Miklos D. Kertai

Statins Are Associated With a Reduced Incidence of Perioperative Mortality in Patients Undergoing Major Noncardiac Vascular Surgery

Background—Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. Methods and Results—To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%;P <0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. Conclusion—This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery.

A meta-analysis comparing the prognostic accuracy of six diagnostic tests for predicting perioperative cardiac risk in patients undergoing major vascular surgery

Objective: To evaluate the discriminatory value and compare the predictive performance of six non-invasive tests used for perioperative cardiac risk stratification in patients undergoing major vascular surgery. Design: Meta-analysis of published reports. Methods: Eight studies on ambulatory electrocardiography, seven on exercise electrocardiography, eight on radionuclide ventriculography, 23 on myocardial perfusion scintigraphy, eight on dobutamine stress echocardiography, and four on dipyridamole stress echocardiography were selected, using a systematic review of published reports on preoperative non-invasive tests from the Medline database (January 1975 and April 2001). Random effects models were used to calculate weighted sensitivity and specificity from the published results. Summary receiver operating characteristic (SROC) curve analysis was used to evaluate and compare the prognostic accuracy of each test. The relative diagnostic odds ratio was used to study the differences in diagnostic performance of the tests. Results: In all, 8119 patients participated in the studies selected. Dobutamine stress echocardiography had the highest weighted sensitivity of 85% (95% confidence interval (CI) 74% to 97%) and a reasonable specificity of 70% (95% CI 62% to 79%) for predicting perioperative cardiac death and non-fatal myocardial infarction. On SROC analysis, there was a trend for dobutamine stress echocardiography to perform better than the other tests, but this only reached significance against myocardial perfusion scintigraphy (relative diagnostic odds ratio 5.5, 95% CI 2.0 to 14.9). Conclusions: On meta-analysis of six non-invasive tests, dobutamine stress echocardiography showed a positive trend towards better diagnostic performance than the other tests, but this was only significant in the comparison with myocardial perfusion scintigraphy. However, dobutamine stress echocardiography may be the favoured test in situations where there is valvar or left ventricular dysfunction.

High-Dose β-Blockers and Tight Heart Rate Control Reduce Myocardial Ischemia and Troponin T Release in Vascular Surgery Patients

Background— Adverse perioperative cardiac events occur frequently despite the use of beta (&bgr;)-blockers. We examined whether higher doses of &bgr;-blockers and tight heart rate control were associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome. Methods and Results— In an observational cohort study, 272 vascular surgery patients were preoperatively screened for cardiac risk factors and &bgr;-blocker dose. Beta-blocker dose was converted to a percentage of maximum recommended therapeutic dose. Heart rate and ischemic episodes were recorded by continuous 12-lead electrocardiography, starting 1 day before to 2 days after surgery. Serial troponin T levels were measured after surgery. All-cause mortality was noted during follow-up. Myocardial ischemia was detected in 85 of 272 (31%) patients and troponin T release in 44 of 272 (16.2%). Long-term mortality occurred in 66 of 272 (24.2%) patients. In multivariate analysis, higher &bgr;-blocker doses (per 10% increase) were significantly associated with a lower incidence of myocardial ischemia (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.51 to 0.75), troponin T release (HR, 0.63; 95% CI, 0.49 to 0.80), and long-term mortality (HR, 0.86; 95% CI, 0.76 to 0.97). Higher heart rates during electrocardiographic monitoring (per 10-bpm increase) were significantly associated with an increased incidence of myocardial ischemia (HR, 2.49; 95% CI, 1.79 to 3.48), troponin T release (HR, 1.53; 95% CI, 1.16 to 2.03), and long-term mortality (HR, 1.42; 95% CI, 1.14 to 1.76). Conclusion— This study showed that higher doses of &bgr;-blockers and tight heart rate control are associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome in vascular surgery patients.

Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: a systematic review and meta-analysis.

