Natalia S. Ivascu, MD, Mario Gaudino, MD, Christopher Lau, MD, Alan Z. Segal, MD, William J. Debois, CCP, MBA, Monica Munjal, MS, and Leonard N. Girardi, MD Departments of Anesthesiology, Cardiothoracic Surgery, and Neurology, New York Presbyterian Hospital, Weill Cornell Medical College, New York, New York
Background. Postoperative seizure (PS) is an infrequent, yet distressing, complication after cardiac surgery. We wished to determine the prognostic significance of these complicated neurologic events. Methods. The Weill Cornell Medical College Department of Cardiothoracic Surgery database and the New York State Department of Health Database were reviewed to identify all patients having PS after cardiac surgery between January 1, 2008, and December 31, 2011. Results. During the study period 3,518 patients had cardiac surgery at the index hospital; 45 of them had PS (1.27%). Overall, patients having PS had a significant increase in 30-day mortality when compared with those not having PS (6.7% versus 1.5%; p < 0.006). The incidence of major postoperative complications in those having PS was also significantly higher (53.3% versus 10.5%; p < 0.001). However, logistic regression failed to demonstrate PS as an independent predictor of perioperative
mortality. When the PS group was further stratified by the presence or absence of cerebrovascular accident, those having both PS and cerebrovascular accident had substantially increased morbidity and mortality (mortality, 0 of 33 versus 3 of 12; major morbidity, 12 of 12 versus 12 of 33; p < 0.01 for both), whereas PS patients without cerebrovascular accident did not have greater risk for either major adverse events or mortality. Conclusions. When PS is associated with acute cerebrovascular accident, a significant increase in postoperative morbidity and mortality can be expected. However, in those with isolated PS (without evidence of new neurologic injury), perioperative mortality and morbidity are comparable to those without any neurologic complications.
N
Murkin and associates [5] reported a series of 24 patients experiencing PS, of which 21 had no evidence of ischemic injury. All of the reported patients had full neurologic recovery and had otherwise uneventful postoperative courses [5]. Conversely, Goldstone and colleagues [6] reported that patients with PS had worse outcomes, including a fivefold increase in hospital mortality. Contradictions in the literature stimulated us to examine our own experience with acute seizure after cardiac surgery in the hopes of elucidating the prognostic implications of PS.
eurologic complications after cardiac surgery include a variety of different clinical presentations. Stroke, short- and long-term memory dysfunction, delirium, cognitive decline, and transient neurologic dysfunction all represent varying degrees of neurologic injury that can impact perioperative outcomes and long-term survival and quality of life [1–4]. To date a considerable amount of evidence exists regarding stroke and postoperative neurologic dysfunction. Although different risk factors have been linked to postoperative seizure (PS), including aortic atherosclerosis, cardiopulmonary bypass time, use of deep hypothermic circulatory arrest, and, most notably, high-dose tranexamic acid, these associations have not been consistent among published studies [5–9]. Far less is known about the incidence, risk factors, and prognostic role of PS. Recently two studies focused on PS after cardiac surgery. Although the incidence of PS was similar in both groups (1.2% to 1.3%), these studies drew conflicting conclusions on the importance of PS with respect to postoperative morbidity and mortality [5, 6].
Accepted for publication Feb 26, 2015. Address correspondence to Dr Ivascu, Department of Clinical Anesthesiology, 525 E 68th St, G 4313d, New York, NY 10065; e-mail: nib9009@ med.cornell.edu.
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2015;100:101–6) Ó 2015 by The Society of Thoracic Surgeons
Material and Methods The primary end point of this study was evaluation of the effect of PS on postoperative mortality. Analysis of the effect of PS on postoperative morbidity and definition of the determinants of PS were secondary end points. The Weill Cornell Medical College Department of Cardiothoracic Surgery’s contribution to the New York State Department of Health Database was reviewed to identify all patients having PS after cardiac surgery from January 2008 to December 2011. Our database is contemporaneously updated and maintained by clinical information analysts. Data collection is validated by means of external and internal controls. Our data are then 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.02.077
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Nonischemic Postoperative Seizure Does Not Increase Mortality After Cardiac Surgery
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further validated by the New York State Department of Health before it is included in the state-mandated Cardiac Surgery Database. Preoperative and postoperative variables are entered prospectively during and immediately after a patient’s hospital stay. The electronic inpatient hospital medical record is also queried to gather additional variables on patients identified as having PS. The Weill Cornell Medical College Institutional Review Board approved this study and waived the need for individual patient consent. Patients were included in the PS group if they had cardiac surgery requiring cardiopulmonary bypass and had either convulsive seizure activity or evidence of nonconvulsive seizure activity documented by electroencephalogram. Patients with a preexisting seizure disorder or those on preoperative anticonvulsant medication were excluded from this analysis. A consulting neurologist confirmed the diagnosis of PS in all cases. All patients experiencing PS were treated immediately with antiepileptic medications. Hemodynamically stable PS patients had a noncontrast head computed tomography once their seizure event resolved. A computed tomography scan was obtained in a delayed fashion in those too hemodynamically unstable for transport at the conclusion of the seizure. Antiepileptic medications were continued throughout the patient’s hospital stay and were discontinued by the neurologist at outpatient follow-up.
