Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients
Ouattara, Alexandre M.D.*; Lecomte, Patrick M.D.†; Le Manach, Yannick M.D.†; Landi, Marc M.D.*; Jacqueminet, Sophie M.D.‡; Platonov, Igor M.D.†; Bonnet, Nicolas M.D.§; Riou, Bruno M.D., Ph.D.∥; Coriat, Pierre M.D.#
Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity.
Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity.
Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7–19.0).
Conclusion: Poor intraoperative control of blood glucose concentrations in diabetic patients undergoing cardiac surgery is associated with a worsened hospital outcome after surgery.
NUMEROUS clinical studies have reported an increase in perioperative morbidity among diabetic patients undergoing cardiac surgical procedures.1–4
Although diabetes mellitus has been identified as an independent risk factor of morbidity and even mortality after cardiac surgery in large cohort studies,3–7
other recent studies have clearly demonstrated that perioperative glycemic control improves early clinical outcome of diabetic patients.8–10
Various mechanisms by which hyperglycemia could affect clinical outcome have been identified. Hyperglycemia provokes numerous deleterious effects on myocardium subjected to ischemia–reperfusion process. In both diabetics and hyperglycemic dogs, the myocardial infarct size is strongly correlated with blood glucose concentration.11
Moreover, high blood glucose concentration abolishes ischemic preconditioning11
and amplifies reperfusion injuries.12
Because hyperglycemia provokes coronary endothelial dysfunction,13,14
it may further increase the incidence of myocardial ischemic events. The beneficial effects of glycemic control may be also related to the metabolic effects of insulin, including a decrease in concentration of free fatty acids15
and the scavenging of free radicals.16
Unfortunately, most clinical studies in which the beneficial effect of glucose control has been demonstrated were focused on the postoperative period. However, cardiopulmonary bypass (CPB) usually induces severe hyperglycemia, which may involve several mechanisms.17–21
Consequently, intraoperative glycemic control may be rendered difficult despite insulin therapy.18,22,23
Although previous studies have reported that strict intraoperative glycemic control during CPB improves immune function of diabetic patients,18
few previous clinical studies have evaluated the impact of intraoperative glycemic control on the postoperative outcomes.10
Therefore, we hypothesized that poor intraoperative glycemic control could be associated with worsened hospital outcome in diabetic patients undergoing heart surgery.
Materials and Methods
This study was approved by our ethical committee (Comité de Protection des Personnes se. Prêtant à la Recherche Biomédicale, CCPPRB Pitié-Salpêtrière, Paris, France). Although care of patients conformed to the standard procedure currently used at our institute, written informed consent was obtained from each patient included in this study. Between January 20, 2003, and September 30, 2003, all diabetic patients requiring active therapy based on oral hypoglycemic drugs or insulin and undergoing on-pump heart surgery were prospectively enrolled in our study. Patients in whom diabetes was controlled by diet alone were excluded from this current study. We excluded also patients undergoing off-pump coronary artery bypass graft. For each patient, preoperative risk factors of morbidity and mortality (i.e., demographic characteristics, principles identified comorbidity factors, preoperative medication) and intraoperative data (type of procedure, duration of cardiopulmonary bypass, requirement for erythrocyte transfusion, intraoperative blood glucose concentrations) were prospectively entered into a database for later analysis.
All treated diabetic patients undergoing cardiac procedures at our institute received a standardized service local protocol established by endocrinologist, surgeons, cardiologists, and anesthesiologists over a 6-month period. The aim of this protocol was to standardize the titration of insulin therapy during the perioperative period. Therefore, for elective cardiac procedures, this protocol required the withdrawal of any preoperative diabetic treatment on the evening of the day before surgery, except for metformin, which was discontinued 1 week before heart surgery. The treatment was replaced with 0.15 U/kg subcutaneous intermediary insulin (Umuline NPH; Lilly, Suresnes, France) with additional subcutaneous fast-acting insulin (Actrapid HM; Novo Nordisk Pharmaceutique, Puteaux, France) according to blood glucose concentrations (BGL). In addition to the implementation of this protocol, an infusion of dextrose solution was started (5 g/h). After fasting overnight, all patients received a premedication based on 1 mg/kg midazolam and 0.1 mg/kg morphine subcutaneously the morning of the surgery. After BGL measurement, all patients systematically received a further subcutaneous injection of 0.15 U/kg intermediary insulin on the morning of surgery (Umuline NPH). All other medications were taken until the day of the surgery, except for antagonists of converting enzyme inhibitors, which were stopped the day before surgery.
During the intraoperative period, the infusion of dextrose was maintained at the same rate (i.e.
