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Perioperative Care of Patients at High Risk for Stroke during or after Non-Cardiac, Non-Neurologic Surgery: Consensus Statement from the Society for Neuroscience in Anesthesiology and Critical Care*

Mashour, George A. MD, PhD*; Moore, Laurel E. MD*; Lele, Abhijit V. MD; Robicsek, Steven A. MD, PhD; Gelb, Adrian W. MBChB§

Journal of Neurosurgical Anesthesiology: October 2014 - Volume 26 - Issue 4 - p 273–285
doi: 10.1097/ANA.0000000000000087
Special Article
Free

This document is supported by the American Society of Anesthesiologists.**

Perioperative stroke can be a catastrophic outcome for surgical patients and is associated with increased morbidity and mortality. This consensus statement from the Society for Neuroscience in Anesthesiology and Critical Care provides evidence-based recommendations and opinions regarding the preoperative, intraoperative, and postoperative care of patients at high risk for the complication.

*Departments of Anesthesiology and Neurosurgery, University of Michigan, Ann Arbor, MI

Departments of Anesthesiology, Neurology, and Neurosurgery, University of Kansas, Kansas City, KS

Department of Anesthesiology, University of Florida, Gainesville, FL

§Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA

*Society Consensus Statements published in the Journal of Neurosurgical Anesthesiology have been reviewed by the JNA Affiliate Societies that submit them for publication. They have not undergone review by the Editorial Board of the Journal of Neurosurgical Anesthesiology.

**This document has not been approved by ASA’s House of Delegates or Board of Directors and does not represent an official or approved statement or policy of ASA.

Disclosures: The authors have no conflicts of interest to declare.

Funding: Departmental and institutional sources.

Reprints: George A. Mashour, MD, PhD, Division of Neuroanesthesiology, Department of Anesthesiology, University of Michigan Medical School, 1500 East Medical Center Drive, 1H247 UH/SPC-5048, Ann Arbor, MI 48109-5048 (e-mail: gmashour@umich.edu).

Stroke can be a catastrophic outcome for patients undergoing noncardiac, nonneurologic surgery and is associated with an adjusted 8-fold increase in mortality.1 Unlike stroke in the community setting, the mechanistic cascade leading to perioperative stroke has a discrete and highly-predictable origin: surgical intervention. Given the fact that surgery and anesthesia are associated with an increased risk of stroke compared to nonsurgical controls,2 establishing perioperative recommendations to minimize risk could be impactful. Stroke after noncardiac, nonneurologic surgery is relatively understudied and there is a need for clarifying the clinical management of surgical patients at high risk for the complication.

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METHODOLOGY

Definition of Perioperative Stroke

Sacco et al have developed a consensus statement regarding the broad definition of stroke.3 However, for the purposes of this consensus statement, “perioperative stroke” is defined as a brain infarction of ischemic or hemorrhagic etiology that occurs during surgery or within 30 days after surgery. We recommend that such a standardized definition be adopted for future reports. It is important to note that this clinical situation is distinct from that of a patient presenting for acute therapy after a stroke has occurred in a nonoperative setting. Periprocedural care of patients presenting for endovascular interventions to treat stroke is described elsewhere.4

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Purpose of the Consensus Statement

The purpose of this consensus statement is to provide evidence-based recommendations regarding (1) preoperative identification of patients at high risk of stroke during or after noncardiac, noncarotid, nonneurologic surgery, (2) preoperative considerations to mitigate risk, (3) intraoperative management to mitigate risk, and (4) appropriate steps for clinical care if stroke is identified in the postoperative period.

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Focus

Patients undergoing carotid endarterectomy and a variety of cardiac surgeries are known to be at high risk for perioperative stroke, with fairly clear etiologies (e.g., embolic event).5 As such, there has been considerable attention to the prevention of stroke in these populations. The focus of the current consensus statement is the prevention and management of ischemic stroke in adult patients undergoing noncardiac, noncarotid, and nonneurologic surgery.

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Application

This consensus statement is intended for use by anesthesiologists, anesthesia providers, surgeons and other perioperative care providers. It may also serve health care professionals such as internists or neurologists who evaluate patients in the perioperative period. For the purposes of this article, anesthesia care refers to general anesthesia, regional anesthesia, or monitored anesthesia care.

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Task Force Members and Consultants

The initial recommendations were developed by five anesthesiologists with expertise in clinical neuroscience and neuroanesthesiology, practicing in academic departments across the U.S. These individuals were chosen from membership of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), an international organization. Applicants were required to have published peer-reviewed research on the subject of perioperative stroke or have documented experience in the care of patients with stroke. An outline of the proposed consensus statement was developed and approved by the Executive Committee and Board of Directors of SNACC. The task force members agreed on criteria for evidence and then evaluated peer-reviewed studies pertaining to perioperative stroke. Recommendations were developed by the task force and then assessed by the Executive Committee of SNACC. After incorporating input from the Executive Committee, the Task Force presented the draft guidelines to the international membership of SNACC through its website; thirty days were allowed for suggested revisions. This input and all further available information were incorporated into the consensus statement. The consensus statement was then reviewed and, after further revision, was supported by the American Society of Anesthesiologists.

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AVAILABILITY AND STRENGTH OF EVIDENCE

This consensus statement was informed by published literature obtained through PubMed and other health-care databases, direct internet searches, task force members, and manual searches of references found in review articles. Peer-reviewed articles were considered that provided either scientific evidence (e.g., randomized controlled trial, RCT) or opinion-based evidence.

  1. a) Scientific Evidence
    1. (i) Category A: Supportive Literature
      1. Level 1: The literature contains multiple RCTs and findings are supported by meta-analysis.
      2. Level 2: The literature contains multiple RCTs, but no meta-analysis is possible.
      3. Level 3: Only one RCT exists in the literature.
    2. (ii) Category B: Suggestive Literature
      1. Level 1: The literature contains observational comparisons of interventions (e.g., case-control study) that indicate statistically significant differences with respect to the outcome of perioperative stroke.
      2. Level 2: The literature contains noncomparative observational studies with associative or descriptive statistics.
      3. Level 3: The literature contains case reports.
    3. (iii) Category C: Equivocal Literature
      1. Level 1: Meta-analysis did not find significant differences.
      2. Level 2: No meta-analysis is possible; RCTs found inconsistent evidence.
      3. Level 3: Observational studies report inconsistent findings that do not permit inference.
    4. (iv) Category D: Insufficient Evidence from the Literature
      1. Silent: No identified studies exist on the relationship between intervention and perioperative stroke.
      2. Inadequate: The literature does not permit clear interpretation of findings due to methodological considerations.
  2. Opinion-based Evidence
    1. Category A: Expert opinion from task-force consultants.
    2. Category B: Membership opinion obtained from survey.
    3. Category C: Informal opinion from open-forum testimony, internet-based comments, and other communications.
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PREOPERATIVE RECOMMENDATIONS

Identifying patients at high risk of stroke

In order to prevent perioperative stroke, it is critical to identify those at high risk for the complication. The incidence of stroke in a broad surgical population (excluding cardiac, carotid, major vascular and neurologic surgery) is approximately 1 per 1000 cases1 and approximately 6 per 1000 cases after major vascular surgery below the diaphragm6; perioperative stroke increased length of hospital stay and risk of death. These data are derived from more than 550,000 patients across two studies of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, which is currently the highest quality dataset available for the epidemiology of perioperative stroke incidence and outcome. The incidence of perioperative stroke stratified by case type can be found in Table 1. The significant majority of perioperative strokes are ischemic rather than hemorrhagic7,8; the ACS-NSQIP database does not distinguish between the two. Preliminary data of the NeuroVision trial, conducted in noncardiac surgery patients with cardiovascular risk factors, suggest that the incidence of covert stroke (i.e., without obvious deficit) is 10%, as identified by magnetic resonance imaging in the postoperative period.9 If confirmed by the larger trial, this finding could have important implications for the study and prevention of perioperative stroke after noncardiac surgery.

