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Ann Thorac Surg 1999;68:391-397
© 1999 The Society of Thoracic Surgeons

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Original Articles

Stroke in cardiac surgical patients: determinants and outcome

^a Zablocki VA Medical Center, Milwaukee, Wisconsin, USA
^b Medical College of Wisconsin, Milwaukee, Wisconsin, USA
^c VA Medical Center at Hines, Illinois, USA
^d VA Medical Center, Denver, Colorado, USA
^e VA Medical Center, Tucson, Arizona, USA

Address reprint requests to Dr Almassi, Division of Cardiothoracic Surgery, Medical College of Wisconsin, 9200 W. Wisconsin Ave, PO Box 26099, Milwaukee, WI 53226
e-mail: galmassi{at}mcw.edu

Presented at the Forty-fifth Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, November 12–14, 1998.

	Abstract

Top Abstract Introduction Material and methods Results Comment Appendix 1 Appendix 2 References

 
Background. Despite improving outcomes in cardiac surgical patients, stroke continues to remain a major complication. Few prospective studies are available on postoperative stroke. The present study was conducted to elucidate the incidence and predictors of stroke in a large group of cardiac surgical patients.

Methods and Results. Prospective data collected on 4,941 patients undergoing cardiac surgery were subjected to univariate and logistic regression analyses (98.4% men; 72% older than 60 years; 9.1% with history of prior stroke; 80.4% underwent isolated coronary artery bypass grafting). Stroke predictors include history of stroke and hypertension, older age, systolic hypertension, bronchodilator and diuretic use, high serum creatinine, surgical priority, great vessel repair, use of inotropic agents after cardiopulmonary bypass, and total cardiopulmonary bypass time (p < 0.05 for all comparisons). Median intensive care unit and hospital stays were longer, and hospital mortality and 6-month mortality were higher for patients with stroke (p < 0.001).

Conclusions. Stroke after cardiac surgical procedures is a morbid event. Identification of predictors and development of strategies to modify these factors should lead to a lower incidence of stroke.

	Introduction

Top Abstract Introduction Material and methods Results Comment Appendix 1 Appendix 2 References

 
Refinements and advances in anesthesia, surgical techniques, and myocardial preservation, as well as, postoperative monitoring and management, have led to a decline in morbidity and mortality for cardiac surgical patients. These advances have made it possible to extend the benefit of cardiac operations to older patients with good short- and long-term results [1, 2]. Stroke and neurologic complications, however, have remained unchanged, occurring in up to 6% of patients [3–6]. The incidence of cognitive and neuropsychological complications are much higher and may exceed 60% [7, 8].

Very few large scale prospective studies are available on the incidence of stroke and the contributing risk factors in cardiac surgical patients. There is also a lack of information on the long-term impact of stroke on patients after hospital discharge. Most studies are from a single institution, with one surgeon or a group of surgeons employing similar surgical techniques and protocols, thus introducing potential bias in the results. The current report is a special substudy of a large, multiinstitutional prospective observational study. This study was conducted to determine the incidence of perioperative stroke in a large group of patients undergoing a variety of open cardiac procedures in the Department of Veterans Affairs to identify the factors that have significant association with stroke and to evaluate its impact on patients’ outcome.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Appendix 1 Appendix 2 References

 
Processes, Structures, and Outcomes of Care in Cardiac Surgery [9] is a multicenter Department of Veterans Affairs cooperative study evaluating the impact of processes and structures of care on the outcome of surgery in patients undergoing open cardiac procedures at 14 participating Veterans Affairs Medical Centers (VAMC) (Appendix 1).Data for this observational study were prospectively collected by a dedicated research nurse at each participating institution. Approximately 1,500 variables were collected for each patient. For the present report, 112 variables were analyzed (Appendix 2).These included preoperative patient demographics, intraoperative practice parameters, and postoperative outcome measures.

