Samuel J. Durham

Effect of blood transfusion on long-term survival after cardiac operation

BACKGROUNDnBlood transfusions have been linked to increased morbidity and mortality. Bleeding during and after cardiac operations and the hemodilution effects of cardiopulmonary bypass commonly result in blood transfusions. Because we could not find any studies evaluating the effects of transfusion on long-term survival after cardiac operation, we sought to determine these effects.nnnMETHODSnWe studied 1,915 patients who underwent first-time isolated coronary artery bypass operations between July 6, 1994 and December 31, 1997 at our institution. Patients with transfusions were compared with those who had not been transfused. Long-term survival data were obtained from the United States Social Security Death Index. Groups were compared by Cox proportional hazard models, Kaplan-Meier survival plots, and hazard functions.nnnRESULTSnSix hundred forty-nine of 1,915 study patients (34%) received a transfusion during their hospitalization. Transfused patients were older, smaller, and more likely to be female, and had more comorbidity. Transfused patients also had twice the 5-year mortality (15% vs 7%) of nontransfused patients. After correction for comorbidities and other factors, transfusion was still associated with a 70% increase in mortality (risk ratio = 1.7; 95% confidence interval = 1.4 to 2.0; p = 0.001). By multivariate analysis, transfusion, peripheral vascular disease, chronic obstructive pulmonary disease, New York Heart Association functional class IV, and age were significant predictors of long-term mortality.nnnCONCLUSIONSnWe found that blood transfusions during or after coronary artery bypass operations were associated with increased long-term mortality.

Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed?

BACKGROUNDnHemodilutional anemia during cardiopulmonary bypass can lead to inadequate oxygen delivery and, consequently, to ischemic organ injury. In adult bypass, the nadir hematocrit can vary widely with body size and prebypass hematocrit variations, yet its effects on perioperative organ dysfunction and patient outcomes remain largely unknown.nnnMETHODSnTo elucidate these effects, we retrospectively analyzed operative results and resource utilization data from 5000 consecutive cardiac operations with cardiopulmonary bypass performed on adults (1994 to 2000). Rolling decile groups (500 patients each; 75% overlapping) of increasing lowest hematocrit values were used to characterize hemodilution-outcome relationships. Intermediate-term (0 to 6 years) survival was assessed for coronary artery bypass patients (n = 3800) via Kaplan-Meier analysis in quintile subgroups based on lowest hematocrit. Multivariate logistic regression (operative mortality and morbidity) and Cox proportional hazard model (0- to 6-year mortality) analyses were used to determine independent predictors of poor outcomes.nnnRESULTSnStroke, myocardial infarction, low cardiac output, cardiac arrest, renal failure, prolonged ventilation, pulmonary edema, reoperation due to bleeding, sepsis, and multiorgan failure were all significantly and systematically increased as lowest hematocrit value decreased below 22%. Consequently, intensive care requirements, hospital stays, operative costs, and operative deaths were also significantly greater as a function of hemodilution severity. Longer-term survival was improved systematically for increasing lowest hematocrit coronary artery bypass grafting quintiles; for example, 6-year survival was 80.5% and 92.3% for quintiles I (lowest hematocrit = 16.1%) and V (lowest hematocrit = 27.5%). The continuous variable lowest hematocrit was an independent predictor of (1) operative mortality, (2) prolonged cardiovascular intensive case (>2 days) and postoperative hospital (>8 days) stays, and (3) worse 0- to 6-year survival.nnnCONCLUSIONSnIncreased hemodilution severity during cardiopulmonary bypass was associated with worse perioperative vital organ dysfunction/morbidity and increased resource use, as well as greater short- and intermediate-term mortality. We speculate that these results derive from inadequate oxygen delivery causing ischemic and/or inflammatory vital organ injury, as recently demonstrated intravitally in cerebral tissues. Although this analysis of a large observational study offers evidence linking low on-pump hematocrit values to these adverse outcomes, prospective randomized trials are needed (1) to establish whether a causal effect of hemodilution on poor outcomes actually exists and (2) to test the potential efficacy of maintaining on-pump hematocrit above 22% for improving outcomes of cardiopulmonary bypass.

Effects of body size on operative, intermediate, and long-term outcomes after coronary artery bypass operation