TABLE 1

TABLE 1

Due to the relative rarity of overt perioperative stroke in the noncardiac population, prospective identification of risk factors has been limited. Data regarding risk profile have therefore been derived from case series, case-control studies, or large database investigations. Table 2 shows the independent predictors of perioperative stroke found in recent major studies of the complication. Three of the most consistent risk factors for perioperative stroke identified in the literature are advanced age, renal failure, and a history of stroke or transient ischemic attack.1,6,10–14 In general terms, all patients presenting for surgery with a history of cerebrovascular compromise should be regarded as high risk for perioperative stroke.

TABLE 2

TABLE 2

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Informed Consent

Perspectives on informed consent from patients in the U.K. suggest that major complications of surgery with an incidence of >1% should be discussed15; a majority of patients surveyed in a U.S. study suggests that rare but serious complications should also be discussed.16 Mashour et al1 showed that patients presenting for noncardiac, non-major-vascular surgery with any three or four of the risk factors listed in Table 2 have a 0.7% incidence of perioperative stroke and with five or more risk factors the incidence rises to 1.9%. It is therefore reasonable to discuss risk of perioperative stroke in patients with a history of stroke and other risk factors.

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Recommendations

  • Screen for risk factors of perioperative stroke, most notably remote or recent history of stroke, and communicate such risk to patients and providers (Category B, Level 2).
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Timing of Surgery After Stroke

Patients with acute or recent stroke have impaired cerebrovascular autoregulation and chemoregulation for months,17–20 rendering them dependent on systemic pressure and passive perfusion. This dependence creates particular risk for cerebral hypoperfusion, especially in the setting of general anesthesia and the physiologic perturbations of surgery (such as hemorrhage, anemia, hypotension). It has been suggested that elective surgery should be delayed from 1 to 3 months after a stroke in order to prevent a secondary cerebrovascular event.21,22 To prevent perioperative stroke in patients with a history of recent cerebrovascular insult, it is likely beneficial to identify the cause of the initial stroke with investigations such as carotid imaging, magnetic resonance angiography, or echocardiogram. Known carotid disease should be treated based on current guidelines.23,24

Despite the intuition that delaying surgery after stroke is beneficial, a study of 173 surgical patients with a history of recent and remote stroke found no relationship between timing of stroke history and incidence of perioperative stroke.21 One retrospective study of hip or knee replacement after stroke or acute coronary syndrome found that stroke within six months prior to surgery was not a predictor of postoperative mortality.25 These findings were similar to a recent retrospective study of cardiac surgical patients; the time interval between stroke and coronary artery bypass graft surgery was not found to be a predictor of postoperative stroke or mortality.26 Ultimately, the decision to proceed with surgery will always be a balance between the risks of perioperative stroke and the risks of delaying surgery further.

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Recommendations

  1. Discuss surgical timing with a neurologist and consider delaying elective surgical cases in patients with recent stroke until the etiology is investigated and the peak of autoregulatory disturbances has passed (likely at one month) (Opinion-based evidence, Category A). However, observational studies to date do not suggest a clear relationship between timing of past stroke history and incidence of postoperative stroke (Category B, Level 2).
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Management of Anti-coagulants and Anti-platelet Drugs

There are two common clinical scenarios in which management of anticoagulants or antiplatelet drugs can be linked to risk of perioperative stroke. The first is management of anticoagulants for patients with atrial fibrillation, a major risk factor for perioperative stroke, and the second is the management of aspirin in patients with cardiovascular or cerebrovascular disease (e.g., for primary or secondary stroke prevention). The clinical dilemma relates to balancing the risks of excessive perioperative bleeding and the risk of rebound hypercoagulability in the setting of the prothrombotic state induced by surgery; a summary of surgical cases with various levels of expected blood loss can be found in Table 3.27 There are few data to guide management of this situation that pertain specifically to perioperative stroke. The American College of Chest Physicians recommends that heparin therapy be considered for postoperative atrial fibrillation in patients with a history of stroke or transient ischemic attack28; an approach to the management of anticoagulation therapy can be found in Table 4.27,29,30

TABLE 3

TABLE 3

TABLE 4

TABLE 4

There are currently no studies of perioperative stroke and antiplatelet drug therapy for noncardiac, noncarotid surgery. Observational studies of cardiac surgery patients taking aspirin within 5 days prior to surgery (vs. not) revealed a protective effect of aspirin with respect to the outcome of perioperative stroke.31,32 These studies are limited by an observational design but are consistent with a large randomized controlled trial finding a benefit to postoperative aspirin in preventing stroke after coronary artery bypass surgery.33 It is as yet unclear how these data apply to noncardiac surgery, although recent studies in patients undergoing hip arthroplasty suggest that aspirin reduces perioperative stroke.34 In a nonoperative population, withdrawal of antiplatelet and antithrombotic medications was associated with a 5.2% incidence of stroke within 60 days of drug cessation.35 Furthermore, nonoperative patients having strokes while off antiplatelet and antithrombotic drugs had greater morbidity and mortality compared to patients who continued taking them.35 However, failing to stop these agents preoperatively may place patients at increased risk of intraoperative hemorrhage, which also increases the risk for perioperative stroke (see section on Intraoperative Recommendations).

Recently, the PeriOperative Ischemic Evaluation (POISE)-2 trial demonstrated that perioperative aspirin did not reduce the incidence of death or nonfatal myocardial infarction after noncardiac surgery, but did increase the risk of major bleeding.36 Of note, patients who had aspirin therapy that was initiated in the course of the study had a reduced incidence of stroke compared to placebo; patients who were continuing aspirin therapy showed no reduction in stroke incidence. Stroke was not a primary outcome of the study and the authors acknowledged that the findings in the initiation group could be spurious. However, the results suggest that some patients at risk of stroke may benefit from preoperative initiation of aspirin therapy, but this must be balanced against the now well-documented risk of significant increases in bleeding and must be demonstrated in a larger trial.

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Recommendations

  • Medically manage atrial fibrillation and continue anticoagulation in patients with atrial fibrillation for minor surgeries or those in which high blood loss is unlikely. Discontinue anticoagulation in surgical patients at high risk of bleeding (with appropriate bridging strategies as indicated), but resume as soon as the risk of surgical bleeding is considered to be low (Opinion-based evidence, Category A).
  • There is no evidence to suggest that continuation of aspirin in patients at risk for vascular complications reduces the risk of stroke after noncardiac surgery (Category A, Level 3).
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Role of Preoperative Beta Blockers and Statins in Perioperative Stroke