Background:There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. Methods:The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessing whether a postoperative troponin or creatine kinase muscle and brain isoenzyme measurement was an independent predictor of mortality or a major cardiovascular event. Independent investigators determined study eligibility and abstracted data in duplicate. Results:Fourteen studies, enrolling 3,318 patients and 459 deaths, demonstrated that an increased troponin measurement after surgery was an independent predictor of mortality (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.2–5.2), but there was substantial heterogeneity (I2 = 56%). The independent prognostic capabilities of an increased troponin value after surgery in the 10 studies that assessed intermediate-term (≤ 12 months) mortality was an OR = 6.7 (95% CI 4.1–10.9, I2 = 0%) and in the 4 studies that assessed long-term (more than 12 months) mortality was an OR = 1.8 (95% CI 1.4–2.3, I2 = 0%; P < 0.001 for test of interaction). Four studies, including 1,165 patients and 202 deaths, demonstrated an independent association between an increased creatine kinase muscle and brain isoenzyme measurement after surgery and mortality (OR 2.5, 95% CI 1.5–4.0, I2 = 4%). Conclusions:An increased troponin measurement after surgery is an independent predictor of mortality, particularly within the first year; limited data suggest an increased creatine kinase muscle and brain isoenzyme measurement also predicts subsequent mortality. Monitoring troponin measurements after noncardiac surgery may allow physicians to better risk stratify and manage their patients.

Anxiety predicts mortality and morbidity after coronary artery and valve surgery--a 4-year follow-up study.

Objective: To explore the long-term effect of anxiety and depression on outcome after cardiac surgery. To date, the relationship between psychosocial factors and future cardiac events has been investigated mainly in population-based studies, in patients after cardiac catheterization or myocardial infarction. Methods: In total, 180 patients who underwent cardiac surgery using cardiopulmonary bypass were prospectively studied and followed up for 4 years. Anxiety (Spielberger State-Trait Anxiety Inventory, STAI-S/STAI-T), depression (Beck Depression Inventory, BDI), living alone, and education level along with clinical risk factors and perioperative characteristics were assessed. Psychological self-report questionnaires were completed preoperatively and 6, 12, 24, 36, and 48 months after discharge. Clinical end-points were mortality and cardiac events requiring hospitalization during follow-up. Results: Average preoperative STAI-T score was 44.6 ± 10. Kaplan-Meier analysis showed a significant effect of preoperative STAI-T >45 points (p = .008) on mortality. In multivariate models, postoperative congestive heart failure (OR: 10.8; 95% confidence interval [CI]:2.9–40.1; p = .009) and preoperative STAI-T (score OR: 1.07; 95% CI: 1.01–1.15; p = .05) were independently associated with mortality. The occurrence of cardiovascular hospitalization was independently associated with postoperative intensive care unit days (OR: 1.41; 95% CI: 1.01–1.96; p = .045) and post discharge 6th month STAI-T (OR: 1.06; 95% CI:1.01–1.13; p = .03). Conclusions: The results of the present study suggest that the assessment of psychosocial factors, particularly the ongoing assessment of anxiety, could help in risk stratification and identification of patients at risk of mortality and cardiovascular morbidity after cardiac surgery. BDI = Beck Depression Inventory; STAI-S = state anxiety subscale; STAI-T = trait anxiety subscale of Spielberger State-Trait Anxiety Inventory; CPB = cardiopulmonary bypass; CABG = coronary artery bypass grafting; CHF = congestive heart failure; CHD = coronary heart disease; ICU = intensive care unit; MI = myocardial infarction; PTSD = posttraumatic stress disorder.

Association of Perioperative Risk Factors and Cumulative Duration of Low Bispectral Index with Intermediate-term Mortality after Cardiac Surgery in the B-Unaware Trial

Background:Current data suggest that mortality after noncardiac surgery may be associated with persistent hypotension and the cumulative duration of low processed electroencephalogram-based bispectral index (BIS). This study assessed the relationships among cumulative duration of low BIS (BIS < 45), intermediate-term mortality, and anesthetic dose after cardiac surgery. Methods:The authors studied 460 patients (mean age, 63.0 ± 13.1 yr; 287 men) who underwent cardiac surgery between September 2005 and October 2006 at Washington University Medical Center, St Louis, Missouri. By using multivariable Cox regression analysis, perioperative factors were evaluated for their potential association with intermediate-term all-cause mortality. Results:A total of 82 patients (17.8%) died during a median follow-up of 3 yr (interquartile range, 2.7–3.3 yr). Comparing patients who died with those who survived, there was no statistically significant difference in the relationship between end-tidal anesthetic gas concentrations during the anesthetic maintenance phase and the BIS. Cumulative duration of low BIS was independently associated with intermediate-term mortality. The 1.29 adjusted hazard ratio (95% CI, 1.12–1.49) for intermediate-term mortality with cumulative duration of low BIS translated into a 29% increased risk of death for every cumulative hour spent with a BIS less than 45. The final multivariable Cox regression model showed a good discriminative ability (c-index of 0.78). Conclusions:This study found an association between cumulative duration of low BIS and mortality in the setting of cardiac surgery. Notably, this association was independent of both volatile anesthetic concentration and duration of anesthesia, suggesting that intermediate-term mortality after cardiac surgery was not causally related to excessive anesthetic dose.

