Perioperative stroke: a question of timing?

Perioperative stroke is a potentially devastating complication with an incidence of 0.1–0.6% in non-cardiac surgery. Although rare, stroke in the perioperative setting is associated with an adjusted 8-fold increase in mortality, thus developing preventive strategies is of paramount importance. The recent consensus statement on the prevention of perioperative stroke from the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) is a step in this direction.1Mashour GA Moore LE Lele AV Robicsek SA Gelb AW 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.J Neurosurg Anesthesiol. 2014; 26: 273-285Crossref PubMed Scopus (92) Google Scholar A history of ischaemic stroke is a strong predictor of perioperative stroke and important recent data from Jorgensen and colleagues2Jorgensen ME Torp-Pedersen C Gislason GH et al.Time elapsed after ischemic stroke and risk of adverse cardiovascular events and mortality following elective noncardiac surgery.JAMA. 2014; 312: 269-277Crossref PubMed Scopus (101) Google Scholar have added further information regarding the optimal interval between the stroke event and elective surgery. In this editorial, the preoperative approach to a patient at high risk of stroke is reviewed based on the SNACC consensus statement, with additional discussion of the crucial question of when to schedule surgery in patients with a history of stroke. The SNACC Perioperative Stroke Task Force recently published a consensus statement regarding the perioperative care of non-cardiac, non-neurological surgery patients at high risk for stroke.1Mashour GA Moore LE Lele AV Robicsek SA Gelb AW 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.J Neurosurg Anesthesiol. 2014; 26: 273-285Crossref PubMed Scopus (92) Google Scholar Here we describe the preoperative recommendations, which focused on the (1) identification of risk factors, (2) role of β-adrenergic receptor blockers, (3) role of anticoagulants and antiplatelet drugs, and (4) timing of elective surgery after recent stroke. Consistent independent predictors of perioperative stroke across multiple epidemiological studies include older age, history of cerebrovascular disease (such as past stroke or transient ischaemic attack), kidney failure, atrial fibrillation, and valvular disease.1Mashour GA Moore LE Lele AV Robicsek SA Gelb AW 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.J Neurosurg Anesthesiol. 2014; 26: 273-285Crossref PubMed Scopus (92) Google Scholar, 3Sharifpour 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: 424-434Crossref PubMed Scopus (77) Google Scholar, 4Bateman BT Schumacher HC Wang S Shaefi S Berman MF Perioperative acute ischemic stroke in noncardiac and nonvascular surgery: incidence, risk factors, and outcomes.Anesthesiology. 2009; 110: 231-238Crossref PubMed Scopus (217) Google Scholar In non-cardiac patients with five or more risk factors, the incidence of stroke approaches 1 in 50. In terms of beta blockade, the POISE-1 trial demonstrated that the administration of perioperative metoprolol to non-cardiac surgical patients with cardiovascular risk factors was associated with a significantly higher incidence of stroke and mortality;5Devereaux 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: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (1722) Google Scholar a recent Cochrane database review supports this interpretation.6Blessberger H Kammler J Domanovits H et al.Perioperative beta-blockers for preventing surgery-related mortality and morbidity.Cochrane Database Syst Rev. 2014; 9 (CD004476)Crossref Scopus (101) Google Scholar One of the central questions in response to this seminal trial was whether the increased risk of stroke was attributable to the study methodology—in particular, the starting dose and titration period in beta blocker–naive patients—rather than the pharmacology of the drug itself. Recent observational studies in large non-cardiac surgical populations suggest that even clinically routine administration of metoprolol is associated with a higher risk of stroke compared with other beta blockers with more selectivity for the β1 adrenergic receptor (such as atenolol or bisoprolol), even when controlling for potential confounders.7Mashour GA Sharifpour M Freundlich RE et al.Perioperative metoprolol and risk of stroke after noncardiac surgery.Anesthesiology. 