The original POISE trial, which evaluated the cardioprotective effects of metoprolol in 8351 noncardiac surgery patients, demonstrated that patients receiving metoprolol had a significantly higher risk of stroke (hazard ratio 2.17, p=0.005) and death (hazard ratio 1.33, p=0.032).37 Data from the POISE trial and other investigations contributed to a meta-analysis suggesting that beta blockers increase risk of nonfatal stroke after noncardiac surgery38; patients from the POISE trial constituted the majority in this study. A retrospective case-control study subsequent to the POISE trial suggested no increased risk of perioperative stroke with clinically routine doses of beta blockers39; a study of low-dose bisoprolol also concluded that there was no increased risk of perioperative stroke.40 Based on these studies it is unclear if there is a drug-specific effect of metoprolol that increases risk of stroke or whether increased risk in the POISE trial was due to bradycardia and hypotension in the treatment group. Based on retrospective data from a single-center observational study, Mashour et al8 demonstrated that routinely prescribed p.o. metoprolol conferred a higher risk of postoperative stroke compared to a matched cohort taking atenolol. These data are consistent with the results of a U.S.-wide Veterans Administration hospital study by London et al showing a higher risk of stroke after noncardiac surgery in patients taking metoprolol compared to atenolol.41 In a single-center observational study, Ashes et al demonstrated that bisoprolol is associated with a lower stroke risk than either metoprolol or atenolol.42 Current guidelines endorse the perioperative continuation of beta blockers in surgical patients who are already taking this class of drug. Large prospective studies are required to confirm that surgical patients who continue perioperative beta blockers are at increased risk of stroke if metoprolol is administered vs. another beta blocker. In surgical patients who are beta-blocker-naïve, high-dose beta blockers should not be administered without dose titration.43

As with beta blockers, discontinuation of statins in the perioperative period may have adverse consequences. With respect to nonoperative stroke, discontinuation of statins in individuals with acute ischemic stroke was associated with a high risk of early neurologic deterioration.44 A recent, preliminary, retrospective study of asymptomatic surgical patients presenting for carotid endarterectomy suggested that statins could reduce neurologic injury, as defined by both stroke and cognitive dysfunction.45 Statins have also been shown to reduce the incidence of atrial fibrillation and other adverse outcomes that may be associated with postoperative stroke.46,47 However, there are no data to suggest that starting statins in the preoperative period can prevent stroke around the time of noncardiac, nonneurologic and noncarotid surgery.

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Recommendations

  • Metoprolol or other beta blockers should only be started in the preoperative period with careful titration (Category A, Level 3).
  • Continue beta blockers and statins throughout the perioperative period in patients already taking them (Opinion-based evidence, Category A with respect to stroke risk).
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INTRAOPERATIVE RECOMMENDATIONS

Intraoperative events are frequently cited as a cause of postoperative stroke, despite controversial evidence. Stroke presenting in the postoperative period on the same day of surgery (which would suggest a clear intraoperative etiology) is relatively infrequent.8 In this section we review the available data guiding intraoperative management of anesthetic technique, ventilation strategy, fluid and blood transfusion, glycemic control and blood pressure.

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Anesthetic Technique

There has been extensive interest in the possible neuroprotective effects of anesthetic agents. Most studies have been in patients for whom cerebral ischemia is predictable; examples of predictable cerebral ischemia include carotid endarterectomy, cerebral aneurysm surgery and procedures requiring deep hypothermic circulatory arrest. For these procedures, anesthetic technique may be adjusted prospectively in an attempt to minimize neurologic injury. However, data supporting anesthetic neuroprotection even for these procedures is limited or absent. Given the low incidence of perioperative stroke in noncardiac and nonvascular surgical patients (making RCT difficult), investigators have studied neurologic outcome after cardiac surgery, in which the stroke risk is higher. Bilotta et al performed an extensive literature review of randomized trials but could not make definitive conclusions due to the small number and heterogeneity of studies.48

It is also important to consider anesthetics that might potentially increase stroke risk. For example, nitrous oxide is associated with an acute increase in plasma homocysteine concentrations, which could impair endothelial function and increase adverse cardiovascular events.49 However, no association has been demonstrated in several large studies between intraoperative administration of nitrous oxide and postoperative stroke.8,49–51

A recent retrospective review of 57,000 patients8 revealed no difference in stroke risk between regional and general anesthesia in noncardiac patients. However, a large database study (>200,000 patients) focusing on knee and hip arthroplasty found that neuraxial anesthesia was associated with a lower incidence of stroke (0.07%) compared to combined neuraxial/general anesthesia (0.12%) and general anesthesia (0.13%, p=0.006).52 Overall 30-day mortality was also reduced in the neuraxial (0.10; n=40,036) and combined neuraxial-general (0.10; n=49,396) groups compared to the general anesthesia group (0.18; n=292,804; p<0.001). Similarly, in a 2010 single center observational study of 18,745 consecutive joint replacements, general anesthesia was an independent predictor of postoperative stroke (OR 3.54, 95% CI 1.01-12.39).53 In another patient population from the GALA trial, which studied carotid endarterectomy patients, there was no difference in stroke rates between general and regional anesthesia.54 Thus, while there are no data in a broad, representative surgical population to support general vs. regional anesthetic technique, there are now at least two large outcomes studies suggesting that regional anesthesia for hip and knee arthroplasty may be associated with a lower risk of perioperative stroke.

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Recommendations

  1. Despite characteristics that would appear to predispose to perioperative stroke, nitrous oxide use has not been associated with an increased incidence of perioperative stroke (Category B, Level 1).
  2. Recent retrospective data suggest that neuraxial techniques may be associated with a lower incidence of perioperative stroke for hip and knee arthroplasty (Category B, Level 1). No such data exist for other surgical populations.
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Intraoperative Use of Beta Blockers

The most important intraoperative pharmacologic association with postoperative stroke is the administration of beta blockers. Mashour et al8 retrospectively studied 57,218 noncardiac patients, of whom 55 had perioperative strokes. Intraoperative metoprolol administration was associated with a 3.3-fold increased risk of perioperative stroke (p=0.003; 95% CI 1.4-7.8). No such association was found for intraoperative esmolol or labetolol. While the investigators also found intraoperative hypotension to be associated with perioperative stroke, no co-linearity existed between intraoperative metoprolol administration and hypotension.

The mechanism of metoprolol’s apparent role in perioperative stroke is unclear. There is wide diversity in beta 1-adrenergic selectivity among beta antagonists, with bisoprolol having the greatest selectivity, atenolol intermediate and metoprolol the least selectivity among clinically used “cardioselective” beta blockers.55 Recent animal data suggest that metoprolol, as a relatively nonselective beta1 antagonist, may reduce brain tissue oxygenation by impairing beta2 mediated cerebral vasodilation in mice.56 Furthermore, in rats, metoprolol impairs the compensatory increase in cardiac output that occurs in response to anemia, reducing cerebral tissue oxygenation.57

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Recommendations

  1. Intraoperative metoprolol administration may place patients at increased risk for stroke (Category B, Level 1); these data have not been separately analyzed for patients taking metoprolol prior to surgery. Beta blockers with a short duration of action such as esmolol should be considered for intraoperative use (Opinion-based evidence, Category A).
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Ventilation Strategies and Risk of Perioperative Stroke

There are limited data on the interaction of intraoperative PaCO2 or EtCO2 and stroke incidence. Any conclusion on ventilation strategies to reduce the risk of stroke is therefore speculative. There are, however, several considerations regarding ventilation and stroke: 1) Intraoperative hyperventilation has multiple systemic deleterious effects including: reduced lung compliance and potential for reduced oxygenation (from impaired V/Q mismatch and increased shunt); increased myocardial oxygen demand and reduced supply (coronary vasoconstriction); potential dysrhythmias; and reduced cerebral blood flow; 2) Although in theory hyperventilation has the potential to favorably redistribute flow from normal brain to relatively ischemic regions (“inverse steal phenomenon”), in animals subjected to middle cerebral artery occlusion this does not happen and in fact there may be an increase in the size of the region at risk for stroke.58–61 3) Nonoperative stroke patients who were hypocapnic had worse outcomes compared to normocapnic patients.62 Until more intraoperative data are available, we are unable to make any conclusions regarding whether hypocapnia places patients at risk for perioperative stroke or whether there are ventilation strategies to reduce the risk of stroke. It seems likely that hypocapnia, because of the reduction in cerebral blood flow, is undesirable in patients with risk factors for perioperative stroke and may be one of several factors that negatively affect outcome in those patients who suffer stroke perioperatively.

