Introduction
Perioperative stroke is a potentially devastating complication of surgery that has an incidence that varies widely with the surgical procedure. A perioperative stroke can occur intraoperatively or in the postoperative period; however, this window of risk is not standardized because studies have used intervals of 3 to 30 days.
A recent review on this topic illustrated the representative incidences based on surgical procedure. These categories included general surgery (0.08% to 0.7%), peripheral vascular surgery (0.8% to 3.0%), resection of head and neck tumors (4.8%), carotid endarterectomy (CEA) in symptomatic patients (3.3% to 6.4%), CEA in asymptomatic patients (1.2% to 3.0%), isolated coronary artery bypass graft (CABG) surgery (1.4% to 3.8%), combined CABG with valve surgery (7.4%), isolated valve surgery (4.8% to 8.8%), double or triple valve surgery (9.7%), and aortic repair (8.7%). Beating-heart CABG has a lower incidence of stroke than does CABG with bypass (1.9% versus 3.8%, respectively).
This variability in perioperative stroke incidence certainly reflects the underlying surgical anatomy, risk of vascular compromise and injury, and patient’s overall preoperative health status. As such, there are likely no simple answers to this complex perioperative complication. The problem has been approached by different specialties with a variety of preventive measures, including intense intraoperative monitoring, novel approaches to the surgical procedure, and development of predictive models. Regardless, the incidence of perioperative stroke has remained a concern.
The implication from the aforementioned reviews is that to achieve an appreciable reduction in the incidence of stroke, it will require universal as well as selective improvements by each surgical subspecialty. A fair appraisal of perioperative stroke thus requires that we present data for general surgery, carotid surgery, and cardiac surgery separately.
Evidence
Evidence from studies of cardiac surgery supports that perioperative hemorrhagic stroke is of the lowest incidence. In cardiac surgery, for example, Likosky and colleagues examined 388 patients who had strokes after isolated CABG surgery. This study used the Northern New England Cardiovascular Disease Study Group classification system, and imaging was performed with computed tomography (CT) or magnetic resonance imaging (MRI). The study revealed that 62.1% of strokes were embolic, 3.1% lacunar, 1.0% thrombotic, 8.8% due to hypoperfusion, 1.0% hemorrhagic, 10.1% multiple causes, and 13.9% unclassified. About 45% of strokes were detected within the first postoperative day, and a slow decrement of detection was seen over time (about 20% more by postoperative day 2, about 12% more by postoperative day 3, and less than 5% beyond postoperative day 10).
The source of emboli (cardiac or artery-to-artery) during any surgery could include arrhythmias such as atrial fibrillation, aortic arch atherosclerosis, perioperative myocardial infarction, and manipulations of the heart and carotid arteries. The release of particulate matter from the cardiopulmonary bypass pump must also not be forgotten. A rare source may also be paradoxical emboli from a patent foramen ovale or fat emboli during orthopedic procedures. In a study of 2630 CABG patients, 2.0% had postoperative strokes. The event occurred after a mean of 3.7 days. In 19 of 52 patients (36.5%), atrial fibrillation preceded the stroke, with a mean of 2.5 episodes of atrial fibrillation before the event.
Tissue injury from surgery results in a prothrombotic state, which lasts up to 14 to 21 days postoperatively. This is supported by decreased levels of tissue plasminogen activator and increased plasminogen activator inhibitor type 1 activity, fibrinogen degradation products, thrombin–antithrombin complex, thrombus precursor protein, and D-dimer. Other factors such as the use of general anesthesia, under-resuscitation leading to postoperative dehydration, and bed rest may all aggravate a hypercoagulable state. Often, antiplatelet and anticoagulant agents are also held in the perioperative period. This may certainly exacerbate a hypercoagulable state and further increase the risk of perioperative stroke. This practice has slowly changed, and it is being found that these agents are likely safe in a large majority of surgeries.