BACKGROUNDnTo investigate the role of body size, if any, on operative and longer term outcomes following coronary artery surgery.nnnMETHODSnA total of 3,560 consecutive patients undergoing coronary artery bypass grafting from 1991 to 1997, including 2,401 (67%) males and a mean +/- SD age of 63 +/- 10 years were ranked based on their body mass index (BMI). The association in these patients of preoperative, long-term, and economic data with variations in BMI were studied using regression analyses. Long-term survival was studied using 5-year Kaplan-Meier survival analysis.nnnRESULTSnOperative mortality, myocardial infarction, cerebrovascular accidents, blood transfusions, and length of hospital stay were all increased in the smallest patients (BMI < or = 24 kg/m2). Obesity did not increase adverse operative outcomes except for a greater rate of sternal wound infections occurring with increasing severity of obesity. Direct variable costs were lowest in patients clustered around normal BMI, with cost increasing similarly at low and high extremes. This effect was correlated with similar BMI effects on ventilatory and intensive care requirements. Excluding operative mortality, 5-year survival trends were similarly worse for the smallest (BMI < or = 24) and most severely obese (BMI > 34) patients. Mild obesity (BMI > or = 30 to BMI < 34) did not affect long-term survival.nnnCONCLUSIONSnAmong study patients, immediate operative outcomes were adversely affected by small body size, which reflected older age (66 +/- 10 years) and an exaggerated adverse impact of cardiopulmonary bypass. Younger age and smaller effects of cardiopulmonary bypass lead to better operative outcomes in the obese. Long-term outcomes were, however, suboptimal in severely obese patients although that group was the youngest (60 +/- 10 years). In addition to their large body habitus, other factors, including substantial prevalence of diabetes, insulin dependence and hypertension, probably played a significant role in the poor long-term outcome in the severely obese.

Safe, highly selective use of pulmonary artery catheters in coronary artery bypass grafting: An objective patient selection method

BACKGROUNDnRoutine versus selective use of pulmonary artery catheter (PAC) monitoring in coronary artery bypass grafting operations is a topic of significant debate. Accordingly, we retrospectively examined operative outcomes in 2,685 consecutive (1994 to 1998) coronary artery bypass grafting patients in whom PAC use was highly selective. Next, we developed a quantitative model of PAC use in terms of its multivariate predictors as a means of providing an objective criterion for patient PAC use selection.nnnMETHODSnSafety of the implemented selective PAC use was assessed by comparisons to contemporaneous coronary artery bypass grafting outcome reported by The Society of Thoracic Surgeons national data. Continuous relations describing PAC use in terms of continuous univariate predictors were obtained using overlapping-range patient cohorts. Next, independent predictors of PAC use were derived by multivariate regression to best fit the categorical variable PAC (Yes = 1, No = 0). Model estimates were a continuous variable (PAC score) with values between 0 and 1.nnnRESULTSnPlanned use of PAC was based on collective consideration of preoperative patient variables, and was not limited to low-risk or preserved ejection fraction patients. Planned and unplanned use of PAC was limited to 176 (planned, 6.6%) and 66 (unplanned, 2.4%) patients, respectively, whereas no PAC was used in 2,443 (91%). Overall patient characteristics and risk factors in this series were comparable to contemporaneous Society of Thoracic Surgeons data, and the incidence of operative deaths was 2.31% (n = 61; observed-to-expected [Society of Thoracic Surgeons risk] mortality = 0.73). Independent predictors of PAC use were ejection fraction, Society of Thoracic Surgeons risk, intraaortic balloon pump, congestive heart failure, reoperative surgery, and New York Heart Association class IV. Expectedly, PAC scores were substantially different for PAC (mean +/- standard deviation, 0.37 +/- 0.20; median, 0.38) and no PAC (0.14 +/- 0.11; median, 0.10) patients (p < 0.001). Area under the receiver operating characteristic curve derived for PAC score was relatively high (area, 0.85). Moreover, the corresponding summed sensitivity (0.68 to 0.91) and specificity (0.85 to 0.62) was maximized at 1.53 for PAC score between 0.15 and 0.31.nnnCONCLUSIONSnOur results indicate that highly selective use of PAC in coronary artery bypass grafting can be accomplished safely, and it need not be limited to patients with preserved ejection fractions or low operative risk. Indeed, coronary artery bypass grafting without PAC may be preferable in the vast majority of patients as it reduces catheter-associated risks and resource utilization without incurring an increased operative risk. Also, pending further prospective confirmation, our analysis suggests that collective consideration of PAC use predictors to derive a PAC score provides an objective criterion to minimize unnecessary use of PAC with an acceptably low probability of error.

Resource utilization in coronary artery bypass operation: does surgical risk predict cost?

BACKGROUNDnCurrent healthcare trends may render financial risk of cardiac operation a key component of clinical decision making. It has been suggested, based on large cohorts of patients stratified by clinical risk, that the cost of operation can be predicted from models of clinical risk since length of stay (LOS) is highly correlated to clinical risk, and LOS is correlated to hospital costs and charges. Direct correlation of actual surgical costs with surgical risk are lacking.nnnMETHODSnVariable direct costs, LOS, and The Society of Thoracic Surgeons predicted mortality risk [STS risk (%)] were collected and analyzed in 628 consecutive patients undergoing coronary artery bypass grafting (CABG) at our institution in 1997.nnnRESULTSnCost of CABG had a near-normal distribution, and cost in 21 outlier patients (cost > two standard deviations above the mean) was an average 5.3 times normal (median cost). For individual patients, cost was well correlated to LOS (R2 = 0.48) but not with STS risk (R2 = 0.12). LOS was also poorly predicted by STS risk (R2 = 0.09). However, despite its poor prediction of cost, STS risk was an unbiased estimator over the entire population. A result manifested, when patients were grouped into similar risk (<1%, 1-2%, 2+ -3%, 3+ -5%, 5+ -10%, and >10%) cohorts, by high correlation between cost and STS risk (R2 = 0.99), cost and LOS risk (R2 = 0.99), and LOS and STS risk (R2 = 0.97).nnnCONCLUSIONSnOur data demonstrated that, in large CABG cohorts, surgical risk models can accurately predict cost of CABG. However, despite a trend for increasing cost with increasing STS risk, surgical risk models based on preoperative data are poor predictors of cost in individual patients. Use of these models should be limited to analysis of cost trends in cardiac operation, but not for predicting financial risk in individual patients during clinical decision making.

Operative and 5-year outcomes of combined carotid and coronary revascularization: review of a large contemporary experience

BACKGROUNDnSurgical treatment of concomitant coronary and carotid disease is controversial. Studies comparing staged versus combined coronary artery bypass grafting and carotid endarterectomy (CABG/CEA) report varying and often conflicting operative results. Also, few studies have investigated the long-term outcomes of combined surgery.nnnMETHODSnWe reviewed the operative outcome and 5-year survival results of 189 consecutive patients (69+/-9 years old, 66 [35%] female patients) who underwent combined CABG/CEA between 1994 and 1999. Survival follow-up was conducted in February 2001 and the incidence of late stroke, carotid surgery, and myocardial infarction was investigated in all surviving patients by mail survey. A phone interview was done by a surgeon of patients with late strokes or repeated CEA.nnnRESULTSnOperative death occurred in 5 of 189 patients (2.65%) 4 of which were in-hospital deaths. A total of 5 (2 permanent, 3 transient [2.65%]) perioperative strokes were documented in these patients, and 1 of the perioperative strokes patients died in the hospital. In all, 156 of 189 patients (82.5%) were alive at the time of the study and completed surveys were collected from 153 of 156 patients (98%). Of these 153 patients, 4 reported a late stroke (2.6%), 5 suffered a myocardial infarction (3.3%), and 16 (10.5%) underwent subsequent CEA (7 ipsilateral to original CEA). Angioplasty (3 of 153, 2.0%) and redo surgery (1 of 153, 0.66%) occurred infrequently. Median survival follow-up was 51 months (range 12 to 84), and the corresponding 5-year Kaplan-Meier survival was 79.4%. This survival was similar to that of age-matched isolated CABG patients (n = 532) with documented history of cerebrovascular disease but no surgical carotid lesions.nnnCONCLUSIONSnOur results suggest that combined CABG/ CEA is safe and may in fact reduce the risk of adverse outcomes in the intermediate term compared with age and risk-matched patients. We speculate the latter may be attributable to a cerebrovascular protective effect of CABG/CEA pending verification by randomized trials. An economic benefit of CABG/CEA may also be inferred from avoiding separate coronary and carotid operations and reduction in the high costs of perioperative stroke.

The c-myc x E2F-1/p21 interactive gene expression index augments cytomorphologic diagnosis of lung cancer in fine-needle aspirate specimens

Morphological analysis of cytologic samples obtained by fine-needle aspirate (FNA) or bronchoscopy is an important method for diagnosing bronchogenic carcinoma. However, this approach has only about 65 to 80% diagnostic sensitivity. Based on previous studies, the c-myc x E2F-1/p21WAF1/CIP1 (p21 hereafter) gene expression index is highly sensitive and specific for distinguishing normal from malignant bronchial epithelial tissues. In an effort to improve sensitivity of diagnosing lung cancer in cytologic specimens, we used Standardized Reverse Transcriptase Polymerase Chain Reaction (StaRT-PCR) to measure the c-myc x E2F-1/p21 index in cDNA samples from 14 normal lung samples (6 normal lung parenchyma and 8 normal bronchial epithelial cell [NBEC] biopsies), and 16 FNA biopsies from 14 suspected tumors. Based on cytomorphologic criteria, 11 of the 14 suspected tumors were diagnosed as bronchogenic carcinoma and three specimens were non-diagnostic. Subsequent biopsy samples confirmed that the three non-diagnostic samples were derived from lung carcinomas. The index value for each bronchogenic carcinoma was above a cut-off value of 7000 and the index value of all but one normal sample was below 7000. Thus the c-myc x E2F-1/p21 index may augment cytomorphologic diagnosis of bronchogenic carcinoma biopsy samples, particularly those considered non-diagnostic by cytomorphologic criteria.

Underutilization of implantable cardioverter defibrillators post coronary artery bypass grafting in patients with systolic dysfunction.

Background: Evaluation of the need for prophylactic internal cardiac defibrillators among patients with ischemic cardiomyopathies should be deferred until at least 3 months after revascularization procedures to allow adequate time for recovery of ventricular function.