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Recommendations

  1. There are no data on which to base recommendations regarding intraoperative ventilation strategies and the incidence of perioperative stroke (Category D, Silent).
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Intraoperative Hemorrhage and Blood Transfusion Therapy

There is evidence linking intraoperative hemorrhage and anemia to postoperative stroke, particularly in cardiac patients. It is difficult to determine whether absolute hematocrit (and thus oxygen carrying capacity), the volume of hemorrhage itself (suggestive of surgical complexity), hypotension and/or physiologic stress accounts for this association with perioperative stroke. In control-matched cardiac surgery patients suffering postoperative stroke, Bahrainwala et al.63 demonstrated that both post-cardiopulmonary bypass hemoglobin level and the volume of blood transfused intraoperatively were independent predictors of stroke. The number of units transfused was directly associated with the risk of stroke and, although transfusion attenuated the relationship between post-bypass hemoglobin and stroke, it did not eliminate risk.

In a retrospective study of 651,775 patients undergoing noncardiac, noncarotid and nonneurologic surgery, patients receiving more than four units of packed red blood cells (as a surrogate for major hemorrhage) had an approximately 2.5 fold increased risk for stroke or Q-wave myocardial infarction.64 The POISE trial also found “significant bleeding” to be an independent predictor of postoperative stroke (adjusted OR 2.18, 95% CI 1.45-8.52) in the population of high risk patients undergoing noncardiac surgery.37 The authors commented on a dose-response relationship between the volume transfused and stroke but did not examine the interaction between hypotension and anemia. There is evidence in nonoperative stroke that anemia is associated with stroke in the absence of hypotension,65,66 and thus it seems reasonable to assume that this association exists in surgical patients as well.67,68 Furthermore, recent observational data suggest that intraoperative anemia (hemoglobin <9 gm/dl) in the setting of beta blockade increases risk of stroke, but the study was not able to distinguish acute from chronic use.42

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Recommendations

  1. For noncardiac, nonneurologic surgical patients already taking a beta blocker, a hemoglobin <9.0 gm/dl should be avoided in order to minimize risk of stroke (Category B, Level 1).
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Glucose Management

Hyperglycemia has long been recognized to have a negative influence on neurologic outcomes following cerebral ischemia.69 This is true for both global and focal ischemia as well as specific surgical populations for which focal ischemia is predictable, including cardiothoracic surgery,70 carotid endarterectomy71 and open cerebral aneurysm ligation.72 It should also be noted that in a relatively small randomized trial of cardiac patients, intensive intraoperative insulin therapy (glucose goal of 80-100 mg/dL) was associated with an increased risk of stroke and death, despite no increases in hypoglycemic events.73 A recent meta-analysis concluded that intravenous insulin for tight glycemic control within 24 hours after nonoperative stroke may not be beneficial and may increase the risk of hypoglycemia.74 This is clearly a complex issue and most authors recommend an intervention with serum glucose exceeding 150 mg/dL, with an absolute upper limit of 180 mg/dL, in hyperglycemic patients undergoing major surgery.75,76

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Recommendations

  1. In patients at high risk for perioperative stroke undergoing surgery, glucose monitoring is recommended, with a target range of 60-180 mg/dL (Opinion-based evidence, Category A).
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Blood Pressure Management

Intraoperative hypotension is frequently cited as a cause of postoperative stroke. Until recently, however, there was very little evidence to support this belief and even the neurology literature concluded that, “Ischemic strokes after general surgery commonly occur after an asymptomatic interval…Hypotension rarely accounts for postoperative strokes.”11 Studying the effect of blood pressure has proven difficult given the diversity of definitions and the very low incidence of perioperative stroke, despite the very high incidence of intraoperative hypotension.77 The 2008 POISE study raised concern regarding the potential role of metoprolol in perioperative stroke but also re-focused attention on the possible role of intra- and postoperative hypotension in its pathogenesis.37 Patients receiving metoprolol had an increased perioperative risk of clinically significant hypotension (HR 1.55, 95% CI 1.38-1.74), which in turn was associated with death and stroke (OR 4.97 95% CI 3.62-6.81). More recently, Bijker et al78 conducted a retrospective case-control study reviewing 48,241 consecutive noncardiac and nonneurosurgical patients and found an overall stroke incidence of 0.09% within 10 days of surgery. They determined that a decrease in intraoperative mean arterial pressure of more than 30% below baseline was associated with postoperative stroke. However, the odds ratio of 1.013 reveals an effect size of unclear clinical significance. The authors posit that unrecognized or poorly quantified hypotension in the postoperative period may be more important to stroke genesis than hypotension during the highly monitored and regulated intraoperative period and suggest that intraoperative hypotension may be predictive of postoperative hemodynamic instability rather than an independent cause of postoperative stroke. They furthermore conclude that “hypotension is best defined as a decrease in mean blood pressure relative to a preoperative baseline, rather than an absolute low blood pressure value.” Mashour et al8 also found that, for median values in a 10-minute epoch, a <20%, <30% or <40% decrease in mean arterial or systolic blood pressure is associated with stroke. Causal relationships were not investigated in this study.

In addition to the timing of perioperative stroke, the low incidence of watershed infarctions in noncardiac surgical patients79 also argues against intraoperative hypotension as a defining risk for postoperative stroke. This is further complicated by the controversy of whether watershed infarcts are indeed produced by systemic hemodynamic factors or local microemboli. Cortical watershed infarcts are probably embolic in nature, especially if the large cerebral conducting vessels are atheromatous, whereas deep white matter infarcts are probably of hemodynamic origin.80,81

Finally, postural hypotension may also play a role in stroke after noncardiac surgery. In 2005, Pohl and Cullen reported four cases of ischemic brain and spinal cord injury after shoulder surgery in the beach chair position.82 Since that time, significant attention has been given to the risk of unrecognized reduced cerebral perfusion pressures and resultant neurologic injury in the beach chair position. Neurologic injuries have occurred in the beach chair position at recorded blood pressures that most anesthesiologists would consider acceptable.83 Assuming a 0.8 mm Hg decrease in MAP for every 1 cm gradient, and a 15-30 cm gradient between the brachial artery (cuff measurement) and the brainstem, the MAP at the level of the brainstem could be 12-24 mm Hg lower than the pressure measured by cuff on the nonoperative arm. Clearly this relationship is greatly worsened if the cuff is placed on the lower extremity84; this differential should also be kept in mind when leveling a transducer if invasive blood pressure monitoring is used. There are numerous studies using near infrared spectroscopy that document a high incidence of desaturations measured in the beach chair position.85–87 The devices are intended to measure saturation in a volume of tissue comprising neural cells, arterioles and veins. A reduction in saturation may represent cellular oxygen desaturation but may also represent a change in the ratio of arterial to venous blood. The latter may occur with vasopressors or head positioning that limits cerebral venous drainage. However, it is important to note that the degree and duration of cerebral desaturation required to produce neurologic injury is also not yet known but a reduction of >20% is thought to be cause for concern.88,89 Some orthopedic surgeons still support the safety of induced hypotension in the beach chair position.90 However, given the frequency of severe hypotension and electroencephalographic changes consistent with cerebral ischemia (6%), this technique cannot be endorsed.

