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Anesthesiology:
Clinical Investigations

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.#

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Abstract

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.
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Materials and Methods

Study Population
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.
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Perioperative Management
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.
Table 1
Table 1
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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).
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Major Outcomes
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.
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Statistical Analysis
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).
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Results

Table 2
Table 2
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Table 3
Table 3
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Fig. 1
Fig. 1
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Fig. 2
Fig. 2
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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.
Table 4
Table 4
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Table 5
Table 5
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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. 2.4%; P < 0.05), and a prolonged intensive care unit duration of stay was more frequently observed (46% vs. 19%; P < 0.001).
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Discussion

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.
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Appendix:
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...
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** From Zerr et al.9; adapted with permission. Cited Here...

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Implementation of an intraoperative glycemic control protocol for cardiac surgery in a high-acuity academic medical center: an observational study
Kohl, BA; Hammond, MS; Ochroch, EA
Journal of Clinical Anesthesia, 25(2): 121-128.
10.1016/j.jclinane.2012.06.019
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Interactive Cardiovascular and Thoracic Surgery
Impact of intraoperative hyperglycaemia on renal dysfunction after off-pump coronary artery bypass
Song, JW; Shim, JK; Yoo, KJ; Oh, SY; Kwak, YL
Interactive Cardiovascular and Thoracic Surgery, 17(3): 473-478.
10.1093/icvts/ivt209
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British Journal of Anaesthesia
Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis
Waldron, NH; Jones, CA; Gan, TJ; Allen, TK; Habib, AS
British Journal of Anaesthesia, 110(2): 191-200.
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Bmc Anesthesiology
Effect of remifentanil infusion rate on stress response in orthopedic surgery using a tourniquet application
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Bmc Anesthesiology, 13(): -.
ARTN 14
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Journal of Cardiothoracic and Vascular Anesthesia
Identification of Inflammatory Mediators and Their Modulation by Strategies for the Management of the Systemic Inflammatory Response During Cardiac Surgery
Hall, R
Journal of Cardiothoracic and Vascular Anesthesia, 27(5): 983-1033.
10.1053/j.jvca.2012.09.013
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Minerva Anestesiologica
Glucose and insulin administration while maintaining normoglycemia: the GIN concept
Carvalho, G; Lattermann, R; Codere-Maruyama, T; Schricker, T
Minerva Anestesiologica, 79(1): 74-82.

Heart & Lung
Effects of intensive glycemic control on outcomes of cardiac surgery
Giakoumidakis, K; Eltheni, R; Patelarou, E; Theologou, S; Patris, V; Michopanou, N; Mikropoulos, T; Brokalaki, H
Heart & Lung, 42(2): 146-151.
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International Journal of Medical Sciences
The Effect of Intraoperative Use of High-Dose Remifentanil on Postoperative Insulin Resistance and Muscle Protein Catabolism: A Randomized Controlled Study
Taniguchi, H; Sasaki, T; Fujita, H; Takano, O; Hayashi, T; Cho, H; Yoshikawa, T; Tsuburaya, A
International Journal of Medical Sciences, 10(9): 1099-1107.
10.7150/ijms.5924
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Anesthesia and Analgesia
Dynamic tight glycemic control during and after cardiac surgery is effective, feasible, and safe
Lecomte, P; Foubert, L; Nobels, F; Coddens, J; Nollet, G; Casselman, F; Van Crombrugge, P; Vandenbroucke, G; Cammu, G
Anesthesia and Analgesia, 107(1): 51-58.
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Critical Care
Tight perioperative glucose control is associated with a reduction in renal impairment and renal failure in non-diabetic cardiac surgical patients
Lecomte, P; Van Vlem, B; Coddens, J; Cammu, G; Nollet, G; Nobels, F; Vanermen, H; Foubert, L
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Clinica Terapeutica
Intensive versus conventional insulinotherapy after elective and on-pump myocardial revascularization: a prospective and randomized study
Caroleo, S; Bisurgi, G; Onorati, F; Rubino, A; Calandese, F; De Munda, C; Renzulli, A; Santangelo, E; Verre, M; Amantea, B
Clinica Terapeutica, 161(2): E33-E37.

