|
|
||||||||
Ann Thorac Surg 2003;75:1392-1399
© 2003 The Society of Thoracic Surgeons
a Departments of Internal Medicine, Greenville, NC, USA
b Surgery, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
Accepted for publication December 5, 2002.
* Address reprint requests to Dr Estrada, The Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Pitt County Memorial Hospital, Teaching Annex Room 389, Greenville, NC 27858, USA
e-mail: estradac{at}mail.ecu.edu
| Abstract |
|---|
|
|
|---|
METHODS: We report a historic cohort study of 1574 patients who had undergone coronary artery bypass grafting between 1998 and 1999, 545 (34.6%) with diabetes. Perioperative blood glucose level was defined as the average of all blood glucose tests obtained on the day of and the day after surgery. Outcomes were 30-day mortality, infection rates (sternum, harvest site, sepsis, pneumonia, urinary tract), and resource utilization.
RESULTS: After adjusting for diabetes status and calculated preoperative mortality or mediastinitis risk scores, each 50 mg/dL (2.78 mmol/L) blood glucose increase was not statistically associated with higher mortality (odds ratio 1.37; 95% confidence interval, 0.98 to 1.92; p = 0.07), or higher infection rate (odds ratio 1.23, 95% confidence interval 0.94 to 1.60; p = 0.14). Each 50 mg/dL blood glucose increase was associated with longer postoperative days by 0.76 days (95% confidence interval 0.36 to 1.17 days; p < 0.001), increased hospitalization charges by $2824 (95% confidence interval $1599 to $4049; p < 0.001), and increased hospitalization cost by $1769 (95% confidence interval $928 to $2610; p < 0.001). In the unadjusted analysis, infections occurred more frequently in patients with diabetes (6.6% vs 4.1%, p = 0.03).
CONCLUSIONS: Perioperative hyperglycemia is associated with increased resource utilization in patients undergoing coronary artery bypass grafting with and without diabetes.
| Introduction |
|---|
|
|
|---|
Based on the evidence, authors recommend that for patients with diabetes undergoing surgery, the blood glucose should be maintained at less than 200 mg/dL [46]. The American College of Cardiology/American Heart Association guidelines for patients undergoing CABG recommends aggressive perioperative glucose control by using continuous intravenous insulin infusion for patients with diabetes [2, 7]. Management of perioperative hyperglycemia in patients without a diagnosis of diabetes has not been extensively studied; whether hyperglycemia is associated with adverse clinical outcomes in such patients is not known.
Insulin infusion among patients with diabetes undergoing cardiac surgery has been associated with improved postoperative glucose control, lower incidence of sternal wound infections [8, 9], shorter length of stay, and lower mortality [9]. However, studies have enrolled few patients [10], the risk adjustment method used has not been validated in cardiac surgery patients [4]; in addition, mortality [4] or other clinical outcomes have not been explored [10]. Differences in outcomes could also be explained by changes in overall perioperative care before and after the institution of intravenous insulin infusion protocols [8, 9].
We sought to measure the relationship between perioperative hyperglycemia among patients undergoing CABG and mortality, infection rates, and resource utilization. We hypothesized that all patients with higher perioperative glucose levels have worse outcomes than patients with lower glucose levels.
| Patients and methods |
|---|
|
|
|---|
Outcomes
The outcomes were (1) 30-day mortality; (2) 30-day infections (infection was defined as any of the following: infection at the harvest site, sepsis, pneumonia, urinary tract infection, or sternal wound infection [usually requiring debridment, flap reconstruction, and intravenous antibiotics]); and (3) resource utilization, measured by postoperative days to discharge (number of days between the date of surgery and the date of hospital discharge), hospitalization charges, and hospitalization costs. A standard incision is performed to harvest veins at our institution.
Data sources
Trained nurses prospectively collected clinical information by using the Society of Thoracic Surgeons database (STS) [11, 12]. The database fields and definitions are available at the Cardiothoracic Surgery Network World Wide Website (URL: http://www.ctsnet.org/doc/4880, last accessed August 7, 2002). We supplemented our infection data with data collected prospectively for infection control purposes on sternal wound or harvest site infections. Perioperative blood glucose levels data were obtained from laboratory databases. Resource utilization data were obtained from administrative databases. Costs were estimated by cost accounting at our institution in 1999 US dollars.