In sum, it seems that there is an association between intraoperative hypotension and perioperative stroke, but the clinical significance of this association is poorly defined. Further prospective research is clearly necessary to make strong evidence-based recommendations regarding intraoperative blood pressure management. It is probable that there are subsets of patients at increased risk for stroke who clearly are harmed by hypotension or low flow states. Some of these populations may include patients with unrecognized critical stenosis of carotid or intracranial arteries or congenital anomalies of the cerebral circulation.91

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Recommendations

  1. There are data to support an association between intraoperative hypotension and perioperative stroke (Category B, Level 1). As such, intraoperative hypotension should be avoided in patients at high risk of perioperative stroke (Opinion-based evidence, Category A).
  2. Intraoperative hypotension should be defined as a percent reduction from baseline blood pressure rather than an absolute value (Category B, Level 1).
  3. For surgery in the beach chair position, noninvasive blood pressure measurement by cuff should always be performed on the nonoperative upper arm (as opposed to lower extremity) and consideration should be given to the blood pressure gradient between the brachial artery and brain (Opinion-based evidence, Category A). Induced hypotension for shoulder surgery in the beach chair position should always be approached with caution, especially in patients at risk for stroke (Opinion-based evidence, Category A).
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POSTOPERATIVE RECOMMENDATIONS

Stroke Team, Networks, and Communication

In the event of an acute stroke, preventing secondary injury and achieving optimal outcome are based on rapid recognition, communication and management. Evaluation and treatment of acute perioperative stroke, which is typically ischemic, should be consistent with the most recent American Heart Association Guidelines for the Management of Patients with Acute Ischemic Stroke.92 The advantage of an acute stroke response algorithm is self-evident, since the activities of multiple personnel must be coordinated efficiently among practitioners in fields such as anesthesiology, neurology, radiology, and interventional neuroradiology. An institutional pathway promotes higher efficiency, more rapid therapeutic intervention, and a more reliable transfer of information pertinent to the patient’s optimal care93

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Recommendations

  1. An organized protocol for emergency evaluation of surgical patients with suspected perioperative stroke is recommended (Category A, Level 3).
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Assessing Stroke

There is a need to develop and evaluate simple, quick screening tools for stroke that can be used in the perioperative period. Such tools need to be suitable for preoperative screening as well as routine use by nursing staff on surgical wards or intensive care units. Examples of such tests that may be suitable for postoperative use include the Face Arm Speech Time (FAST),94 Los Angeles Prehospital Stroke Screen (LAPSS),95 Melbourne Ambulance Stroke Screen (MASS),96 and Recognition of Stroke in the Emergency Room (ROSIER).97

Various physiologic, pharmacologic and pathologic factors in the postanesthetic period can mask symptoms of intraoperative or postoperative stroke. Careful evaluation and resolution of pharmacologic contributions to a neurologic deficit is paramount to reduce delay in stroke diagnosis.98 Certain drugs that are commonly used during the intraoperative period can be reversed, including narcotics (with naloxone), benzodiazepines (with flumazenil), and neuromuscular blockers (with a cholinesterase inhibitor or sugammadex, where available). Although the presence of residual inhaled anesthetics can be quantified routinely in the operating room at the end of a surgical case, the effect of drugs such as propofol and dexmedetomidine cannot be conveniently measured in real time.

Delayed emergence, altered mental status and/or the presence of new focal neurologic deficit in the absence of convincing confounders should raise suspicion for stroke.99 A detailed neurologic examination should include the use of the National Institutes of Health Stroke Scale (NIHSS) (Table 5; see also: http://www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf or http://www.ninds.nih.gov/doctors/NIH_Stroke_Scale_Booklet.pdf). Clinical evaluation also includes measurement of blood pressure, oxygen saturation, temperature, blood glucose, serum electrolytes, complete blood count and coagulation status. Immediate diagnostic studies of all patients with suspected stroke should include noncontrast computed tomography (CT) or magnetic resonance imaging (MRI) of the brain to determine whether the stroke is ischemic or hemorrhagic in origin and to correlate neurologic deficit with radiologic findings.100 The role of CT angiography and CT perfusion imaging is to provide supplementary information, especially in determining the need for urgent endovascular intervention. The presence of a large ischemic penumbra or thrombus in a major vessel (e.g., middle cerebral artery) would prompt consideration of endovascular therapy. One of the limitations of conventional MRI is the duration of the scan; however, diffusion-perfusion MRI enables the identification of an ischemic penumbra and identification of patients who may benefit from late thrombolysis.101

TABLE 5

TABLE 5

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Recommendations

  1. Use of a stroke rating scale, preferably the NIHSS, is recommended (Category A, Level 3).
  2. Emergency imaging of the brain is recommended before initiating any specific therapy to treat acute postoperative stroke (Category A, Level 1).
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Acute management of ischemic stroke

In considering the management of acute perioperative stroke, it will be helpful to apply, where appropriate, therapeutic strategies for ischemic stroke treatment in nonsurgical settings. Ischemic stroke is the most common form of perioperative stroke and thus the present recommendations are directed at its treatment. Identification of a hemorrhagic stroke with head CT in the surgical patient will prompt a distinct pathway of investigation and management, with distinct recommendations for blood pressure control.102,103

Interventions such as recombinant tissue plasminogen activator (rtPA) should be considered with a multidisciplinary team that includes stroke neurology, interventional neuroradiology and the primary surgical service. The risk/benefit balance will vary depending on the patient, severity and location of the stroke, and type of surgical intervention.

Intravenous rtPA is the drug of choice for thrombotic strokes, but it is contraindicated in a number of situations (Table 6). Importantly, major surgery—with the exception of intracranial or spinal surgery—is a relative rather than absolute contraindication, but there is a paucity of literature regarding the management of stroke after a noncardiac, nonvascular or nonneurologic procedure. Oral administration of aspirin (initial dose is 325 mg) within 24 to 48 hours after stroke onset is recommended but is not a substitute for other acute interventions such as rtPA.92 Furthermore, the administration of aspirin (or other antiplatelet agents) as an adjunctive therapy within 24 hours of intravenous fibrinolysis is not recommended.92 Urgent anticoagulation with the goal of preventing early recurrent stroke, halting neurological deterioration or improving outcomes after ischemic stroke is not recommended,92 nor is the initiation of anticoagulation therapy within 24 hours of treatment with intravenous rtPA. In addition to intravenous rtPA, intra-arterial thrombolysis has American Heart Association Class IIa, Level C evidence of safety and efficacy.100,104 Although endovascular mechanical thrombolysis has recently been shown not to be superior to intravenous rtPA,105 it may be an attractive alternative in the postoperative patient. Again, all interventions should be discussed with a multidisciplinary team including neurologists, neuroradiologists, and the primary surgical service, while keeping in mind that “time is brain.”

TABLE 6

TABLE 6

The initial treatment of stroke is usually best achieved in a subspecialty acute care setting such as a neurocritical care or stroke unit. Maintaining appropriate physiologic stability is critical during acute stroke care. Hypoxemia is associated with poor neurologic/ outcomes and should therefore be monitored with pulse oximetry; supplemental oxygen should be used to maintain SpO2 saturation greater than 94%.92 The airway should be secured in patients with depressed levels of consciousness (Glasgow Coma Scale <8), signs of brainstem dysfunction, or inability to protect the airway. Tracheal intubation and mechanical ventilation may also be helpful in the management of increased intracranial pressure or for those who have suspected malignant brain edema.

