Milton Hollenberg

Prophylactic atenolol reduces postoperative myocardial ischemia

Background Perioperative myocardial ischemia occurs in 20–40% of patients at risk for cardiac complications and is associated with a ninefold increase in risk for perioperative cardiac death, myocardial infarction, or unstable angina, and a twofold long‐term risk. Perioperative atenolol administration reduces the risk of death for as long as 2 yr after surgery. This randomized, placebo‐controlled, double‐blinded trial tested the hypothesis that perioperative atenolol administration reduces the incidence and severity of perioperative myocardial ischemia, potentially explaining the observed reduction in the risk for death. Methods Two‐hundred patients with, or at risk for, coronary artery disease were randomized to two study groups (atenolol and placebo). Monitoring included a preoperative history and physical examination and daily assessment of any adverse events. Twelve‐lead electrocardiography (ECG), three‐lead Holter ECG, and creatinine phosphokinase with myocardial banding (CPK with MB) data were collected 24 h before until 7 days after surgery. Atenolol (0, 5, or 10 mg) or placebo was administered intravenously before induction of anesthesia and every 12 h after operation until the patient could take oral medications. Atenolol (0, 50, or 100 mg) was administered orally once a day as specified by blood pressure and heart rate. Results During the postoperative period, the incidence of myocardial ischemia was significantly reduced in the atenolol group: days 0–2 (atenolol, 17 of 99 patients; placebo, 34 of 101 patients; P = 0.008) and days 0–7 (atenolol, 24 of 99 patients; placebo, 39 of 101 patients; P = 0.029). Patients with episodes of myocardial ischemia were more likely to die in the next 2 yr (P = 0.025). Conclusions Perioperative administration of atenolol for 1 week to patients at high risk for coronary artery disease significantly reduces the incidence of postoperative myocardial ischemia. Reductions in perioperative myocardial ischemia are associated with reductions in the risk for death at 2 yr.

PERIOPERATIVE MYOCARDIAL ISCHEMIA IN PATIENTS UNDERGOING NONCARDIAC SURGERY. I, INCIDENCE AND SEVERITY DURING THE 4 DAY PERIOPERATIVE PERIOD

To determine the incidence and characteristics of perioperative myocardial ischemia, the electrocardiographic (ECG) changes consistent with ischemia during the 4 day perioperative period were documented and characterized in 100 patients with or at risk for coronary artery disease undergoing noncardiac surgery. Using continuous two channel ECG monitoring (leads CC5 and CM5), the frequency and severity of ECG ischemic episodes defined by ST segment depression greater than or equal to 1 mm or elevation greater than or equal to 2 mm during the preoperative (up to 2 days), intraoperative and early postoperative (first 2 days) periods were compared. Preoperatively, 28 patients (28%) exhibited 105 episodes of ischemia; intraoperatively, 27 patients exhibited 39 episodes and postoperatively, 42 patients exhibited 187 episodes. There was no difference between the pre- and intraoperative episode characteristics. However, postoperative ischemic episodes were the most severe. The mean ST change was 1.5, 2 and 2.6 mm for pre-, intra- and postoperative episodes, respectively (p less than 0.0001 postoperative versus pre- or intraoperative); duration of ischemic episodes was 69, 45 and 207 min, respectively (p less than 0.005 postoperative versus preoperative, p less than 0.001 versus intraoperative) and area under the ST curve was 88, 74 and 383 mm.min (p less than 0.009 postoperative versus preoperative, p less than 0.005 versus intraoperative). Ninety-four percent of all postoperative ischemic episodes were silent; 80% of all episodes occurred without acute change (+/- 20% of control) in heart rate and 77% of intraoperative episodes occurred without acute change in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative myocardial ischemia. Therapeutic trials using intensive analgesia following surgery