Bispectral index monitoring, duration of bispectral index below 45, patient risk factors, and intermediate-term mortality after noncardiac surgery in the B-unaware trial

Background:Postoperative mortality has been associated with cumulative anesthetic duration below an arbitrary processed electroencephalographic threshold (bispectral index [BIS] <45). This substudy of the B-Unaware Trial tested whether cumulative duration of BIS values lower than 45, cumulative anesthetic dose, comorbidities, or intraoperative events were independently associated with postoperative mortality. Methods:The authors studied 1,473 patients (mean ± SD age, 57.9 ± 14.4 yr; 749 men) who underwent noncardiac surgery at Barnes-Jewish Hospital in St. Louis, Missouri. Multivariable Cox regression analysis was used to determine whether perioperative factors were independently associated with all-cause mortality. Results:A total of 358 patients (24.3%) died during a follow-up of 3.2 ± 1.1 yr. There were statistically significant associations among various perioperative risk factors, including malignancy and intermediate-term mortality. BIS-monitored patients did not have lower mortality than unmonitored patients (24.9 vs. 23.7%; difference = 1.2%, 95% CI, −3.3 to 5.6%). Cumulative duration of BIS values less than 45 was not associated with mortality (multivariable hazard ratio, 1.03; 95% CI, 0.93–1.14). Increasing mean and cumulative end-tidal anesthetic concentrations were not associated with mortality. The multivariable Cox regression model showed a good discriminative ability (c-index = 0.795). Conclusions:This study found no evidence that either cumulative BIS values below a threshold of 40 or 45 or cumulative inhalational anesthetic dose is injurious to patients. These results do not support the hypothesis that limiting depth of anesthesia either by titration to a specific BIS threshold or by limiting end-tidal volatile agent concentrations will decrease postoperative mortality.

A meta-analysis of safety and effectiveness of perioperative beta-blocker use for the prevention of cardiac events in different types of noncardiac surgery

ObjectivePerioperative &bgr;-blocker therapy has been proposed to improve outcome. Most of the trials conducted, however, lacked statistical power to evaluate the incidence of hard cardiac events and the relationship to the type of surgery. Therefore, we conducted a meta-analysis of all randomized controlled trials in which &bgr;-blocker therapy was evaluated. MethodsAn electronic search of published reports on Medline was undertaken to identify studies published between January 1980 and November 2004 in English language journals. All studies reported on at least one of three endpoints: perioperative myocardial ischemia, perioperative nonfatal myocardial infarction, and cardiac mortality. Type of surgery, defined as low, intermediate, and high risk according to the American College of Cardiology/American Heart Association guidelines, was noted. ResultsIn total, 15 studies were identified, which enrolled 1077 patient. No significant differences were observed in baseline clinical characteristics between patients randomized to &bgr;-blocker therapy and control/placebo. Beta-blocker therapy was associated with a 65% reduction in perioperative myocardial ischemia (11.0% vs. 25.6%; odds ratio 0.35, 95% confidence interval 0.23–0.54; P<0.001). Furthermore, a 56% reduction in myocardial infarction (0.5% vs. 3.9%, odds ratio 0.44, 95% confidence interval 0.20–0.97; P=0.04) and a 67% reduction (1.1% vs. 6.1%, odds ratio 0.33, 95% confidence interval 0.17–0.67; P=0.002) in the composite endpoint of cardiac death and nonfatal myocardial infarction were observed. No statistical evidence was observed for heterogeneity in the treatment effect in subgroups according to type of surgery (P for heterogeneity 0.2). ConclusionThis meta-analysis shows that &bgr;-blocker use in noncardiac surgical procedures is associated with a significant reduction of perioperative cardiac adverse events.