Patients with acute cerebral ischemia should have cardiac monitoring for at least the first 24 hours, and any serious arrhythmia should be treated.92 Myocardial ischemia and cardiac arrhythmias are potential sequelae of acute cerebrovascular disease and systemic hypertension is common after stroke. Common postoperative conditions that may contribute to hypertension include stress response to surgery, pain, nausea, hypervolemia, full bladder, or physiological response to hypoxia. Every effort should be made to preserve cerebral perfusion pressure during the first 24 hours. Unless the patient is eligible for acute reperfusion intervention, systolic blood pressure is usually treated only if it is greater than 220 mm Hg, and diastolic pressure is treated only if it is greater than 120 mm Hg.92 In patients who receive rtPA (intravenous or intra-arterial) or undergo mechanical clot retrieval, systolic blood pressure above 180 mm Hg and diastolic pressure above 105 mm Hg should be treated with anti-hypertensive drugs such as labetolol or nicardipine.92 However, no data are available to guide selection of medications for the lowering (or raising) of blood pressure in the setting of acute ischemic stroke. Both hypovolemia and unstable cardiac arrhythmias may result in arterial hypotension, which is detrimental in the setting of stroke. As such, correction of hypovolemia with normal saline and restoration of normal sinus rhythm is beneficial.92

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Recommendations

  1. If not contraindicated based on multidisciplinary discussion regarding risks of hemorrhage, intravenous/intra-arterial rtPa or mechanical thrombolysis should be considered as soon as possible for the surgical patient with an acute ischemic stroke (Opinion-based evidence, Category A).
  2. In patients who receive rtPA (intravenous or intra-arterial) or undergo mechanical clot retrieval, systolic blood pressure above 180 mm Hg and diastolic pressure above 105 mm Hg should be treated with anti-hypertensive drugs such as labetolol or nicardipine (Category A, Level 1).
  3. The administration of aspirin (or other antiplatelet agents) as an adjunctive therapy within 24 hours of intravenous fibrinolysis is not recommended (Opinion-based evidence, Category A).
  4. Supplemental oxygen should be provided to maintain oxygen saturation >94% (Opinion-based evidence, Category A).
  5. Airway support and ventilator assistance are recommended for treatment of patients with decreased consciousness or bulbar dysfunction that causes compromise of respiration (Opinion-based evidence, Category A).
  6. Baseline electrocardiogram and troponin assessment is recommended (Category A, Level 3).
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CONCLUSIONS

Perioperative stroke can be a devastating adverse outcome for surgical patients and their families and further research is clearly required. Recognition of patients at high risk for stroke during or after noncardiac, nonneurologic surgery is critical. Consistent risk factors include advanced age, renal disease and history of stroke or transient ischemic attack. Continuation of beta blockers and statins is important for prevention; if indicated, beta blockers should only be started in the perioperative period with careful titration. Recent evidence suggests that continuation of aspirin in patients at risk of stroke after noncardiac surgery is not indicated and may increase bleeding risk. Intraoperative hypotension should be avoided in surgical patients at high risk of perioperative stroke and for those in the beach chair position. Postoperative vigilance and appropriate stroke screening for high risk surgical patients is prudent. For surgical patients manifesting symptoms or signs of stroke, timely neurology/stroke consultation and emergent neuroimaging are essential. Major noncardiac, nonneurologic surgery is not an absolute contraindication to intravascular administration of rtPa; mechanical thrombolysis is also an option for those at high risk of surgery-related hemorrhage.

