G. Roach

Cerebral Injury After Cardiac Surgery Identification of a Group at Extraordinary Risk

BACKGROUND AND PURPOSE Cerebral injury after cardiac surgery is now recognized as a serious and costly healthcare problem mandating immediate attention. To effect solution, those subgroups of patients at greatest risk must be identified, thereby allowing efficient implementation of new clinical strategies. No such subgroup has been identified; however, patients undergoing intracardiac surgery are thought to be at high risk, but comprehensive data regarding specific risk, impact on cost, and discharge disposition are not available. METHODS We prospectively studied 273 patients enrolled from 24 diverse US medical centers, who were undergoing intracardiac and coronary artery surgery. Patient data were collected using standardized methods and included clinical, historical, specialized testing, neurological outcome and autopsy data, and measures of resource utilization. Adverse outcomes were defined a priori and determined after database closure by a blinded independent panel. Stepwise logistic regression models were developed to estimate the relative risks associated with clinical history and intraoperative and postoperative events. RESULTS Adverse cerebral outcomes occurred in 16% of patients (43/273), being nearly equally divided between type I outcomes (8.4%; 5 cerebral deaths, 16 nonfatal strokes, and 2 new TIAs) and type II outcomes (7.3%; 17 new intellectual deterioration persisting at hospital discharge and 3 newly diagnosed seizures). Associated resource utilization was significantly increased--prolonging median intensive care unit stay from 3 days (no adverse cerebral outcome) to 8 days (type I; P<0.001) and from 3 to 6 days (type II; P<0.001), and increasing hospitalization by 50% (type II, P=0.04) to 100% (type I, P<0.001). Furthermore, specialized care after hospital discharge was frequently necessary in those with type I outcomes, in that only 31% returned home compared with 85% of patients without cerebral complications (P<0.001). Significant risk factors for type I outcomes related primarily to embolic phenomena, including proximal aortic atherosclerosis, intracardiac thrombus, and intermittent clamping of the aorta during surgery. For type II outcomes, risk factors again included proximal aortic atherosclerosis, as well as a preoperative history of endocarditis, alcohol abuse, perioperative dysrhythmia or poorly controlled hypertension, and the development of a low-output state after cardiopulmonary bypass. CONCLUSIONS These prospective multicenter findings demonstrate that patients undergoing intracardiac surgery combined with coronary revascularization are at formidable risk, in that 1 in 6 will develop cerebral complications that are frequently costly and devastating. Thus, new strategies for perioperative management--including technical and pharmacological interventions--are now mandated for this subgroup of cardiac surgery patients.

The Risk of Myocardial Ischemia in Patients Receiving Desflurane versus Sufentanil Anesthesia for Coronary Artery Bypass Graft Surgery

Desflurane, a coronary vasodilator, may induce myocardial ischemia in patients with coronary artery disease. To determine whether desflurane is safe to administer to the at-risk patient population (with known coronary artery disease), we compared the incidence and characteristics of perioperative myocardial ischemia in 200 patients undergoing coronary artery bypass graft (CABG) surgery randomly assigned to receive desflurane (thiopental adjuvant) versus sufentanil anesthesia. Under conditions of hemodynamic control, perioperative ischemia was assessed using continuous echocardiography (precordial: during induction; transesophageal: during surgery) and Holter electrocardiography (ECG); hemodynamics (including pulmonary artery pressure) were measured continuously. Hemodynamic results: During induction, no significant changes in hemodynamics occurred in the sufentanil group, while in the desflurane group, heart rate, systemic and pulmonary arterial pressure increased and stroke volume decreased significantly. During the intraoperative period, the incidence of hemodynamic variations was low in both anesthetic groups; however, the prebypass incidence of tachycardia (greater than 120% of preoperative baseline heart rate) was greater in the desflurane group (4 +/- 7% of total time monitored) than in the sufentanil group (1 +/- 6%) (P = 0.0003). Similarly, the incidence of prebypass hypotension (less than 80% of preoperative baseline systolic arterial blood pressure) was greater in the desflurane group (21 +/- 14%) than in the sufentanil group (15 +/- 16%) (P = 0.01). ECG results: Preoperatively, 15% (28/191) of patients developed ECG ischemia, with no difference between patients who received desflurane, 13% (12/96) or sufentanil, 16% (16/95) (P = 0.6). During anesthetic induction, 9% (9/99) of patients who received desflurane developed ECG ischemia, compared with 0% (0/98) who received sufentanil (P = 0.007). During the prebypass period, 5% (10/197) of patients developed ECG ischemia, with no difference between patients who received desflurane, 7% (7/99) or sufentanil, 3% (3/98) (P = 0.3). Postbypass, 12% (24/194) of patients developed ECG ischemic changes, with no difference between patients who received desflurane, 13% (13/97) or sufentanil, 11% (11/96) (P = 0.9). Echocardiographic results: The incidence of precordial echocardiographic ischemia during anesthetic induction was 13% (5/39) in the desflurane group versus 0% (0/29) in the sufentanil group (P = 0.1). Moderate to severe transesophageal echocardiographic (TEE) ischemic episodes occurred in 12% (21/175) of patients during prebypass, with no significant difference between the desflurane group, 16% (15/91) and the sufentanil group, 7% (6/84) (P = 0.09). TEE ischemic episodes occurred in 27% (49/178) of patients during the postbypass period, with no difference between the desflurane, 29% (27/92) and sufentanil, 25% (22/86) groups (P = 0.7).(ABSTRACT TRUNCATED AT 400 WORDS)