, 5 g/h). BGL was measured immediately after the induction of anesthesia and was repeated every 30 min. An aggressive insulin therapy, based on continuous infusion of fast-acting insulin (Actrapid HM), was initiated as soon as BGL exceeded 180 mg/dl. Subsequently, its infusion rate was titrated according to a protocol (appendix
) modified from the Portland protocol.9
The objective of the current protocol was to maintain an intraoperative blood glucose concentration between 150 and 200 mg/dl as previously recommended.9,10,18
To ensure that intravenous insulin therapy was rapidly administered to the patient, it was systematically infused through a peripheral venous catheter into which dextrose was also infused. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease until the end of the surgical procedure despite the insulin therapy administered according to the protocol. For all patients, a total intravenous anesthesia protocol, based on midazolam or propofol and sufentanil or remifentanil, was used. No inhaled anesthetics agent was used intraoperatively. Antibiotic cover during the study followed our normal protocol and was based on cefamandole, except for patients with allergy for penicillin, in whom vancomycin associated with gentamicin was preferentially used. Antifibrinolytic treatment was based on aprotinin (1 million Kallikrein Inactivator Units after induction of anesthesia and in the priming solution followed by a continuous infusion of 250,000 Kallikrein Inactivator Units/h until the end of the surgery). The CPB used a membrane oxygenator with nonpulsatile flow. The choice of normothermia (36°–37°C), mild hypothermia (32°–36°C), and hypothermia (30°–32°C) during the CPB was left to the discretion of the surgeon. No dextrose solution was included in the priming volume. All drugs used intraoperatively were diluted in sterile water or saline solution. During the postoperative period, all patients were aggressively treated with either subcutaneous or continuous intravenous insulin therapy to maintain a BGL less than 140 mg/dl throughout the stay in the intensive care unit, as was recently recommended.24
A continuous fast-acting insulin infusion (Actrapid HM) was used in the intensive care unit according to a standard protocol (table 1
) in following circumstances: (1) when insulin therapy was the usual antidiabetic treatment of the patient, (2) if inotropic support was required for weaning from CPB, (3) if the intraoperative infusion insulin rate exceeded 2 U/h, (4) if there was an unstable hemodynamic state necessitating any drugs, (5) if an intensive care unit duration of stay greater than 24 h was expected, or (6) if the postoperative glycemic control was difficult by subcutaneous insulin therapy. In other cases, subcutaneous insulin therapy was administered according to the following protocol: An intermediary insulin (Umuline NPH) was given subcutaneously twice daily (0.15 U/kg). Additionally, BGL were adjusted every 4 h by subcutaneous fast-acting insulin (Actrapid HM): less than 110 mg/dl, 0 U; 110–144 mg/dl, 2 U; 145–179 mg/dl, 4 U; 180–219 mg/dl, 6 U; greater than 220 mg/dl, 8 U. Measurements of BGL were performed by finger stick or arterial line drop sampling by using a glucose analyzer (AccuData GTS; Boehringer Mannheim Corporation, Indianapolis, IN).
The primary outcome was severe in-hospital morbidity as recently defined in the cardiac surgical population25,26
and including at least one of the following adverse outcomes: (1) cardiovascular outcome (low cardiac output and/or hypotension treated with an intraaortic balloon pump and/or two or more intravenous inotropes or vasopressors greater than 24 h, malignant arrhythmia [asystole, ventricular tachycardia, or fibrillation] requiring cardiopulmonary resuscitation, antiarrhythmia therapy, or defibrillator implantation); (2) respiratory outcome (mechanical ventilation for more than 48 h, reintubation, tracheostomy); (3) neurologic outcome (focal brain injury with permanent functional deficit, irreversible encephalopathy); (4) renal outcome (acute renal failure necessitating dialysis); (5) infectious outcome (septic shock with positive blood cultures, deep sternal or leg wound infection requiring intravenous antibiotics and/or surgical debridement); or (6) other outcome (any surgical or invasive procedure necessary to treat a postoperative adverse event associated with the initial cardiac surgery). The secondary outcomes were the in-hospital mortality and a prolonged stay in the intensive care unit (> 96 h). The postoperative data were prospectively collected in a database for further analysis. All data were reviewed by two independent investigators (A. O. and P. L). In case of disagreement between the two experts, a consensus was reached with a third expert.
The sample size was based on the facts that, in our cardiac surgical population, the occurrence of diabetes mellitus was approximately of 20%, and the severe postoperative morbidity rate was approximately of 25%. With an α error of 0.05, a β error of 0.20 (power = 80%), and r 2 of 0.3 for other usual predictors of severe morbidity as defined, 189 patients were required to detect an odds ratio of 2.0. Anticipating a 5% loss to follow-up, this number was increased to 200 patients.
