Edward R. Marcantonio

Derivation and Prospective Validation of a Simple Index for Prediction of Cardiac Risk of Major Noncardiac Surgery

BACKGROUND Cardiac complications are important causes of morbidity after noncardiac surgery. The purpose of this prospective cohort study was to develop and validate an index for risk of cardiac complications. METHODS AND RESULTS We studied 4315 patients aged > or = 50 years undergoing elective major noncardiac procedures in a tertiary-care teaching hospital. The main outcome measures were major cardiac complications. Major cardiac complications occurred in 56 (2%) of 2893 patients assigned to the derivation cohort. Six independent predictors of complications were identified and included in a Revised Cardiac Risk Index: high-risk type of surgery, history of ischemic heart disease, history of congestive heart failure, history of cerebrovascular disease, preoperative treatment with insulin, and preoperative serum creatinine >2.0 mg/dL. Rates of major cardiac complication with 0, 1, 2, or > or = 3 of these factors were 0.5%, 1.3%, 4%, and 9%, respectively, in the derivation cohort and 0.4%, 0.9%, 7%, and 11%, respectively, among 1422 patients in the validation cohort. Receiver operating characteristic curve analysis in the validation cohort indicated that the diagnostic performance of the Revised Cardiac Risk Index was superior to other published risk-prediction indexes. CONCLUSIONS In stable patients undergoing nonurgent major noncardiac surgery, this index can identify patients at higher risk for complications. This index may be useful for identification of candidates for further risk stratification with noninvasive technologies or other management strategies, as well as low-risk patients in whom additional evaluation is unlikely to be helpful.

One-Year Health Care Costs Associated With Delirium in the Elderly Population

BACKGROUND While delirium has been increasingly recognized as a serious and potentially preventable condition, its long-term implications are not well understood. This study determined the total 1-year health care costs associated with delirium. METHODS Hospitalized patients aged 70 years and older who participated in a previous controlled clinical trial of a delirium prevention intervention at an academic medical center between 1995 and 1998 were followed up for 1 year after discharge. Total inflation-adjusted health care costs, calculated as either reimbursed amounts or hospital charges converted to costs, were computed by means of data from Medicare administrative files, hospital billing records, and the Connecticut Long-term Care Registry. Regression models were used to determine costs associated with delirium after adjusting for patient sociodemographic and clinical characteristics. RESULTS During the index hospitalization, 109 patients (13.0%) developed delirium while 732 did not. Patients with delirium had significantly higher unadjusted health care costs and survived fewer days. After adjusting for pertinent demographic and clinical characteristics, average costs per day survived among patients with delirium were more than 2(1/2) times the costs among patients without delirium. Total cost estimates attributable to delirium ranged from

Cognitive trajectories after postoperative delirium.

16 303 to

The Impact of Postoperative Pain on the Development of Postoperative Delirium

64 421 per patient, implying that the national burden of delirium on the health care system ranges from

Impact of Age on Perioperative Complications and Length of Stay in Patients Undergoing Noncardiac Surgery

38 billion to

The association of intraoperative factors with the development of postoperative delirium

152 billion each year. CONCLUSIONS The economic impact of delirium is substantial, rivaling the health care costs of falls and diabetes mellitus. These results highlight the need for increased efforts to mitigate this clinically significant and costly disorder.

Delirium accelerates cognitive decline in Alzheimer disease.

