December 1, 2013 Volume 77, Number 12
Brain Attack Milad Sharifpour, M.S., M.D.

George A. Mashour, M.D., Ph.D.
Committee on Neuroanesthesia

It is Monday morning and you have been assigned the following case: a 76-year-old woman presenting for an elective hemicolectomy with a past medical history of hypertension, chronic atrial fibrillation (anticoagulation therapy with Coumadin discontinued five days before surgery) and stroke without residual neurologic deficit. The intraoperative course was complicated by episodic hypotension, which was treated with bolus doses of phenylephrine, and atrial fibrillation with rapid ventricular response, which was treated with five milligrams of intravenous metoprolol. Emergence from anesthesia and clinical course in the postanesthesia care unit were uneventful. However, on postoperative day one, the patient was observed to have a new-onset left-sided hemiparesis. A non-contrast computed tomography scan ruled out intracranial hemorrhage and magnetic resonance imaging (MRI) revealed an acute ischemic stroke in the right middle cerebral artery distribution. The patient was taken emergently to the interventional radiology suite and endovascular mechanical thrombolysis was performed.


Although you may not have appreciated it from the initial presentation, this patient had an approximately 1 percent chance of a perioperative stroke just by virtue of being 76 years old and undergoing a hemicolectomy1; the additional risk factors of past stroke, atrial fibrillation and hypertension likely made the risk much higher. The field of anesthesiology has made great strides in recognizing risk profiles and implementing preventive strategies for heart attacks – so why do we seem to know and do so little to prevent “brain attacks”?

Perioperative stroke is a potentially catastrophic compli-cation of surgery with an incidence that varies with the type of procedure and patient comorbidities. Stroke occurs with an incidence of 0.1-1.0 percent after noncardiac, non-neuro-surgical procedures, 0.6-3.0 percent after noncarotid majorvascular surgery, 2.0-3.0 percent after carotid endarterectomy, and more than 5.0 percent after cardiac and valvular surgery.1-5 Importantly, it is associated with a three- to eight-fold increase in 30-day mortality and increased surgical length of stay.1-3 Perioperative strokes are primarily ischemic (versus hemorrhagic) in origin and result from embolism, thrombus or hypoperfusion.6 Recent analyses of large-scale clinical and administrative databases have identified female sex, age ≥62, history of stroke or transient ischemic attack, atrial fibrillation, valvular disease, myocardial infarction within six months before surgery, and acute renal failure or dialysis dependence as independent predictors of perioperative stroke.1-3


However, there are several important limitations associated with such analyses. Primarily, the observational nature of these studies prevents us from establishing the etiology of perioperative stroke. Similarly, the number of potential risk factors for perioperative stroke that can be studied are confined to the variables included in each database, and additional data cannot be collected for patients exhibiting the outcome of interest. Consequently, we have a limited ability to address the contribution to perioperative stroke of variables such as intra- and postoperative hypotension, arrhythmias, administration of perioperative β-blockers and perioperative anticoagulation practices. Furthermore, since the majority of perioperative strokes occur in the days following surgery, database studies often do not provide guidance on the postoperative events that place patients at increased risk for stroke.3,6 Finally, asymptomatic cerebral infarctions (known as covert strokes) are not documented in large databases because they can only be detected with neuroimaging. The striking prevalence of covert stroke was recently highlighted in an abstract that reported a 10 percent incidence after noncardiac, non-neurosurgical and nonvascular surgical procedures, detected only by brain MRI between postoperative days three and 10.7


Intraoperative hypotension is a frequent event and has been traditionally thought to contribute to the development of perioperative strokes. However, the role of intra- and postoperative hypotension in stroke is not well studied and the effect size is of unclear significance.8,9 This is in part due to lack of a clear definition for hypotension; in a review of four major anesthesia journals, Bijker et al. found more than 50 different definitions for hypotension.10 Similarly, a clear definition for baseline blood pressure is lacking, and while some clinicians use the blood pressure in the immediate preoperative period, others use values obtained from preoperative clinic visits and/or primary care office visits as the reference value. Finally, there is no consensus on a minimum duration of intraoperative hypotension that would lead to an adverse neurologic outcome.9 These obstacles, in addition to the relatively low incidence of perioperative stroke in the noncardiac population, make it difficult to study the association between perioperative hypotension and stroke.