Proceedings of the National Academy of Sciences of the United States of America
Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology
Yu, TZ; Robotham, JL; Yoon, Y
Proceedings of the National Academy of Sciences of the United States of America, 103(8): 2653-2658.
10.1073/pnas.0511154103
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Annals of Thoracic Surgery
Cardiopulmonary Bypass Increases Postoperative Glycemia and Insulin Consumption After Coronary Surgery
Knapik, P; Nadziakiewicz, P; Urbanska, E; Saucha, W; Herdynska, M; Zembala, M
Annals of Thoracic Surgery, 87(6): 1859-1865.
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European Journal of Cardio-Thoracic Surgery
Hyperglycaemia after Stage I palliation does not adversely affect neurodevelopmental outcome at 1 year of age in patients with single-ventricle physiology
Ballweg, JA; Ittenbach, RF; Bernbaum, J; Gerdes, M; Dominguez, TE; Zackai, EH; Clancy, RR; Gaynor, JW
European Journal of Cardio-Thoracic Surgery, 36(4): 688-693.
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Pediatric Cardiology
Impact of postoperative hyperglycemia following surgical repair of congenital cardiac defects
Falcao, G; Ulate, K; Kouzekanani, K; Bielefeld, MR; Morales, JM; Rotta, AT
Pediatric Cardiology, 29(3): 628-636.
10.1007/s00246-007-9178-8
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Saudi Medical Journal
Prevalence and intensity of hyperglycemia in non-diabetic patients undergoing coronary artery bypass graft surgery with and without cardiopulmonary bypass
Azarfarin, R; Asl, AA
Saudi Medical Journal, 29(9): 1294-1298.

Liver Transplantation
Acute Kidney Injury During Liver Transplantation as Determined by Neutrophil Gelatinase-Associated Lipocalin
Niemann, CU; Walia, A; Waldman, J; Davio, M; Roberts, JP; Hirose, R; Feiner, J
Liver Transplantation, 15(): 1852-1860.
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World Journal of Surgery
Evidence-based Guidelines for Perioperative Management of Diabetes in Cardiac and Vascular Surgery
Wong, J; Zoungas, S; Wright, C; Teede, H
World Journal of Surgery, 34(3): 500-513.
10.1007/s00268-009-0380-0
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British Journal of Anaesthesia
Blood glucose concentration profile after 10 mg dexamethasone in non-diabetic and type 2 diabetic patients undergoing abdominal surgery
Hans, P; Vanthuyne, A; Dewandre, PY; Brichant, JF; Bonhomme, V
British Journal of Anaesthesia, 97(2): 164-170.
10.1093/bja/ae1111
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Anaesthesist
Type 1 diabetes mellitus - Perioperative management of children and adolescents
Herbst, A; Kiess, W
Anaesthesist, 56(5): 454-460.
10.1007/s00101-007-1168-y
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Journal of Cardiothoracic and Vascular Anesthesia