BACKGROUND Delirium is common after cardiac surgery and may be associated with long-term changes in cognitive function. We examined postoperative delirium and the cognitive trajectory during the first year after cardiac surgery. METHODS We enrolled 225 patients 60 years of age or older who were planning to undergo coronary-artery bypass grafting or valve replacement. Patients were assessed preoperatively, daily during hospitalization beginning on postoperative day 2, and at 1, 6, and 12 months after surgery. Cognitive function was assessed with the use of the Mini-Mental State Examination (MMSE; score range, 0 to 30, with lower scores indicating poorer performance). Delirium was diagnosed with the use of the Confusion Assessment Method. We examined performance on the MMSE in the first year after surgery, controlling for demographic characteristics, coexisting conditions, hospital, and surgery type. RESULTS The 103 participants (46%) in whom delirium developed postoperatively had lower preoperative mean MMSE scores than those in whom delirium did not develop (25.8 vs. 26.9, P<0.001). In adjusted models, those with delirium had a larger drop in cognitive function (as measured by the MMSE score) 2 days after surgery than did those without delirium (7.7 points vs. 2.1, P<0.001) and had significantly lower postoperative cognitive function than those without delirium, both at 1 month (mean MMSE score, 24.1 vs. 27.4; P<0.001) and at 1 year (25.2 vs. 27.2, P<0.001) after surgery. With adjustment for baseline differences, the between-group difference in mean MMSE scores was significant 30 days after surgery (P<0.001) but not at 6 or 12 months (P=0.056 for both). A higher percentage of patients with delirium than those without delirium had not returned to their preoperative baseline level at 6 months (40% vs. 24%, P=0.01), but the difference was not significant at 12 months (31% vs. 20%, P=0.055). CONCLUSIONS Delirium is associated with a significant decline in cognitive ability during the first year after cardiac surgery, with a trajectory characterized by an initial decline and prolonged impairment. (Funded by the Harvard Older Americans Independence Center and others.).

Breast Cancer Among the Oldest Old: Tumor Characteristics, Treatment Choices, and Survival

We performed a prospective observational study to examine the role of postoperative pain and its treatment on the development of postoperative delirium.Pain was measured in direct patient interviews using a visual analog scale (VAS) and was assessed for pain at rest, pain with movement, and maximal pain over the previous 24 h. Postoperative delirium was diagnosed during these interviews by using the confusion assessment method (CAM) and/or by using data from the medical record and the hospitals nursing intensity index. The method of postoperative analgesia, type of opioid, and cumulative opioid dose were also recorded. After controlling for known preoperative risk factors for delirium (age, alcohol abuse, cognitive function, physical function, serum chemistries, and type of surgery), higher pain scores at rest was associated with an increased risk of delirium over the first 3 postoperative days (adjusted risk ratio 1.20, P = 0.04). Pain with movement and maximal pain were not associated with delirium. Method of postoperative analgesia, type of opioid, and cumulative opioid dose were not associated with an increased risk of delirium. We conclude that more effective control of postoperative pain reduces the incidence of postoperative delirium. Implications: We performed daily interviews in a large population of patients undergoing noncardiac surgery to measure their level of pain and development of delirium. We found an association between higher pain levels at rest and the development of delirium. Our results suggest that better control of postoperative pain may reduce this serious complication. (Anesth Analg 1998;86:781-5)

Delirium Symptoms in Post-Acute Care: Prevalent, Persistent, and Associated with Poor Functional Recovery