Cumulative Duration of “Triple Low” State of Low Blood Pressure, Low Bispectral Index, and Low Minimum Alveolar Concentration of Volatile Anesthesia Is Not Associated with Increased Mortality

Background:Mortality after noncardiac surgery has been associated with the “triple low state,” a combination of low mean arterial blood pressure (<75 mmHg), low bispectral index (<45), and low minimum alveolar concentration of volatile anesthesia (<0.70). The authors set out to determine whether duration of a triple low state and aggregate risk associated with individual diagnostic and procedure codes are independently associated with perioperative and intermediate-term mortality. Methods:The authors studied 16,263 patients (53 ± 16 yr) who underwent noncardiac surgery at Duke University Medical Center between January 2006 and December 2009. Multivariable logistic and Cox regression analyses were used to determine whether perioperative factors were independently associated with perioperative and intermediate-term all-cause mortality. Results:The 30-day mortality rate was 0.8%. There were statistically significant associations between 30-day mortality and various perioperative risk factors including age, American Society of Anesthesiologists Physical Status, emergency surgery, higher Cleveland Clinic Risk Index score, and year of surgery. Cumulative duration of triple low state was not associated with 30-day mortality (multivariable odds ratio, 0.99; 95% CI, 0.92 to 1.07). The clinical risk factors for 30-day mortality remained predictors of intermediate-term mortality, whereas cumulative duration of triple low was not associated with intermediate-term mortality (multivariable hazard ratio, 0.98; 95% CI, 0.97 to 1.01). The multivariable logistic regression (c-index = 0.932) and Cox regression (c-index = 0.860) models showed excellent discriminative abilities. Conclusion:The authors found no association between cumulative duration of triple low state and perioperative or intermediate-term mortality in noncardiac surgery patients.

Comparison between serum creatinine and creatinine clearance for the prediction of postoperative mortality in patients undergoing major vascular surgery.

BACKGROUND Poor renal function prior to surgery is associated with increased risk for mortality in patients undergoing major vascular surgery. Traditionally, this function is assessed by serum creatinine concentration (SeCreat). However, SeCreat is also influenced by age, gender and body weight. Hence, creatinine clearance (C(Cr)) is considered to be a better reflection of renal function. This study was undertaken to explore the prognostic value of preoperative calculated Cc, compared to SeCreat for the prediction of postoperative mortality. PATIENTS AND METHODS The study group comprised 852 consecutive patients who underwent elective major vascular surgery at the Erasmus Medical Center, Rotterdam. Preoperative C(Cr) was calculated based on the Cockroft-Gault equation using preoperative SeCreat, age, body weight and gender. Univariable logistic regression analyses were used to study the relation between preoperative SeCreat, C(Cr) and postoperative mortality. Furthermore, multivariable logistic regression analysis was applied to evaluate the additional predictive value of age, body weight and gender additional to SeCreat. The receiver operating characteristic (ROC) curve was determined to evaluate the predictive power of several regression models for perioperative mortality. RESULTS Postoperative mortality was 5.9% (50/852) within 30 days of surgery. In a univariable analysis, 10 micromol/l increment of SeCreat were associated with a 20% increased risk of postoperative mortality (OR = 1.2, 95% CI, 1.1-1.3) with an area under the ROC curve of 0.64 (95% CI, 0.56-0.71). If age, gender and body weight were added, the area under the ROC curve increased to 0.70 (95% CI, 0.63-0.77; p < 0.001), indicating that these risk factors had additional prognostic value. Indeed, in a separate regression analysis 10 ml/min decrease in C(Cr) was associated with a 40% increased risk of postoperative mortality (OR = 1.4,95% CI, 1.2-1.5; ROC area: 0.70, 95% CI, 0.63-0.76). ROC curve analysis showed that the cut-off value of 64 ml/min for C(Cr) yielded the highest sensitivity/specificity to predict postoperative mortality. CONCLUSION Preoperative SeCreat was strongly associated with postoperative mortality, and adding age, gender, and body weight to the model showed improved predictive power indicating that preoperative C(Cr) calculated with these data has additional prognostic value.