Gottesman and colleagues presented a different view of stroke in cardiac surgery. They studied 98 patients who had MRI after a clinical stroke. The group identified watershed infarcts in 68% of the diffusion-weighted imaging sequences of MRI versus 37% of brain CTs. In fact, 48% of diffusion-weighted MRI scans demonstrated bilateral watershed infarcts versus 22% of CT scans. Patients with bilateral watershed infarcts were more likely to have undergone an aortic procedure than a simple or second CABG. These patients trended toward longer bypass times (nearly significant; p = 0.055). Univariate and multivariate logistic regression revealed that patients with a drop in mean arterial pressure (MAP) of at least 10 mm Hg from their preoperative baselines were greater than four times more likely to develop bilateral watershed infarcts as those with a small or no decrement in blood pressure. Importantly, absolute intraoperative blood pressure was almost identical in the bilateral watershed infarct group versus other infarct patterns. Watershed infarcts may be due to a mechanistic interplay of hypoperfusion and embolization. The theory is that a state of reduced perfusion (due to reduced MAP or due to carotid arterial narrowing) may impede washout of microemboli showered during cardiac surgery; these particulates then have a predilection to settle in watershed areas.
In keeping with this theory, a randomized study by Gold and colleagues of 248 patients undergoing elective CABG revealed that patients maintained at a higher MAP (80 to 100 mm Hg) during bypass had a lower incidence of stroke. This group also conducted a follow-up study in 412 patients undergoing elective CABG comparing a higher MAP (80 mm Hg) with a patient’s prebypass baseline MAP but did not detect a difference in the stroke rate. These studies have been criticized for lack of power to draw any widely applicable conclusions. In contrast, van Wermeskerken and colleagues analyzed outcomes from 2862 patients undergoing CABG. After controlling for bypass time and preoperative stroke risk index, the authors found that patients with a lower pressure during bypass (MAP < 50 mm Hg) had a decreased incidence of stroke and coma.
In general, hypoperfusion is believed to be an uncommon cause of perioperative stroke. The term hypoperfusion can imply global hypoperfusion (i.e., resulting in bilateral watershed infarctions) or relative hypoperfusion through a pre-existing stenosis (i.e., unilateral watershed infarction due to carotid stenosis). The aforementioned study from van Wermeskerken and colleagues supports a limited role of hypoperfusion. In addition, Whitney and colleagues concluded that hypoperfusion ischemia is rare during CEA, even when the contralateral carotid is occluded. Naylor and colleagues. reviewed the literature to assess the role of carotid stenosis as a perioperative stroke risk factor for CABG. Ninety-one percent of screened CABG patients had insignificant disease and had a less than 2% risk of stroke. The risk increased to 3% for asymptomatic unilateral stenosis of 50% to 99%, 5% in bilateral 50% to 99% stenosis, and 7% to 11% in those with an occluded carotid. As a consequence of such data, the current practice is to perform CEA before CABG or even intraoperatively immediately before CABG. Venkatachalam and colleagues recently reviewed the perioperative stroke risk of patients who underwent staged or combined CEA–CABG and found a 4% risk for combined CEA–CABG, 2% for CEA followed by CABG, 5% for CABG followed by CEA, and 2% for carotid endovascular revascularization followed by CABG.
Studies looking specifically at the mechanisms of stroke in the general surgery patient are rare and, in general, are not contemporary studies. Hart and Hindman performed a retrospective review of 24,500 general surgery patients. Forty-two percent of strokes were believed to be embolic, and atrial fibrillation was present in 33% of patients at the time of the events. Interestingly, most perioperative strokes in the general surgery population occur well into the postoperative period: on average on the seventh day. A recent case control study reiterated the relative rarity of intraoperative strokes; evidence was found for only 10 of 61 strokes occurring intraoperatively. Of these studies, Parikh and Cohen found the highest incidence (53%) of cerebrovascular accident (CVA) within 24 hours after surgery.
Again, taken as a whole, these observations highlight the fact that the mechanisms of perioperative stroke should be reviewed in each surgical population separately.
Systematic Review
No meta-analysis has specifically assessed the risk factors for perioperative stroke in the general surgery population. The best level evidence is in the form of prospective observational studies, but given that an extensive literature search identified only one such study, several retrospective and case control investigations were included for review. A retrospective analysis of patients undergoing noncarotid vascular surgery is also included ( Tables 6-1 and 6-2 ).