2013; 119: 1340-1346Crossref PubMed Scopus (55) Google Scholar, 8Ashes C Judelman S Wijeysundera DN et al.Selective β1-antagonism with bisoprolol is associated with fewer postoperative strokes than atenolol or metoprolol: single-center cohort study of 44,092 consecutive patients.Anesthesiology. 2013; 119: 777-787Crossref PubMed Scopus (76) Google Scholar, 9London MJ Hur K Schwartz GG Henderson WG Association of perioperative beta-blockade with mortality and cardiovascular morbidity following major noncardiac surgery.JAMA. 2013; 309: 1704-1713Crossref PubMed Scopus (179) Google Scholar In terms of perioperative aspirin and stroke, the recent POISE-2 trial found that continuation of aspirin in the perioperative period for non-cardiac surgical patients with cardiovascular risk factors did not reduce stroke risk, but increased clinically significant bleeding.10Devereaux PJ Mrkobrada M Sessler DI et al.Aspirin in patients undergoing noncardiac surgery.N Engl J Med. 2014; 370: 1494-1503Crossref PubMed Scopus (588) Google Scholar In contrast, the initiation of aspirin was associated with a lower risk of stroke, but the authors themselves questioned the validity of this finding.10Devereaux PJ Mrkobrada M Sessler DI et al.Aspirin in patients undergoing noncardiac surgery.N Engl J Med. 2014; 370: 1494-1503Crossref PubMed Scopus (588) Google Scholar Finally, the SNACC consensus statement addressed the timing of elective surgery after recent stroke. Although the recommendations suggested a delay of at least 1 month between stroke and elective surgery, despite prior studies suggesting no increased risk of adverse events,11Sanders 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: 901-907Crossref PubMed Scopus (30) Google Scholar, 12Landercasper J Merz BJ Cogbill TH et al.Perioperative stroke risk in 173 consecutive patients with a past history of stroke.Arch Surg. 1990; 125: 986-989Crossref PubMed Scopus (77) Google Scholar there were virtually no data to support this recommendation.1Mashour GA Moore LE Lele AV Robicsek SA Gelb AW 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.J Neurosurg Anesthesiol. 2014; 26: 273-285Crossref PubMed Scopus (92) Google Scholar The recent epidemiological study by Jorgensen and colleagues2Jorgensen ME Torp-Pedersen C Gislason GH et al.Time elapsed after ischemic stroke and risk of adverse cardiovascular events and mortality following elective noncardiac surgery.JAMA. 2014; 312: 269-277Crossref PubMed Scopus (101) Google Scholar provides much needed guidance in this aspect of perioperative stroke prevention. An elusive question in preoperative assessment and risk modification has been when to operate on patients with recent major vascular events. For example, the timing of surgery in patients with recent acute coronary syndrome is well investigated11Sanders 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: 901-907Crossref PubMed Scopus (30) Google Scholar, 13Devereaux PJ Chan MT Alonso-Coello P et al.Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery.JAMA. 2012; 307: 2295-2304Crossref PubMed Scopus (721) Google Scholar, 14Goldman L Caldera DL Nussbaum SR et al.Multifactorial index of cardiac risk in noncardiac surgical procedures.N Engl J Med. 1977; 297: 845-850Crossref PubMed Scopus (2076) Google Scholar (if not solved), whereas the timing of surgery in patients with a history of stroke has been inadequately addressed. This is clearly important, as prior cerebrovascular disease is an important risk factor for perioperative stroke. Since publication of the consensus statement, new data have been published on the timing of non-cardiac surgery following ischaemic stroke.2Jorgensen ME Torp-Pedersen C Gislason GH et al.Time elapsed after ischemic stroke and risk of adverse cardiovascular events and mortality following elective noncardiac surgery.JAMA. 2014; 312: 269-277Crossref PubMed Scopus (101) Google Scholar While previous studies did not find an association of surgical timing after preoperative stroke with adverse outcomes (such as mortality) following elective surgery,11Sanders 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: 901-907Crossref PubMed Scopus (30) Google Scholar, 12Landercasper J Merz BJ Cogbill TH et al.Perioperative stroke risk in 173 consecutive patients with a past history of