Recent data suggest that postbypass and postoperative myocardial ischemia are related to adverse cardiac outcome following myocardial revascularization. Therapeutic trials to suppress postoperative ischemia are warranted. Because anesthetics can suppress a variety of physiologic responses to stress as well as myocardial ischemia intraoperatively, we examined whether use of intensive analgesia in the stressful postoperative period could decrease postoperative ischemia. In 106 patients undergoing elective myocardial revascularization, we standardized the anesthetic prior to bypass (sufentanil 5-10 micrograms/kg [induction] and 4.2-6.0 micrograms.kg-1.h-1 [infusion] supplemented with up to 0.5 mg/kg of diazepam). During bypass, patients were randomly assigned to receive either morphine sulfate (group M, n = 54, up to 2 mg/kg) or sufentanil (group S, n = 52, 1 microgram/kg and 1 microgram.kg-1.h-1). In the intensive care unit (ICU), group M received low-dose analgesia (morphine sulfate 1-10 mg intravenously every 30 min, average dose = 2.2 +/- 2.1 mg/h), while group S continued to receive intensive analgesia (infusion of sufentanil at 1 microgram.kg-1.h-1). Both groups received supplemental midazolam in the ICU (group M = 1.1 +/- 1.1 mg/h; group S = 0.6 +/- 0.6 mg/h; P = 0.01). All analgesic and sedative-hypnotic medications were discontinued at 18 hours following myocardial revascularization. Using continuous two-channel electrocardiographic (ECG) monitoring (CC5 and CM5), we documented and characterized ECG changes consistent with ischemia during the preoperative, intraoperative (pre- and postbypass), and postoperative (on- and off-treatment) periods. The total ECG monitoring time was 8,486 h, averaging 81 h per patient. During the prebypass (anesthetic control) period, groups M and S had a similar incidence, but group S episodes were more severe: maximum ST-segment change (median), S versus M: -1.8 mm versus -1.4 mm (P = 0.04). During the postbypass period, both groups had a similar incidence of ischemia, but episodes in group S were less severe: maximum ST-segment change, S versus M: -1.8 mm versus -2.7 mm (P = 0.0005). During the ICU-on-therapy period, the incidence of ischemic episodes was less in group S patients, and the severity was less: area-under-the-ST-time curve, S versus M: -21 mm.min versus -161 mm.min (P = 0.05). After discontinuation of the drug regimen in the ICU, the incidence and severity of ischemic episodes was similar. The incidence of hypotension, hypertension, and tachycardia was similar in both groups in both the intraoperative and ICU periods.(ABSTRACT TRUNCATED AT 400 WORDS)

Prognostic Importance of Postbypass Regional Wall-Motion Abnormalities in Patients Undergoing Coronary Artery Bypass Graft Surgery

Regional wall motion abnormalities (RWMA) detected by intraoperative transesophageal echocardiography (TEE) are thought to be sensitive markers of myocardial ischemia. To assess the prognostic significance of RWMA as compared with other less costly technologies such as electrocardiography (ECG) and hemodynamic measurements [blood pressure (BP) and pulmonary artery (PA) pressure], 50 patients were prospectively studied who were undergoing elective coronary artery bypass graft (CABG) surgery using continuous TEE, ECG (Holter), and hemodynamic measurements during the prebypass, postbypass, and early postoperative intensive care unit (ICU) periods (first 4 h). Echocardiographic and ECG evidence of ischemia was characterized during each of these three periods and related to adverse clinical outcomes (postoperative myocardial infarction, ventricular failure, and cardiac death). Clinicians were blinded to the TEE and ECG information. The prevalence of myocardial ischemia during the perioperative periods was as follows: prebypass, 20% (TEE) versus 7% (ECG); postbypass, 36% (TEE) versus 25% (ECG); ICU 25% (TEE) versus 16% (ECG). Neither prebypass TEE ischemia nor ECG ischemia occurring in any of the three periods predicted adverse outcome. In contrast, postbypass TEE ischemia was predictive of outcome: six of 18 patients with postbypass TEE ischemia had adverse outcomes versus 0 of 32 without TEE ischemia (P = 0.001). Seventy-three percent of the echocardiographic ischemic episodes occurred without acute change (+/- 20% of control) in heart rate, BP, or PA pressure. The authors conclude that: 1) prebypass myocardial ischemia was relatively uncommon, 2) the incidence of ECG and TEE ischemia was highest in the postbypass period, and 3) postbypass RWMA were related to adverse clinical outcome.