Statistical analyses
We used Students-t test and the
2 test for the unadjusted analyses. We used logistic regression to test the association of perioperative glycemia on mortality and infection rate adjusting for diabetes status and mortality risk score or mediastinitis risk score, respectively, and used linear regression to test the association with resource utilization adjusting for diabetes status and mortality risk score [13, 14]. Glucose was entered into the models as a continuous variable (increments of 1 mg/dL). Because differences in outcomes based on 1 mg/dL increments of glucose is not clinically meaningful, we converted the odds ratios and beta coefficients to reflect changes of an arbitrary glucose increment of 50 mg/dL. Both estimates are mathematically equivalent. We tested the linearity assumption of the effect of average perioperative blood glucose level on mortality and infections by including a quadratic term and an interaction term; the linearity assumption was maintained. The risk scores with the weights as initially published were reproducible in our setting (see results), providing evidence of generalizability and transportability of the scores. We also reanalyzed the data using the original values of the variables included in the risk score, added the glucose testing frequency, and added other clinical variables. The reanalyses yielded more conservative estimates, but the direction of the effect or the significance level were not changed. When we replaced the average perioperative glucose with the highest level, we obtained less conservative estimates. Thus, in the overall analyses, the mortality and resource utilization models included diabetes status, average perioperative blood glucose level, and the Northern New England Cardiovascular Disease mortality risk score. The infections rate model included diabetes status, average perioperative blood glucose level, and the Northern New England Cardiovascular Disease mediastinitis risk score. In the subgroup analyses separate models were done for patients with and without diabetes. The variables in the models were average perioperative blood glucose level, and mortality risk score or mediastinitis risk score. We analyzed the data with SPSS software (Version 10.0; SPSS, Chicago, IL) and report odds ratios, beta coefficients, and 95% confidence intervals. All analyses were planned a priori and hypotheses in the primary analyses were tested at
= 0.05.
| Results |
|---|
|
|
|---|
|
|
|
|
Postoperative days
Patients with diabetes stayed in the hospital after surgery 0.97 days longer (95% confidence interval 0.3 to 1.6 days) than patients without diabetes (p = 0.004). In the unadjusted analyses, higher perioperative glucose levels were associated with similar postoperative days among patients with diabetes (p = 0.28), and longer postoperative days among patients without diabetes (p = 0.001), illustrated in Figure 1. In the linear regression analysis, after adjustment for diabetes and preoperative mortality risk score, each 50 mg/dL blood glucose increase was associated with an increase in postoperative days by 0.76 days (95% confidence interval 0.36 to 1.17; p < 0.001), illustrated in Figure 3.
|
Subgroup analyses
In the logistic regression analyses, after adjustment for preoperative risk score, higher perioperative glucose was not statistically associated with higher mortality and infections among patients with or without diabetes (Table 3).
Among patients with diabetes, after adjustment for preoperative mortality risk score, each 50 mg/dL glucose increase was associated with an increase in postoperative days by 0.99 days (p = 0.01), hospitalization charges by $4320 (p
0.001), and hospitalization cost by $2870 (p < 0.001), see Table 3. Similarly, among patients without diabetes, each 50 mg/dL glucose increase was associated with an increase in postoperative days by 0.58 days (p < 0.01), hospitalization charges by $1552 (p = 0.02), and a nonstatistically significant trend towards higher hospitalization cost by $782 (p = 0.07), as depicted in Table 3.
|
| Comment |
|---|
|
|
|---|
First, the direction, magnitude, and range in the confidence intervals of the estimate suggest an increased mortality risk. Most values in the confidence interval are above the number one. Mortality was an infrequent outcome; the number of patients in our cohort did not provide a large enough sample to be statistically significant. Other studies suggest that hyperglycemia in patients with diabetes undergoing CABG is a risk factor for infections [4]. The risk of infection was increased by 78% (253 to 352 mg/dL), 86% (230 to 252 mg/dL), and 17% (207 to 229 mg/dL) compared with patients in the lower quartile (121 to 206 mg/dL) [4].