Patients
Between September 9, 1992 and December 31, 1996, a total of 4,969 patients entered the study. This represents approximately 51.5% of patients undergoing cardiac surgery at participating institutions during the same period. Patients were selected using a systematic sample. Twenty-eight patients were excluded from the analysis because of lack of complete data (10 patients) or intraoperative death (18 patients). The final study population was 4,941 patients. The research nurse interviewed and examined each patient before surgery, as well as during the postoperative period. Patients also were seen in follow-up at 6 months by the research nurse, at which time, a detailed examination and appropriate laboratory tests were performed.

Definitions
History of cerebrovascular disease
This was defined as a history of symptomatic obstructive or atherosclerotic disease of the arteries either to the head, within the head, or both, as manifested by a previous stroke, transient ischemic attack, prior surgical repair, such as carotid endarterectomy, 50% luminal stenosis on contrast angiography, or duplex ultrasound examination, or a combination of these factors.

Stroke (CVA)
This was defined as any new neurologic deficit or deterioration lasting for more than 30 minutes.

Statistical methods
A total of 112 variables that included preoperative clinical and laboratory risk factors and perioperative processes of care and outcomes were evaluated for their possible association with postoperative stroke. The t test was used to compare values of continuous variables between patients who developed stroke versus those with no stroke. Comparisons of dichotomous or categoric variables used the ² test. The one-way analysis of variance was used to compare stroke rate for the type of cardiac surgery performed. The log rank test was used to compare intensive care unit (ICU) and postoperative lengths of stay. Patients who died in the ICU or before discharge from the hospital were excluded from these comparisons. All tests were two sided. Variables with p < 0.20 from these univariate analyses were selected for possible inclusion in a logistic regression analysis. These variables were entered into a stepwise logistic regression model. A p value of 0.05 was used to both enter and eliminate variables. The C index was used to evaluate the predictive power of the multiple logistic regression model [10]. The reliability of the model was assessed by the Hosmer-Lemeshow statistic [11]. The odds ratio (OR) and 95% confidence interval (CI) for each independent variable in the final regression model are presented.

	Results

Top Abstract Introduction Material and methods Results Comment Appendix 1 Appendix 2 References

 
Patient demographics are depicted in Table 1. The average age was 63.8 ± 9.5 (range 25–88 years). Patients older than 60 years constituted 72% of the study population (Fig 1). The majority were men (98.4%) and 9.1% had a history of prior stroke or transient ischemic attack (TIA). Table 2 lists the surgical procedures performed. Grouped under others in Table 2 are a variety of procedures such as ventricular aneurysm repair, aortic surgery, and cardiac transplantation.

View larger version (27K): [in this window] [in a new window]   Fig 1. Age distribution of patients. The majority are older (72%) than 60 years.

View larger version (19K): [in this window] [in a new window]   Fig 2. Postoperative stroke rate according to the surgical procedure. AVR = aortic valve replacement; CABG = coronary artery bypass grafting; MVR = mitral valve replacement.

View larger version (37K): [in this window] [in a new window]   Fig 3. Relation between increasing age and postoperative stroke rate.

View larger version (16K): [in this window] [in a new window]   Fig 4. Relation between the level of systolic blood pressure and stroke. Note that this is not a linear relationship.

	Comment

Top Abstract Introduction Material and methods Results Comment Appendix 1 Appendix 2 References

 
Central nervous system complications of cardiopulmonary bypass are very common. These range from subtle neuropsychiatric abnormalities, detected only with sophisticated tests, to frank and clinically evident neurologic deficit. A permanent neurologic deficit or stroke occurs in up to 6% of patients undergoing cardiac surgery [3, 12–14]. This is a dreadful complication for the surgeon and devastating to the patient. The incidence of stroke in the present series was 3.4%, which is similar to other reported series in the literature. Any new neurologic deficit that persisted for more than 30 min is regarded as a stroke in this report and, therefore, the incidence for permanent deficits may be lower.