Clinical and laboratory correlates of excessive and persistent blood glucose elevation during cardiac surgery in nondiabetic patients: A retrospective study
Prasad, AA; Kline, SM; Schuler, HG; Sukernik, MR
Journal of Cardiothoracic and Vascular Anesthesia, 21(6): 843-846.
10.1053/j.jvca.2006.12.014
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Diabetes & Metabolism
Desflurane-induced postconditioning of diabetic human right atrial myocardium in vitro
Lemoine, S; Durand, C; Zhu, L; Ivasceau, C; Lepage, O; Babatasi, G; Massetti, M; Gerard, JL; Hanouz, JL
Diabetes & Metabolism, 36(1): 21-28.
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Journal of Thoracic and Cardiovascular Surgery
Strict glycemic control reduces EuroSCORE expected mortality in diabetic patients undergoing myocardial revascularization
D'Alessandro, C; Leprince, P; Golmard, JL; Ouattara, A; Aubert, S; Pavie, A; Gandjbakhch, I; Bonnet, N
Journal of Thoracic and Cardiovascular Surgery, 134(1): 29-37.
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Advances in Chronic Kidney Disease
Acute kidney injury and chronic kidney disease after cardiac surgery
Stafford-Smith, M; Patel, UD; Phillips-Bute, BG; Shaw, AD; Swaminathan, M
Advances in Chronic Kidney Disease, 15(3): 257-277.
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Acta Anaesthesiologica Scandinavica
Correlation between pre-operative metabolic syndrome and persistent blood glucose elevation during cardiac surgery in non-diabetic patients
Donatelli, F; Cavagna, P; Di Dedda, G; Catenacci, A; Di Nicola, M; Lorini, L; Fumagalli, R; Carli, F
Acta Anaesthesiologica Scandinavica, 52(8): 1103-1110.
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European Journal of Vascular and Endovascular Surgery
Perioperative Blood Glucose Monitoring and Control in Major Vascular Surgery Patients
van Kuijk, JP; Schouten, O; Flu, WJ; den Uil, CA; Bax, JJ; Poldermans, D
European Journal of Vascular and Endovascular Surgery, 38(5): 627-634.
10.1016/j.ejvs.2009.06.009
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Medical Clinics of North America
Surgery in the Patient with Endocrine Dysfunction
Kohl, BA; Schwartz, S
Medical Clinics of North America, 93(5): 1031-+.
10.1016/j.mcna.2009.05.003
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Journal of Clinical Anesthesia
Perioperative blood glucose management in patients undergoing tumor hepatectomy
Cammu, G; Vermeiren, K; Lecomte, P; De Gendt, S; Deloof, T; Foubert, L
Journal of Clinical Anesthesia, 21(5): 329-335.
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Archives Des Maladies Du Coeur Et Des Vaisseaux
Prognostic factors of coronary artery bypass surgery
Pavie, A; Dogue, F; Bonnet, N
Archives Des Maladies Du Coeur Et Des Vaisseaux, 100(2): 128-132.