Second, the association between perioperative hyperglycemia and resource utilization among patients without diabetes has not been previously reported. The association seems to be present after adjusting for severity of illness. Hyperglycemia in such patients may be explained by stress hyperglycemia, glucose intolerance, or undiagnosed diabetes. Clinicians caring for such patients may need to entertain the diagnosis of diabetes and treat them accordingly. Any level of perioperative hyperglycemia may be a more sensitive marker for adverse outcomes. Other evidence suggests that hyperglycemia in patients with diabetes undergoing CABG is associated with increased length of stay [15]. The economic implications of these findings in patients with and without diabetes cannot be ignored.
Hyperglycemia and glucose control are also important in other settings. Data on aggressive glycemic control among patients with diabetes and cardiac ischemia provide supporting evidence of its benefits. Stress hyperglycemia after myocardial infarction is associated with an increased risk for in-hospital death in patients with and without diabetes [16]. Mild elevation of blood glucose has also been associated with increased mortality in patients without diabetes undergoing percutaneous coronary artery interventions [17]. In the diabetes and insulin-glucose infusion in acute myocardial infarction trial [18, 19], insulin infusion in the hospital followed by intensive glucose control for 1 year lowered mortality from 44% to 33%. The mean glucose value at 24 hours was lower in the intensive glucose control group (172 mg/dL vs 210 mg/dL). Significantly, age, congestive heart failure, blood glucose at admission, and glycated hemoglobin contributed to the prediction of long-term mortality, and high blood glucose levels at admission predicted in-hospital mortality [18, 19].
Our study adds to the evidence of the association of perioperative hyperglycemia and adverse outcomes. We included unselected patients seen at a primary and tertiary care center. We used contemporary data, adjusted for risk using validated methods in cardiac surgery, and explored clinical and resource utilization outcomes. Also, we included patients without a prior diagnosis of diabetes.
We acknowledge limitations to this study. First, no uniform agreement exists as to the best method to adjust outcomes in cardiac surgery patients; however, the method that we used has been proposed in recent guidelines [2, 7] and included variables deemed important at a recent consensus conference [20]. Other methods of mortality or infection risk adjustment may have yielded different results [11, 2123]. Secondly, due to the nature of the historic cohort design, frequency of glucose testing was not standardized. Finally, our study was not designed to explore causality bewteen perioperative glucose control and outcomes. The efficacy of postoperative glucose control has been reported in a recent study [24]. Intensive insulin therapy (goal of 80 to110 mg/dL) reduced mortality and septicemia when compared with conventional therapy (goal of 180 to 200 mg/dL), 4.6% versus 8% and 4.2% versus 7.8%, respectively [24].
Data from our historic cohort study and the recent randomized trial has increased the awareness of the significance of perioperative glycemic control on outcomes at our institution. Glucose management is undergoing change aiming at better glucose control.
Perioperative hyperglycemia is associated with increased resource utilization in patients with and without diabetes undergoing coronary artery bypass grafting. The perioperative glycemic control of patients without diabetes warrants further study.
| Acknowledgments |
|---|
|
|
|---|
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
American College of Cardiology Foundation, American Heart Association Task Force on Practice, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interve, Society for Vascular Medicine, Society for Vascular Surgery, L. A. Fleisher, et al. 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery J. Am. Coll. Cardiol., November 24, 2009; 54(22): e13 - e118. [Full Text] [PDF] |
||||
![]() |
