Abstract & Commentary
This study was conducted to test the hypothesis that perioperative b-adrenergic receptor (bAR) antagonist administration provides protection against adverse cerebral complications during cardiac surgery. Subjects were 2575 patients, identified from the Duke Heart Center database, who underwent elective coronary artery bypass grafting surgery (CABG) over a 2.5-year period (June 1994 to December 1996). Patients were excluded if they underwent valvular surgery or noncardiac procedures that might increase neurologic complications, eg, carotid endarterectomy or abdominal aortic aneurysm repair. Perioperative drug administration was defined to include bAR antagonist administration within 48 hours of surgery or during surgery. Postoperative neurologic complications were defined as stroke, coma, transient ischemic attack (TIA), or clinical cognitive change (confusion or delirium) before hospital discharge. All complications were confirmed by retrospective chart review by a board-certified neurologist.
A total of 2296 (89%) patients received bAR antagonist therapy and 279 (11%) did not. There were 113 (4.4%) postoperative neurologic complications, including stroke (n = 44), coma (n = 12), TIA (n = 3), and confusion or delirium (n = 54). Adverse neurologic events occurred in 3.9% of patients who received perioperative bAR antagonist administration, compared to 8.2% of patients who did not receive these medications (odds ratio, 0.45; 95% confidence interval [CI], 0.28-0.73; p = 0.003). Severe neurologic outcomes (stroke and coma) occurred in 1.9% of patients who received bAR antagonists and 4.3% of patients who did not receive these medications (odds ratio, 0.43; 95% CI, 0.23-0.83; p = 0.016). The time of administration (preoperative, intraoperative, both) had no effect on neurologic outcome. Patients who did not receive bAR antagonists were older (p = 0.0026) and more likely to have a preoperative diagnosis of CHF (p = 0002) or COPD (P < 0.0001), but these patients did not differ in gender or incidence of hypertension, diabetes, prior stroke, or peripheral vascular disease. The incidence of atrial fibrillation was higher in the non-bAR antagonist group (25.1%), compared to the bAR antagonist group (20.5%), but the difference was not significant (p = 0.0863). (Amory DW, et al. Neuroprotection is associated with beta-adrenergic receptor antagonists during cardiac surgery: Evidence from 2575 patients. J Cardiothorac Vasc Anesth. 2002;16:270-277.)
Comment by Leslie A. Hoffman, RN, PhD
Despite advances in management, neurologic complications continue to be a major cause of morbidity and mortality after cardiac surgery. This study was conducted in response to anecdotal observations by the cardiac anesthesiology team suggesting that bAR antagonists might decrease adverse neurologic outcomes. Results of this retrospective analysis suggest that administration of bAR antagonists prior to or during cardiac surgery results in a substantial reduction in the total number of adverse neurologic events (3.9% with bAR antagonists; 8.2% without), an effect not previously reported.
Several actions of these medications might contribute to these positive outcomes. Propranolol has been found to shift the oxyhemoglobin dissociation curve to the right, which could increase availability of oxygen to ischemic tissue. Other bAR antagonists have been shown to improve neurologic outcomes in an animal model of transient cerebral ischemia. Atrial fibrillation is a common complication of CABG surgery, and the development of this complication significantly increases the risk of stroke. There was a tendency for patients who received bAR antagonists to have a lower incidence of atrial fibrillation, but the difference was not significant.
The study did not test a protocol for drug administration. Consequently, study results shed no light on optimal timing, dosing, or whether some drugs are more effective than others. Patients received bAR antagonists at the discretion of the anesthesiologist. General indications were continuation of b-blockade in patients already receiving bAR antagonists, initiation of new b-blockade to prevent or ameliorate heart rate responses to surgery, and prophylaxis to enhance myocardial protection during the entire operative period. The drugs used were atenolol, propranolol, and metoprolol. A strength of the study was the step of confirming all neurologic complications through retrospective chart review by a board-certified neurologist.
Although study findings are exciting, they were collected retrospectively and, therefore, do not provide confirmation of a neuroprotective effect of bAR antagonists during cardiac surgery. A prospective, randomized, blinded trial would be necessary to confirm study findings. If confirmed, use of bAR antagonists could represent an important and inexpensive method to decrease neurologic complications following cardiac surgery.
Dr. Hoffman is Professor Medical-Surgical Nursing Chair, Department of Acute/Tertiary Care, Massachusetts General Hospital, Cambridge, MA.
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