Univariate comparisons between patients with or without severe morbidity during their intensive care unit stay were performed by using a chi-square test or Fisher exact test where appropriate for dichotomous variables and by the Student t test or Wilcoxon rank test according to their distribution for continuous variables. All perioperative predictors identified in the univariate analysis were included in a multivariate logistic regression analysis. A backward conditional method was used for variable selection. No more than 1 variable per 10 outcome events was entered in the final logistic model to avoid overfitting. Calibration and discrimination of the logistic model were assessed using the Hosmer and Lemeshow chi-square statistic (P > 0.05 for no difference between predictive model and observed data) and the receiver operating characteristic curve, respectively. Colinearity between potential predictors was assessed with a bivariate analysis. To reveal possible heterogeneity in odds ratios between subgroups of patients, interactions terms were assessed. The 95% confidence interval (CI) of ratios was calculated. Perioperative blood glucose concentrations were compared by using repeated-measures analysis of variance and the Newman-Keuls test. Data are expressed as mean ± SD. Percentages are associated with their 95% CIs. All P values were two tailed, and a P value of less than 0.05 was considered significant. All analyses were performed using SPSS 11.5 (Chicago, IL).
Between January and September 2003, 1,146 consecutive patients underwent cardiac surgical procedures in our heart institute. Among these patients, 207 (18%) patients were known as diabetic patients under medical treatment. Seven patients were excluded from this study (5 patients in whom an off-pump coronary artery bypass grafting procedure was finally decided by the surgeon and 2 patients in whom intraoperative blood glucose concentrations were not available). Consequently, a total of 200 patients were included in our analysis. The overall in-hospital severe morbidity rate was 29% (95% CI, 23–35%). The distribution of different morbidities is summarized in table 2
. Baseline clinical characteristics of patients with and without severe morbidity are presented in table 3
. During the intraoperative period, an insulin infusion was initiated in 71 patients (36%; 95% CI, 29–42%). Among these patients, 35 (50%; 95% CI, 34–67%) had poor intraoperative glycemic control despite aggressive insulin therapy. During the period spent in intensive care unit, BGLs were comparable between patients with and without postoperative morbidity (data not shown). However, because BGLs at arrival in the intensive care unit were significantly higher in patients who exhibited poor intraoperative glycemic control (208 ± 54 vs.
148 ± 41 mg/dl; P
< 0.001), BGL in this group was more difficult to normalize in the early postoperative period (data not shown). Poor intraoperative glycemic control was significantly more frequent in patients with severe intrahospital morbidity (table 3
). Intraoperative BGLs were significantly higher in patients with severe postoperative morbidity (fig. 1A
) and in patients in whom intraoperative glycemic control was poor (fig. 1B
). As shown in figure 2
, all in-hospital morbidities, except for infectious morbidity (P
= 0.09), were significantly more frequent in patients who exhibited poor intraoperative glycemic control.
Multivariate analysis identified poor glycemic control as an independent risk factor of severe morbidity (table 4
). The adjusted odds ratio for postoperative severe morbidity among diabetic patients who had poor intraoperative glycemic control as compared with patients who were well controlled was 7.2 (95% CI, 2.7–19.0). The Hosmer and Lemeshow statistic was 7.57 (P
= 0.48), and the area under the receiver operating characteristic curve was 0.86 (95% CI, 0.81–0.92). No heterogeneity in the increase of morbidity among the patients with poor intraoperative glycemic control was found between subgroups of patients according to main risk factors in cardiac surgery (table 5
). In diabetic patients who exhibited poor intraoperative glycemic control, the overall in-hospital mortality rate was significantly higher (11.4% vs.
< 0.05), and a prolonged intensive care unit duration of stay was more frequently observed (46% vs.
The main findings of this prospective observational study in diabetic patients undergoing cardiac surgery are that (1) poor intraoperative glycemic control despite aggressive insulin therapy occurred in 18% of cases, and (2) poor intraoperative glycemic control is associated with a worsened in-hospital outcome after cardiac surgery.
Diabetes mellitus has been identified as an independent risk factor of adverse outcome after cardiac surgery.4–7
The prevalence of diabetes mellitus in our cardiac population was 18% and was consistent with previous studies.2,27
Although diabetes mellitus is a well-recognized risk factor of poor outcomes after cardiac surgery,4–7
few trials have identified the independent risk factors of poor outcome in diabetic patients undergoing heart surgery. In a large prospective cohort of diabetic patients undergoing coronary artery bypass grafting, Thourani et al.4
identified age, procedure status, female sex, and hypertension as independent risk factors of mortality. In our study, by using multivariate analysis, we identified six perioperative risk factors of severe in hospital morbidity, including poor intraoperative glycemic control. Nevertheless, the strongest of these risk factors was a preoperative pulmonary hypertension, a variable that has previously been shown to be an important risk factor in the general cardiac surgical population.27,28
We also identified the use of systemic hypothermia during CPB as an independent risk factor of severe in-hospital morbidity. The CPB-induced hyperglycemia is principally related to the release of stress hormone decrease in peripheral use of glucose and decrease in insulin secretion.17,20,21
This latter seems to be more severely affected during hypothermic CPB.17,21
Although we did not measure intraoperative plasma insulin concentrations, we were unable to find significant interaction between hypothermic CPB and poor intraoperative glycemic control to predict severe postoperative morbidity (table 5
). Several randomized studies previously demonstrated the advantages of normothermic CPB on either postoperative early hemodynamic profile or transfusion requirement.29,30
Nevertheless, to our knowledge, our study is the first to demonstrate an association between hypothermic systemic perfusion and worse outcome in diabetic patients. Perioperative glycemic control by aggressive insulin therapy has been reported to improve outcome in diabetic patients undergoing cardiac surgery.8–10,15,31
A beneficial effect of postoperative glycemic control on outcome has been recently demonstrated in diabetic and nondiabetic patients admitted to a surgical intensive care unit, principally after cardiac surgery.32
Although numerous clinical trials have suggested that intraoperative glycemic control may be rendered difficult during on-pump cardiac surgery,18,23,33
no study has reported its impact on outcomes after cardiac surgery in diabetic patients. We hypothesized that poor intraoperative glycemic control would be associated with worsened hospital outcome. Hyperglycemia has been previously reported to exert deleterious effects on myocardium subjected to ischemia–reperfusion process,11,12,14,34,35
and two recent studies have demonstrated that intraoperative adverse myocardial events assessed by early cardiac I troponin release may influence in-hospital as well as long-term outcome after cardiac surgery.36,37
We found that poor intraoperative glycemic control is associated with an increase in intrahospital severe morbidity. Our findings are consistent with previous studies that reported beneficial effects of tight glycemic control in different clinical settings.8,10,24,31,32,38
However, the current study is the first to report the real impact of intraoperative glycemic control on in-hospital outcome after cardiac surgery in diabetics patients. Although the current study was purely observational, the available data in the literature allow speculation on underlying mechanisms. As previously mentioned, hyperglycemia has been described to be, in itself, potentially deleterious for myocardium11,12,14,34,35
and may be responsible for endothelial dysfunction.14,39
Moreover, the intraoperative refractory hyperglycemia observed in our study suggests a possible insulin resistance, which has been previously reported during cardiac surgery.40
This phenomenon contributes to an increase in the concentration of in circulating free fatty acids due to increased lipolysis. These compounds are well recognized to be detrimental during ischemic myocardium by inducing increase myocardial oxygen demand, arrhythmias, calcium overload, and myocardial dysfunction.10,15,41
All of these cardiac adverse effects could contribute to an increase in morbidity in diabetic patients who exhibit poor intraoperative glycemic control despite insulin therapy.
The following points must to be considered in the assessment of the clinical relevance of our study. First, we cannot exclude that more aggressive insulin therapy might normalize intraoperative BGL, although our protocol is in accord with the more recent recommendations8
and represents a major effort to control BGL. Second, because our study was purely observational, we cannot establish a causal relation between difficult intraoperative glycemic control and an increase in severe in-hospital morbidity. Two hypotheses may be suggested, both of which require further study: (1) poor glycemic control identifies patients at higher risk or (2) is responsible for an increased risk. These two hypotheses may not be mutually exclusive. Third, the power of our study was not sufficient to evaluate the impact of intraoperative glycemic control on mortality. Nevertheless, in the univariate analysis, the overall mortality rate was significantly higher in patients who exhibited poor intraoperative glycemic control.
In conclusion, in treated diabetic patients undergoing on-pump cardiac surgery, the intraoperative glycemic control can be rendered difficult in spite of aggressive insulin therapy. In these patients, the occurrence of a poor intraoperative glycemic control is associated with a worsened hospital outcome.
The authors thank David Baker, M.D., F.R.C.A. (Staff Anesthesiologist, Department of Anesthesiology and Critical Care, Centre Hospitalier Universitaire Necker-Enfants Malades, Paris, France), for reviewing the manuscript.
Intraoperative Insulin Protocol**
The infusion of insulin was initiated according to the following protocol: < 180 mg/dl, 0 U/h; 180–220 mg/dl, 1 U/h; 221–249 mg/dl, 2 U/h; > 249 mg/dl, 3 U/h. Subsequently, blood glucose concentrations were measured every 30 min, and the insulin infusion rate was titrated according the following protocol: < 140 mg/dl, rate of infusion was maintained at 0 until 180 mg/dl. Then, the insulin infusion was restarted at a rate 50% of the previous rate; 140–179 mg/dl, decrease the rate by 0.5 U/h; 180–220 mg/dl, no changes in the infusion rate; 221–249 mg/dl, if the blood glucose concentration was lower than in the last test, the rate of infusion was unchanged, and if the blood glucose concentration was greater than in the last test, the infusion rate was increased by 0.5 U/h; ≥ 250 mg/dl, the rate of infusion was increased by 1 U/h. If the blood glucose concentration did not decrease after three successive measures, the insulin infusion rate was doubled. Cited Here...