T. Alserius, N. Hammar, T. Nordqvist, and T. Ivert Improved survival after coronary artery bypass grafting has not influenced the mortality disadvantage in patients with diabetes mellitus. J. Thorac. Cardiovasc. Surg., November 1, 2009; 138(5): 1115 - 1122. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Pleva, J. M. Mirtallo, and S. M. Steinberg Hyperglycemic Events in Non-Intensive Care Unit Patients Receiving Parenteral Nutrition Nutr Clin Pract, October 1, 2009; 24(5): 626 - 634. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Graf, D. Sohr, A. Haverich, C. Kuhn, P. Gastmeier, and I. F. Chaberny Decrease of deep sternal surgical site infection rates after cardiac surgery by a comprehensive infection control program Interactive CardioVascular and Thoracic Surgery, August 1, 2009; 9(2): 282 - 286. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Knapik, P. Nadziakiewicz, E. Urbanska, W. Saucha, M. Herdynska, and M. Zembala Cardiopulmonary Bypass Increases Postoperative Glycemia and Insulin Consumption After Coronary Surgery. Ann. Thorac. Surg., June 1, 2009; 87(6): 1859 - 1865. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. S. Moghissi, M. T. Korytkowski, M. DiNardo, D. Einhorn, R. Hellman, I. B. Hirsch, S. E. Inzucchi, F. Ismail-Beigi, M. S. Kirkman, and G. E. Umpierrez American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control Diabetes Care, June 1, 2009; 32(6): 1119 - 1131. [Full Text] [PDF] |
||||
![]() |
D. L. Ngaage, A. A. Jamali, S. Griffin, L. Guvendik, M. E. Cowen, and A. R. Cale Non-infective morbidity in diabetic patients undergoing coronary and heart valve surgery Eur. J. Cardiothorac. Surg., February 1, 2009; 35(2): 255 - 259. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. E. Umpierrez, T. Hor, D. Smiley, A. Temponi, D. Umpierrez, M. Ceron, C. Munoz, C. Newton, L. Peng, and D. Baldwin Comparison of Inpatient Insulin Regimens with Detemir plus Aspart Versus Neutral Protamine Hagedorn plus Regular in Medical Patients with Type 2 Diabetes J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 564 - 569. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Anzalone Equivalence of Earlobe Site Blood Glucose Testing With Finger Stick Clin Nurs Res, November 1, 2008; 17(4): 251 - 261. [Abstract] [PDF] |
||||
![]() |
J. Malaskovitz and C. Hodge A Look at System-Wide Data Collection Processes to Improve Patient Outcomes Diabetes Spectr, October 1, 2008; 21(4): 262 - 267. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. S. Manchester Diabetes Education in the Hospital: Establishing Professional Competency Diabetes Spectr, October 1, 2008; 21(4): 268 - 271. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. E. Antunes, J. F. de Oliveira, and M. J. Antunes Coronary surgery in patients with diabetes mellitus: a risk-adjusted study on early outcome. Eur. J. Cardiothorac. Surg., August 1, 2008; 34(2): 370 - 375. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Sadhu, A. C. Ang, L. A. Ingram-Drake, D. S. Martinez, W. A. Hsueh, and S. L. Ettner Economic Benefits of Intensive Insulin Therapy in Critically Ill Patients: The Targeted Insulin Therapy to Improve Hospital Outcomes (TRIUMPH) Project Diabetes Care, August 1, 2008; 31(8): 1556 - 1561. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Kawano, K. Tanaka, K. Mawatari, S. Oshita, A. Takahashi, and Y. Nakaya Hyperglycemia Impairs Isoflurane-Induced Adenosine Triphosphate-Sensitive Potassium Channel Activation in Vascular Smooth Muscle Cells Anesth. Analg., March 1, 2008; 106(3): 858 - 864. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. A. Fleisher, J. A. Beckman, K. A. Brown, H. Calkins, E. L. Chaikof, K. E. Fleischmann, W. K. Freeman, J. B. Froehlich, E. K. Kasper, J. R. Kersten, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery J. Am. Coll. Cardiol., October 23, 2007; 50(17): e159 - e242. [Full Text] [PDF] |
||||
![]() |
L. A. Fleisher, J. A. Beckman, K. A. Brown, H. Calkins, E. L. Chaikof, K. E. Fleischmann, W. K. Freeman, J. B. Froehlich, E. K. Kasper, J. R. Kersten, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Circulation, October 23, 2007; 116(17): e418 - e500. [Full Text] [PDF] |
||||
![]() |
