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Ann Thorac Surg 2002;74:712-719
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Early postoperative outcome and medium-term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting

^a Department of Cardiothoracic Anesthesia, Linköping Heart Center, University Hospital, Linköping, Sweden
^b Department of Cardiothoracic Surgery, Linköping Heart Center, University Hospital, Linköping, Sweden

Accepted for publication April 25, 2002.

* Address reprint requests to Dr Svedjeholm, Department of Cardiothoracic Surgery, Linköping Heart Center, University Hospital, S-581 85 Linköping, Sweden
e-mail: rolf.svedjeholm{at}lio.se

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. An increasing proportion of patients undergoing coronary artery bypass grafting (CABG) are diabetics. Patient characteristics, early postoperative outcome, and midterm survival in diabetic patients after CABG were investigated.

Methods. A total of 2779 consecutive patients undergoing isolated CABG during 1995 to 1999 were studied, 19.4% of whom had diabetes mellitus. Demographic and peri-procedural data were registered prospectively in a computerized institutional database.

Results. The diabetic group was younger and included a higher proportion of women, and patients with hypertension, triple-vessel disease, and unstable angina. They required a higher number of bypasses, and longer cross-clamp and cardiopulmonary bypass times. Intensive care unit and hospital stays were prolonged and the need for inotropic agents, hemotransfusions, and dialysis was higher in the diabetic group. Renal failure, stroke (4.3% versus 1.7%), mediastinitis, and wound infections were more frequently encountered. Thirty-day mortality was 2.6% versus 1.6% (p = 0.15). Cumulative 5-year survival was 84.4% versus 91.3% (p < 0.001).

Conclusions. Short-term mortality was acceptable in diabetic patients after CABG but they had increased postoperative morbidity in comparison with nondiabetic patients, particularly with regard to renal function, cerebral complications, and infections. Midterm survival was impaired in diabetic patients mainly because of a less favorable outcome in patients treated with insulin.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Diabetes mellitus is a recognized risk factor for the development of the coronary artery disease and an independent risk factor for mortality from myocardial infarction [1]. Diabetes is also a risk factor in association with myocardial revascularization procedures but, according to recent studies, coronary artery bypass grafting (CABG) may be the treatment of choice in this group of patients [2]. A consequence of the evolution of coronary angioplasty is that a higher proportion of patients undergoing CABG today either have extensive coronary artery disease or diabetes mellitus. A previous large scale Scandinavian study demonstrated a more than twofold increase in early postoperative mortality among diabetic patients [3]. Therefore, the purpose of this study was to investigate short-term outcome in terms of postoperative morbidity and 30-day mortality and medium-term survival in all diabetic patients undergoing CABG in the southeast health region of Sweden.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Patients
The University Hospital in Linköping is the referral center for the southeast region of Sweden serving a population of approximately 1 million. From January 1995 to December 31, 1999, all 2779 patients undergoing isolated CABG were studied. Five hundred forty (19.4%) of these patients had a history of diabetes mellitus on admission that had necessitated active therapy with diet or medication (45% were on insulin treatment and 38.0% on oral antidiabetic agents). Demographic and perioperative data are given in Table 1.

Clinical management
After an overnight’s fast, and administration of their beta-blockers and calcium-antagonists, the patients were premedicated with 4 to 10 mg oxicone and 0.2 to 0.5 mg scopolamine intramuscularly. Anesthesia was induced with thiopentone 1 to 2 mg/kg body weight (BW) and fentanyl 10 µg/kg BW. Pancuronium bromide was used for neuromuscular blockade. Anesthesia was maintained with intermittent doses of fentanyl and isoflurane.

Most patients underwent CABG using standard techniques with cardiopulmonary bypass (CPB) and aortic cross-clamping. Ringer’s acetate and mannitol were used for priming the extracorporeal circuit. Moderate hemodilution (hematocrit 20% to 25%) and light hypothermia (33° to 36°C) were usually used. Antegrade or combined ante- and retrograde delivery of a modified St. Thomas’ cold crystalloid cardioplegic solution (Plegisol, Abbot, IL) was used for myocardial protection. Weaning from CPB was started at a rectal temperature of 35° to 36°C. Heparin was neutralized with protamine chloride. A total of 4.3% of the procedures were done without the aid of CPB. Ringer’s acetate was used for volume substitution postoperatively. Shed mediastinal blood was routinely retransfused in the intensive care unit (ICU). Postoperative rewarming was facilitated by radiant heat provided by a thermal ceiling.