Journal of Clinical Anesthesia
Preinduction glycemia and body mass index are important predictors of perioperative insulin management in patients undergoing cardiac surgery
Cammu, G; Lecomte, P; Casselman, F; Demeyer, I; Coddens, J; Morias, K; Deloof, T; Nobels, F; Van Crombrugge, P; Foubert, L
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International Journal of Artificial Organs
Prevention of cardiac surgery-associated acute kidney injury
Schetz, M; Bove, T; Morelli, A; Mankad, S; Ronco, C; Kellum, JA
International Journal of Artificial Organs, 31(2): 179-189.

Journal of Thoracic and Cardiovascular Surgery
Glycemic profile in infants who have undergone the arterial switch operation: Hyperglycemia is not associated with adverse events
Rossano, JW; Taylor, MD; Smith, EO; Fraser, CD; McKenzie, ED; Price, JF; Dickerson, HA; Nelson, DP; Mott, AR
Journal of Thoracic and Cardiovascular Surgery, 135(4): 739-745.
10.1016/j.jtcvs.2007.11.030
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Circulation
Inadequate blood glucose control is associated with in-hospital mortality and morbidity in diabetic and nondiabetic patients undergoing cardiac surgery
Ascione, R; Rogers, CA; Rajakaruna, C; Angelini, GD
Circulation, 118(2): 113-123.
10.1161/CIRCULATIONAHA.107.706416
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Journal of Anesthesia
Effect of intraoperative acetated Ringer's solution with 1% glucose on glucose and protein metabolism
Yamasaki, K; Inagaki, Y; Mochida, S; Funaki, K; Takahashi, S; Sakamoto, S
Journal of Anesthesia, 24(3): 426-431.
10.1007/s00540-010-0926-1
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Medicina Intensiva
Stress hyperglycemia and its control with insulin in critically ill patients. Current evidence
Manzanares, W; Aramendi, I
Medicina Intensiva, 34(4): 273-281.
10.1016/j.medin.2009.10.003
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Annals of Thoracic Surgery
Intraoperative hyperglycemia and cognitive decline after CABG
Puskas, F; Grocott, HP; White, WD; Mathew, JP; Newman, MF; Bar-Yosef, S
Annals of Thoracic Surgery, 84(5): 1467-1473.
10.1016/j.athoracsur.2007.06.023
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Circulation
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 A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Fleisher, LA; Beckman, JA; Brown, KA; Calkins, H; Chaikof, EL; Fleischmann, KE; Freeman, WK; Froehlich, JB; Kasper, EK; Kersten, JR; Riegel, B; Robb, JF; Buller, CE; Valentine, RJ; Jacobs, AK; Smith, SC; Anderson, JL; Creager, MA; Ettinger, SM; Guyton, RA; Halperin, JL; Hochman, JS; Krumholz, HM; Kushner, FG; Lytle, BW; Nishimura, R; Page, RL; Stevenson, WG; Tarkington, LG; Yancy, CW
Circulation, 120(): E169-E276.
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Annales Francaises D Anesthesie Et De Reanimation
Comparison of three ventilatory modes during immediate postoperative transfer of cardiac surgical patients
Ouattara, A; Benhaoua, H; Breant, V; Ayeb, H; Amour, J; Barraket, M; Ziad, A; Regan-Mastret, M; Coriat, P
Annales Francaises D Anesthesie Et De Reanimation, 28(): 844-849.
10.1016/j.annfar.2009.07.089
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Annales Francaises D Anesthesie Et De Reanimation
False capillary hyperglycaemia and true iatrogenic postoperative hypoglycaemia
Marguerite, C; Provost, D; Compere, V; Jean, J; Dureuil, B
Annales Francaises D Anesthesie Et De Reanimation, 28(): 704-705.
10.1016/j.annfar.2009.06.004
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Journal of the American College of Cardiology
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 A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Jacobs, AK; Smith, SC; Anderson, JL; Buller, CE; Creager, MA; Ettinger, SM; Guyton, RA; Halperin, JL; Hochman, JS; Krumholz, HM; Kushner, FG; Lytle, BW; Nishimura, R; Page, RL; Stevenson, WG; Tarkington, LG; Yancy, CW
Journal of the American College of Cardiology, 54(): E13-E118.
10.1016/j.jacc.2009.07.010
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Annals of Vascular Surgery
Morbidity and Mortality Caused by Cardiac Adverse Events after Revascularization for Critical Limb Ischemia
Flu, HC; Lardenoye, JHP; Veen, EJ; Aquarius, AE; Henegouwen, DPV; Hamming, JF
Annals of Vascular Surgery, 23(5): 583-597.
10.1016/j.avsg.2009.06.012
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Anesthesia and Analgesia
Scientific Principles and Clinical Implications of Perioperative Glucose Regulation and Control
Akhtar, S; Barash, PG; Inzucchi, SE
Anesthesia and Analgesia, 110(2): 478-497.
10.1213/ANE.0b013e3181c6be63
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Journal of Surgical Research
Effect of intraoperative hyperglycemia during liver transplantation
Ammori, JB; Sigakis, M; Englesbe, MJ; O'Reilly, M; Pelletier, SJ
Journal of Surgical Research, 140(2): 227-233.
10.1016/j.jss.2007.02.019
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Critical Care
The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting
Heringlake, M; Wernerus, M; Grunefeld, J; Klaus, S; Heinze, H; Bechtel, M; Bahlmann, L; Poeling, J; Schon, J
Critical Care, 11(2): -.
ARTN R51
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Annals of Internal Medicine
Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery - A randomized trial
Gandhi, GY; Nuttall, GA; Abel, MD; Mullany, CJ; Schaff, HV; O'Brien, PC; Johnson, MG; Williams, AR; Cutshall, SM; Mundy, LM; Rizza, RA; McMahon, MM
Annals of Internal Medicine, 146(4): 233-243.

Journal of Cardiothoracic and Vascular Anesthesia
Improved neurologic outcome after implementing evidence-based guidelines for cardiac surgery
Suojaranta-Ylinen, RT; Roine, RO; Vento, AE; Niskanen, MIM; Salmenpera, MT
Journal of Cardiothoracic and Vascular Anesthesia, 21(4): 529-534.
10.1053/j.jvca.2006.12.019
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Anesthesia and Analgesia
Thinking like a pancreas: A look ahead at diabetes technology in the perioperative setting
Torjman, MC; Goldberg, ME; Hirsh, RA; Littman, J
Anesthesia and Analgesia, 105(2): 545.
10.1213/01.ane.0000268137.50113.3a
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Circulation
ACC/AHA 2007 guidelines on Perioperative cardiovascular evaluation and care for noncardiac surgery
Fleisher, LA; Beckman, JA; Brown, KA; Calkins, H; Chaikof, E; Fleischmann, KE; Freeman, WK; Froehlich, JB; Kasper, EK; Kersten, JR; Riegel, B; Robb, JF; Smith, SC; Jacobs, AK; Adams, CD; Anderson, JL; Antman, EM; Buller, CE; Creager, MA; Ettinger, SM; Faxon, DP; Fuster, V; Halperin, JL; Hiratzka, LF; Hunt, SA; Lytle, BW; Nishimura, R; Ornato, JP; Page, RL; Riegel, B; Tarkington, LG; Yancy, CW; Lewin, JC; Arend, TE; Fobbs, KN; Keller, S; Barrett, EA
Circulation, 116(): E418-E499.
10.1161/CIRCULATIONAHA.107.185699
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Annals of Thoracic Surgery
Hyperglycemia after infant cardiac surgery does not adversely impact neurodevelopmental outcome
Ballweg, JA; Wernovsky, G; Ittenbach, RF; Bernbaum, J; Gerdes, M; Gallagher, PR; Dominguez, TE; Zackai, E; Clancy, RR; Nicolson, SC; Spray, TL; Gaynor, JW
Annals of Thoracic Surgery, 84(6): 2052-2058.
10.1016/j.athoracsur.2007.06.099
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Annals of Thoracic Surgery
Changing Operative Characteristics of Patients Undergoing Operations for Coronary Artery Disease: Impact on Early Outcomes
Ngaage, DL; Griffin, S; Guvendik, L; Cowen, ME; Cale, ARJ
Annals of Thoracic Surgery, 86(5): 1424-1430.
10.1016/j.athoracsur.2008.07.050
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Journal of Cardiothoracic and Vascular Anesthesia
Pro: Tight Perioperative Glycemic Control
Carvalho, G; Schricker, T
Journal of Cardiothoracic and Vascular Anesthesia, 23(6): 901-905.
10.1053/j.jvca.2009.04.015
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Journal of Thoracic and Cardiovascular Surgery
An evidence-based review of the practice of cardiopulmonary bypass in adults: A focus on neurologic injury, glycemic control, hemodilution, and the inflammatory response
Shann, KG; Likosky, DS; Murkin, JM; Baker, RA; Baribeau, YR; Defoe, GR; Dickinson, TA; Gardner, TJ; Grocott, HP; O'Connor, GT; Rosinski, DJ; Sellke, FW; Willcox, TW
Journal of Thoracic and Cardiovascular Surgery, 132(2): 283-U52.
10.1016/j.jtcvs.2006.03.027
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Expert Opinion on Pharmacotherapy
Pharmacological interventions and concepts of fast-track perioperative medical care for enhanced recovery programs
Kranke, P; Redel, A; Schuster, F; Muellenbach, R; Eberhart, L
Expert Opinion on Pharmacotherapy, 9(9): 1541-1564.
10.1517/14656560802098402
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Current Drug Targets
Anesthetic and Adjunctive Drugs for Fast-Track Surgery
Baldini, G; Carli, F
Current Drug Targets, 10(8): 667-686.

Acta Cirurgica Brasileira
Does propofol and isoflurane protect the kidney against ischemia/reperfusion injury during transient hyperglycemia?
Carraretto, AR; Vianna, PTG; Castiglia, YMM; Golim, MD; de Souza, AVG; de Carvalho, LR; Deffune, E; Vianna, PTG
Acta Cirurgica Brasileira, 28(3): 161-166.

Journal of Wound Ostomy & Continence Nursing
Impact of Tight Glucose Control on Postoperative Infection Rates and Wound Healing in Cardiac Surgery Patients
Patel, KL
Journal of Wound Ostomy & Continence Nursing, 35(4): 397-404.
10.1097/01.WON.0000326659.47637.d0
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The Endocrinologist
Inadequate Glucose Control in the Intensive Care Unit: A Cohort Study of Incidence and Risk Factors
Levin, PD; Kiss, A
The Endocrinologist, 18(6): 304-309.
10.1097/TEN.0b013e31818fee7c
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Predictors Associated with Terminal Renal Function in Deceased Organ Donors in the Intensive Care Unit
Blasi-Ibanez, A; Hirose, R; Feiner, J; Freise, C; Stock, PG; Roberts, JP; Niemann, CU
Anesthesiology, 110(2): 333-341.
10.1097/ALN.0b013e318194ca8a
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Perioperative Glycemic Control: An Evidence-based Review
Lipshutz, AK; Gropper, MA
Anesthesiology, 110(2): 408-421.
10.1097/ALN.0b013e3181948a80
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Obesity and Diabetes: Evidence of Increased Perioperative Risk?
Neligan, PJ; Fleisher, LA
Anesthesiology, 104(3): 398-400.

