Correspondence
Neurocognitive Function after Coronary-Artery Bypass Surgery
N Engl J Med 2001; 345:543-545August 16, 2001
- Article
To the Editor:
Coronary-artery surgery remains the most scrutinized treatment used today. Associated neurocognitive dysfunction is of intense interest to medical professionals and the lay public. We feel compelled to address the shortcomings of the study by Newman et al. (Feb. 8 issue)1 and the accompanying editorial by Selnes and McKhann2 and to place the findings in the proper perspective.
The conclusions regarding neurocognitive dysfunction are limited by the highly selected population studied and the lack of controls. Confounding variables include the effects of general anesthesia, age, coexistent cerebrovascular disease, and the attendant decline in neurocognitive function independent of procedural variables. All coronary procedures are not the same, and modifications have occurred in the seven years since the patients were enrolled that address neurocognitive issues.
Progress has been made to address intraoperative factors that are responsible for injury to the brain during surgery: embolism, hypoperfusion, and the systemic inflammatory response. “Off-pump” coronary-artery bypass grafting (CABG) (which now accounts for over 20 percent of all CABG surgery performed in the United States) may reduce the risk of brain injury due to cardiopulmonary bypass and manipulation of the aorta. The numbers of gaseous and platelet microemboli from cardiopulmonary bypass as well as atherosclerotic macroemboli from cannulation or clamping of the aorta are reduced. Small, randomized studies of off-pump CABG demonstrate decreased emboli and improved neurocognitive outcomes.3 Additional measures to improve neurologic outcomes include the avoidance of grafts on the ascending aorta and the use of protective filters, anastomotic connectors (clampless proximal anastomosis), and pharmacologic agents that minimize the inflammatory response.
Future studies addressing the cognitive decline after CABG surgery should account for all variables that lead to adverse neurocognitive outcomes. CABG is not one operation, and modifications now exist that may improve neurologic and neurocognitive outcomes.
3 ReferencesMichael J. Mack, M.D.
Mitchell J. Magee, M.D.
Todd M. Dewey, M.D.
Cardiopulmonary Research Science and Technology Institute, Dallas, TX 75231
mjmack@earthlink.net 1
Newman MF ,Kirchner JL ,Phillips-Bute B , et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med 2001;344:395-402
Full Text | Web of Science | Medline2
Selnes OA ,McKhann GM . Coronary-artery bypass surgery and the brain. N Engl J Med 2001;344:451-452
Full Text | Web of Science | Medline3
Diegeler A ,Hirsch R ,Schneider F , et al. Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation. Ann Thorac Surg 2000;69:1162-1166
CrossRef | Web of Science | Medline
To the Editor:
Newman et al. present a careful analysis of neurocognitive dysfunction in patients who underwent CABG with cardiopulmonary bypass from 1989 to 1993. They appropriately conclude that their findings “underscore the importance of preventing or reducing perioperative cognitive decline . . . in the growing population of elderly patients undergoing cardiac surgery.” I was surprised, however, that there is no mention in their discussion, or in the accompanying editorial, of the role of CABG without cardiopulmonary bypass (off-pump CABG) and other surgical advances in achieving this goal.
Cardiopulmonary bypass and manipulation of the aorta are the two most likely sources of neurocognitive dysfunction during conventional CABG.1 Cardiopulmonary bypass, however, is no longer a necessary component of CABG. It has been estimated that 20 percent of the CABG procedures currently performed in the United States are off-pump procedures.2 In addition, manipulation of the atherosclerotic aorta is not, as the editorial states, “required by the CABG procedure,” particularly in off-pump CABG. Epiaortic scanning can screen for atherosclerotic disease, and manipulation of the aorta can be completely avoided by the use of pedicled grafts and alternative proximal anastomotic sites. Soon, automated proximal anastomotic devices should eliminate the need for partial aortic clamping during off-pump CABG.
Several small studies have suggested that off-pump CABG results in dramatically fewer cerebral microemboli,3 less serologic evidence of brain injury,4 and less neurocognitive dysfunction1,4 than conventional CABG. Although these preliminary findings must be corroborated by larger studies, eliminating cardiopulmonary bypass and manipulation of the diseased aorta may be the most powerful means of reducing neurocognitive dysfunction after CABG.
4 ReferencesLishan Aklog, M.D.
Brigham and Women's Hospital, Boston, MA 02115
laklog@partners.org 1
Murkin JM ,Boyd WD ,Ganapathy S ,Adams SJ ,Peterson RC . Beating heart surgery: why expect less central nervous system morbidity? Ann Thorac Surg 1999;68:1498-1501
CrossRef | Web of Science | Medline2
Mack MJ . Minimally invasive and robotic surgery. JAMA 2001;285:568-572
CrossRef | Web of Science | Medline3
Bowles BJ ,Lee JD ,Dang CR , et al. Coronary artery bypass performed without the use of cardiopulmonary bypass is associated with reduced cerebral microemboli and improved clinical results. Chest 2001;119:25-30
CrossRef | Web of Science | Medline4
Diegeler A ,Hirsch R ,Schneider F , et al. Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation. Ann Thorac Surg 2000;69:1162-1166
CrossRef | Web of Science | Medline
To the Editor:
Newman et al. demonstrate decreased performance on cognitive tests in 53 percent of patients who underwent CABG and argue that CABG increases the five-year risk of neurocognitive decline. However, an earlier meta-analysis of 44 studies1 reported perioperative dysfunction in only 32 percent of patients and concluded that CABG remains an inadequately understood factor.