Anesthetic and Surgical Technique All patients underwent induction of anesthesia with midazolam, fentanyl, and either propofol or thiopental. Type of neuromuscular blockade (rocuronium, cisatracurium, or vecuronium) varied depending on the choice of the anesthesiologist. All patients were given 10-g loading dose of aminocaproic acid followed by an infusion of 1 g/h for the duration of the case. Patients undergoing deep hypothermic circulatory arrest (DHCA) or reoperative sternotomy were given an infusion of 2 g/h. Anesthesia was maintained throughout surgery with fentanyl and volatile anesthetic, according to standard protocol. Patients had a complete transesophageal echocardiographic assessment examination of their heart and aorta; aortic atherosclerosis was graded according to previously reported guidelines [10, 11]. Mean arterial pressure during cardiopulmonary bypass was maintained between 70 and 90 mm Hg, and the hematocrit was maintained at greater than 20%. Patients having cardiac surgery without the need for DHCA were cooled to a minimum temperature between 25 and 32 C during the period of cardiac arrest. Those requiring DHCA were cooled for a minimum of 30 minutes until the bladder or tympanic temperature reached 18 C; in all DHCA cases retrograde cerebral perfusion through the superior vena cava was used and thiopental (1,000 mg) or methohexital (500 mg) were given before commencing circulatory arrest [12]. Patients were warmed until a bladder temperature of 35 C was obtained. During the warming period a maximal temperature gradient of 10 C was maintained between the perfusate and the patient’s bladder temperature. An alpha-stat strategy was used for
Ann Thorac Surg 2015;100:101–6
acid-base management in all patients. Removal of air from the bypass circuit was performed according to standard techniques and was judged adequate on the basis of the absence of air within the cardiac chambers on intraoperative transesophageal echocardiography.
Statistical Analysis Data were analyzed using IBM SPSS Statistics version 22 (IBM, Corp, Armonk, NY). Comparison of various subgroups was made using c2 test and Fisher’s exact test for categorical variables as appropriate. The Student’s t test was used for the comparison of the continuous variables. To analyze the subgroups and determine the factors contributing to mortality and PS, multivariable logistic regression was used. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All tests required an alpha less than 0.05 for significance. Preoperative and intraoperative factors considered in the logistic regression were age, sex, surgical priority, Canadian Cardiovascular Society angina class, preoperative ejection fraction, preoperative serum creatinine, coronary artery disease, valvular disease, previous cardiac surgery, previous myocardial infarction, cerebrovascular disease, peripheral vascular disease, hemodynamic status at time of surgery, past or present congestive heart failure, chronic lung disease, aortic atherosclerosis, diabetes, renal and hepatic insufficiency, active endocarditis, and use of DHCA as defined in the New York State Department of Health Database. Postoperative factors considered were stroke (cerebrovascular accident [CVA]), Q wave myocardial infarction, deep sternal wound infection, reexploration for bleeding, sepsis, gastrointestinal events, dialysis-dependent renal failure, tracheal intubation longer than 72 hours, and unplanned cardiac reoperation or interventional procedure. All deaths occurring before hospital discharge or within 30 days of surgery were included as mortality.