The concordance of intraoperative left ventricular wall-motion abnormalities and electrocardiographic S-T segment changes: Association with outcome after coronary revascularization

BACKGROUND Transesophageal echocardiography (TEE) and Holter electrocardiography (ECG) are used to detect intraoperative ischemia during coronary artery bypass graft surgery (CABG). Concordance of these modalities and sensitivity as indicators of adverse perioperative cardiac outcomes are poorly defined. The authors tried to determine whether routine use of Holter ECG and TEE in patients with CABGs has clinical value in identifying those patients in whom myocardial infarction (MI) is likely to develop. METHODS A total of 351 patients with CABG and both ECG- and TEE-evaluable data were examined for the occurrence of ischemia and infarction. The TEE and five-lead Holter ECGs were performed continuously during cardiac surgery. The incidence of MI (creatine kinase-MB > or = 100 ng/ml) within 12 h of arrival in the intensive care [ICU] unit, new ECG Q wave on ICU admission or on the morning of postoperative day 1, or both, were recorded. RESULTS Electrocardiographic or TEE evidence of intraoperative ischemia was present in 126 (36%) patients. The concordance between modalities was poor (positive concordance = 17%; Kappa statistic = 0.13). Myocardial infarction occurred in 62 (17%) patients, and 32 (52%) of them had previous intraoperative ischemia. Of these, 28 (88%) were identified by TEE, whereas 13 (41%) were identified by ECG. Prediction of MI was greater for TEE compared with ECG. CONCLUSIONS Wall-motion abnormalities detected by TEE are more common than S-T segment changes detected by ECG, and concordance between the two modalities is low. One half of patients with MI had preceding ECG or TEE ischemia. Logistic regression revealed that TEE is twice as predictive as ECG in identifying patients who have MI.

Cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass

Central nervous system (CNS) complications are common after cardiac surgery.Death due to cardiac causes has decreased, but the number of deaths due to CNS injury has increased. As a first stage in the evaluation of its cerebral protection potential, we evaluated the cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. Thirty patients without history of cerebral vascular disease were randomized to two study groups: control group (n = 15) who received sufentanil and vecuronium, or propofol group (n = 15) who received the control anesthetic and propofol infused to maintain electroencephalogram (EEG) burst suppression. Catheters were placed in the radial artery and right jugular bulb for sampling of systemic arterial and jugular bulb venous blood.133 Xe clearance was used to determine cerebral blood flow (CBF) at the start of normothermic bypass, during stable hypothermia, and when rewarmed to 35-37 degrees C nasopharyngeal temperature. Pharmacologic burst suppression with propofol produced a statistically significant reduction in CBF, cerebral oxygen delivery (DO2), and cerebral metabolic rate (CMRO2) at each measurement interval (P < 0.05 vs control). Cerebral arterial venous oxygen difference (C(a-V)O2), and jugular bulb venous oxygen saturation (SJVO2) were not statistically different between groups, indicating maintenance of cerebral metabolic autoregulation (coupling). The reduction in CBF and CMRO2, prominent during the normothermic phases of cardiopulmonary bypass (CPB), indicates a potential for propofol to reduce cerebral exposure to the embolic load during CPB. (Anesth Analg 1995;81:452-7)

