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Eur J Cardiothorac Surg 2009;35:255-259. doi:10.1016/j.ejcts.2008.08.009
Copyright © 2009, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
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Non-infective morbidity in diabetic patients undergoing coronary and heart valve surgery

Dumbor L. Ngaage*, Afil A. Jamali, Steven Griffin, Levent Guvendik, Michael E. Cowen, Alexander R. Cale

Cardiothoracic centre, Castle Hill Hospital, Kingston-Upon-Hull, East Yorkshire, United Kingdom

Received 12 June 2008; received in revised form 15 August 2008; accepted 18 August 2008.

* Corresponding author. Address: Department of Cardiothoracic Surgery, Castle Hill Hospital, Kingston-Upon-Hull, East Yorkshire HU16 5JQ, United Kingdom. Tel.: +44 1482 623256; fax: +44 1482 623257. (Email: dngaage{at}yahoo.com).


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
Objective: Studies of postoperative morbidity in diabetics have focussed on infection; however, autonomic and cardiovascular complications of diabetes potentially increase the risk for non-infective morbidity. We sought to investigate major non-infective early postoperative complications in diabetic patients. Methods: We identified diabetics who underwent CABG and/or valve operation from 1998 through 2007, and compared their clinical characteristics and outcome with a contemporaneous cohort of non-diabetic patients. Results: The demographic characteristics of 1145 diabetics were similar to 5534 non-diabetic patients (mean age 66 ± 9 years vs 66 ± 10 years, p = 0.45, female 27.5% vs 26.7%, p = 0.59, respectively). Class III/IV angina symptoms (43.9% vs 34.9%, p < 0.0001), intravenous nitrates therapy (10.4% vs 6.6%, p < 0.0001), heart failure (24.8% vs 20.4%, p = 0.001), prior myocardial infarction (37% vs 31%, p < 0.0001), ejection fraction ≤0.50 (34.5% vs 23.0%, p < 0.0001), triple vessel disease (66.3% vs 54.8%, p < 0.0001), renal insufficiency (3.6% vs 1.5%, p < 0.0001) and peripheral vascular disease (16.1% vs 8.7%) were prevalent amongst diabetics. The predominant operation was CABG (diabetic 84.8% vs non-diabetic 73.9%). Low cardiac output (28.3% vs 24.0%, p = 0.002), renal dialysis (2.0% vs 0.8%, p < 0.0001) and cerebrovascular events (5.1% vs 3.8%, p = 0.04) more often complicated recovery of diabetic patients, but operative mortality was similar for both groups. However, postoperative myocardial infarction was less common in diabetics (0.5% vs 1.4%, p = 0.02). Diabetes was not a risk factor for the composite endpoint of major non-infective morbidity and operative mortality (OR 1.15, 95% CI 0.97–1.37, p = 0.10). Diabetic patients were prone to longer postoperative hospitalisation (9.7±10.5 days vs 8.4 ± 6.7 days, p < 0.0001) and discharge to a convalescence facilities (9.8% vs 6.9%, p < 0.0001). Conclusions: Diabetic patients present for surgery with higher prevalence of cardiovascular risk factors and are more likely to develop major non-infective complications, including cardiac, renal and neurological dysfunction, even though diabetes does not directly influence non-infective postoperative morbidity following CABG and/or valve operations.

Key Words: Diabetes • Coronary artery bypass grafting • Heart valve repair/replacement • Outcomes (morbidity/mortality)


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 References
 
Diabetic patients with coronary artery disease are increasingly undergoing coronary artery bypass grafting (CABG) because of the prognostic advantage of surgical revascularisation over drug-eluting stents in this cohort of patients [1,2]. Diabetes mellitus has widespread multi-system and multi-organ effects culminating in autonomic, immune, cardiovascular, renal, gastrointestinal and ophthalmic sequelae [3,4] that potentially increase the risk for postoperative morbidity. Although a strong association has been reported between diabetes mellitus and wound infections in cardiac surgery patients [5,6], data about non-infective postoperative complications are lacking. Consequently, while strategies to mitigate wound infections due to perioperative hyperglycaemia have evolved, there are no directed measures at decreasing non-infective complications in diabetic patients.

Therefore, the objectives of this retrospective analysis were to: (1) investigate the prevalence of risk factors between diabetic and non-diabetic patients, (2) report comparative incidence rates of early major non-infective postoperative morbidity in diabetic and non-diabetic patients after CABG and/or heart valve surgery and, (3) determine the association of diabetes with these complications.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 References
 
2.1 Patients
After obtaining approval for this study from the medical and ethics committee of our institution, we interrogated our cardiothoracic surgery database and retrieved prospectively collected clinical data. The database of our institution is managed by dedicated data analysts employed to regularly update and validate entries. Patients operated for infective endocarditis and, those with missing data for the principal independent covariate (diabetes mellitus) and the dependent variables (non-infective complications and mortality), were excluded from the study. Preoperative characteristics, intraoperative details and postoperative complications for all patients who underwent primary CABG and/or valve replacement or repair between 1999 and 2007 were collated. Non-infective early postoperative morbidities of interest were major cardiac, cerebrovascular and renal complications. Major cardiac complications included postoperative myocardial infarction (new and persistent S-T changes, new Q-waves on electrocardiography) and low cardiac output state requiring inotrope with or without mechanical support using intra-aortic balloon pump counterpulsation and/or ventricular assist device. Cerebrovascular events were confusion/delirium, transient and permanent neurological deficit. Renal replacement therapy after surgery in patients who did not require dialysis before operation was considered a major renal complication.