Prevention and treatment of postoperative heart failure differed from traditional treatment by frequent use of metabolic interventions with intravenous glutamate or high-dose glucose-insulin-potassium (GIK). Details about these treatments have been given previously [4, 5]. Postoperatively the patients received heparin or dalteparin 5000 IU twice daily until fully mobilized. Salicylic acid 160 mg daily was given during the first week and thereafter changed to 75 mg daily.

Definitions
Patients were classified as diabetic only if they had an established diagnosis of diabetes mellitus according to medical records that could be confirmed by the patient. Registration in the database also required active treatment on admission ranging from diet to insulin. Thus, history of diabetes was not based on actual laboratory values after admission. Complications presented refer to in-hospital events occurring at our institution. Perioperative myocardial infarction was defined by combined electrocardiogram and enzyme criteria. Electrocardiographic criteria included appearance of new Q-waves in at least two or more contiguous leads or the appearance of pathologic R-wave progression together with inversion of T-waves in at least two leads on a 12-lead electrocardiogram. Enzyme criteria included ASAT exceeding 3.0 µkat/L with alanine aminotransferase less than half of the aspartate aminotransferase value, usually supported by a creatine kinase MB fraction of more than 70 µg/L on the first postoperative morning or by a sustained elevation of troponin-T of more than 2.0 µg/L on the third to fourth postoperative day. Stroke was defined as a permanent or transient central neurologic deficit. Most patients with suspected neurologic injury were examined by computed tomography scan. Cognitive dysfunction was not assessed. Postoperative renal failure was defined as a serum creatinine level exceeding 170 µ mol/L regardless of preoperative value. Use of inotropic agents was defined as the use of either catecholamines or phosphodiesterase inhibitors. Sepsis was defined as a septic clinical condition with positive blood cultures. Hospital stay refers to hospital stay at the University Hospital (most patients were discharged to the referring hospitals). The cause of death was defined as the event initiating multiorgan failure if several potential causes were described. The other variables in the database were defined according to definitions of the Society of Thoracic Surgery Cardiac and Thoracic Databases.

Statistical analysis
Data are presented as mean ± standard deviation (SD). Nonparametric tests, the Mann-Whitney U test for continuous variables, and the Fisher exact test for categorical variables were used for comparison of patients with and without diabetes mellitus. The ² test for unordered categories was used to compare the incidence of different complications within the diabetic cohort depending on the type of antidiabetic therapy on admission. Cumulative long-term survival was assessed with Kaplan-Meier analysis. Statistical significance was defined as p less than 0.05. Statistical analyses were performed with computerized statistical packages (Statistica 5.5, StatSoft, Inc, Tulsa, OK; Statview for Windows 5.0.1, SAS Institute, Cary, NC).

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Preoperative data
The diabetic group was characterized by lower mean age, higher body mass index, a higher proportion of female patients, and more patients with hypertension, triple-vessel disease, and unstable angina. Left-main stenosis was less frequently encountered in the diabetic group. Details are given in Table 1.

Intraoperative data
Most (95.7%) of the procedures were performed with CPB in both groups; arterial grafts were used in 95.4% of the diabetic patients and 94.0% of the nondiabetic patients. The diabetic group was characterized by a higher number of distal anastomoses, and longer aortic cross-clamp and CPB times. No significant difference was found in the use of inotropic agents, but high-dose GIK was more frequently used in diabetic patients. Details are given in Table 2.

Overall metabolic interventions with high-dose GIK including use intraoperatively and postoperatively were recorded in 20.4% of the diabetic patients compared with 10.5% of the nondiabetic patients (p < 0.001). No difference in the overall use of intravenous glutamate was found (4.8% versus 4.6%; p = 0.82).

The use of inotropic agents did not differ intraoperatively (6.5% versus 4.6%) but was higher in the diabetic group during their ICU stay (13.9% versus 8.9%; p = 0.006).

Postoperative data
The diabetic group had longer ICU and hospital stays. Hemotransfusions were more frequently used in the diabetic group. Stroke, renal failure, use of dialysis, wound infections, and reoperations for mediastinitis were more often observed in the diabetic patients.

Overall results are given in Table 3 and the major complications are described below. Univariate analysis of diabetes as a risk factor for major complications is given in Table 4. Intergroup differences regarding mortality and major complications depending on diabetic treatment on admission is given in Figure 1.