1. Herlitz J, Wognsen GB, Emanuelsson H, Haglid M, Karlson BW, Karlsson T, Albertsson P, Westberg S: Mortality and morbidity in diabetic and nondiabetic patients during a 2-year period after coronary artery bypass grafting. Diabetes Care 1996; 19:698–703
2. Szabo Z, Hakanson E, Svedjeholm R: Early postoperative outcome and medium-term survival in 540 diabetic and 2239 nondiabetic patients undergoing coronary artery bypass grafting. Ann Thorac Surg 2002; 74:712–9
3. Morricone L, Ranucci M, Denti S, Cazzaniga A, Isgro G, Enrini R, Caviezel F: Diabetes and complications after cardiac surgery: Comparison with a non-diabetic population. Acta Diabetol 1999; 36:77–84
4. Thourani VH, Weintraub WS, Stein B, Gebhart SSP, Craver JM, Jones EL, Guyton RA: Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting. Ann Thorac Surg 1999; 67:1045–52
5. Herlitz J, Wognsen GB, Karlson BW, Sjoland H, Karlsson T, Caidahl K, Hartford M, Haglid M: Mortality, mode of death and risk indicators for death during 5 years after coronary artery bypass grafting among patients with and without a history of diabetes mellitus. Coron Artery Dis 2000; 11:339–46
6. Carson JL, Scholz PM, Chen AY, Peterson ED, Gold J, Schneider SH: Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery. J Am Coll Cardiol 2002; 40:418–23
7. Bucerius J, Gummert JF, Walther T, Doll N, Falk V, Onnasch JF, Barten MJ, Mohr FW: Impact of diabetes mellitus on cardiac surgery outcome. Thorac Cardiovasc Surg 2003; 51:11–6
8. Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Storm Flotem H, Starr A: Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003; 125:1007–21
9. Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A: Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg 1997; 63:356–61
10. Lazar HL, Chipkin S, Philippides G, Bao Y, Apstein C: Glucose-insulin-potassium solutions improve outcomes in diabetics who have coronary artery operations. Ann Thorac Surg 2000; 70:145–50
11. Kersten JR, Toller WG, Gross ER, Pagel PS, Warltier DC: Diabetes abolishes ischemic preconditioning: Role of glucose, insulin and osmolality. Am J Physiol 2000; 278:H1218–24
12. Verma S, Maitland A, Weisel RD, Li S, Fedak PWM, Pomroy NC, Mickle DAG, Li R, Ko L, Rao V: Hyperglycemia exaggerates ischemia-reperfusion-induced cardiomyocyte injury: Reversal with endothelin antagonism. J Thorac Cardiovasc Surg 2002; 123:1120–4
13. Koltai MZ, Hadhazy P, Posa I, Kocsis E, Winkler G, Rosen P, Pogatsa G: Characteristics of coronary endothelial dysfunction in experimental diabetes. Cardiovasc Res 1997; 34:157–63
14. Gross ER, LaDisa JF, Weihrauch D, Olson LE, Kress TT, Hettrick DA, Pagel PS, Warltier DC, Kersten JR: Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia. Am J Physiol 2003; 284:H1552–9
15. Lazar HL, Chipkin SR, Fitzgerald CA, Bao Y, Cabral H, Apstein CS: Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events. Circulation 2004; 109:1497–502
16. Hess ML, Okabe E, Poland J, Warner M, Stewart JR, Greenfield LJ: Glucose, insulin, potassium protection during the course of hypothermic global ischemia and reperfusion: A new proposed mechanism by the scavenging of free radicals. J Cardiovasc Pharmacol 1983; 5:35–43
17. Lehot JJ, Piriz H, Villard J, Cohen R, Guidollet J: Glucose homeostasis: Comparison between hypothermic and normothermic cardiopulmonary bypass. Chest 1992; 102:106–11
18. Rassias AJ, Marrin CAS, Arruda J, Whalen PK, Beach M, Yeager MP: Insulin infusion improves neutrophil function in diabetic cardiac surgery patients. Anesth Analg 1999; 88:1011–6
19. Braden H, Cheema-Dhadli S, Mazer CD, McKnight DJ, Singer W, Halperin ML: Hyperglycemia during normothermic cardiopulmonary bypass: The role of the kidney. Ann Thorac Surg 1998; 65:1588–93
20. Kuntschen FR, Galleti PM, Hahn C, Arnulf JJ, Isetta C, Dor V: Alterations of insulin and glucose metabolism during cardiopulmonary bypass under normothermia. J Thorac Cardiovasc Surg 1985; 89:97–106