Intraoperative myocardial ischemia: localization by continuous 12-lead electrocardiography

Based primarily on results obtained during exercise treadmill testing, electrocardiographic (ECG) leads II and V5 are the suggested optimal leads for detecting intraoperative myocardial ischemia. However, these recommendations have not been validated in this setting using all 12 ECG leads. Accordingly, the authors studied 105 patients with known or suspected coronary artery disease (CAD) undergoing noncardiac surgery with general anesthesia by continuously recording the 12-lead ECG intraoperatively in all patients. The average duration of monitoring was 8.2 ± 2.7 h (mean ± SD). Ischemic episodes (i.e., ± 1-mm horizontal or downsloping ST depression, ± 1.5-mm slowly upsloping ST depression or ± 1.5-mm ST of 51 ischemic episodes, 45 involved ST depression alone, and the remaining six involved both ST depression and elevation. ST segment changes occurred in a single lead only in 134 episodes, while multiple leads were involved in 37 episodes. Lead sensitivity was estimated assuming that all St segment changes were true positive responses. Sensitivity using a single lead was greatest in V5 (75%) and V4 (61%), and intermediate in II, V3 and V6 (33%, 24%, and 37%, respectively). The remaining seven leads demonstrated very low sensitivity (2–14%) or exhibited no ischemic changes (I and a V1). Combining leads V4 and V5 increased sensitivity to 90%, while the standard clinical combination, II and V5, was only 80% sensitive. Sensitivity increased to 96% by combining II, V4, and V5. The further addition of V2 and V3 (five leads) increased sensitivity to 100%. This study confirms previous recommendations for the routine use of a V5 lead (either uni- or bipolar) in all patients at risk for ischemia. V4 is more sensitive than lead II, and should be considered as a second choice. However, lead II, superior for detection of atrial dysrhythmias, is more easily obtained with conventional monitors. The use of all three would appear to be the optimal arrangement for most clinical needs, and is recommended if the clinician has the capability.

Dipyridamole thallium-201 scintigraphy as a preoperative screening test. A reexamination of its predictive potential. Study of Perioperative Ischemia Research Group.

BACKGROUND We examined the value of dipyridamole thallium-201 (201Tl) scintigraphy as a preoperative screening test for perioperative myocardial ischemia and infarction. METHODS AND RESULTS We prospectively studied 60 patients undergoing elective vascular surgery. We performed 201Tl scintigraphy preoperatively and blinded all treating physicians to the results. Historical, clinical, laboratory, and physiological data were gathered throughout hospitalization. Myocardial ischemia was assessed during the intraoperative period using continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography (TEE) and during the postoperative period using continuous two-lead ambulatory ECG. Adverse cardiac outcomes (cardiac death, myocardial infarction, unstable angina, severe ischemia, or congestive heart failure) were assessed daily throughout hospitalization. Twenty-two patients (37%) had defects that improved or reversed on delayed scintigrams (redistribution defects), 18 (30%) had persistent defects, and 20 (33%) had no defects on 201Tl scintigraphy. There was no association between redistribution defects and adverse cardiac outcomes: 54% (seven of 13) of adverse outcomes occurred in patients without redistribution defects, and the risk of an adverse outcome was not significantly increased in patients with redistribution defects (relative risk 1.5, 95% confidence interval 0.6-3.9, p = 0.43). Consistent with these findings, there was also no association between redistribution defects and perioperative ischemia: 54% (19 of all 35) of perioperative ECG and TEE ischemic episodes and 58% (14 of 24) of severe ischemic episodes occurred in patients without redistribution defects. The sensitivity of 201Tl scintigraphy for perioperative ischemia and adverse outcomes ranged from 40% to 54%, specificity from 65% to 71%, positive predictive value from 27% to 47% and negative predictive value from 61% to 82%. CONCLUSIONS These results differ from those of previous studies and suggest that the routine use of 201Tl scintigraphy for preoperative screening of patients undergoing vascular surgery may not be warranted.