During the study period, postoperative glycaemic control was uniform for both diabetic and non-diabetic patients. Blood glucose levels were routinely checked hourly and insulin infusion commenced when necessary, to maintain blood glucose between 5 mmol/l and 10 mmol/l. In the later period of the study, a stricter glucose control between 6 mmol/l and 8 mmol/l was targeted for all patients. The sliding scale insulin was continued till euglycaemia was achieved and diabetic patients returned to their preoperative management regime, usually by the third postoperative day.

2.2 Data analysis
Dichotomous variables are reported as percentages and compared between diabetic and non-diabetic groups using Pearson’s chi-square test. Continuous variables with symmetric distribution are reported as mean ± standard deviation (SD) and compared between the groups using Student’s t-test and, for continuous variables with asymmetric distribution, the median are reported with the 25th and 75th percentiles as interquartile range (IQR) and compared between the groups using Mann–Whitney U test. A backward, stepwise, multifactorial logistic regression model was constructed with all the variables listed in Table 1 , to determine the independent association of diabetes with adverse outcomes. A two-sided p value of 0.05 or less was considered significant. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 15.0 for windows, (SPSS Inc. 2005, Chicago, IL).


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  		Table 1 Baseline characteristics of diabetic and non-diabetic patients undergoing coronary artery bypass grafting and/or valve surgery
 

   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 References
 
3.1 Baseline characteristics
The mean age and gender distribution were similar between diabetic (n = 1145) and non-diabetic patients (n = 5524) but the former had higher mean body mass index (Table 1). At the time of surgery, more diabetic patients had advanced and unstable symptoms. Clinical features indicative of advanced cardiovascular disease were more prevalent amongst diabetic patients and included: prior myocardial infarction, treated heart failure, left ventricular systolic dysfunction (ejection fraction ≤ 0.50) and triple vessel coronary artery disease. Diabetic patients were also more likely than non-diabetic patients to present with comorbidities such as previous cerebrovascular events, renal insufficiency and peripheral vascular disease. Table 1 compares the clinical profiles of the groups.

3.2 Operative outcomes
Coronary artery bypass grafting was the predominant operation for both diabetic (93%) and non-diabetic patients (83%). By comparison, however, more diabetics underwent isolated CABG (84.8% vs 73.9% for non-diabetic patients) than valve surgery (Fig. 1 ). The average EuroScore predicted risk of operative mortality was greater for diabetic patients (4.1 ± 2.7 vs 3.9 ± 2.6, p = 0.03), but the observed operative mortality did not differ significantly between groups for CABG (2.3% for diabetic vs 1.7% for non-diabetic patients, p = 0.25) and aortic valve replacement (3.2% for diabetic, vs 1.9% for non-diabetic, p = 0.49). On the contrary, major cardiac, cerebrovascular and renal complications occurred more frequently amongst diabetic compared to non-diabetic patients. Postoperatively, 28.3% of the diabetic group were treated for low cardiac output compared to 24.0% of non-diabetics (p = 0.002), but postoperative myocardial infarction was less frequent in diabetics (0.5% vs 1.4%, p = 0.02). More diabetic patients received renal replacement therapy (haemofiltration or dialysis) for acute renal failure (2% vs 0.8%, p < 0.001) and this was also true for cerebrovascular events (5.1% vs 3.8%, p = 0.04). Table 2 lists the incidence rates of postoperative complications for the two groups. Diabetic patients were more prone to develop mechanical sternal wound dehiscence than non-diabetic patients (1.7% vs 1.0%, p = 0.03). Duration of intensive care and hospital stays after surgery were longer for diabetic patients, and at discharge, they were more likely to be transferred to medical convalescence facilities.


Figure 1
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  		Fig. 1. Bar chart of the operative procedures performed in the diabetic and non-diabetic patients.

 

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  		Table 2 Perioperative details of diabetic and non-diabetic patients
 
The composite endpoint comprising major postoperative cardiac morbidity, cerebrovascular event, renal complication and operative mortality occurred predominantly in diabetic patients (n = 363, 31.7% vs n = 1433, 25.9% for non-diabetics, p < 0.0001). The risk factors for this composite endpoint are shown on Table 3 . Diabetes mellitus was not a determinant of these adverse outcomes (OR 1.15, 95% CI 0.97–1.37, p = 0.10).