The causes of stroke are multifactorial. In most reported series, advancing age has been identified as the single most important predictor of perioperative stroke [3, 5, 12, 14, 15]. Advancing age is associated with atherosclerosis and an increased risk of embolization [16]. Increasingly, the patients undergoing cardiac operations are older. In the CASS Registry data, 2.45% of patients were older than 70 years [17]. This group represents 31.5% of patients in the present series. The average age of our patients was 63.8 years, but the mean age was 68.1 years for patients who developed stroke (Table 1). The odds ratio for developing stroke was 1.36 for each additional decade of life. In Gardner’s series, patients 60 years of age or younger had a 3% stroke rate, which increased to 7.1% for patients 75 years or older [5]. Our data confirm the same trend of higher stroke rate for older patients. Patients below 60 years of age had a 1.6% incidence of stroke that increased to 5.25% for patients above 70 years (Fig 3). Although we did not have information on the use of intraoperative epiarotic ultrasonography in this study, we recommend its routine use in the operating room to identify patients with aortic atherosclerosis that would require alteration and modification of surgical techniques for prevention of embolic stroke.

A history of prior stroke or cerebrovascular disease is a strong predictor of recurrent stroke [3, 5, 15]. Such a history denotes the existence of pathologic conditions within the cerebrovascular system. The recurrent stroke is usually at a different site in those patients with a remote (> 3 months) prior stroke [18]. History of prior stroke was the strongest preoperative predictor in the present series, with an odds ratio of 2.20. On boot strapping, this variable was present in 98% of the models. The incidence of new stroke in this group of patients was 7.81%. Rorich and Furlan reported a 13.4% incidence for new stroke [18]. Shaw and associates observed a 7.7% incidence of stroke in this group of patients versus 2.3% in patients without prior history of stroke [19].

Patients with a history of hypertension, and those with elevated systolic blood pressure above 120 mm Hg, were found to be at an increased risk for perioperative stroke (OR = 1.52 and 1.84, respectively). Isolated systemic hypertension was found to be a risk factor for stroke in older patients by the Systolic Hypertension in the Elderly Program Cooperative Research Group [16]. Over-zealous reduction of blood pressure in hypertensive patients may precipitate an ischemic stroke [20]. Therefore, in this group of patients, management of blood pressure in the perioperative period is very critical.

Use of bronchodilators within 2 weeks of cardiac operation proved to be a predictor for stroke (OR = 1.58). The need for bronchodilators implies advanced or significant pulmonary disease. The reason, though, for the association between stroke and bronchodilator therapy is not clear to us. We can speculate that these patients have markedly elevated hemoglobin that might predispose them to stroke, but unlike the Shaw and associates report [19], the level of hemoglobin in the present study was not a significant risk factor for stroke. Alternatively, excessive carbon dioxide retention with its associated changes in cerebral vasoreactivity may have predisposed this group of patients to a higher risk of stroke [15]. A significant association between a history of pulmonary disease and postoperative stroke was found in the prospective multicenter study of Newman and associates [15] and Roach and associates [3].

Operations on great vessels, and as a result of an intraoperative complication, carried a high risk for stroke (OR = 4.78). This is understandable as these procedures would have required a longer cardiopulmonary bypass time, itself a marker for increased stroke rate, as well as the fact that more chances existed for air or particulate embolization. We are not aware of other reports in the literature regarding this strong association between repair of great vessels and perioperative stroke.

The total time spent on cardiopulmonary bypass was another predictor of stroke (OR = 1.47). The longer the time, the higher the probability for stroke. The long pump time may denote technical difficulties in executing the planned operation, unfavorable anatomy, surgical inexperience, or intraoperative complications. The stroke rate between participating institutions varied between 1.7% and 9%. There was a trend for longer cardiopulmonary bypass time for institutions with a higher stroke rate, but this was not statistically significant (p > 0.05). The strong association between prolonged cardiopulmonary bypass time and major stroke has been found by other investigators as well [4, 5, 12, 21].

Postoperative atrial fibrillation was significantly related to stroke on univariate analysis (p < 0.001), but because of lack of information regarding the onset of atrial fibrillation and stroke, this variable was not entered into the logistic regression model. We have previously reported the high association between postoperative atrial fibrillation and stroke in this group of patients [22]. Such a close relationship between postoperative atrial fibrillation and stroke calls for immediate therapeutic interventions to terminate this rhythm abnormality and to consider prophylactic anticoagulation protocol for prevention of embolic stroke [23].