stroke.Arch Surg. 1990; 125: 986-989Crossref PubMed Scopus (77) Google Scholar this recent analysis showed a plausible association between operating within 6–9 months of a stroke and increased risks of perioperative mortality, stroke, and major adverse cardiac events.2Jorgensen ME Torp-Pedersen C Gislason GH et al.Time elapsed after ischemic stroke and risk of adverse cardiovascular events and mortality following elective noncardiac surgery.JAMA. 2014; 312: 269-277Crossref PubMed Scopus (101) Google Scholar Jorgensen and colleagues included a greater number of surgeries occurring less than 6 months following the stroke compared with previous studies,11Sanders 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: 901-907Crossref PubMed Scopus (30) Google Scholar, 12Landercasper J Merz BJ Cogbill TH et al.Perioperative stroke risk in 173 consecutive patients with a past history of stroke.Arch Surg. 1990; 125: 986-989Crossref PubMed Scopus (77) Google Scholar with a consequent increase in statistical power to identify an effect of the timing of surgery on stroke. Although observational, the data suggest that, if possible, elective surgery should be deferred until 6 months after a stroke. Given that contemporary data show that non-cardiac surgery is associated with higher risk for 6 months–1 year following an acute coronary syndrome,7Mashour GA Sharifpour M Freundlich RE et al.Perioperative metoprolol and risk of stroke after noncardiac surgery.Anesthesiology. 2013; 119: 1340-1346Crossref PubMed Scopus (55) Google Scholar, 9London MJ Hur K Schwartz GG Henderson WG Association of perioperative beta-blockade with mortality and cardiovascular morbidity following major noncardiac surgery.JAMA. 2013; 309: 1704-1713Crossref PubMed Scopus (179) Google Scholar it seems unsurprising that stroke may exert a similar effect. Importantly, even minor surgeries after ischaemic stroke were associated with adverse outcomes. In a previous analysis of data from England and Wales, Sanders and colleagues11Sanders 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: 901-907Crossref PubMed Scopus (30) Google Scholar included 414 985 patients having elective major joint arthroplasty, but only 118 patients (0.02%) had a stroke in the prior 6 months. This led the authors to speculate that clinicians avoid elective surgery shortly after a stroke because they consider this a higher-risk period. The data from Jorgensen and colleagues focusing on a diverse non-cardiac, non-neurological surgery population support the clinical decision making inferred based on data from major joint arthroplasty, clarifying the situation greatly. When to conduct emergency surgery, such as hip fracture repair, following a stroke remains unclear. Here the pressure to treat an emergent or urgent condition leads to a clinical dilemma. These decisions must be a compromise between the cerebrovascular vulnerability (or other medical issues) and treatment of the surgical pathology. Indeed, delaying surgery in certain high-risk situations may be associated with greater harm than conducting early surgery.15Moja L Piatti A Pecoraro V et al.Timing matters in hip fracture surgery: Patients operated within 48 hours have better outcomes. A meta-analysis and meta-regression of over 190,000 patients.PLoS One. 2012; 7: e46175Crossref PubMed Scopus (371) Google Scholar At present there are incomplete data to guide clinical practice in patients with acute surgical pathology and co-existent acute stroke. Regarding time-sensitive surgery (such as for cancer), it may still be prudent to delay surgery since increasing time elapsed following a stroke is associated with a reduced risk of postoperative mortality and perioperative stroke. However, we should recognize that the absolute mortality and morbidity rate for some cancer operations remains low and clinical judgment remains the key determinant. A prudent approach should include discussion with the patient of the timing of surgery following a vascular event, and consideration should be given to delaying surgery if possible to reduce perioperative risk. Further details of this consent process are mentioned in the consensus statement.1Mashour GA Moore LE Lele AV Robicsek SA Gelb AW 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.J Neurosurg Anesthesiol. 