Effects of Perioperative Dexmedetomidine Infusion in Patients Undergoing Vascular Surgery

Background Dexmedetomidine, a highly selective alpha2 ‐adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease. Methods Twenty‐four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12‐lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively. Results Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, dexmedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results. Conclusions Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate.

Perioperative myocardial ischemia: importance of the preoperative ischemic pattern.

Previous studies investigating the incidence of myocardial ischemia in patients undergoing coronary-artery bypass grafting (CABG) surgery have not considered the potential significance of the preoperative myocardial ischemia and infarction. Accordingly, the authors compared the frequency and severity of pre-, intra-, and postoperative ischemic episodes (ST-segment depression ≥ mV or elevation ≥ 0.2 mV) in 50 men with severe coronary artery disease scheduled for elective CABG. All subjects were monitored by continuous electrocardiography (ECG) (Holter monitor) for 2 preoperative days, intraoperatively, and 2 postoperative days (total monitoring time = 4,363 h). Routine anti-anginal medications were continued until the morning of surgery, and the anesthetic management of the patient was not controlled. During the preoperative period, 42% of the patients had ECG ischemic episodes, 87% of which were clinically silent. Only 18% developed intraoperative ischemia. Postoperatively, the incidence increased to 40%. The number of ischemic episodes/hour (epis/h) of monitoring among the three monitoring periods was similar (0.09 ± 0.12 epis/h preoperatively, 0.11 ± 0.20 epis/h intraoperatively, and 0.05 ± 0.08 epis/h postoperatively; P = NS). The median duration of ischemic episodes was similar pre- and intraoperatively (16 vs. 18.5 min, P = NS), but greater postoperatively (41 min, P < 0.05). Seventy-six per cent of the perioperative ECG ischemia occurred without acute change (±20% of control) in blood pressure of heart rate. Intraoperative myocardial ischemia occurred in 33% of those patients with preopearative ischemia, but in only 7% of patients without preoperative ischemia (P < 0.05). However, neither pre- nor intraoperative ischemia predicted the development of postoperative ischemia, Major outcome (myocardial infarction and/or death) occured in seven patients. Although all seven major outcomes were preceded by ischemic episodes at some time during the study, perioperatiye ischemia was not a specific predictor of major outcome. The authors conclude that: 1) CABG patients have frequent preoperative episodes of myocardial ischemia, most of which are silent; 2) anesthesia and surgery do not worsen the prcoperative ischemic pattern; 3) ECG changes suggestive of myocardial ischemia fequently follow CABG surgery, although their pathogenesis and significance is as yet unknown; 4) the majority of perioperative ischemic ECG changes occur without acute hemodynamic changes prior to the onset of ischemia; and 5) because the prcoperative ischemic pattern appears to be recapitulated intraoperatively, it is relevant to examine the preoperative ischemic pattern to assess the impact of anesthesia and surgery in the development of intraoperative myocardial ischemia.