| Study, Year | Number of Subjects | Study Design | Stroke Incidence | Significant Risk Factors |
|---|---|---|---|---|
| 1982 | 24,500 (general surgical procedures excluding carotid and cardiac surgery) | R | 0.07% | Atrial fibrillation Cardiac disease |
| 1988 | 2463 (noncardiac, noncarotid artery surgery) | PO | 0.2% | Previous cerebrovascular disease Heart disease PVD (eightfold increased risk) Hypertension (threefold-fourfold increased risk) |
| 1990 | 173 (patients with prior CVA subsequently underwent general surgery) | R | 2.9% | Use of preoperative heparin sodium (usually as a substitute for warfarin) General anesthesia (as opposed to regional) Hypotension in recovery room |
| 1993 | 24,641 (general and vascular general surgery excluding CEA) | R | 0.08% | Hypertension Smoking Previous neurologic symptoms Abnormal rhythm on ECG |
| 1998 | 61 cases (general surgery) 122 randomly assigned control subjects (matched for age, sex, procedure, and year of procedure) | CC | N/A | Previous cerebrovascular disease (AOR 1 , 12.57; AOR 2 , 14.70) * COPD (AOR 1 , 7.51; AOR 2 , 10.04) PVD (AOR 1 , 5.35) Higher MAP on admission (AOR 2 , 1.05) Blood urea at time of stroke (AOR 2 , 1.04) Postoperative MI (4 cases versus 0 control) Diffuse intravascular coagulation (4 cases versus 0 control) |
| 2000 | 1455 cases (surgery) 1455 control subjects (age and sex matched) | CC | N/A | Perioperative period after general anesthesia extending for 30 days postoperatively (OR adjusted for known independent stroke risk factor: 3.9 for all surgeries and 2.9 for general surgery) |
| 2004 | 2251 (abdominal aortic aneurysmectomy) 2616 (aortobifemoral bypass) 6866 (lower extremity bypass) 7442 (major lower extremity amputation) | R | 0.4%-0.6% | Preoperative ventilation (OR, 11) Previous stroke or TIA (OR, 4.2) Postoperative MI (OR, 3.3) Need to return to operating room (OR, 2.2) |
| 2005 | 172,592 | PO | 0.03% | Most cases in ASA 3 patients † 26% of stroke cases had prior history of CVA |
| 2009 | 201,235 (total hip replacement) 131,067 (hemicolectomy) 39,339 (lobectomy) 327,628 control subjects (CABG) | R | 0.2% (total hip replacement) 0.7% (hemicolectomy) 0.6% (lobectomy) | Age Female sex Diabetes mellitus Atrial fibrillation Congestive heart failure History of prior stroke Renal disease Cardiac valvular disease |
| 2010 | 18,745 (total joint arthroplasty) | CC | 0.2% | Noncoronary cardiac disease (OR, 4.13) Urgency of surgery (OR, 5.89) General anesthesia (OR, 3.54) Intraoperative arrhythmia (OR, 1.06) |
* AOR 1 is from the univariate analysis. AOR 2 is from the multivariate analysis. Noted values are those that reached statistical significance.
† Requested copy of study from author. Unable to obtain. Data entered from abstract only.
| Study, Year | Number of Trials | Number of Subjects (intervention/no intervention) | Intervention (30-day stroke percent) | Control (30-day stroke percent) | Outcomes (OR/RR with confidence interval) |
|---|---|---|---|---|---|
| 2003 | 53 (38 trials included data on stroke) | 34,126 (not noted/not noted) | Not noted | Not noted | OR, 0.55 (0.43-0.69) |
| 2005 | 37 (21 trials included data on stroke) | 2859 (1425 off-pump CABG versus 1434 conventional CABG) | 0.4 | 1.0 | OR, 0.68 (0.33-1.40) |
| 2011 | 10 (7 trials included data on stroke) | 15,034 (2887/12,147) | 0.38 | 1.87 | RR, 0.27 (0.14-0.53) |
| 2012 | 43 (21 trials included data on stroke) | 6336 (3196/3140) | Not noted | Not noted | OR, 0.80 (0.52-1.22) |
The existing meta-analyses in cardiac surgery compared conventional CABG and off-pump CABG in terms of global outcomes. Table 6-2 only addresses stroke. The 2003 and 2011 analyses included nonrandomized trials, but it was believed that the inclusion of these data did not bias their results.