Newman et al. define neurocognitive function only in terms of performance on cognitive tests rather than as a clinical syndrome. They argue that a decline of 1 SD in test performance “is similar to the difference in function between 40- and 60-year-old subjects,” but this assertion, even if true, is clinically nonspecific, diagnostically inconclusive, and prognostically unreliable.
The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)2 defines the neurocognitive disorders — including dementia, delirium, and amnestic disorder — as cognitive impairment accompanied by deterioration in executive function, labile mood, social deterioration, or fluctuating consciousness. Each disorder has its own prognosis — witness Alzheimer's disease versus acute alcohol intoxication — and cannot be diagnosed solely on the basis of performance on cognitive tests.
The differential diagnosis of a decrease of 1 SD in performance on cognitive tests includes dementia. But it also includes inattention, anxiety, and treatment with sedatives in a neurocognitively healthy person whose condition is not insidiously deteriorating. Test performance may suggest but does not define a clinical syndrome, much less a poor neurocognitive prognosis.
The study by Newman et al. unnecessarily arouses anxiety about CABG. By ignoring clinical neuropsychiatry, the study leaves us with an unexplained temporal relation between CABG and performance on cognitive tests rather than with a deeper understanding of the causes of dementia.
2 ReferencesAsher P. Wilner, M.D.
McGill University Medical School, Montreal, QC H3A 1A1, Canada
mdaw@musica.mcgill. ca 1
Smith LW ,Dimsdale JE . Postcardiotomy delirium: conclusions after 25 years? Am J Psychiatry 1989;146:452-458
Web of Science | Medline2
Diagnostic and statistical manual of mental disorders. 4th ed. Washington, D.C.: American Psychiatric Association, 1994.
To the Editor:
Newman et al. reported evidence of substantial and persistent cognitive decline after CABG. A considerable number of patients undergoing cardiac surgery also have symptoms of depression both preoperatively and postoperatively.1,2 The authors excluded patients with psychiatric illnesses, but it is unclear whether depression was a specific criterion for exclusion. If so, it is difficult to interpret their findings for the large proportion of patients (nearly half) who may be expected to exhibit symptoms of depression before cardiac surgery.
It is also unclear how the authors addressed the complexity of assessing the cognitive status of patients with clinically significant symptoms of depression after surgery. Although McKhann et al.3 reported only a minimal correlation or none at all between depression and eight measures of cognitive outcome after CABG, Stockton et al.4 reported that depression was a confounding factor in the assessment of cognitive decline in older patients undergoing surgery. Dijkstra et al.5 reported that cognitive symptoms after major surgery may reflect depression rather than actual changes in cognitive performance.
5 ReferencesJulie E. Malphurs, Ph.D.
Lori A. Roscoe, Ph.D.
University of South Florida, Tampa, FL 33612
jmalphur@luna.cas. usf. edu 1
Pirraglia PA ,Peterson JC ,Williams-Russo P ,Gorkin L ,Charlson ME . Depressive symptomatology in coronary artery bypass graft surgery patients. Int J Geriatr Psychiatry 1999;14:668-680
CrossRef | Web of Science | Medline2
Burker EJ ,Blumenthal JA ,Feldman M , et al. Depression in male and female patients undergoing cardiac surgery. Br J Clin Psychol 1995;34:119-128
Web of Science | Medline3
McKhann GM ,Borowicz LM ,Goldsborough MA ,Enger C ,Selnes OA . Depression and cognitive decline after coronary artery bypass grafting. Lancet 1997;349:1282-1284
CrossRef | Web of Science | Medline4
Stockton P ,Cohen-Mansfield J ,Billig N . Mental status change in older surgical patients: cognition, depression, and other comorbidity. Am J Geriatr Psychiatry 2000;8:40-46
CrossRef | Web of Science | Medline5
Dijkstra JB ,Houx PJ ,Jolles J . Cognition after major surgery in the elderly: test performance and complaints. Br J Anaesth 1999;82:867-874
Web of Science | Medline
To the Editor:
Two important omissions weaken the inferences and conclusions drawn by Newman and colleagues in their study of neurocognitive decline after cardiac surgery.
When based on dichotomous outcomes, such as a decline of 1 SD, single-case definitions of cognitive dysfunction are influenced strongly by regression toward the mean. Regression toward the mean is the statistical phenomenon whereby extreme base-line scores become less extreme after repeated examinations, even though a “true” change has not occurred.1 We reported that regression toward the mean alone resulted in a greater proportion of patients who performed very well at base line subsequently being classified as cognitively impaired when the classification was based on such outcomes.2 In the absence of a relevant control group, it is likely that it was the patients who performed well at base line that constituted the largest proportion of those classified as impaired at discharge, and hence any systematic change could be due to regression toward the mean.