Strengths and limitations
The strengths of our report include its prospective, multicenter design, a dedicated, trained research nurse evaluating each patient, and collection of a large body of data for each patient. Rigorous evaluation of data and multiple cleansing of the data prevented entrance of marginally significant variables into the final analyses. Limitations of the study include: (1) lack of information about exact timing of postoperative events and, as such, we were not able to establish a temporal relation between stroke and these events; (2) majority of patients were men (98.4%), therefore, we were not able to evaluate the effect of gender, if any, on the incidence of postoperative stroke; and (3) lack of information regarding severity, type, and location of stroke. The study, however, has the advantage of a 6-month follow-up showing an increased mortality for patients with stroke who were discharged from the hospital.

In conclusion, stroke after cardiac surgical procedures remains a serious and morbid complication with a high mortality rate. Several patient-associated risk factors, as well as surgical practice parameters, were identified as predictors of stroke. Postoperative atrial fibrillation is a contributing factor. Modification of patient-related factors and changes in surgical procedures to alter the practice-related predictors as well as careful management of blood pressure and maintenance of a sinus rhythm in the postoperative period should lead to a reduction in postoperative stroke rate.

	Acknowledgments

 
Supported by the Department of Veterans Affairs Cooperative Studies Program as CSHS 5, Processes, Structures, and Outcomes of Care in Cardiac Surgery.

	Appendix 1

Top Abstract Introduction Material and methods Results Comment Appendix 1 Appendix 2 References

 
Participating VA Medical Centers in PSOCS Study

Institution Participants Denver, CO Karl E. Hammermeister, MD (Co-Chairman) Frederick L. Grover, MD (Co-Chairman) Principal Investigator/Research Nurse Ann Arbor, MI Marvin M. Kirsh, MD/Connie Newman, RN Asheville, NC John Lucke, MD/Sheryl P. Davis, RN Charleston, SC John R. Handy, MD/Lisa A. Colton, RN Denver, CO David A. Fullerton, MD/Janet Baltz, RN Hines, IL Donald J. DePinto, MD/Louise M. Barder, RN Little Rock, AR Kwabena Mawulawde, MD/Michael Smith, RN Milwaukee, WI G. Hossein Almassi, MD/Tracy K. Sommers, RN Minneapolis, MN Herbert B. Ward, MD/Ellie Carson, RN Nashville, TN Walter H. Merrill, MD/James Shaw, RN New York, NY Richard A. Esposito, MD/Rosemary A. Mannix, RN San Antonio, TX O. LaWayne Miller, MD/Marina Silguero, RN San Diego, CA Riyad Y. Tarazi, MD/Cecilia Garcia, RN Tucson, AZ Gulshan K. Sethi, MD/Gayle Murad, RN West Roxbury, MA Shukri F. Khuri, MD/Janet E. Bannister, RN Coordinators and Consultants Hines, IL William G. Henderson, PhD (Director) (Coordinating Center) Thomas E. Moritz, MS (Biostatistician) Nancy K. Ellis, MS (National Data Coordinator) Raslan O. Othman, MS (Systems Analyst) Lizy G. Thottapurathu, MS (Statistical Programmer) Denver, CO A. Laurie W. Shroyer, PhD (Health Services Researcher) Catherine B. VillaNueva, RN (National Research Nurse Coordinator) Samantha MaWhinney, ScD (Biostatistian) Martin J. London, MD (Anesthesia Consultant) Northwestern University, Chicago, IL Martin J. McCarthy Jr, PhD (Health Research Scientist)

CPB = cardiopulmonary bypass; CVD = cerebrovascular disease;HTN = hypertension; SPB = systolic blood pressure.