The role of β-blockers in the development of perioperative stroke is another controversial subject. The POISE trial reported a significant increase in the risk of perioperative stroke in noncardiac surgical patients given metoprolol versus placebo.11 This finding was associated with an increased incidence of “clinically significant hypotension.” It has been argued that the dose of metoprolol used in this study does not reflect current clinical practice and was significantly higher than routine doses used in the perioperative period. However, Mashour et al. and Ashes et al. have recently reported an association between routine use of preoperative metoprolol and perioperative stroke after noncardiac surgery that was not observed with drugs more selective for the β-1 adrenergic receptor.12,13 Furthermore, intraoperative metoprolol, but not labetalol or esmolol, was associated with an increased risk of stroke.12 Whether alternative β-blockers are safer than metoprolol with respect to stroke risk in the perioperative period is an active area of investigation.


Stroke can be a devastating perioperative complication and, based on preliminary work identifying covert strokes, may be far more common in the noncardiac surgical population than currently appreciated. A history of stroke is one of the most consistent predictors of stroke in the perioperative period.1-3,6 Unfortunately, our limited knowledge regarding physiologic management (e.g., intraoperative blood pressure) and pharmacologic management (e.g., anticoagulants and β-blockers) makes it difficult to give hard recommendations. A task force of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) is in the process of developing guidelines for the care of noncardiac surgical patients at high risk of stroke. One thing is clear: significantly more research is needed if our sophistication at stratifying risk and preventing perioperative heart attacks is ever going to be achieved with perioperative brain attacks.

Milad Sharifpour, M.S., M.D. is an anesthesiology resident, Massachusetts General Hospital, Boston.


George A. Mashour, M.D., Ph.D. is Associate Chair for Faculty Affairs, Associate Professor of Anesthesiology, Faculty, Neuroscience Graduate Program, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor.



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2. Mashour GA, Shanks AM, Kheterpal S. Perioperative stroke and associated mortality after noncardiac, nonneurologic surgery. Anesthesiology. 2011;114(6):1289-1296.

3. Sharifpour M, Moore LE, Shanks AM, Didier TJ, Kheterpal S, Mashour GA. Incidence, predictors and outcomes of perioperative stroke in noncarotid major vascular surgery. Anesth Analg. 2013;116(2):424-434.

4. Cruz CP, Drouilhet JC, Southern FN, Eidt JF, Barnes RW, Moursi MM. Abdominal aortic aneurysm repair. J Vasc Surg. 2001;35(5):335-344.

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7. Mrkobrada M, Hill MD, Chan MT, et al. The Neurovision pilot study: non-cardiac surgery carries a significant risk of acute covert stroke [abstract]. Stroke. 2013;44:ATMP9. Accessed October 7, 2013.

8. Bijker JB, Persoon S, Peelen LM, et al. Intraoperative hypotension and perioperative ischemic stroke after general surgery: a nested case-control study. Anesthesiology. 2012;116(3):658-664.

9. Bijker JB, Gelb AW. The role of hypotension in perioperative stroke. Can J Anaesth. 2013;60(2):159-167.

10. Bijker JB, van Klei WA, Kappen TH, van Wolfswinkel L, Moons KG, Kalkman CJ. Incidence of intraoperative hypotension as a function of the chosen definition: literature definitions applied to a retrospective cohort using automated data collection. Anesthesiology. 2007;107(2):213-220.

11. Devereaux PJ, Yang H, Yusuf S, et al.; POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomized controlled trial. Lancet. 2008;371(9627):1839-1847.

12. Mashour GA, Sharifpour M, Freundlich RE, et al. Perioperative metoprolol and risk of stroke after noncardiac surgery [published online ahead of print April 22, 2013]. Anesthesiology. doi: 10.1097/ALN.0b013e318295a25f.

13. Ashes C, Judelman S, Wijeysundera DN, et al. Selective β1-antagonism with bisoprolol is associated with fewer postoperative strokes than atenolol or metoprolol: a single-center
cohort study of 44,092 consecutive patients [published online ahead of print July 1, 2013]. Anesthesiology. 2013;119(4):777-787. doi: 10.1097/ALN.0b013e3182a17f12.