Clevidipine in adult cardiac surgical patients: A dose-finding study

Background Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium channel antagonist, clevidipine, in the treatment of hypertension in postoperative cardiac surgical patients. Methods Postoperative cardiac surgical patients were randomized to receive placebo or one of six doses of clevidipine. Hemodynamic parameters were recorded and blood samples were drawn for determination of clevidipine plasma concentrations during infusion and after discontinuation of clevidipine. The concentration–response relation was analyzed using logistic regression, and pharmacokinetic models were applied to the data using population analysis. Results There were significant decreases in mean arterial blood pressure and systemic vascular resistance at doses greater than or equal to 1.37 &mgr;g · kg−1 · min−1. There were no changes in heart rate, central venous pressure, pulmonary artery occlusion pressure, or cardiac index with increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater decrease in mean arterial pressure was 9.7 &mgr;g/l and for a 20% or greater decrease in mean arterial pressure was 26.3 &mgr;g/l. The pharmacokinetics of clevidipine were best described with a three-compartment model with a volume of distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug disposition had a half-life of 0.6 min. The context-sensitive half-time is less than 2 min for up to 12 h of administration. Conclusion Clevidipine is a calcium channel antagonist with a very short duration of action that effectively decreases systemic vascular resistance and mean arterial pressure without changing heart rate, cardiac index, or cardiac filling pressures.

Urine and Plasma Catecholamine and Cortisol Concentrations after Myocardial Revascularization Modulation by Continuous Sedation

Background: Cardiopulmonary bypass is associated with substantial release of catecholamines and cortisol for 12 or more h. A technique was assessed that may mitigate the responses with continuous 12‐h postoperative sedation using propofol. Methods: One hundred twenty‐one patients having primary elective cardiopulmonary bypass graft (CABG) surgery were enrolled in a double‐blind, randomized trial and anesthetized using a standardized sufentanil‐midazolam regimen. When arriving at the intensive care unit (ICU), patients were randomly assigned to either group SC (standard care), in which intermittent bolus administration of midazolam and morphine were given as required to keep patients comfortable; or group CP (continuous propofol), in which 12 h of continuous postoperative infusion of propofol was titrated to keep patients deeply sedated. Serial perioperative measurements of plasma and urine cortisol, epinephrine, norepinephrine, and dopamine were obtained; heart rate and blood pressure were recorded continuously, and medication use, including requirements for opioids and vasoactive drugs, was recorded. Repeated‐measures analysis was used to assess differences between study groups for plasma catecholamine and cortisol levels at each measurement time. Results: In the control state‐before the initiation of postoperative sedation in the ICU‐no significant differences between study groups were observed for urine or plasma catecholamine or cortisol concentrations. During the ICU study period, for the first 6–8 h, significant differences were found between study groups SC and CP in plasma cortisol (SC = 28 +/‐ 15 mg/dl; CP = 19 +/‐ 12 mg/dl; estimated mean difference [EMD] = 9 mg/dl; P = 0.0004), plasma epinephrine (SC = 132 +/‐ 120 micro gram/ml; CP = 77 +/‐ 122 micro gram/ml; EMD = 69 micro gram/ml; P = 0.009), urine cortisol (SC = 216 +/‐ 313 micro gram/ml; CP = 93 +/‐ 129 micro gram/ml; EMD = 127 micro gram/ml; P = 0.007), urine dopamine (SC = 85 +/‐ 48 micro gram; CP = 52 +/‐ 43 micro gram; EMD = 32 micro gram; P = 0.002), urine epinephrine (SC = 7 +/‐ 8 micro gram; CP = 4 +/‐ 5 micro gram; EMD = 3 micro gram; P = 0.009), and urine norepinephrine (SC = 24 +/‐ 14 mg; CP = 13 +/‐ 9 mg; EMD = 11 mg; P = 0.0004). Reductions in urine and plasma catecholamine and cortisol concentrations found for the CP group generally persisted during the 12‐h propofol infusion period and then rapidly returned toward control (SC group) values after propofol was discontinued. Postoperative opioid use was reduced in the CP group (SC = 97%; CP = 49%; P = 0.001), as was the incidence of (SC = 79%; CP = 60%; P = 0.04) and hypertension (SC = 58%; CP = 33%; P = 0.01), but the incidence of hypotension was increased (SC = 49%; CP = 81%; P = 0.001). Conclusions: Cardiopulmonary bypass graft surgery is associated with substantial increases in plasma and urine catecholamine and cortisol concentrations, which persist for 12 or more h. This hormonal response may be mitigated by a technique of intensive continuous 12‐h postoperative sedation with propofol, which is associated with a decrease in tachycardia and hypertension and an increase in hypotension.