Oxygen uptake efficiency slope: an index of exercise performance and cardiopulmonary reserve requiring only submaximal exercise ☆

OBJECTIVES We sought to evaluate, in adults, the efficacy of the Oxygen Uptake Efficiency Slope (OUES), an index of cardiopulmonary functional reserve that can be based upon a submaximal exercise effort. BACKGROUND Maximal oxygen uptake (VO2,max), the most reliable measure of exercise capacity, is seldom attained in standard exercise testing. The OUES, which relates oxygen uptake to total ventilation during exercise, was proposed by Baba and coworkers (7) in a study of pediatric cardiac patients. They felt this submaximal index of cardiopulmonary reserve might be more practical than VO2max and more appropriate than the commonly used peak oxygen consumption (VO2 peak). METHODS Treadmill exercise tests with simultaneous respiratory gas measurement were performed in 998 older subjects free of clinically recognized cardiovascular disease and 12 male patients with congestive heart failure. During incremental exercise, oxygen uptake was plotted against the logarithm of total ventilation, and the OUES was determined. RESULTS The OUES, when calculated only from the first 75% of the exercise test, differed by 1.9% from the OUES calculated from 100% of exercise time in subjects with a peak respiratory exchange rate > or =1.10. On serial tests the OUES was less variable than exercise duration or VO2 peak. It correlated strongly with VO2max, with forced expiratory volume in 1 s and negatively with a history of current smoking. The OUES declined linearly with age in both women and men. A small sample of patients with congestive heart failure had OUES values much lower than those of older subjects without cardiovascular disease. CONCLUSIONS The OUES is an objective, reproducible measure of cardiopulmonary reserve that does not require a maximal exercise effort. It integrates cardiovascular, musculoskeletal and respiratory function into a single index that is largely influenced by pulmonary dead space ventilation and exercise-induced lactic acidosis.

Electrocardiographic and hemodynamic changes and their association with myocardial infarction during coronary artery bypass surgery : A multicenter study

Background Electrocardiographic (ECG) changes during coronary artery bypass graft surgery have not been described in detail in a large multicenter population. The authors describe these ECG changes and evaluate them, along with demographic and clinical characteristics and intraoperative hemodynamic alterations, as predictors of myocardial infarction (MI) as defined by two sets of criteria. Methods Data from 566 patients at 20 clinical sites, collected as part of a clinical trial to evaluate the efficacy of acadesine for reducing MI, were analyzed at core laboratories. Perioperative ECG changes were identified using continuous three‐lead Holter ECG. Systolic blood pressure, diastolic blood pressure, and heart rate were recorded each minute during operation. The occurrence of MI by Q wave or myocardial fraction of creatine kinase (CK‐MB) or autopsy criteria, and by (Q wave and CK‐MB) or autopsy criteria was determined. Results During perioperative Holter monitoring, episodes of ST segment deviation, major cardiac conduction changes greater or equal to 30 min, or use of ventricular pacing greater or equal to 30 min occurred in 58% patients, primarily in the first 8 h after release of aortic occlusion. Of the 25% patients who met the Q wave or CK‐MB or autopsy criteria for MI, 19% had increased CK‐MB as well as ECG changes. (Q wave and CK‐MB) or autopsy criteria for MI were met by 4% of patients. The CK‐MB concentration generally peaked by 16 h after release of aortic occlusion. In patients with (n = 187) and without a perioperative episode of ST segment deviation, the incidence of MI was 36% and 19%, respectively (P < 0.01), by Q wave or CK‐MB or autopsy criteria, and 6% and 3%, respectively (P = 0.055), by (Q wave and CK‐MB) or autopsy criteria. Multiple logistic regression analysis showed that intraoperative ST segment deviation, intraventricular conduction defect, left bundle branch block, duration of hypotension (systolic blood pressure < 90 mmHg) after cardiopulmonary bypass, and duration of cardiopulmonary bypass are independent predictors of Q wave or CK‐MB or autopsy MI. The independent predictors of (Q wave and CK‐MB) or autopsy MI are intraoperative ST segment deviation and duration of aortic occlusion. Conclusions Major ECG changes occurred in 58% of patients during coronary artery bypass graft surgery, primarily within 8 h after release of aortic occlusion. Multicenter data collection revealed a substantial variation in the incidence of MI and an overall incidence of up to 25%, with most MI occurring within 16 h after release of aortic occlusion. Intraoperative monitoring of ECG and hemodynamics has incremental value for predicting MI.