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  		Table 3 Risk factors for major cardiac morbidity, cerebrovascular event, renal replacement therapy and operative mortality after primary coronary artery bypass grafting and/or heart valve surgery
 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
References
 
This study shows a comparatively higher incidence of non-infective major postoperative complication following CABG and/or valve surgery in patients with diabetes. Even though diabetes per se, was not a determinant of major non-infective complication, it can be argued that by its deleterious multi-system and multi-organ effects, it indirectly increases the propensity for postoperative morbidity. The widespread adverse effects of diabetes mellitus include left ventricular systolic and diastolic dysfunction [7,8], vascular disease [9], cerebrovascular disorders [10], and renal failure [11]. This, therefore, explains the greater prevalence of pre-existing cardiac morbidity, renal and cerebrovascular comorbidities amongst diabetic patients, which presage the development of major complications in the respective organ systems. In addition, studies have shown that diabetic patients mount aberrant local [12] and systemic [4,13,14], response to stress. Kumbhani et al. [12] reported a rapid onset of myocardial acidosis in diabetic patients during cardiac surgery and this correlated with poor outcomes. Hamdy et al. [4], Jaffer et al. [13], and Jandric-Balen et al. [14], respectively demonstrated increased levels of pro-inflammatory markers and adhesion molecules, impaired rhythmic vasomotor and hyperaemic response, and lower levels of antioxidant enzyme activity, in diabetic patients. These defective homeostatic mechanisms place diabetic patients at greater risk of complications after cardiac surgery. The impact of adequate perioperative glycaemic control is not very clear. Although perioperative hyperglycaemia, an indication of poor diabetic control, is associated with increased postoperative infection [6,15], merely achieving euglycaemia perioperatively does not necessarily improve non-infective morbidity [16,17] despite its beneficial influence on operative mortality [18,19].

The higher rates of infective and non-infective postoperative morbidity notwithstanding, the operative mortality for diabetic patients was comparable to the rate for non-diabetic patients. These findings are corroborated by other series [15,20–22]. However, the implications of a higher operative morbidity are substantial. Prolonged hospitalisation and frequent discharge to other medical facilities for continued convalescence increase resource utilisation. Pre-emptive management strategies are therefore warranted. Testing for the adequacy of long-standing glucose control preoperatively, using glycosylated haemoglobulin level (HbA1c), is more appropriate than preoperative blood glucose levels [23] in assessing the potential for adverse outcomes in diabetic patients. Studies have shown that maintaining the HbA1c level within normal limits reduces cardiovascular risk [24]. Patients with myocardial infarction who had high levels of Hb1Ac on admission, suffered higher mortality [25]. In diabetic patients undergoing cardiac surgery, it may therefore, be of prognostic value to ensure normal HbA1c levels preoperatively, in addition to tight perioperative glucose control.

The inherent limitations of a retrospective study design apply to this analysis and our findings should be interpreted in that context. However, the large sample size, even though not evenly distributed between the two groups, and the exclusion of patients with missing principal dependent and independent variables, strengthens this paper. We did not have sufficient data to distinguish type 1 and type 2 diabetics however, the significance of long-term adequate control in order to minimise comorbidities is applicable to both types of diabetes. Even though the univariate association between diabetes and major postoperative complications was not maintained by multivariate analysis, the predominance of the risk factors in patients with diabetes warrants further investigation to improve our management of diabetic patients to obtain operative results.

In conclusion, diabetic patients present for surgery with high cardiac morbidity and, cerebrovascular, renal and peripheral vascular comorbidities, which predisposes them to major non-infective postoperative morbidity. Despite higher rates of postoperative complications, operative mortality in diabetics is comparable to non-diabetic patients. Prospective randomised trials are necessary to define the role of HbA1c, in addition to tight perioperative glucose control, in minimising major complications after cardiac surgery in diabetic patients.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 

  1. Ben-Gal Y, Moshkovitz Y, Nesher N, Uretzky G, Braunstein R, Hendler A, Zivi E, Herz I, Mohr R. Drug-eluting stents versus coronary artery bypass grafting in patients with diabetes mellitus. Ann Thorac Surg 2006;82(5):1692-1697.[Abstract/Free Full Text]
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  13. Jaffer U, Aslam M, Standfield N. Impaired hyperaemic and rhythmic vasomotor response in type 1 diabetes mellitus patients: a predictor of early peripheral vascular disease. Eur J Vasc Endovasc Surg 2008;35(5):603-606.[CrossRef][Medline]
  14. Jandric-Balen M, Bozikov V, Bistrovic D, Jandric I, Bozikov J, Romic Z, Balen I. Antioxidant enzymes activity in patients with peripheral vascular disease, with and without presence of diabetes mellitus. Coll Antropol 2003;27(2):735-743.[Medline]
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