Results A total of 3,518 patients had cardiac surgery during the study period. Forty-five of them had PS (1.27%). Preoperative characteristics are presented in Table 1. The PS group had a significantly greater percentage that were male, a greater percentage with advanced Canadian Cardiovascular Society class, worse renal function, a higher percentage of valvular heart disease, more previous open heart procedures, and higher incidences of endocarditis and current and previous congestive heart failure. Postoperative morbidity and mortality is demonstrated in Table 2. Patients with PS had a substantially higher incidence of early (10 of 45, 22.2% versus 10 of 3473, 0.3%; p < 0.001) and late CVA (2 of 45, 4.4% versus 25 of 3,473, 0.7%; p < 0.001) after surgery. They had a greater need for hemodialysis (4 of 45, 8.9% versus 61 of 3,473, 1.8%; p < 0.001) and prolonged respiratory support (20 of 45, 20% versus 206 of 3,473, 5.9%; p < 0.001) after surgery. Thirty-day and inhospital unadjusted mortality was significantly greater
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103 ADULT CARDIAC
Ann Thorac Surg 2015;100:101–6
Table 1. Characteristics of the Overall Population and According to the Occurrence of Seizuresa Subgroups Variable
Entire Cohort (n ¼ 3,518)
Seizures (n ¼ 45)
No Seizures (n ¼ 3,473)
66.15 14.38 2,274 (64.6)
70.98 13.8 22 (48.9)
66.09 14.38 2,252 (64.8)
0.575 0.026
2,036 (57.9) 1,482 (42.1)
23 (51.1) 22 (48.8)
2,013 (57.9) 1,460 (42)
0.610
714 (20.3) 0.49 0.12 1.23 1.77 1,577 (44.8) 2,253 (64) 497 (14.1) 16 (0.5) 594 (16.9) 357 (10.1) 900 (25.6) 60 (1.7) 25 (0.7) 1,107 (31.5) 585 (16.6) 281 (8) 183 (5.2) 694 (19.7) 7 (0.2) 96 (2.7) 65 (1.8)
17 (37.8) 0.48 0.14 2.75 6.34 22 (48.9) 38 (84.4) 18 (40) 0 (0) 8 (17.8) 8 (17.8) 12 (26.7) 1 (2.2) 0 (0) 21 (46.7) 17 (37.8) 4 (8.9) 5 (11.1) 8 (17.8) 0 (0) 3 (6.7) 3 (6.7)
697 (20.1) 0.49 0.12 1.21 1.62 1,555 (44.8) 2,215 (63.8) 479 (13.8) 16 (0.05) 586 (16.9) 349 (10) 888 (25.6) 59 (1.7) 25 (0.7) 1,086 (31.3) 568 (16.4) 277 (8) 178 (5.1) 686 (19.8) 7 (0.2) 93 (2.7) 62 (1.8)
0.011 0.084
Background. Postoperative seizure (PS) is an infrequent, yet distressing, complication after cardiac surgery. We wished to determine the prognostic significance of these complicated neurologic events. Methods. The Weill Cornell Medical College Department of Cardiothoracic Surgery database and the New York State Department of Health Database were reviewed to identify all patients having PS after cardiac surgery between January 1, 2008, and December 31, 2011. Results. During the study period 3,518 patients had cardiac surgery at the index hospital; 45 of them had PS (1.27%). Overall, patients having PS had a significant increase in 30-day mortality when compared with those not having PS (6.7% versus 1.5%; p < 0.006). The incidence of major postoperative complications in those having PS was also significantly higher (53.3% versus 10.5%; p < 0.001). However, logistic regression failed to demonstrate PS as an independent predictor of perioperative
mortality. When the PS group was further stratified by the presence or absence of cerebrovascular accident, those having both PS and cerebrovascular accident had substantially increased morbidity and mortality (mortality, 0 of 33 versus 3 of 12; major morbidity, 12 of 12 versus 12 of 33; p < 0.01 for both), whereas PS patients without cerebrovascular accident did not have greater risk for either major adverse events or mortality. Conclusions. When PS is associated with acute cerebrovascular accident, a significant increase in postoperative morbidity and mortality can be expected. However, in those with isolated PS (without evidence of new neurologic injury), perioperative mortality and morbidity are comparable to those without any neurologic complications.
N
Murkin and associates [5] reported a series of 24 patients experiencing PS, of which 21 had no evidence of ischemic injury. All of the reported patients had full neurologic recovery and had otherwise uneventful postoperative courses [5]. Conversely, Goldstone and colleagues [6] reported that patients with PS had worse outcomes, including a fivefold increase in hospital mortality. Contradictions in the literature stimulated us to examine our own experience with acute seizure after cardiac surgery in the hopes of elucidating the prognostic implications of PS.