View larger version (39K): [in this window] [in a new window]   Fig 1. Thirty-day mortality and the incidence of stroke, renal failure, and sternal wound infections after coronary artery bypass grafting in nondiabetic (control, n = 2239) and diabetic patients depending on diabetic therapy (diet, n = 97; tablet, n = 205; insulin, n = 238). *Statistically significant difference between the diet and insulin-treated groups (2 test for unordered categories) within the diabetic cohort of patients.

Renal complications
Preoperative dialysis was observed in 0.6% of the diabetic group and 0.4% of the nondiabetic gourp. The need for postoperative dialysis in the remaining patients was higher in the diabetic group (0.9% versus 0.2%; p = 0.03). A postoperative s-creatinine level exceeding 170 µmol/L was observed in 3.9% of the diabetic patients compared with 2.2% of the nondiabetic patients (p = 0.03).

Neurologic outcome
The total incidence of stroke was 4.3% in the diabetic group and 1.7% in the nondiabetic group (p < 0.001). The neurologic deficit had resolved during the hospital stay in 17% of the diabetic patients and 22% of the nondiabetic patients.

Mortality
Thirty-day mortality was 2.6% in the diabetic group and 1.6% in nondiabetic group (p = 0.15). The primary cause of early mortality was cardiac in 41.7% in the diabetic patients and 67.6% of the nondiabetic patients. Neurologic injury was the cause of the early death in 33.3% of the diabetic patients compared with 14.7% in the nondiabetic patients. Median follow-up was 32 months (range 3 to 63 months). The crude mortality during this period was 10.2% in the diabetic group compared with 5.6% in the nondiabetic group (p < 0.001). Cumulative 5-year survival (Kaplan-Meier) was 84.4% in the diabetic patients and 91.3% in the nondiabetic patients (p < 0.001; Fig 2).

View larger version (19K): [in this window] [in a new window]   Fig 2. Cumulative 5-year survival (Kaplan-Meier) in diabetic and nondiabetic patients after coronary artery bypass grafting.

View larger version (21K): [in this window] [in a new window]   Fig 3. Cumulative 5-year survival (Kaplan-Meier) after coronary artery bypass grafting in diabetic patients depending on method of antidiabetic therapy on admission.

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
An increasing proportion of patients undergoing CABG are diabetic [6]. However, the proportions of CABG patients that are diabetic vary markedly even within the European community. A recent survey of risk factor variation demonstrated that the proportions of diabetic patients ranged from 11.8% to 27.7% [7]. In the present study, 19.4% of the patients were diabetic when all patients with an established diagnosis and active treatment ranging from diet to insulin were included.

Before the results are discussed some aspects of study design deserve comment. The major strengths of the study were the completeness of survival data, prospective data collection, and that the material represented all diabetic patients undergoing CABG in the southeast region of Sweden during the given time interval.

The limitations of the study included aspects inherent to large data registries with various degrees of incomplete data, hazards associated with definitions of data entries, and possible misclassification of some individual data. To attenuate these limitations, only reasonably complete data were assessed. Mortality data were checked against the Swedish Civil Registry.

The mean age was younger in diabetic patients, which is consistent with studies demonstrating a more rapidly evolving atherosclerotic progress in diabetic individuals [8]. Accordingly, triple-vessel disease was overrepresented in diabetic patients. As in previous studies, female sex and hypertension also were overrepresented in the diabetic group [3, 9, 10].

Data in the literature conflict regarding the influence of diabetes on outcome after cardiac operations [3, 9–14]. It is generally accepted that diabetic individuals have a higher mortality and morbidity in association with CABG, but the influence of diabetes per se on outcome has been under debate. Some studies have found associated risk factors to explain the differences in postoperative mortality [11], whereas other studies have claimed diabetes to be an independent risk factor for mortality even after adjustment for confounding factors [3, 9, 10]. In the present study a sufficiently broad set of validated and complete data were not considered to be available to permit reliable multivariable analysis of diabetes per se as an independent risk factor. With the exception of studies that have either included a limited number of patients [12] or matched surgical populations [13, 14], most studies have found diabetes to be associated with an increased early postoperative mortality [3, 9–11]. In our study the difference in postoperative 30-day mortality between diabetic and nondiabetic patients did not reach statistical significance. However, in agreement with previous studies we found an untoward effect of diabetes on late outcome, with a 1.9-fold increased risk of late mortality during the follow-up compared with nondiabetic patients. Also, in agreement with previous studies an increased risk of postoperative morbidity particularly with regard to renal failure, neurologic injury, and wound infections was observed [3, 10, 13, 15, 16].