21. Kuntschen FR, Galleti PM, Hahn C: Glucose-insulin interactions during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1986; 91:451–9
22. Chaney MA, Nikolov MP, Blakeman BP, Bakhos M: Attempting to maintain normoglycemia during cardiopulmonary bypass with insulin may initiate postoperative hypoglycemia. Anesth Analg 1999; 89:1091–5
23. Rassias AJ, Givan AL, Marrin CAS, Whalen K, Pahl J, Yeager MP: Insulin increases neutrophil count and phagocytic capacity after cardiac surgery. Anesth Analg 2002; 94:1113–9
24. Finney SJ, Zekveld C, Elia A, Evans TW: Glucose control and mortality in critically ill patients. JAMA 2003; 290:2041–47
25. Dupuis JY, Wang F, Nathan H, Lam M, Grimes S, Bourke M: The cardiac anesthesia risk evaluation score: A clinically useful predictor of mortality and morbidity after cardiac surgery. Anesthesiology 2001; 94:194–204
26. Ouattara A, Niculescu M, Ghazouani S, Babolian A, Landi M, Lecomte P, Boccara G, Varnous S, Leprince P, Riou B, Coriat P: Predictive performance and variability of the cardiac anesthesia risk evaluation. Anesthesiology 2004; 100:1405–10
27. Roques F, Nashef SAM, Michel P, Gauducheau E, de Vincentiis C, Baudet E, Cortina J, David M, Faichney A, Gabrielle F, Gams E, Harjula A, Jones MT, Pintor PP, Salamon R, Thulin L: Risk factors and outcome in European cardiac surgery: Analysis of the EuroSCORE multinational database of 19030 patients. Eur J Cardiothorac Surg 1999; 15:816–23
28. Parsonnet V, Dean D, Bernstein AD: A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease. Circulation 1989; 79:I3–I12
29. Birdi I, Regragui I, Izzat MB, Bryan AJ, Angelini GD: Influence of normothermic systemic perfusion during coronary artery bypass operations: A randomized prospective study. J Thorac Cardiovasc Surg 1997; 114:475–81
30. Tönz M, Mihaljevic T, von Segesser LK, Schmid ER, Joller-Jemelka HI, Pei P, Turina MI: Normothermia versus hypothermia during cardiopulmonary bypass: A randomized, controlled trial. Ann Thorac Surg 1995; 59:137–43
31. Golden SH, Peart-Vigilance C, Kao WHL, Brancati FL: Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes. Diabetes Care 1999; 22:1408–14
32. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R: Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345:1359–67
33. Carvalho G, Moore A, Qizilbash B, Lachapelle K, Schricker T: Maintenance of normoglycemia during cardiac surgery. Anesth Analg 2004; 99:319–24
34. Gu W, Pagel PS, Warltier DC, Kersten JR: Modifying cardiovascular risk in diabetes mellitus. Anesthesiology 2003; 98:774–9
35. Kersten JR, Schmeling TJ, Orth KG, Pagel PS, Warltier DC: Acute hyperglycemia abolishes ischemic preconditioning in vivo. Am J Physiol 1998; 275:H721–H725
36. Lasocki S, Provenchere S, Benessiano J, Vicaut E, Lecharny JB, Desmonts JM, Dehoux M, Philip I: Cardiac troponin I is an independent predictor of in-hospital death after adult cardiac surgery. Anesthesiology 2002; 97:405–11
37. Fellahi JL, Gue X, Richomme X, Monier E, Guillou L, Riou B: Short- and long-term prognostic value of postoperative cardiac troponin I concentration in patients undergoing coronary artery bypass grafting. Anesthesiology 2003; 99:270–4
38. Malmberg K, Ryden L, Efendic S, Herlitz J, Nicol P, Waldenström A, Wedel H, Welin L: Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): Effects on mortality at 1 year. J Am Coll Cardiol 1995; 26:57–65
39. Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simonson DC, Creager MA: Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation 1998; 97:1695–701
40. Svensson S, Svedjeholm R, Ekroth R, Milocco I, Nilsson F, Sabel KG, William-Olsson G: Trauma metabolism and the heart: Uptake of substrates and effects of insulin early after cardiac operations. J Thorac Cardiovasc Surg 1990; 99:1063–73
41. Stranders I, Diamant M, van Gelder RE, Spruijt HJ, Twisk JWR, Heine RJ, Visser FC: Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus. Arch Intern Med 2004; 164:982–8
** From Zerr et al.9
; adapted with permission. Cited Here...
This article has been cited 82 time(s).