2014; 26: 273-285Crossref PubMed Scopus (92) Google Scholar Other unanswered questions remain about the heterogeneity of the stroke diagnosis (including severity, clinical symptoms and signs, and cerebrovascular territories involved) and the relative impacts on further perioperative stroke, the management of ischaemic vs haemorrhagic preoperative stroke, the impact of covert stroke on surgical outcomes, how to manage patients with prior transient ischaemic attacks, and the management of perioperative pharmacological agents such as the relative benefit of more highly selective β1 adrenergic agonists.7Mashour GA Sharifpour M Freundlich RE et al.Perioperative metoprolol and risk of stroke after noncardiac surgery.Anesthesiology. 2013; 119: 1340-1346Crossref PubMed Scopus (55) Google Scholar, 8Ashes C Judelman S Wijeysundera DN et al.Selective β1-antagonism with bisoprolol is associated with fewer postoperative strokes than atenolol or metoprolol: single-center cohort study of 44,092 consecutive patients.Anesthesiology. 2013; 119: 777-787Crossref PubMed Scopus (76) Google Scholar, 9London MJ Hur K Schwartz GG Henderson WG Association of perioperative beta-blockade with mortality and cardiovascular morbidity following major noncardiac surgery.JAMA. 2013; 309: 1704-1713Crossref PubMed Scopus (179) Google Scholar Further information is still needed on perioperative risk factors such as haemodynamic control and arrhythmias. Although patients at risk of perioperative stroke, including those with preoperative stroke and other vascular risk factors, can have impaired cerebral autoregulation,16Sanders RD Degos V Young WL Cerebral perfusion under pressure: Is the autoregulatory 'plateau' a level playing field for all?.Anaesthesia. 2011; 66: 968-972Crossref PubMed Scopus (26) Google Scholar evidence is lacking for optimal management of their blood pressure in the perioperative period.1Mashour GA Moore LE Lele AV Robicsek SA Gelb AW 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.J Neurosurg Anesthesiol. 2014; 26: 273-285Crossref PubMed Scopus (92) Google Scholar Furthermore, as preoperative atrial fibrillation is a risk factor for perioperative stroke,1Mashour GA Moore LE Lele AV Robicsek SA Gelb AW 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.J Neurosurg Anesthesiol. 2014; 26: 273-285Crossref PubMed Scopus (92) Google Scholar it would seem highly plausible that new-onset perioperative atrial fibrillation may predispose to perioperative stroke. Recent data show that perioperative atrial fibrillation increases the risk of long-term stroke.17Gialdini G Nearing K Bhave PD et al.Perioperative atrial fibrillation and the long-term risk of ischemic stroke.JAMA. 2014; 312: 616-622Crossref PubMed Scopus (224) Google Scholar Given the issues over perioperative beta blockade, the prevention and management of perioperative atrial fibrillation in non-cardiac surgery requires further attention. In conclusion, stroke remains a potentially disastrous complication of modern perioperative care; as such, the SNACC consensus statement provides important guidance and highlights the numerous gaps in our current clinical understanding.1Mashour GA Moore LE Lele AV Robicsek SA Gelb AW 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.J Neurosurg Anesthesiol. 2014; 26: 273-285Crossref PubMed Scopus (92) Google Scholar Given the rarity of this condition in the non-cardiac surgical population, outcomes research probing large datasets offers an important opportunity to inform clinical care of patients at risk of stroke. In this regard, we are optimistic that further modifiable non-cardiac surgical2Jorgensen ME Torp-Pedersen C Gislason GH et al.Time elapsed after ischemic stroke and risk of adverse cardiovascular events and mortality following elective noncardiac surgery.JAMA. 2014; 312: 269-277Crossref PubMed Scopus (101) Google Scholar, 11Sanders 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: 901-907Crossref PubMed Scopus (30) Google Scholar and cardiac surgical risk18Bottle A Mozid A Grocott HP et al.Preoperative stroke and outcomes after coronary artery bypass graft surgery.Anesthesiology. 2013; 118: 885-893Crossref PubMed Scopus (24) Google Scholar factors for perioperative stroke will be identified. Dr Sanders is a member of the BJA Editorial Board. None of the authors have declared any conflict of interests with regards to this editorial.