R. K. Campbell Etiology and effect on outcomes of hyperglycemia in hospitalized patients Am. J. Health Syst. Pharm., May 15, 2007; 64(10_Supplement_6): S4 - S8. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Garg, H. Bhutani, E. Alyea, and M. Pendergrass Hyperglycemia and Length of Stay in Patients Hospitalized for Bone Marrow Transplantation Diabetes Care, April 1, 2007; 30(4): 993 - 994. [Full Text] [PDF] |
||||
![]() |
C. Rajakaruna, C. A. Rogers, C. Suranimala, G. D. Angelini, and R. Ascione The effect of diabetes mellitus on patients undergoing coronary surgery: A risk-adjusted analysis J. Thorac. Cardiovasc. Surg., October 1, 2006; 132(4): 802 - 810. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. G. Shann, D. S. Likosky, J. M. Murkin, R. A. Baker, Y. R. Baribeau, G. R. DeFoe, T. A. Dickinson, T. J. Gardner, H. P. Grocott, G. T. O'Connor, et al. An evidence-based review of the practice of cardiopulmonary bypass in adults: A focus on neurologic injury, glycemic control, hemodilution, and the inflammatory response. J. Thorac. Cardiovasc. Surg., August 1, 2006; 132(2): 283 - 290.e3. [Full Text] [PDF] |
||||
![]() |
The ACE/ADA Task Force on Inpatient Diabetes American College of Endocrinology and American Diabetes Association Consensus Statement on Inpatient Diabetes and Glycemic Control: A call to action Diabetes Care, August 1, 2006; 29(8): 1955 - 1962. [Full Text] [PDF] |
||||
![]() |
A. S. Dronge, M. F. Perkal, S. Kancir, J. Concato, M. Aslan, and R. A. Rosenthal Long-term Glycemic Control and Postoperative Infectious Complications Arch Surg, April 1, 2006; 141(4): 375 - 380. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Butterworth, L. E. Wagenknecht, C. Legault, D. J. Zaccaro, N. D. Kon, J. W. Hammon Jr, A. T. Rogers, B. T. Troost, D. A. Stump, C. D. Furberg, et al. Attempted control of hyperglycemia during cardiopulmonary bypass fails to improve neurologic or neurobehavioral outcomes in patients without diabetes mellitus undergoing coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., November 1, 2005; 130(5): 1319 - 1319. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. X. Freire, L. Bridges, G. E. Umpierrez, D. Kuhl, and A. E. Kitabchi Admission Hyperglycemia and Other Risk Factors as Predictors of Hospital Mortality in a Medical ICU Population Chest, November 1, 2005; 128(5): 3109 - 3116. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. G. Fowler Jr, S. M. O'Brien, L. H. Muhlbaier, G. R. Corey, T. B. Ferguson, and E. D. Peterson Clinical Predictors of Major Infections After Cardiac Surgery Circulation, August 30, 2005; 112(9_suppl): I-358 - I-365. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Veiraiah Hyperglycemia, Lipoprotein Glycation, and Vascular Disease Angiology, July 1, 2005; 56(4): 431 - 438. [Abstract] [PDF] |
||||
![]() |
G. Y. Gandhi, G. A. Nuttall, M. D. Abel, C. J. Mullany, H. V. Schaff, B. A. Williams, L. M. Schrader, R. A. Rizza, and M. M. McMahon Intraoperative Hyperglycemia and Perioperative Outcomes in Cardiac Surgery Patients Mayo Clin. Proc., July 1, 2005; 80(7): 862 - 866. [Abstract] [PDF] |
||||
![]() |
F. H. Edwards, V. A. Ferraris, D. M. Shahian, E. Peterson, A. P. Furnary, C. K. Haan, and C. R. Bridges Gender-Specific Practice Guidelines for Coronary Artery Bypass Surgery: Perioperative Management Ann. Thorac. Surg., June 1, 2005; 79(6): 2189 - 2194. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. M Conner, K. R Flesner-Gurley, and J. C Barner Hyperglycemia in the Hospital Setting: The Case for Improved Control Among Non-Diabetics Ann. Pharmacother., March 1, 2005; 39(3): 492 - 501. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. T. Bloomgarden Inpatient Diabetes Control: Approaches to treatment Diabetes Care, September 1, 2004; 27(9): 2272 - 2277. [Full Text] [PDF] |
||||
![]() |
W. H. Merrill, S. A. Akhter, R. K. Wolf, E. W. Schneeberger, and J. B. Flege Jr Simplified treatment of postoperative mediastinitis Ann. Thorac. Surg., August 1, 2004; 78(2): 608 - 612. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. S. Krinsley Effect of an Intensive Glucose Management Protocol on the Mortality of Critically Ill Adult Patients Mayo Clin. Proc., August 1, 2004; 79(8): 992 - 1000. [Abstract] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |