imaging has been difficult due to short time between hospital admission and surgery. In a study from Japan, MRI was obtained before surgery in 421 CABG candidates; 30% of them had small brain infarction and 20% multiple infarcts. Thus half of these patients had brain abnormalities before surgery. Patients with single or multiple infarctions had lower preoperative cognitive performance and were more likely to have postoperative decline than the patients without infarctions. Thus silent ischemic cerebral disease is common in candidates for CABG and is associated with increased risk for cognitive decline.
Off pump studies
Comparison of cognitive results following CABG and off pump beating heart surgery may conclusively establish whether the adverse effects of conventional CABG were especially due to cardiopulmonary by pass. There is substantial evidence that the use of off pump surgery is associated with fewer emboli to the brain, but the benefits in cognitive outcome are less obvious. In a large randomized study there was no difference in the incidence of decline between patients having conventional on pump versus off pump surgery at 3-12 months. It is unknown whether the degree of late decline in these patients differs from that observed in CABG patients.
Subjective cognitive symptoms
Attempts to correlate postoperative subjective reports of memory loss with performance of objective neuropsychological tests have found only modest or nonsignificant association. As opposed to this association between measures of mood and subjective memory complaints have been reported; hence many investigators have concluded that subjective memory complaints are caused by underlying depression. Subjective memory complaints are not unique to CABG. In a study, similar occurrence of subjective memory complaints was found in subjects 2 year after CABG or percutaneous transluminal coronary angioplasty. There was also no difference in the frequency of subjective memory complaints after CABG and off pump surgery. It is possible that these changes in memory may not be captured by the standard tests of new verbal memory and delayed recall.
| Conclusions|| |
Despite the large amount of data, the potential risk and possible mechanism of cognitive dysfunction after CABG remain elusive due to discrepancies in patients selection and methods of assessment of cognitive decline. Cognitive changes involving memory, executive function and motor speed do occur in first few days to week after CABG. These short-term changes reverse by 3 months after CABG in most patients. Late cognitive decline occurring between 1 and 5 years after surgery is controversial. Employing objective neurophysiological techniques such as electroencephalography and cognitive evoked potential and correlating these with cognitive dysfunction and controlling confounding variables may give the desired answer.
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