	Appendix 2

Top Abstract Introduction Material and methods Results Comment Appendix 1 Appendix 2 References

 
Variables analyzed with univariate analysis

Age ECG MI Lowest hematocrit post-CPB Sex (Male) Resting ST segment depression Use of safety features in CPB circuit Height Severity of aortic stenosis Weight Surgical priority Use of membrane oxygenator ADL functional class Preop use of IABP Lowest mean arterial pressure Mobility status Use of narcotics Type of CPB pump Systolic blood pressure Use of benzodiazapines Urine output during CPB Diastolic blood pressure Use of muscle relaxants Difficulty weaning from CPB Pulse Use of volatile agents Need for IABP History of cerebrovascular disease Cardiac arrest requring CPB within 24 h preceding surgery Need for ventricular assist device History of peripheral vascular disease Excessive bleeding requiring > 4 units packed red cells History of COPD Total CPB time (h) Angina functional class Ischemic time (h) Return to CPB requiring reheparinization New York Heart Association function class Method of cardioplegia Cold antegrade cardioplegia Accidental cut of previous IMA or vein graft Diabetes No cardiac venting techniques used Glucose Warm antegrade cardioplegia Accidental cardiac perforation Prior heart surgery Topical ice slush Great vessel injury prolonging the operation Prior MI Topical cold saline Beta blocker use preop Heart jacket Takedown and redo of distal anastomoses Digoxin use within 2 weeks Any myocardial temperature monitoring Diuretic use within 2 weeks Difficulty in valve replacement increasing the pump time Calcium channel blocking agent use Myocardial pH monitoring Bronchodilator therapy within 2 weeks of surgery Composition of cardioplegia Difficulty in valve repair increasing the pump time Cardiac venting techniques: aorta Nitroglycerin use within 2 weeks of surgery Cardiac venting techniques: left ventricle via right superior pulmonary vein Air embolism from operative field Air embolism originating outside operative field Use of aspirin within 1 weeks of surgery Left ventricle apex vented Other perfusion complications Hemoglobin Left atrium right superior pulmonary vein Cardiac arrest in OR before cannulation or after removal of cannulae Cardiomegaly Creatinine Pulmonary artery vented Pulmonary rales Aortic valve replacement Anesthesia complications Smoking pack years Mitral valve replacement Transfusion reactions requiring therapy Alcohol abuse Tricuspid valve replacement Current smoker Tricuspid valve repair Chest left open after surgery Left bundle branch block Aortic valve repair Reaction to protamine requiring inotropic support Hx of liver disease Mitral valve repair Hepatomegaly LV aneurysmectomy Other major complications Permanent pacemaker Great vessel repair Hospital stay Long acting nitrates used Coronary bypass grafting Readmission to ICU Pulmonary or alveolar infiltrate Lowest myocardial temperature Persistent CHF systems Left ventricular hypertrophy Lowest systemic temperature Perioperative MI Pleural effusion Inotropic agents/devices used for 30 min Atrial fibrillation Pulmonary venous engorgement Reintubation

CPB = cardiopulmonary bypass; CVD = cerebrovascular disease;HTN = hypertension; SPB = systolic blood pressure.

ADL = activity of daily living; COPD = chronic obstructive pulmonary disease; CPB = cardiopulmonary bypass; IABP = intraaortic balloon pump; MI = myocardial infarction.

	References

Top Abstract Introduction Material and methods Results Comment Appendix 1 Appendix 2 References

 

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				C. Schmitz and E. H. Blackstone International Council of Emboli Management (ICEM) Study Group results: risk adjusted outcomes in intraaortic filtration Eur. J. Cardiothorac. Surg., November 1, 2001; 20(5): 986 - 991. [Abstract] [Full Text] [PDF]

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				J. C. Cleveland Jr, A. L. W. Shroyer, A. Y. Chen, E. Peterson, and F. L. Grover Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity Ann. Thorac. Surg., October 1, 2001; 72(4): 1282 - 1289. [Abstract] [Full Text] [PDF]

T. M. Dewey, M. J. Magee, J. R. Edgerton, M. Mathison, D. Tennison, and M. J. Mack Off-pump bypass grafting is safe in patients with left main coronary disease Ann. Thorac. Surg., September 1, 2001; 72(3): 788 - 792. [Abstract] [Full Text] [PDF]