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REFERENCES

1. Mashour GA, Shanks AM, Kheterpal S. Perioperative stroke and associated mortality after noncardiac, nonneurologic surgery. Anesthesiology. 2011;114:1289–1296.
2. Wong GY, Warner DO, Schroeder DR, et al.. Risk of surgery and anesthesia for ischemic stroke. Anesthesiology. 2000;92:425–432.
3. Sacco RL, Kasner SE, Broderick JP, et al.. An updated definition of stroke for the 21st century: A statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2013;44:2064–2089.
4. Talke PO, Sharma D, Heyer EJ, et al.. Society for Neuroscience in Anesthesiology and Critical Care expert consensus statement: Anesthetic management of endovascular treatment of acute ischemic stroke. J Neurosurg Anesthesiol. 2014;26:95–108.
5. Bucerius J, Gummert JF, Borger MA, et al.. Stroke after cardiac surgery: A risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg. 2003;75:472–478.
6. Sharifpour M, Moore LE, Shanks AM, et al.. Incidence, predictors, and outcomes of perioperative stroke in noncarotid major vascular surgery. Anesth Analg. 2013;116:424–434.
7. Ng JL, Chan MT, Gelb AW. Perioperative stroke in noncardiac, nonneurosurgical surgery. Anesthesiology. 2011;115:879–890.
8. Mashour GA, Sharifpour M, Freundlich RE, et al.. Perioperative metoprolol and risk of stroke after noncardiac surgery. Anesthesiology. 2013;119:1340–1346.
9. Mrkobrada M, Hill M, Chan M, et al.. Abstract tmp9: The neurovision pilot study: Non-cardiac surgery carries a significant risk of acute covert stroke. Stroke. 201344ATMP9.
10. Parikh S, Cohen JR. Perioperative stroke after general surgical procedures. N Y State J Med. 1993;93:162–165.
11. Limburg M, Wijdicks EF, Li H. Ischemic stroke after surgical procedures: Clinical features, neuroimaging, and risk factors. Neurology. 1998;50:895–901.
12. Kikura M, Takada T, Sato S. Preexisting morbidity as an independent risk factor for perioperative acute thromboembolism syndrome. Arch Surg. 2005;140:1210–1217.
13. Popa AS, Rabinstein AA, Huddleston PM, et al.. Predictors of ischemic stroke after hip operation: A population-based study. J Hosp Med. 2009;4:298–303.
14. Bateman BT, Schumacher HC, Wang S, et al.. Perioperative acute ischemic stroke in noncardiac and nonvascular surgery: Incidence, risk factors, and outcomes. Anesthesiology. 2009;110:231–238.
15. Jamjoom AA, White S, Walton SM, et al.. Anaesthetists' and surgeons' attitudes towards informed consent in the UK: An observational study. BMC Med Ethics. 2010;11:2.
16. Burkle CM, Pasternak JJ, Armstrong MH, et al.. Patient perspectives on informed consent for anaesthesia and surgery: American attitudes. Acta Anaesthesiol Scand. 2013;57:342–349.
17. Dawson SL, Blake MJ, Panerai RB, et al.. Dynamic but not static cerebral autoregulation is impaired in acute ischaemic stroke. Cerebrovasc Dis. 2000;10:126–132.
18. Rubin G, Levy EI, Scarrow AM, et al.. Remote effects of acute ischemic stroke: A xenon ct cerebral blood flow study. Cerebrovasc Dis. 2000;10:221–228.
19. Dawson SL, Panerai RB, Potter JF. Serial changes in static and dynamic cerebral autoregulation after acute ischaemic stroke. Cerebrovasc Dis. 2003;16:69–75.
20. Aries MJ, Elting JW, De Keyser J, et al.. Cerebral autoregulation in stroke: A review of transcranial doppler studies. Stroke. 2010;41:2697–2704.
21. Landercasper J, Merz BJ, Cogbill TH, et al.. Perioperative stroke risk in 173 consecutive patients with a past history of stroke. Arch Surg. 1990;125:986–989.
22. Blacker DJ, Flemming KD, Link MJ, et al.. The preoperative cerebrovascular consultation: Common cerebrovascular questions before general or cardiac surgery. Mayo Clin Proc. 2004;79:223–229.
23. Hobson RW 2nd, Mackey WC, Ascher E, et al.. Management of atherosclerotic carotid artery disease: Clinical practice guidelines of the society for vascular surgery. J Vasc Surg. 2008;48:480–486.
24. Liapis CD, Bell PR, Mikhailidis D, et al.. Esvs guidelines. Invasive treatment for carotid stenosis: Indications, techniques. Eur J Vasc Endovasc Surg. 2009;37:1–19.
25. Sanders RD, Bottle A, Jameson SS, et al.. Independent preoperative predictors of outcomes in orthopedic and vascular surgery: The influence of time interval between an acute coronary syndrome or stroke and the operation. Ann Surg. 2012;255:901–907.
26. Bottle A, Mozid A, Grocott HP, et al.. Preoperative stroke and outcomes after coronary artery bypass graft surgery. Anesthesiology. 2013;118:885–893.
27. Darvish-Kazem S, Douketis JD. Perioperative management of patients having noncardiac surgery who are receiving anticoagulant or antiplatelet therapy: An evidence-based but practical approach. Semin Thromb Hemost. 2012;38:652–660.
28. Epstein AE, Alexander JC, Gutterman DD, et al.. Anticoagulation: American college of chest physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest. 2005;128:24S–27S.
29. Douketis JD, Spyropoulos AC, Spencer FA, et al.. Perioperative management of antithrombotic therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141:e326S–e350S.
30. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013;368:2113–2124.
31. Cao L, Silvestry S, Zhao N, et al.. Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: A sub-group and cohort study. PLoS ONE. 2012;7:e30094.
32. Cao L, Young N, Liu H, et al.. Preoperative aspirin use and outcomes in cardiac surgery patients. Ann Surg. 2012;255:399–404.
33. Mangano DT. Aspirin and mortality from coronary bypass surgery. N Engl J Med. 2002;347:1309–1317.
34. Lalmohamed A, Vestergaard P, Cooper C, et al.. Timing of stroke in patients undergoing total hip replacement and matched controls: A nationwide cohort study. Stroke. 2012;43:3225–3229.
35. Broderick JP, Bonomo JB, Kissela BM, et al.. Withdrawal of antithrombotic agents and its impact on ischemic stroke occurrence. Stroke. 2011;42:2509–2514.
36. Devereaux PJ, Mrkobrada M, Sessler D, et al.. Asprin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370:1494–1503.
37. Devereaux PJ, Yang H, Yusuf S, et al.. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): A randomised controlled trial. Lancet. 2008;371:1839–1847.
38. Bangalore S, Wetterslev J, Pranesh S, et al.. Perioperative beta blockers in patients having non-cardiac surgery: A meta-analysis. Lancet. 2008;372:1962–1976.
39. van Lier F, Schouten O, van Domburg RT, et al.. Effect of chronic beta-blocker use on stroke after noncardiac surgery. Am J Cardiol. 2009;104:429–433.
40. van Lier F, Schouten O, Hoeks SE, et al.. Impact of prophylactic beta-blocker therapy to prevent stroke after noncardiac surgery. Am J Cardiol. 2010;105:43–47.
41. London MJ, Hur K, Schwartz GG, et al.. Association of perioperative beta-blockade with mortality and cardiovascular morbidity following major noncardiac surgery. JAMA. 2013;309:1704–1713.
42. Ashes C, Judelman S, Wijeysundera DN, et al.. Selective beta1-antagonism with bisoprolol is associated with fewer postoperative strokes than atenolol or metoprolol: A single-center cohort study of 44,092 consecutive patients. Anesthesiology. 2013;119:777–787.
43. Fleischmann KE, Beckman JA, Buller CE, et al.. 2009 ACCF/AHA focused update on perioperative beta blockade. J Am Coll Cardiol. 2009;54:2102–2128.
44. Blanco M, Nombela F, Castellanos M, et al.. Statin treatment withdrawal in ischemic stroke: A controlled randomized study. Neurology. 2007;69:904–910.
45. Heyer EJ, Mergeche JL, Bruce SS, et al.. Statins reduce neurologic injury in asymptomatic carotid endarterectomy patients. Stroke. 2013;44:1150–1152.
46. Winchester DE, Wen X, Xie L, et al.. Evidence of pre-procedural statin therapy a meta-analysis of randomized trials. J Am Coll Cardiol. 2010;56:1099–1109.
47. Chopra V, Wesorick DH, Sussman JB, et al.. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: A systematic review and meta-analysis. Arch Surg. 2012;147:181–189.
48. Bilotta F, Gelb AW, Stazi E, et al.. Pharmacological perioperative brain neuroprotection: A qualitative review of randomized clinical trials. Br J Anaesth. 2013;110Suppl 1i113–i120.
49. Leslie K, Myles PS, Chan MT, et al.. Nitrous oxide and long-term morbidity and mortality in the enigma trial. Anesth Analg. 2011;112:387–393.
50. Leslie K, Myles P, Devereaux PJ, et al.. Nitrous oxide and serious morbidity and mortality in the POISE trial. Anesth Analg. 2013;116:1034–1040.
51. Sanders RD, Graham C, Lewis SC, et al.. Nitrous oxide exposure does not seem to be associated with increased mortality, stroke, and myocardial infarction: A non-randomized subgroup analysis of the general anaesthesia compared with local anaesthesia for carotid surgery (gala) trial. Br J Anaesth. 2012;109:361–367.
52. Memtsoudis SG, Sun X, Chiu YL, et al.. Perioperative comparative effectiveness of anesthetic technique in orthopedic patients. Anesthesiology. 2013;118:1046–1058.
53. Mortazavi SM, Kakli H, Bican O, et al.. Perioperative stroke after total joint arthroplasty: Prevalence, predictors, and outcome. J Bone Joint Surg Am. 2010;92:2095–2101.
54. Lewis SC, Warlow CP, Bodenham AR, et al.. General anaesthesia versus local anaesthesia for carotid surgery (gala): A multicentre, randomised controlled trial. Lancet. 2008;372:2132–2142.