Biochemical and Biophysical Research CommunicationsAnesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of ratsBiochemical and Biophysical Research Communications
Annales Francaises D Anesthesie Et De ReanimationPredictive factors of organ failure in patients admitted in intensive care unit for acute gastrointestinal bleedingAnnales Francaises D Anesthesie Et De Reanimation
Analytical ChemistryFabrication, Optimization, and Use of Graphene Field Effect SensorsAnalytical Chemistry
AnaesthesistAspects of perioperative care in patients with diabetesAnaesthesist
Turk Gogus Kalp Damar Cerrahisi Dergisi-Turkish Journal of Thoracic and Cardiovascular SurgeryCardiac surgery and anesthesia approach in an elderly patient populationTurk Gogus Kalp Damar Cerrahisi Dergisi-Turkish Journal of Thoracic and Cardiovascular Surgery
Journal of Clinical AnesthesiaImplementation of an intraoperative glycemic control protocol for cardiac surgery in a high-acuity academic medical center: an observational studyJournal of Clinical Anesthesia
Interactive Cardiovascular and Thoracic SurgeryImpact of intraoperative hyperglycaemia on renal dysfunction after off-pump coronary artery bypassInteractive Cardiovascular and Thoracic Surgery
British Journal of AnaesthesiaImpact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysisBritish Journal of Anaesthesia
Bmc AnesthesiologyEffect of remifentanil infusion rate on stress response in orthopedic surgery using a tourniquet applicationBmc Anesthesiology
Journal of Cardiothoracic and Vascular AnesthesiaIdentification of Inflammatory Mediators and Their Modulation by Strategies for the Management of the Systemic Inflammatory Response During Cardiac SurgeryJournal of Cardiothoracic and Vascular Anesthesia
Glucose and insulin administration while maintaining normoglycemia: the GIN concept
Minerva Anestesiologica, 79(1):
Heart & LungEffects of intensive glycemic control on outcomes of cardiac surgeryHeart & Lung
International Journal of Medical SciencesThe Effect of Intraoperative Use of High-Dose Remifentanil on Postoperative Insulin Resistance and Muscle Protein Catabolism: A Randomized Controlled StudyInternational Journal of Medical Sciences
Anesthesia and AnalgesiaDynamic tight glycemic control during and after cardiac surgery is effective, feasible, and safeAnesthesia and Analgesia
Critical CareTight perioperative glucose control is associated with a reduction in renal impairment and renal failure in non-diabetic cardiac surgical patientsCritical Care
Intensive versus conventional insulinotherapy after elective and on-pump myocardial revascularization: a prospective and randomized study
Clinica Terapeutica, 161(2):
Proceedings of the National Academy of Sciences of the United States of AmericaIncreased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphologyProceedings of the National Academy of Sciences of the United States of America
Annals of Thoracic SurgeryCardiopulmonary Bypass Increases Postoperative Glycemia and Insulin Consumption After Coronary SurgeryAnnals of Thoracic Surgery
European Journal of Cardio-Thoracic SurgeryHyperglycaemia after Stage I palliation does not adversely affect neurodevelopmental outcome at 1 year of age in patients with single-ventricle physiologyEuropean Journal of Cardio-Thoracic Surgery
Pediatric CardiologyImpact of postoperative hyperglycemia following surgical repair of congenital cardiac defectsPediatric Cardiology
Saudi Medical Journal
Prevalence and intensity of hyperglycemia in non-diabetic patients undergoing coronary artery bypass graft surgery with and without cardiopulmonary bypass
Saudi Medical Journal, 29(9):
Liver TransplantationAcute Kidney Injury During Liver Transplantation as Determined by Neutrophil Gelatinase-Associated LipocalinLiver Transplantation
World Journal of SurgeryEvidence-based Guidelines for Perioperative Management of Diabetes in Cardiac and Vascular SurgeryWorld Journal of Surgery
British Journal of AnaesthesiaBlood glucose concentration profile after 10 mg dexamethasone in non-diabetic and type 2 diabetic patients undergoing abdominal surgeryBritish Journal of Anaesthesia
AnaesthesistType 1 diabetes mellitus - Perioperative management of children and adolescentsAnaesthesist
Journal of Cardiothoracic and Vascular AnesthesiaClinical and laboratory correlates of excessive and persistent blood glucose elevation during cardiac surgery in nondiabetic patients: A retrospective studyJournal of Cardiothoracic and Vascular Anesthesia
Diabetes & MetabolismDesflurane-induced postconditioning of diabetic human right atrial myocardium in vitroDiabetes & Metabolism
Journal of Thoracic and Cardiovascular SurgeryStrict glycemic control reduces EuroSCORE expected mortality in diabetic patients undergoing myocardial revascularizationJournal of Thoracic and Cardiovascular Surgery
Advances in Chronic Kidney DiseaseAcute kidney injury and chronic kidney disease after cardiac surgeryAdvances in Chronic Kidney Disease
Acta Anaesthesiologica ScandinavicaCorrelation between pre-operative metabolic syndrome and persistent blood glucose elevation during cardiac surgery in non-diabetic patientsActa Anaesthesiologica Scandinavica
European Journal of Vascular and Endovascular SurgeryPerioperative Blood Glucose Monitoring and Control in Major Vascular Surgery PatientsEuropean Journal of Vascular and Endovascular Surgery
Medical Clinics of North AmericaSurgery in the Patient with Endocrine DysfunctionMedical Clinics of North America
Journal of Clinical AnesthesiaPerioperative blood glucose management in patients undergoing tumor hepatectomyJournal of Clinical Anesthesia