As the U.S. population ages, major surgical procedures are being performed in elderly patients with increasing frequency (1), but few data are available to guide preoperative risk stratification. Several studies have described correlates of cardiac morbidity and mortality in patients undergoing noncardiac surgery (2-8), but the number of elderly patients in most series has been small. Furthermore, few data are available on noncardiac complications, the overall complication rate, and length of stay. We describe the influence of age on perioperative complication and mortality rates in a large cohort of patients undergoing noncardiac surgery. As discussed elsewhere, age was not an independent correlate of major cardiac complications in this cohort (7). This analysis tests the hypothesis that advanced age is a correlate of the overall rate of complications, after adjustment for functional status. Methods Patients All patients 50 years of age or older who underwent major nonemergent noncardiac procedures at Brigham and Womens Hospital, Boston, Massachusetts, from 18 July 1989 to 28 February 1994 were eligible for the study. Major noncardiac procedures were defined as those with an expected length of stay of 2 or more days. Procedures were electively scheduled or were performed nonemergently during inpatient admissions. Eligibility criteria included the ability to speak English and adequate cognitive function to give informed consent. The enrollment and clinical data collection protocols were approved by the institutional review board of Brigham and Womens Hospital. The full study protocol included preoperative interviews by clinical study personnel (physicians or research nurses). Of the 4315 patients who provided informed consent to participate, 621 (14.4%) did not provide consent before surgery for the serial interview portion of the study, which included interviews 1 and 6 months after surgery. Patients who were not interviewed before surgery were not excluded on the basis of age or clinical status, but solely according to the availability of study personnel. Data Collection The data collection protocol is described elsewhere (7, 9, 10). In brief, patients who provided informed consent to the full study protocol underwent preoperative evaluation by clinical investigators (physicians or research nurses) using a structured data form. These evaluations included detailed medical histories, physical examinations, and laboratory tests. For patients who did not undergo this evaluation because they could not be approached or because they declined participation in the interview portion of the study, we obtained clinical data from the structured evaluation by the anesthesiologist found in the medical record. This data source was also used to obtain American Society of Anesthesiologists classification for all patients. Hence, prospectively recorded clinical data were available for all patients. Consenting patients agreed to postoperative sampling of creatine kinase and, if total creatine kinase levels were elevated, measurement of creatine kinaseMB immediately after surgery, at 8 p.m. on the evening of surgery, and on the next two mornings. In all other enrolled patients, creatine kinaseMB was measured according to the physicians orders. Among all participants, the mean (SD) number of cardiac enzyme samples obtained was 4.0 2.2. Electrocardiography was performed in the recovery room and on the first, third, and fifth postoperative days if the patient remained hospitalized. The Charlson Comorbidity Index, a weighted comorbidity score based on the number and the severity of 16 selected medical diseases, was used to quantify the burden of medical comorbid conditions (11). The mean number of other common comorbid conditions in this population was calculated for all patients. Preoperative functional status was assessed in 3890 patients by performing structured interviews using the Specific Activity Scale, an ordinally scaled, four-class instrument based on metabolic expenditure in various personal care, housework, occupational, and recreational activities (12, 13). This group included 196 patients who consented to preoperative interviews but did not consent to the full study protocol, including long-term follow-up. Classification of Outcomes The occurrence of major cardiac events postoperatively was classified by a single reviewer who was blinded to preoperative clinical data and who evaluated only postoperative clinical information, including cardiac enzyme measurements, electrocardiograms, and clinical events. Myocardial infarction was diagnosed on the basis of creatine kinaseMB levels and electrocardiographic findings (10). Major cardiac complications were unstable angina (postoperative typical chest pain associated with ischemic electrocardiographic changes), myocardial infarction, cardiogenic pulmonary edema, documented ventricular tachycardia, ventricular fibrillation or primary cardiac arrest, and sustained complete heart block requiring pacemaker. Major noncardiac events were pulmonary embolism documented by autopsy, angiography, or a high-probability ventilationperfusion scan; respiratory failure requiring intubation for more than 2 days or reintubation; noncardiogenic pulmonary edema; lobar pneumonia confirmed by chest radiography and requiring antibiotic therapy; acute renal failure requiring dialysis; or cerebrovascular accident with new neurologic deficit. In-hospital mortality was also recorded, and the combined end point of major cardiac or noncardiac complications or death was used in these analyses. Statistical Analysis To evaluate the impact of age on postoperative complications, we performed analyses