The existing data on perioperative stroke in cardiac surgery are limited to multiple prospectively collected, retrospectively analyzed observational studies. One case control design and multiple retrospective studies are found in the literature. The data are summarized in Table 6-3 , and a small study by Bucerius and colleagues with similar surgical breakdown has been included for comparison. Also included at the end of the table are two recent larger prospective studies on thoracic aortic surgery because these studies likely best fit in the cardiac surgery category.
| Study, Year | Number of Subjects | Study Design | Stroke Incidence | Significant Risk Factors (Multivariate Analysis Unless Otherwise Noted) |
|---|---|---|---|---|
| 1992 | 130 | ?P | 3.85% | Protruding aortic arch atheroma (OR, 5.8; CI, 1.2-27.9) |
| 1996 | 189 | P | 4.76% by 1 wk postoperatively | Univariate analysis on aortic atheromatous grade by TEE: advancing aortic atheroma grade was a predictor of CVA ( p = 0.00001) |
| 1999 | 4518 | PO | 2.0% CVA; 0.7% TIA | Known cerebral vascular disease (OR, 2.5); renal failure (OR, 1.6); MI (OR, 1.5); DM (OR, 1.5); age > 70 (OR, 1.5); also associated with postoperative low EF and atrial fibrillation |
| 1999 | 2972 | PO | 1.6% (0.6% early and 1.0% delayed) | Early stroke (immediately after surgery): history of stroke (OR, 11.6); ascending aortic atherosclerosis (OR, 2.0); duration of cardiopulmonary bypass (OR, 1.1); female sex (OR, 6.9) Delayed stroke: history of stroke (OR, 27.6); DM (OR, 2.8); female sex (OR, 2.4); ascending aortic atherosclerosis (OR, 1.4); combined endpoints of atrial fibrillation and low cardiac output (OR, 1.7) |
| 2000 | 1987 CABG only 84 CABG and CEA | PO | 1.7% CABG; 4.7% combined | Age: 76 versus 71.9 yr (OR, 1.09); hypertension (OR, 2.67); extensively calcified aorta (OR, 2.82); prolonged bypass time (OR, 1.01; CI, 1.00-1.02) |
| 2000 | 472 | P | 3.4% | Severity of extracranial carotid artery stenosis (OR, 6.59) |
| 2000 | 19,224 | P | 1.4% | Calcified aorta (OR, 3.013); prior stroke (OR, 1.909); increasing age—null of 60 (OR, 1.522 per 10 yr); pre-existing carotid artery disease (OR, 1.590); duration of CPB (OR, 1.27 per 60 min); renal failure (OR, 2.032); PVD (OR, 1.62); cigarette smoking in past year (OR, 1.621); DM (OR, 1.373) |
| 2001 | 6682 | PO | 1.5% | Age > 70 (OR, 5.4); LVEF < 40% (OR, 4.1); history of CVA/TIA (OR, 3.0); normothermic CPB (OR, 2.2); DM (OR, 1.9); PVD (OR, 1.9) |
| 2001 | 16,528 | PO | 2.0% | CRI (OR, 2.8); recent MI (OR, 2.5); previous stroke (OR, 1.9); carotid artery disease (OR, 1.9) hypertension (OR, 1.6); DM (OR, 1.4); age > 75 yr (OR, 1.4); preoperative moderate/severe LV dysfunction (OR, 1.3); postoperative low cardiac output syndrome (OR, 2.1); postoperative atrial fibrillation (OR, 1.7) |
| 2002 | 2711 | PO | 2.7% | Past stroke (OR, 2.11); hypertension (OR, 1.97); age 65-75 (OR, 2.39); age ≥ 75 (OR, 5.02) |
| 2002 | 4077 (45 stroke cases; 4032 “no stroke” control subjects) | P, CC | 1.1% | Increasing age (OR, 1.06 per year); unstable angina (OR, 2.69); preoperative creatinine > 150 mcg/mL (OR, 2.64); previous CVA (OR, 2.26); pre-existing PVD (OR, 2.99); salvage operation (OR, 16.1) |
| 2003 | 2972 (1900 men; 1072 women) | PO | 2.8% women, 0.95% men ( p < 0.001) | Women: history of stroke (OR, 44.5); ascending aortic atherosclerosis (OR, 2.1); low cardiac output (OR, 6.7); DM (OR, 2.2) Men: history of stroke (OR, 305.8) |