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Transient Hyperglycemia Affects the Extent of Ischemia-Reperfusion-induced Renal Injury in Rats
Hirose, R; Xu, F; Dang, K; Liu, T; Behrends, M; Brakeman, PR; Wiener-Kronish, J; Niemann, CU
Anesthesiology, 108(3): 402-414.
10.1097/ALN.0b013e318164cff8
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Metabolic Syndrome and Insulin Resistance: Perioperative Considerations
Bagry, HS; Raghavendran, S; Carli, F
Anesthesiology, 108(3): 506-523.
10.1097/ALN.0b013e3181649314
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Diabetic Cardiomyopathy and Anesthesia: Bench to Bedside
Amour, J; Kersten, JR
Anesthesiology, 108(3): 524-530.
10.1097/ALN.0b013e3181649369
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Strict Glucose Control Does Not Affect Mortality after Aneurysmal Subarachnoid Hemorrhage
Thiele, RH; Pouratian, N; Zuo, Z; Scalzo, DC; Dobbs, HA; Dumont, AS; Kassell, NF; Nemergut, EC
Anesthesiology, 110(3): 603-610.
10.1097/ALN.0b013e318198006a
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Blood Glucose Variability: A New Paradigm in Critical Care?
Ouattara, A; Grimaldi, A; Riou, B
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Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients
Egi, M; Bellomo, R; Stachowski, E; French, CJ; Hart, G
Anesthesiology, 105(2): 244-252.

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The Anesthesiologist's Role in the Prevention of Surgical Site Infections
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Altered Contractile Response due to Increased β3-Adrenoceptor Stimulation in Diabetic Cardiomyopathy: The Role of Nitric Oxide Synthase 1–derived Nitric Oxide
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Anesthesiology, 107(3): 452-460.
10.1097/01.anes.0000278909.40408.24
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Aggressive Control of Intraoperative Blood Glucose Concentration: A Shifting Paradigm?
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Deterioration of Regional Wall Motion Immediately after Coronary Artery Bypass Graft Surgery Is Associated with Long-term Major Adverse Cardiac Events
Swaminathan, M; Morris, RW; De Meyts, DD; Podgoreanu, MV; Jollis, JG; Grocott, HP; Milano, CA; Newman, MF; Mathew, JP
Anesthesiology, 107(5): 739-745.
10.1097/01.anes.0000287008.70453.81
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Glucose control in the intensive care unit
Fahy, BG; Sheehy, AM; Coursin, DB
Critical Care Medicine, 37(5): 1769-1776.
10.1097/CCM.0b013e3181a19ceb
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Current Opinion in Anesthesiology
Glycemic control during cardiac surgery: a moving target?
O'Connor, CJ
Current Opinion in Anesthesiology, 23(1): 47-48.
10.1097/ACO.0b013e328333c115
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Current controversies around tight glucose control in critically ill patients
Devos, P; Preiser, J
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10.1097/MCO.0b013e3280147d2d
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Glycemic control and prevention of perioperative infection
Blondet, JJ; Beilman, GJ
Current Opinion in Critical Care, 13(4): 421-427.
10.1097/MCC.0b013e32826388a1
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Glycaemic control in critically ill patients with cardiovascular disease
Wade, AO; Cordingley, JJ
Current Opinion in Critical Care, 12(5): 437-443.
10.1097/01.ccx.0000244123.39247.b9
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Kinetic analysis of cardiac troponin I release is no more accurate than a single 24‐h measurement in predicting in‐hospital outcome after cardiac surgery
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European Journal of Anaesthesiology (EJA), 25(6): 490-497.
10.1017/S0265021508003827
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Severe Intraoperative Hyperglycemia Is Independently Associated With Surgical Site Infection After Liver Transplantation
Park, C; Hsu, C; Neelakanta, G; Nourmand, H; Braunfeld, M; Wray, C; Steadman, RH; Hu, K; Cheng, RT; Xia, VW
Transplantation, 87(7): 1031-1036.
10.1097/TP.0b013e31819cc3e6
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