Effects of acadesine on the incidence of myocardial infarction and adverse cardiac outcomes after coronary artery bypass graft surgery

Background Acadesine (AICA riboside) (5-amino-1-[beta-D-ribofuranosy]imidazole-4-carboxamide) is a purine nucleoside analog belonging to a new class of agents generally termed adenosine regulating agents (ARAs) that increase the availability of adenosine locally in ischemic tissues. The effects of acadesine on the incidence of fatal and nonfatal myocardial infarction (MI) and on the incidence of all adverse cardiovascular outcomes (cardiac death, MI, congestive heart failure, life-threatening dysrhythmia, or cerebrovascular accident) was investigated in patients undergoing coronary artery bypass graft (CABG) surgery.

Predictive value of the National Institutes of Health Stroke Scale and the Mini-Mental State Examination for neurologic outcome after coronary artery bypass graft surgery

OBJECTIVE We intended to define the role of the National Institutes of Health Stroke Scale and the Mini-Mental State Examination in identifying adverse neurologic outcomes in a large international sample of patients undergoing cardiac surgery. METHODS We evaluated 4707 patients undergoing cardiac surgery with cardiopulmonary bypass at 72 centers in 17 countries between November 1996 and June 2000. Prespecified overt neurologic outcomes were categorized as type I (clinically diagnosed stroke, transient ischemic attack, encephalopathy, or coma) or type II (deterioration of intellectual function). The National Institutes of Health Stroke Scale and Mini-Mental State Examination were administered preoperatively and on postoperative day 3, 4, or 5. Receiver operating characteristic curves were plotted to determine the predictive value of worsening in National Institutes of Health Stroke Scale and Mini-Mental State Examination scores with respect to type I and II outcomes. RESULTS The receiver operating characteristic area under the curve for changes in National Institutes of Health Stroke Scale score (n = 4620) was 0.89 for type I outcomes and 0.66 for type II outcomes. A 1-point worsening in National Institutes of Health Stroke Scale score provided excellent discrimination (86% specificity; 84% sensitivity) of type I outcomes. The receiver operating characteristic area under the curve for changes in Mini-Mental State Examination score (n = 4707) was 0.75 for type I outcomes and 0.71 for type II outcomes. A 2-point worsening in Mini-Mental State Examination score provided only fair discrimination (73% specificity; 62% sensitivity) of type II outcomes. CONCLUSION We used baseline controls and postoperative worsening in National Institutes of Health Stroke Scale and Mini-Mental State Examination scores to predict both serious adverse neurologic outcome and deterioration of intellectual function. Our findings provide the only reference for evaluating these tests that are used in cardiac surgical clinical trials.

The Concordance of Intraoperative Left Ventricular Wall-motion Abnormalities and Electrocardio-graphic S-T Segment Changes: Association with Outcome After Coronary Revascularization

Background Transesophageal echocardiography (TEE) and Holter electrocardiography (ECG) are used to detect intraoperative ischemia during coronary artery bypass graft surgery (CABG). Concordance of these modalities and sensitivity as indicators of adverse perioperative cardiac outcomes are poorly defined. The authors tried to determine whether routine use of Holter ECG and TEE in patients with CABGs has clinical value in identifying those patients in whom myocardial infarction (MI) is likely to develop. Methods A total of 351 patients with CABG and both ECG‐and TEE‐evaluable data were examined for the occurrence of ischemia and infarction. The TEE and five‐lead Holter ECGs were performed continuously during cardiac surgery. The incidence of MI (creatine kinase‐MB >or= to 100 ng/ml) within 12 h of arrival in the intensive care [ICU] unit, new ECG Q wave on ICU admission or on the morning of postoperative day 1, or both, were recorded. Results Electrocardiographic or TEE evidence of intraoperative ischemia was present in 126 (36%) patients. The concordance between modalities was poor (positive concordance = 17%; Kappa statistic = 0.13). Myocardial infarction occurred in 62 (17%) patients, and 32 (52%) of them had previous intraoperative ischemia. Of these, 28 (88%) were identified by TEE, whereas 13 (41%) were identified by ECG. Prediction of MI was greater for TEE compared with ECG. Conclusions Wall‐motion abnormalities detected by TEE are more common than S‐T segment changes detected by ECG, and concordance between the two modalities is low. One half of patients with MI had preceding ECG or TEE ischemia. Logistic regression revealed that TEE is twice as predictive as ECG in identifying patients who have MI.