in which age was considered as a continuous variable and as four categories (50 to 59 years, 60 to 69 years, 70 to 79 years, and 80 years). Because age was not linearly associated with the risk for outcomes, categorized age variables are used throughout this report. Univariate correlations between clinical characteristics and age category were analyzed by using the chi-square test and the Fisher exact test for categorical variables and a t-test or Wilcoxon test for continuous variables. Because several clinical and laboratory variables are associated with age and because it is difficult to exclude the association of age with the event of interest, we included all relevant clinical variables in the multivariate analysis. Logistic regression analysis was used to determine the independent association of age with postoperative complications while controlling for the presence of comorbid conditions, sex, ethnicity, functional status as measured by Specific Activity Scale class, type of procedure, and preoperative laboratory data. Patients for whom data on selected variables were missing were excluded from the model. Clinically relevant variables from the regression model were analyzed for potential interactions, and potentially significant interaction terms were considered in the regression models. A two-sided P value less than 0.05 was considered statistically significant in all analyses. Linear regression models were used to estimate the independent variation in length of stay attributable to age, controlling for sex, ethnicity, preoperative clinical characteristics, American Society of Anesthesiologists classification, type of procedure, postoperative events, and in-hospital mortality. The logarithmic transformation of length of stay was used because of the non-normal distribution of this variable. The percentage change in the geometric mean of length of stay in the final model was used to estimate the numbers of adjusted hospital days attributable to age groups. All analyses were performed by using SAS statistical software for Windows, version 6.12 (SAS Institute, Inc., Cary, North Carolina). Role of the Funding Source The funding source had no role in data collection and analysis or in subsequent decisions about publication of manuscripts. Results Patients The study sample constituted 4315 patients who had a mean age of 67 9 years; 2096 patients (48%) were male and 3903 (90%) were white. Twenty-four percent (1015 patients) were younger than 59 years, 38% (1646 patients) were 60 to 69 years of age, 31% (1341 patients) were 70 to 79 years of age, and 7% (313 patients) were older than 80 years of age. These patients undergoing elective surgery had a low prevalence of comorbid conditions, and 3187 (74%) patients had Charlson Comorbidity Index scores of 0 through 2. The types of procedures performed were orthopedic (35%), intrathoracic (12%), abdominal (12%), abdominal aortic aneurysm (5%), other vascular (17%), and other general surgical procedures (33%). In the oldest age group, significantly fewer patients were male and nonwhite compared with the younger age groups (Table 1). The number of comorbid conditions and the average Charlson Comorbidity Index scores increased with increasing age. The distribution of Specific Activity Scale class and American Society of Anesthesiology class was also significantly worse in the older age groups; a greater proportion of patients 70 to 79 years of age and 80 years of age was classified as class 3 or 4. As expected, the type of surgical procedure performed varied among age groups. Higher percentages of older patients underwent orthopedic procedures, aortic aneurysm repair, and other vascular surgeries (Table 1). Table 1. Patient Characteristics Perioperative Complications Major or fatal perioperative complications occurred in 44 (4.3%) patients younger than 59 years of age, 93 (5.7%) patients 60 to 69 years of age, 129 (9.6%) patients 70 to 79 years of age, and 39 (12.5%) patients 80 years of age or older (P<0.001) (Figure). Age was significantly associated with a higher risk for cardiogenic pulmonary edema, myocardial infarction, ventricular arrhythmias, bacterial pneumonia, respiratory failure requiring intubation, and in-hospital mortality. All other major complications e

Postoperative Delirium: Acute Change with Long-Term Implications

PURPOSE To examine the association of intraoperative factors, including route of anesthesia, hemodynamic complications, and blood loss, with the development of postoperative delirium. PATIENTS AND METHODS We studied 1,341 patients 50 years of age and older admitted for major elective noncardiac surgery at an academic medical center. Data on route of anesthesia, intraoperative hypotension, bradycardia and tachycardia, blood loss, number of blood transfusions, and lowest postoperative hematocrit were obtained from the medical record. Delirium was diagnosed by using daily interviews with the Confusion Assessment Method, as well as from the medical record and the hospitals nursing intensity index. RESULTS Postoperative delirium occurred in 117 (9%) patients. Route of anesthesia and intraoperative hemodynamic complications were not associated with delirium. Delirium was associated with greater intraoperative blood loss, more postoperative blood transfusions, and postoperative hematocrit <30%. After adjusting for preoperative risk factors, postoperative hematocrit <30% was associated with an increased risk of delirium (odds ratio = 1.7, 95% confidence interval 1.1-2.7). CONCLUSIONS Further study is required to determine whether transfusion to keep postoperative hematocrit above 30% can reduce the incidence of postoperative delirium.