Previous studies that investigated subgroups of diabetic patients have found the method of therapy on admission, preoperative blood glucose level, and presence of proteinuria to predict an adverse outcome [10, 17–19]. Our database did not provide information about blood glucose control on admission or the presence of proteinuria, but in agreement with previous studies diabetic patients dependent on insulin treatment had worse long-term survival and seemed to account for the difference in midterm outcome between the diabetic and nondiabetic groups (Figures 2 and 3). The diabetic treatment required on admission was also related to early postoperative morbidity particularly with regard to renal failure and wound infections (Fig 1). As the complications presented only refer to in-hospital events, the incidence of some complications such as neurologic injury, and in particular wound infections, may have been underestimated.

In general the incidence of complications was comparable to that reported in the literature and the short-term mortality compared favorably with most previous studies (Table 5). With the exception of a low rate of redo procedures, our case-mix does not seem to be less severe compared with most other studies on this issue. The mean age and the proportion of patients with unstable angina was higher than in most studies [3, 9, 10, 17, 20, 21]. However, the results regarding unstable angina have to be interpreted with regard to a shift toward a larger proportion of Braunwald Class II C patients being operated during recent years, particularly after the FRISC II trial [22]. Furthermore, due to differences in case-mix between countries even within the European community and even within countries using similar principles for case selection and therapy, comparisons have to be made cautiously. In a similar large scale Swedish study, the 30-day mortality rate was more than twofold higher [3]. Our results do not provide any clear explanations for this discrepancy, but the previous study included a higher proportion of redo procedures and patients with previous history of cerebrovascular disease. Also, differences between institutions in perioperative management deserve consideration.

The perioperative care in our study differed from traditional management by the use of metabolic treatment with high-dose GIK and glutamate for prevention and treatment of perioperative heart failure [4, 5]. This difference could explain the comparatively low use of inotropic agents intraoperatively in both groups of patients. Whether these characteristics of perioperative care contributed to the overall results remains to be established.

An interesting observation is that other investigators who have used insulin or GIK for metabolic control in diabetic patients undergoing CABG have presented favorable results [13, 26]. The role of insulin and strict blood glucose control for outcome in association with cardiac -elated critical conditions has received increasing attention over the last few years. In critically ill surgical patients, intensive insulin treatment to achieve strict blood glucose control was found to reduce both morbidity and mortality [27]. Approximately two thirds of these patients had undergone cardiac operative procedures and in this subgroup the unadjusted reduction in ICU mortality was 59%. The benefit from insulin treatment in diabetic patients was not as evident as in nondiabetic patients. However, strict metabolic control with insulin infusion after cardiac operation has been demonstrated to reduce the incidence of wound infections in diabetic patients [28]. Furthermore, in diabetic patients with acute myocardial infarction, insulin infusions have been shown to reduce late mortality [29]. The latter study is particularly interesting as it suggests that optimization of metabolic control in the acute phase and during follow-up can enhance long-term survival in diabetic patients. Thus, a sustained strict metabolic control with insulin may prove more important for outcome than intensive insulin treatment during the acute phase in diabetic patients. Considering the impaired long-term survival in diabetic patients after CABG, similar approaches deserve evaluation after cardiac operations.

To conclude, diabetic patients can undergo CABG with an acceptable mortality risk only marginally different from that found in nondiabetic patients. Cardiac causes for early death were predominant in both diabetic and nondiabetic patients, but neurologic injury accounted for a comparatively higher proportion of early deaths in the diabetic group. The risk for postoperative morbidity with regard to neurologic, infectious, and renal complications was increased and partly related to type of diabetic therapy on admission and, hence, severity of diabetic disease. Moreover, midterm survival was markedly impaired, particularly in insulin-treated diabetic patients. Further efforts are warranted to address early postoperative morbidity and late outcome as diabetic patients are accounting for an increasing proportion of the patients undergoing CABG.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
The authors are grateful to Dr Lars Löfström and RN Inger Huljebrant for assistance with retrieval of data from the institutional database. The study was supported by Stina och Birger Johansson Stiftelse Sweden and the Swedish Heart Lung Foundation.

	References

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