eurologic complications after cardiac surgery include a variety of different clinical presentations. Stroke, short- and long-term memory dysfunction, delirium, cognitive decline, and transient neurologic dysfunction all represent varying degrees of neurologic injury that can impact perioperative outcomes and long-term survival and quality of life [1–4]. To date a considerable amount of evidence exists regarding stroke and postoperative neurologic dysfunction. Although different risk factors have been linked to postoperative seizure (PS), including aortic atherosclerosis, cardiopulmonary bypass time, use of deep hypothermic circulatory arrest, and, most notably, high-dose tranexamic acid, these associations have not been consistent among published studies [5–9]. Far less is known about the incidence, risk factors, and prognostic role of PS. Recently two studies focused on PS after cardiac surgery. Although the incidence of PS was similar in both groups (1.2% to 1.3%), these studies drew conflicting conclusions on the importance of PS with respect to postoperative morbidity and mortality [5, 6].
Accepted for publication Feb 26, 2015. Address correspondence to Dr Ivascu, Department of Clinical Anesthesiology, 525 E 68th St, G 4313d, New York, NY 10065; e-mail: nib9009@ med.cornell.edu.
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2015;100:101–6) Ó 2015 by The Society of Thoracic Surgeons
Material and Methods The primary end point of this study was evaluation of the effect of PS on postoperative mortality. Analysis of the effect of PS on postoperative morbidity and definition of the determinants of PS were secondary end points. The Weill Cornell Medical College Department of Cardiothoracic Surgery’s contribution to the New York State Department of Health Database was reviewed to identify all patients having PS after cardiac surgery from January 2008 to December 2011. Our database is contemporaneously updated and maintained by clinical information analysts. Data collection is validated by means of external and internal controls. Our data are then 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.02.077
ADULT CARDIAC
Nonischemic Postoperative Seizure Does Not Increase Mortality After Cardiac Surgery
ADULT CARDIAC
102
IVASCU ET AL POSTOPERATIVE SEIZURE AND MORTALITY
further validated by the New York State Department of Health before it is included in the state-mandated Cardiac Surgery Database. Preoperative and postoperative variables are entered prospectively during and immediately after a patient’s hospital stay. The electronic inpatient hospital medical record is also queried to gather additional variables on patients identified as having PS. The Weill Cornell Medical College Institutional Review Board approved this study and waived the need for individual patient consent. Patients were included in the PS group if they had cardiac surgery requiring cardiopulmonary bypass and had either convulsive seizure activity or evidence of nonconvulsive seizure activity documented by electroencephalogram. Patients with a preexisting seizure disorder or those on preoperative anticonvulsant medication were excluded from this analysis. A consulting neurologist confirmed the diagnosis of PS in all cases. All patients experiencing PS were treated immediately with antiepileptic medications. Hemodynamically stable PS patients had a noncontrast head computed tomography once their seizure event resolved. A computed tomography scan was obtained in a delayed fashion in those too hemodynamically unstable for transport at the conclusion of the seizure. Antiepileptic medications were continued throughout the patient’s hospital stay and were discontinued by the neurologist at outpatient follow-up.
Anesthetic and Surgical Technique All patients underwent induction of anesthesia with midazolam, fentanyl, and either propofol or thiopental. Type of neuromuscular blockade (rocuronium, cisatracurium, or vecuronium) varied depending on the choice of the anesthesiologist. All patients were given 10-g loading dose of aminocaproic acid followed by an infusion of 1 g/h for the duration of the case. Patients undergoing deep hypothermic circulatory arrest (DHCA) or reoperative sternotomy were given an infusion of 2 g/h. Anesthesia was maintained throughout surgery with fentanyl and volatile anesthetic, according to standard protocol. Patients had a complete transesophageal echocardiographic assessment examination of their heart and aorta; aortic atherosclerosis was graded according to previously reported guidelines [10, 11]. Mean arterial pressure during cardiopulmonary bypass was maintained between 70 and 90 mm Hg, and the hematocrit was maintained at greater than 20%. Patients having cardiac surgery without the need for DHCA were cooled to a minimum temperature between 25 and 32 C during the period of cardiac arrest. Those requiring DHCA were cooled for a minimum of 30 minutes until the bladder or tympanic temperature reached 18 C; in all DHCA cases retrograde cerebral perfusion through the superior vena cava was used and thiopental (1,000 mg) or methohexital (500 mg) were given before commencing circulatory arrest [12]. Patients were warmed until a bladder temperature of 35 C was obtained. During the warming period a maximal temperature gradient of 10 C was maintained between the perfusate and the patient’s bladder temperature. An alpha-stat strategy was used for
Ann Thorac Surg 2015;100:101–6
acid-base management in all patients. Removal of air from the bypass circuit was performed according to standard techniques and was judged adequate on the basis of the absence of air within the cardiac chambers on intraoperative transesophageal echocardiography.