55. Baker JG. The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol. 2005;144:317–322.
56. El Beheiry MH, Heximer SP, Voigtlaender-Bolz J, et al.. Metoprolol impairs resistance artery function in mice. J Appl Physiol. 2011;111:1125–1133.
57. Ragoonanan TE, Beattie WS, Mazer CD, et al.. Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats. Anesthesiology. 2009;111:988–1000.
58. Ruta TS, Drummond JC, Cole DJ. The effect of acute hypocapnia on local cerebral blood flow during middle cerebral artery occlusion in isoflurane anesthetized rats. Anesthesiology. 1993;78:134–140.
59. Fourcade HE, Larson CP Jr, Ehrenfeld WK, et al.. The effects of co2 and systemic hypertension on cerebral perfusion pressure during carotid endarectomy. Anesthesiology. 1970;33:383–390.
60. Boysen G, Ladegaard-Pedersen HJ, Henriksen H, et al.. The effects of paco2 on regional cerebral blood flow and internal carotid arterial pressure during carotid clamping. Anesthesiology. 1971;35:286–300.
61. Michenfelder JD, Milde JH. Failure of prolonged hypocapnia, hypothermia, or hypertension to favorably alter acute stroke in primates. Stroke. 1977;8:87–91.
62. Stringer WA, Hasso AN, Thompson JR, et al.. Hyperventilation-induced cerebral ischemia in patients with acute brain lesions: Demonstration by xenon-enhanced CT. AJNR Am J Neuroradiol. 1993;14:475–484.
63. Bahrainwala ZS, Grega MA, Hogue CW, et al.. Intraoperative hemoglobin levels and transfusion independently predict stroke after cardiac operations. Ann Thorac Surg. 2011;91:1113–1118.
64. Kamel H, Johnston SC, Kirkham JC, et al.. Association between major perioperative hemorrhage and stroke or q-wave myocardial infarction. Circulation. 2012;126:207–212.
65. Tsai CF, Yip PK, Chen CC, et al.. Cerebral infarction in acute anemia. J Neurol. 2010;257:2044–2051.
66. Kimberly WT, Wu O, Arsava EM, et al.. Lower hemoglobin correlates with larger stroke volumes in acute ischemic stroke. Cerebrovasc Dis Extra. 2011;1:44–53.
67. Karkouti K, Djaiani G, Borger MA, et al.. Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery. Ann Thorac Surg. 2005;80:1381–1387.
68. Hare GM, Tsui AK, McLaren AT, et al.. Anemia and cerebral outcomes: Many questions, fewer answers. Anesth Analg. 2008;107:1356–1370.
69. Wass CT, Lanier WL. Glucose modulation of ischemic brain injury: Review and clinical recommendations. Mayo Clin Proc. 1996;71:801–812.
70. Murkin JM. Pro: Tight intraoperative glucose control improves outcome in cardiovascular surgery. J Cardiothorac Vasc Anesth. 2000;14:475–478.
71. McGirt MJ, Woodworth GF, Brooke BS, et al.. Hyperglycemia independently increases the risk of perioperative stroke, myocardial infarction, and death after carotid endarterectomy. Neurosurgery. 2006;58:1066–1073discussion 1066–1073.
72. Pasternak JJ, McGregor DG, Schroeder DR, et al.. Hyperglycemia in patients undergoing cerebral aneurysm surgery: Its association with long-term gross neurologic and neuropsychological function. Mayo Clin Proc. 2008;83:406–417.
73. Gandhi GY, Nuttall GA, Abel MD, et al.. Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: A randomized trial. Ann Intern Med. 2007;146:233–243.
74. Bellolio MF, Gilmore RM, Ganti L. Insulin for glycaemic control in acute ischaemic stroke. Cochrane Database Syst Rev. 201423CD005346.
75. Engelhard K. Anaesthetic techniques to prevent perioperative stroke. Curr Opin Anaesthesiol. 2013;26:368–374.
76. Jacobi J, Bircher N, Krinsley J, et al.. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med. 2012;40:3251–3276.
77. Bijker JB, van Klei WA, Kappen TH, et al.. Incidence of intraoperative hypotension as a function of the chosen definition: Literature definitions applied to a retrospective cohort using automated data collection. Anesthesiology. 2007;107:213–220.
78. Bijker JB, Persoon S, Peelen LM, et al.. Intraoperative hypotension and perioperative ischemic stroke after general surgery: A nested case-control study. Anesthesiology. 2012;116:658–664.
79. Bijker JB, Gelb AW. Review article: The role of hypotension in perioperative stroke. Can J Anaesth. 2013;60:159–167.
80. Momjian-Mayor I, Baron JC. The pathophysiology of watershed infarction in internal carotid artery disease: Review of cerebral perfusion studies. Stroke. 2005;36:567–577.
81. Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neurol. 1998;55:1475–1482.
82. Pohl A, Cullen DJ. Cerebral ischemia during shoulder surgery in the upright position: A case series. J Clin Anesth. 2005;17:463–469.
83. Cullen DJ, Kirby RR. Beach chair position may decrease cerebral perfusion. APSF Newsletter. 2007;22:25–27.
84. Malhotra A, Cohen D, Syms C, et al.. Blood pressure changes in the leg on standing. J Clin Hypertens (Greenwich). 2002;4:350–354.
85. Murphy GS, Szokol JW, Marymont JH, et al.. Cerebral oxygen desaturation events assessed by near-infrared spectroscopy during shoulder arthroscopy in the beach chair and lateral decubitus positions. Anesth Analg. 2010;111:496–505.
86. Salazar D, Sears BW, Andre J, et al.. Cerebral desaturation during shoulder arthroscopy: A prospective observational study. Clin Orthop Relat Res. 2013;47:4027–4034.
87. Salazar D, Sears BW, Aghdasi B, et al.. Cerebral desaturation events during shoulder arthroscopy in the beach chair position: Patient risk factors and neurocognitive effects. J Shoulder Elbow Surg. 2013;22:1228–1235.
88. Moritz S, Kasprzak P, Arlt M, et al.. Accuracy of cerebral monitoring in detecting cerebral ischemia during carotid endarterectomy: A comparison of transcranial doppler sonography, near-infrared spectroscopy, stump pressure, and somatosensory evoked potentials. Anesthesiology. 2007;107:563–569.
89. Samra SK, Dy EA, Welch K, et al.. Evaluation of a cerebral oximeter as a monitor of cerebral ischemia during carotid endarterectomy. Anesthesiology. 2000;93:964–970.
90. Gillespie R, Shishani Y, Streit J, et al.. The safety of controlled hypotension for shoulder arthroscopy in the beach-chair position. J Bone Joint Surg Am. 2012;94:1284–1290.
91. Drummond JC, Lee RR, Howell JP Jr. Focal cerebral ischemia after surgery in the “beach chair” position: The role of a congenital variation of circle of willis anatomy. Anesth Analg. 2012;114:1301–1303.
92. Jauch EC, Saver JL, Adams HP Jr, et al.. Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2013;44:870–947.
93. Reason J. Human error: Models and management. BMJ. 2000;320:768–770.
94. Nor AM, McAllister C, Louw SJ, et al.. Agreement between ambulance paramedic- and physician-recorded neurological signs with face arm speech test (fast) in acute stroke patients. Stroke. 2004;35:1355–1359.
95. Kidwell CS, Starkman S, Eckstein M, et al.. Identifying stroke in the field. Prospective validation of the los angeles prehospital stroke screen (lapss). Stroke. 2000;31:71–76.
96. Bray JE, Martin J, Cooper G, et al.. Paramedic identification of stroke: Community validation of the melbourne ambulance stroke screen. Cerebrovasc Dis. 2005;20:28–33.
97. Nor AM, Davis J, Sen B, et al.. The recognition of stroke in the emergency room (rosier) scale: Development and validation of a stroke recognition instrument. Lancet Neurol. 2005;4:727–734.
98. Norris JW, Hachinski VC. Misdiagnosis of stroke. Lancet. 1982;1:328–331.
99. Martin DP, Jankowski CJ, Keegan MT, et al.. Postoperative confusion and basilar artery stroke. Neurocrit Care. 2006;4:147–150.
100. Adams HP Jr, del Zoppo G, Alberts MJ, et al.. Guidelines for the early management of adults with ischemic stroke: A guideline from the american heart association/american stroke association stroke council, clinical cardiology council, cardiovascular radiology and intervention council, and the atherosclerotic peripheral vascular disease and quality of care outcomes in research interdisciplinary working groups: The american academy of neurology affirms the value of this guideline as an educational tool for neurologists. Circulation. 2007;115:e478–e534.
101. Morales-Vidal S, Schneck M, Golombieski E. Commonly asked questions in the management of perioperative stroke. Expert Rev Neurother. 2013;13:167–175.
102. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al.. Guidelines for the management of spontaneous intracerebral hemorrhage: A guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2010;41:2108–2129.
103. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al.. Guidelines for the management of aneurysmal subarachnoid hemorrhage: A guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2012;43:1711–1737.
104. Blackham KA, Meyers PM, Abruzzo TA, et al.. Endovascular therapy of acute ischemic stroke: Report of the standards of practice committee of the society of neurointerventional surgery. J Neurointerv Surg. 2012;4:87–93.
105. Ciccone A, Valvassori L, Nichelatti M, et al.. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013;368:904–913.
Keywords:

stroke; ischemic stroke; perioperative stroke; cerebrovascular; cerebrovascular accident; noncardiac surgery; neurologic complication

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