Archives Des Maladies Du Coeur Et Des Vaisseaux
Prognostic factors of coronary artery bypass surgery
Archives Des Maladies Du Coeur Et Des Vaisseaux, 100(2):
Journal of Clinical AnesthesiaPreinduction glycemia and body mass index are important predictors of perioperative insulin management in patients undergoing cardiac surgeryJournal of Clinical Anesthesia
International Journal of Artificial Organs
Prevention of cardiac surgery-associated acute kidney injury
International Journal of Artificial Organs, 31(2):
Journal of Thoracic and Cardiovascular SurgeryGlycemic profile in infants who have undergone the arterial switch operation: Hyperglycemia is not associated with adverse eventsJournal of Thoracic and Cardiovascular Surgery
CirculationInadequate blood glucose control is associated with in-hospital mortality and morbidity in diabetic and nondiabetic patients undergoing cardiac surgeryCirculation
Journal of AnesthesiaEffect of intraoperative acetated Ringer's solution with 1% glucose on glucose and protein metabolismJournal of Anesthesia
Medicina IntensivaStress hyperglycemia and its control with insulin in critically ill patients. Current evidenceMedicina Intensiva
Annals of Thoracic SurgeryIntraoperative hyperglycemia and cognitive decline after CABGAnnals of Thoracic Surgery
Circulation2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice GuidelinesCirculation
Annales Francaises D Anesthesie Et De ReanimationComparison of three ventilatory modes during immediate postoperative transfer of cardiac surgical patientsAnnales Francaises D Anesthesie Et De Reanimation
Annales Francaises D Anesthesie Et De ReanimationFalse capillary hyperglycaemia and true iatrogenic postoperative hypoglycaemiaAnnales Francaises D Anesthesie Et De Reanimation
Journal of the American College of Cardiology2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice GuidelinesJournal of the American College of Cardiology
Annals of Vascular SurgeryMorbidity and Mortality Caused by Cardiac Adverse Events after Revascularization for Critical Limb IschemiaAnnals of Vascular Surgery
Anesthesia and AnalgesiaScientific Principles and Clinical Implications of Perioperative Glucose Regulation and ControlAnesthesia and Analgesia
Journal of Surgical ResearchEffect of intraoperative hyperglycemia during liver transplantationJournal of Surgical Research
Critical CareThe metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass graftingCritical Care
Annals of Internal Medicine
Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery - A randomized trial
Annals of Internal Medicine, 146(4):
Journal of Cardiothoracic and Vascular AnesthesiaImproved neurologic outcome after implementing evidence-based guidelines for cardiac surgeryJournal of Cardiothoracic and Vascular Anesthesia
Anesthesia and AnalgesiaThinking like a pancreas: A look ahead at diabetes technology in the perioperative settingAnesthesia and Analgesia
CirculationACC/AHA 2007 guidelines on Perioperative cardiovascular evaluation and care for noncardiac surgeryCirculation
Annals of Thoracic SurgeryHyperglycemia after infant cardiac surgery does not adversely impact neurodevelopmental outcomeAnnals of Thoracic Surgery
Annals of Thoracic SurgeryChanging Operative Characteristics of Patients Undergoing Operations for Coronary Artery Disease: Impact on Early OutcomesAnnals of Thoracic Surgery
Journal of Cardiothoracic and Vascular AnesthesiaPro: Tight Perioperative Glycemic ControlJournal of Cardiothoracic and Vascular Anesthesia
Journal of Thoracic and Cardiovascular SurgeryAn evidence-based review of the practice of cardiopulmonary bypass in adults: A focus on neurologic injury, glycemic control, hemodilution, and the inflammatory responseJournal of Thoracic and Cardiovascular Surgery
Expert Opinion on PharmacotherapyPharmacological interventions and concepts of fast-track perioperative medical care for enhanced recovery programsExpert Opinion on Pharmacotherapy
Current Drug Targets
Anesthetic and Adjunctive Drugs for Fast-Track Surgery
Current Drug Targets, 10(8):
Acta Cirurgica Brasileira
Does propofol and isoflurane protect the kidney against ischemia/reperfusion injury during transient hyperglycemia?
Acta Cirurgica Brasileira, 28(3):
AnesthesiologyPerioperative Glycemic Control: An Evidence-based ReviewAnesthesiology
AnesthesiologyDiabetic Cardiomyopathy and Anesthesia: Bench to BedsideAnesthesiology
Critical Care MedicineGlucose control in the intensive care unitCritical Care Medicine
Current Opinion in AnesthesiologyGlycemic control during cardiac surgery: a moving target?Current Opinion in Anesthesiology
Current Opinion in Clinical Nutrition & Metabolic CareCurrent controversies around tight glucose control in critically ill patientsCurrent Opinion in Clinical Nutrition & Metabolic Care
Current Opinion in Critical CareGlycemic control and prevention of perioperative infectionCurrent Opinion in Critical Care
Current Opinion in Critical CareGlycaemic control in critically ill patients with cardiovascular diseaseCurrent Opinion in Critical Care
Journal of Wound Ostomy & Continence NursingImpact of Tight Glucose Control on Postoperative Infection Rates and Wound Healing in Cardiac Surgery PatientsJournal of Wound Ostomy & Continence Nursing
© 2005 American Society of Anesthesiologists, Inc.
Publication of an advertisement in Anesthesiology Online does not constitute endorsement by the American Society of Anesthesiologists, Inc. or Lippincott Williams & Wilkins, Inc. of the product or service being advertised.