Statistical Analysis Data were analyzed using IBM SPSS Statistics version 22 (IBM, Corp, Armonk, NY). Comparison of various subgroups was made using c2 test and Fisher’s exact test for categorical variables as appropriate. The Student’s t test was used for the comparison of the continuous variables. To analyze the subgroups and determine the factors contributing to mortality and PS, multivariable logistic regression was used. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All tests required an alpha less than 0.05 for significance. Preoperative and intraoperative factors considered in the logistic regression were age, sex, surgical priority, Canadian Cardiovascular Society angina class, preoperative ejection fraction, preoperative serum creatinine, coronary artery disease, valvular disease, previous cardiac surgery, previous myocardial infarction, cerebrovascular disease, peripheral vascular disease, hemodynamic status at time of surgery, past or present congestive heart failure, chronic lung disease, aortic atherosclerosis, diabetes, renal and hepatic insufficiency, active endocarditis, and use of DHCA as defined in the New York State Department of Health Database. Postoperative factors considered were stroke (cerebrovascular accident [CVA]), Q wave myocardial infarction, deep sternal wound infection, reexploration for bleeding, sepsis, gastrointestinal events, dialysis-dependent renal failure, tracheal intubation longer than 72 hours, and unplanned cardiac reoperation or interventional procedure. All deaths occurring before hospital discharge or within 30 days of surgery were included as mortality.
Results A total of 3,518 patients had cardiac surgery during the study period. Forty-five of them had PS (1.27%). Preoperative characteristics are presented in Table 1. The PS group had a significantly greater percentage that were male, a greater percentage with advanced Canadian Cardiovascular Society class, worse renal function, a higher percentage of valvular heart disease, more previous open heart procedures, and higher incidences of endocarditis and current and previous congestive heart failure. Postoperative morbidity and mortality is demonstrated in Table 2. Patients with PS had a substantially higher incidence of early (10 of 45, 22.2% versus 10 of 3473, 0.3%; p < 0.001) and late CVA (2 of 45, 4.4% versus 25 of 3,473, 0.7%; p < 0.001) after surgery. They had a greater need for hemodialysis (4 of 45, 8.9% versus 61 of 3,473, 1.8%; p < 0.001) and prolonged respiratory support (20 of 45, 20% versus 206 of 3,473, 5.9%; p < 0.001) after surgery. Thirty-day and inhospital unadjusted mortality was significantly greater
IVASCU ET AL POSTOPERATIVE SEIZURE AND MORTALITY
103 ADULT CARDIAC
Ann Thorac Surg 2015;100:101–6
Table 1. Characteristics of the Overall Population and According to the Occurrence of Seizuresa Subgroups Variable
Entire Cohort (n ¼ 3,518)
Seizures (n ¼ 45)
No Seizures (n ¼ 3,473)
66.15 14.38 2,274 (64.6)
70.98 13.8 22 (48.9)
66.09 14.38 2,252 (64.8)
0.575 0.026
2,036 (57.9) 1,482 (42.1)
23 (51.1) 22 (48.8)
2,013 (57.9) 1,460 (42)
0.610
714 (20.3) 0.49 0.12 1.23 1.77 1,577 (44.8) 2,253 (64) 497 (14.1) 16 (0.5) 594 (16.9) 357 (10.1) 900 (25.6) 60 (1.7) 25 (0.7) 1,107 (31.5) 585 (16.6) 281 (8) 183 (5.2) 694 (19.7) 7 (0.2) 96 (2.7) 65 (1.8)
17 (37.8) 0.48 0.14 2.75 6.34 22 (48.9) 38 (84.4) 18 (40) 0 (0) 8 (17.8) 8 (17.8) 12 (26.7) 1 (2.2) 0 (0) 21 (46.7) 17 (37.8) 4 (8.9) 5 (11.1) 8 (17.8) 0 (0) 3 (6.7) 3 (6.7)
697 (20.1) 0.49 0.12 1.21 1.62 1,555 (44.8) 2,215 (63.8) 479 (13.8) 16 (0.05) 586 (16.9) 349 (10) 888 (25.6) 59 (1.7) 25 (0.7) 1,086 (31.3) 568 (16.4) 277 (8) 178 (5.1) 686 (19.8) 7 (0.2) 93 (2.7) 62 (1.8)
0.011 0.084