Second, there is substantial evidence that postoperative cognitive decline is not unique to cardiac surgery but is also common after other forms of major surgery.3,4 Furthermore, the implication that cardiopulmonary bypass is the sole cause of this dysfunction after cardiac surgery is not true. Indeed, we documented a similar pattern of cognitive decline and recovery in patients undergoing coronary surgery with and without cardiopulmonary bypass and suggested that anesthesia and general surgical injury must also have a substantial role.5
5 ReferencesD.P. Taggart, M.D., Ph.D.
John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
david.taggart@orh. nhs. uk S.M. Browne, M.D.
Royal Rehabilitation Centre, Sydney 2112, AustraliaP.W. Halligan, Ph.D.
Cardiff University, Cardiff CF 103YG, United Kingdom1
Kim H . Regression of lateral asymmetry scores towards the mean. Cortex 1994;30:331-341
Web of Science | Medline2
Browne SM ,Halligan PW ,Wade DT ,Taggart DP . Cognitive performance after cardiac operation: implications of regression towards the mean. J Thorac Cardiovasc Surg 1999;117:481-485
CrossRef | Web of Science | Medline3
Williams-Russo P ,Sharrock NE ,Mattis S ,Szatrowski TP ,Charlson ME . Cognitive effects after epidural vs general anesthesia in older adults. JAMA 1995;274:44-50
CrossRef | Web of Science | Medline4
Moller TJ ,Cluitmans P ,Rasmussen LS , et al. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study. Lancet 1998;351:857-861
CrossRef | Web of Science | Medline5
Taggart DP ,Browne SM ,Halligan PW ,Wade DT . Is cardiopulmonary bypass still the cause of cognitive dysfunction after cardiac operations? J Thorac Cardiovasc Surg 1999;118:414-420
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Although substantial progress has been made in the field since our study was instituted, attempts to reduce the risk of neurocognitive dysfunction have been countered by the large proportion of increasingly elderly, high-risk patients undergoing surgery. Off-pump CABG may provide improved neurocognitive function,1,2 but large-scale, randomized clinical trials are needed to confirm this potential benefit.
Rather than obtain a typical clinical diagnosis according to the DSM-IV, we sought to assess the effects of surgery on long-term neurocognitive function. Our assessment was consistent with the statement of consensus on neurobehavioral outcomes after cardiac surgery1 for both the incidence and the overall severity of change in neurocognitive function. A 20 to 30 percent reduction in neurocognitive function would result in a substantial decrease in the ability of patients to function at their previous level, even if the reduction did not meet the criteria for a DSM-IV diagnosis of delirium or dementia. Rather than arouse anxiety, we hoped to highlight the need for continued study and the introduction of interventions designed to protect long-term neurocognitive function.
Depression is an important problem after cardiovascular events. To minimize any effect of depression on neurocognitive function, we excluded patients with any history of psychiatric illness, including depression, from our study. Although cognitive symptoms may relate to depression, our data reflect actual neurocognitive function, not the patients' perceptions of their level of cognitive functioning.
Regression toward the mean is pertinent in the definition of cognitive decline as an SD decline or a dichotomous outcome. We included base-line cognitive function as a covariate to help control for this possibility. Furthermore, our “composite cognitive index” includes decline and improvement to evaluate the overall change in neurocognitive function. Both outcomes identified a substantial effect of early neurocognitive decline on long-term neurocognitive deterioration, indicating that regression to the mean is not the primary factor in this association.
Cognitive decline does occur after other types of surgery besides cardiac surgery. On the basis of reports by the International Study of Post-Operative Cognitive Dysfunction investigators, we conclude that although neurocognitive decline does occur, it occurs at a lower rate than that associated with cardiac surgery.3 We agree that we cannot rule out a role for general anesthesia and overall surgical stress in neurocognitive dysfunction. However, regardless of the mechanism, the most important issue our study illustrates is that there is a correlation between early postsurgical neurocognitive decline and late neurocognitive deterioration.
3 ReferencesMark F. Newman, M.D.
James A. Blumenthal, Ph.D.
Duke University Medical Center, Durham, NC 27710
newma005@mc.duke. edu 1
Murkin JM ,Newman S ,Stump DA ,Blumenthal JA . Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg 1995;59:1289-1295
CrossRef | Web of Science | Medline2
Moller JT ,Cluitmans P ,Rasmussen LS , et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. Lancet 1998;351:857-861
CrossRef | Web of Science | Medline3
Abildstrom H ,Rasmussen LS ,Rentowl P , et al. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. Acta Anaesthesiol Scand 2000;10:1246-1251
CrossRef | Web of Science
- Citing Articles (1)
Citing Articles
1
Jacoba E. de Klerk, Wynand F. du Plessis, Hendrik S. Steyn, Mike Botha. (2004) Hypnotherapeutic Ego Strengthening with Male South African Coronary Artery Bypass Patients. American Journal of Clinical Hypnosis 47:2, 79-92
CrossRef
