Stroke in Surgical Patients: A Narrative Review

Phillip E. Vlisides, M.D.; Laurel E. Moore, M.D.

Disclosures

Anesthesiology. 2021;134(3):480-492. 

In This Article

Preoperative Risk Modification

Optimal perioperative care for patients with high stroke risk begins with preoperative evaluation and the informed consent process. Patient survey data suggest that severe complications, even if uncommon, should be discussed.[39] Those with high stroke risk also tend to underestimate their risk of stroke.[40] As such, appropriate counseling for high-risk patients seems warranted to increase risk awareness and improve the informed consent process. Risk prediction models discussed previously can be used to estimate risk for a noncardiac surgery patient.[4,11] In the following paragraphs, we review evidence-based strategies for risk reduction (Figure 1).

Figure 1.

Proposed framework for evaluating patients with high risk of perioperative stroke. *Independent risk factors have been elucidated across large-scale, epidemiologic studies as described in the text and outlined in table 2. †Longitudinal epidemiologic analysis suggests that risk of new perioperative stroke levels off by approximately 9 months after previous stroke. ‡The Canadian Cardiovascular Society, the American College of Surgeons, and the American College of Cardiology have all published recent anticoagulation guideline updates (see text for references). Likewise, the American Heart Association/American Stroke Association, the European Stroke Association, and Heart and Stroke Foundation of Canada have published recurrent guidelines for the early management of patients with acute ischemic stroke (see text for references).

Surgical Timing

As discussed above, cerebrovascular disease history is a risk factor for postoperative stroke.[9,12] Previous stroke can impair cerebral autoregulation, and the presence of cerebrovascular disease is associated with increased oxygen extraction and cerebral malperfusion.[41–43] It is thus unsurprising that surgery is associated with new stroke given the physiologic perturbations inherent to the surgical setting. To assess optimal timing between previous ischemic stroke and elective surgery, a retrospective epidemiologic cohort study of more than 480,000 noncardiac surgery patients was conducted using Danish National Patient Register data.[12] Stroke history was associated with new postoperative stroke, and risk was highest within the first 3 months after a previous stroke. Risk then leveled off by 9 months. Important limitations are worth noting. This was a large-scale observational study, and factors other than previous stroke may have driven increased postoperative stroke risk. Previous stroke also predisposes to recurrent risk outside of the surgical setting.[44] The authors addressed this latter possibility by comparing stroke risk in surgical and nonsurgical patients using population data from Denmark. In this analysis, stroke incidence remained higher in surgical patients across each time point studied.[45] As such, surgery seems to impose stroke risk, and delaying elective surgery for at least 9 months after a previous ischemic stroke may be warranted, when possible.[12]

Medication Optimization

Preoperative medication optimization represents one strategy for the mitigating risk of adverse perioperative outcomes. For example, β-blocker therapy can attenuate catecholaminergic tone and, by extension, risk of adverse cardiac events.[46] However, β-adrenergic receptor antagonism can also create conditions for reduced cerebral perfusion pressure by reducing cardiac output and cerebrovascular vasodilatation.[47–49] In the landmark PeriOperative ISchemic Evaluation (POISE) trial, patients randomized to metoprolol demonstrated a significantly higher stroke risk (approximately two-fold) compared to placebo.[46] A follow-up 2014 systematic analysis of nine randomized controlled trials, including POISE, demonstrated that preoperative β blockade initiation was associated with increased risk of nonfatal stroke.[13] These results stand in contrast to observational studies reporting on stroke risk in relation to chronic β blockade. For patients with hypertension,[50] previous coronary revascularization,[51] diabetes mellitus,[52] and multiple cardiovascular risk factors,[53] there does not appear to be an association between chronic β blockade and perioperative stroke. One explanation is that chronic administration allows for appropriate titration. In the POISE trial, patients were started on 200 mg of metoprolol extended release 2 to 4 h before surgery, and daily administration continued postoperatively. Appropriate dose titration over an extended period of time, before surgical interventions, may allow for appropriate dosing and hemodynamic optimization.

Like β blockers, statins have been studied in relation to perioperative cardiovascular and cerebrovascular outcomes. Postulated mechanisms of action include modification of endothelial function,[54] attenuation of inflammatory processes,[55] and increased atherosclerotic plaque stability.[56] These properties are relevant to the perioperative setting, because these mechanisms might reduce atherothrombotic events (e.g., myocardial infarction, stroke) in surgical patients. In 2018, a meta-analysis of 12 randomized controlled trials (2004 to 2017) involving more than 4,700 noncardiac surgery patients was conducted to investigate whether statins improve such perioperative outcomes.[57] Compared to the control arms, the statin groups demonstrated a reduced incidence of myocardial infarction, atrial fibrillation, and a composite outcome including mortality. However, groups randomized to statin therapy did not demonstrate a significant reduction in perioperative stroke or transient ischemic attack risk. These findings align with large-scale observational studies involving noncardiac surgery patients that demonstrate reduced mortality and risk of major adverse cardiac events but no effect on stroke risk.[53,58] Thus, although perioperative statin administration is associated with reduced mortality and adverse cardiovascular events, there does not appear to be a clearly defined association with stroke risk. Continuation of perioperative statin therapy may nonetheless be helpful for reducing cardiovascular morbidity and mortality.

Perioperative Anticoagulation

Anticoagulation strategies must balance the need for thromboembolic prevention against the risk of major surgical bleeding. Table 4 illustrates the current anticoagulation strategy proposed by the American College of Surgeons. For vitamin K antagonists, such as warfarin, heparin-based bridging therapies are generally reserved for high-risk patients, such as those with mechanical heart valves, rheumatic heart disease, high CHA2DS2-VASc (Congestive heart failure/left ventricular dysfunction, Hypertension, Age ≥75, Diabetes mellitus, Stroke/transient ischemic attack/thromboembolism, Vascular disease, Age 65–74, Female sex) scores (6 or higher), recent thromboembolism, thromboembolism while on anticoagulation therapy, or known cardiac thrombus.[19–21] For low- to moderate-risk patients, bridging therapy increases the risk of hemorrhage without reducing the incidence of thromboembolism.[59] For direct oral anticoagulants, the last dose is typically administered 2 to 3 days before the surgical procedure depending on thromboembolic risk, surgical bleeding risk, and comorbidities (e.g., renal function).[19] Bridging is not required for these anticoagulants, because such therapy tends to increase the risk of major bleeding without reducing thromboembolic events.[60] The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study prospectively evaluated the safety of a standardized protocol for perioperative management of direct oral anticoagulants (apixaban, dabigatran, rivaroxaban).[61] The risks of stroke and major perioperative bleeding were both low across the study cohort. The last dose of each anticoagulant was administered 2 to 3 days before surgery for those with creatinine clearance of more than 50 ml/min, and protocol adherence was high throughout the study. This study mirrored the strategy outlined in Table 4 for direct oral anticoagulants and demonstrates feasibility with implementing such a protocol in practical settings. Overall, anticoagulation bridging is reserved only for high-risk patients on vitamin K antagonists, such as warfarin. For direct oral anticoagulants, these medications are held 2 to 3 days before surgery and resumed 1 to 3 days postoperatively, depending on thromboembolic and bleeding risks (Table 4).

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