| 2003 | 4567 | PO | 2.5% | Cerebrovascular disease (OR, 2.66); PVD (OR, 2.33); number of periods of aortic cross clamping (OR, 1.31 for each period); LV dysfunction (OR, 1.82); increased age (OR, 1.28 for each 10 years); nonelective surgery (OR, 1.83; p = 0.08) |
| 2003 | 11,825 | P | 1.5% | Prediction model incorporated known preoperative RFs: age, DM, urgent surgery, EF < 40%, creatinine ≥ 2.0; additional intraoperative and postoperative RFs: CPB 90-113 min (OR, 1.59), CPB ≥ 114 min (OR, 2.36), atrial fibrillation (OR, 1.82), prolonged ionotrope use (OR, 2.59) |
| 2003 | 16,184 total: group 1—8917 CABG only; group 2—1842 beating heart CABG; group 3—1830 aortic valve surgery; group 4—708 mitral valve surgery; group 5—381 multiple valve surgery; group 6—2506 CABG + valve surgery | PO | 4.6% overall; 3.8% in 1; 1.9% in 2; 4.8% in 3; 8.8% in 4; 9.7% in 5; 7.4% in 6 | History of CVD (OR, 3.55); PVD (OR, 1.39); DM (OR, 1.31); hypertension (OR, 1.27); urgent operation (OR, 1.47); preoperative infection (OR, 2.39); prior cardiac surgery (OR, 1.33); CPB time > 2 h (OR, 1.42); intraoperative hemofiltration (OR, 1.25); high transfusion requirement (OR, 6.04); beating heart CABG (OR, 0.53; CI, 0.37-0.77) |
| 2005 | 4380 | PO | 1.2% | History of stroke (OR, 6.3); DM (OR, 3.5); older age (OR, 1.1); temperature of CPB was insignificant |
| 2005 | 783 total: group 1—582 CABG only; group 2—101 single VR; group 3—70 combined CABG + VR; group 4—30 multiple VR | R | CVA and TIA: 1.7% in 1; 3.6% in 2; 3.3% in 3; 6.7% in 4 | Previous neurologic event (OR, 6.8); age > 70 (OR, 4.5); preoperative anemia (OR, 4.2); aortic atheroma (OR, 3.7); duration of myocardial ischemia (OR, 2.8); number of bypasses (OR, 2.3); LVEF < 0.35 (OR, 2.2); insulin-dependent DM (OR, 1.5) |
| 2006 | 810 | PO | CVA and TIA: 1.85% | Redo cardiac surgery (OR, 7.45); unstable cardiac status (OR, 4.74); history of cerebrovascular disease (OR, 4.14); PVD (OR, 3.55); preoperative use of statins (OR, 0.24; CI, 0.07-0.78) |
| 2007 | 5085 | PO | 2.6% | Female sex (OR, 1.7); age > 60 (OR, 1.2 per 5-yr interval); aortic surgery (OR, 3.9); previous stroke (OR, 2.1); critical preoperative state (OR, 2.5); poor ventricular function (OR, 2.0); DM (OR, 1.7); PVD (OR, 1.8); unstable angina (OR, 1.7); pulmonary hypertension (OR, 1.8) |
| 2007 | 720 | PO | 3.9% in men; 1.3% in women ( p = 0.066) | Prior cerebral infarction (OR, 1.987 per grade); atherosclerosis of ascending aorta (OR, 1.990 per grade) |
| 2011 | 9122 (7839 CABG, 297 off-pump CABG, 986 combined CABG and valve procedures) | PO | 2.7% (overall); 1.6% (early: on extubation); 1.1% (late: symptom-free period after extubation) | For early strokes: age ≥ 80 (OR, 5.63); creatinine >200 µmol/L (OR, 4.90); severe aortic wall calcification (OR, 5.32); CPB time >150 min (OR, 2.96) For late strokes: female sex (OR, 2.18); unstable angina (OR, 1.86); prior CVA (OR, 2.16); inotropic support (OR, 2.17); postoperative atrial fibrillation (OR, 2.56) |
| 2007 | 171 serial TEVAR cases | PO | 5.8% | Prior stroke (OR, 9.4); involvement of the proximal descending thoracic aorta (OR, 5.5); CT demonstrating severe atheromatous disease of aortic arch (OR, 14.8) |
| 2007 | 606 stent/graft cases | PO | 3.1% stroke; 2.5% paraplegia | Stroke: duration of the intervention (OR, 6.4); female sex (OR, 3.3) Paraplegia: left subclavian artery covering without revascularization (OR, 3.9); renal failure (OR, 3.6); concomitant open abdominal aorta surgery (OR, 5.5); three or more stent grafts used (OR, 3.5) |
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