None of the trials examined the effects of the interventions in terms of costs .
AUTHORS ' CONCLUSIONS The included trials did not demonstrate significant differences for most of the outcomes when targeting intensive perioperative glycaemic control compared with conventional glycaemic control in patients with diabetes mellitus .
However , posthoc analysis indicated that intensive glycaemic control was associated with an increased number of patients experiencing hypoglycaemic episodes .
BACKGROUND Patients with diabetes mellitus are at increased risk of postoperative complications .
Data from r and omised clinical trials and meta-analyses point to a potential benefit of intensive glycaemic control , targeting near-normal blood glucose , in patients with hyperglycaemia ( with and without diabetes mellitus ) being su bmi tted to surgical procedures .
However , there is limited evidence concerning this question in patients with diabetes mellitus undergoing surgery .
OBJECTIVES To assess the effects of perioperative glycaemic control for diabetic patients undergoing surgery .
Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery
Context Intensive insulin therapy used to maintain normoglycemia during intensive care after cardiac surgery improves perioperative outcomes . Its effect during cardiac surgery is unknown . Contributions The authors r and omly assigned 400 cardiac surgical patients to tight glycemic control ( blood glucose level , 4.4 to 5.6 mmol/L [ 80 to 100 mg/dL ] ) during surgery or usual intraoperative care . All patients received tight glycemic control in the cardiac intensive care unit . The groups had the same risk for perioperative adverse events ( risk ratio , 1.0 [ 95 % CI , 0.8 to 1.2 ] ) . The intensive treatment group had more strokes ( 8 vs. 1 ) and more deaths ( 4 vs. 0 ) than the conventional treatment group . Caution The authors performed the study at a single center . Implication s Maintaining normoglycemia during cardiac surgery does not improve outcomes and might worsen them . The Editors Hyperglycemia occurs frequently in patients with and without diabetes during cardiac surgery , especially during cardiopulmonary bypass surgery ( 1 , 2 ) . In a study by Van den Berghe and colleagues ( 3 ) , intensive insulin therapy after surgery reduced morbidity and death in critically ill patients , most of whom underwent cardiac surgery . As a result , professional organizations have recommended rigorous glycemic control in hospitalized patients ( 4 ) and strict glycemic control is now routine practice during the postoperative period in cardiac surgical patients . However , no consensus exists on the optimal management of intraoperative hyperglycemia in cardiac surgical patients because of the lack of evidence from r and omized trials . Research ers are increasingly extrapolating evidence from studies that assess the role of strict postoperative glycemic control in critically ill patients to advocate for intravenous insulin therapy for patients in the operating room ( 3 , 57 ) . Evidence , strictly from observational studies , suggests that tight intraoperative glycemic control may reduce postoperative complications ( 810 ) . We recently reported , in a retrospective , observational study of 409 cardiac surgical patients , that intraoperative hyperglycemia was an independent risk factor for perioperative complications , including death , after adjustment for postoperative glucose concentrations . Each 1.1-mmol/L ( 20 mg/dL ) increase in glucose concentration greater than 5.6 mmol/L ( > 100 mg/dL ) during surgery was associated with a 34 % increase in the likelihood of postoperative complications ( 8) . An association between intraoperative hyperglycemia and adverse outcomes based on observational studies does not prove causality . Because hyperglycemia can adversely affect immunity , wound healing , and vascular function , the concept that normoglycemia be maintained during the relatively brief duration of cardiac surgery seems plausible ( 1116 ) . On the other h and , the degree of intraoperative hyperglycemia may merely reflect the severity of underlying stress . If so , prevention of hyperglycemia might not reduce perioperative complications , and the risks and costs of intensive intraoperative glycemic management may outweigh the benefits . Simple , safe , and effective insulin infusion algorithms that achieve rigorous intraoperative glycemic control are lacking . To address these questions , we conducted a r and omized , controlled trial at 1 center to determine whether maintenance of near normoglycemia during cardiac surgery by using intraoperative intravenous insulin infusion reduced perioperative death and morbidity when added to rigorous postoperative glycemic control . Methods Design Overview This was a r and omized , open-label , controlled trial with blinded assessment . We r and omly assigned patients to receive intensive insulin therapy to maintain intraoperative glucose levels between 4.4 ( 80 mg/dL ) and 5.6 mmol/L ( 100 mg/dL ) or conventional treatment . By design , both groups were postoperatively treated with strict glycemic control to ensure that the observed difference in outcome could be attributed to the effects of intraoperative glycemic control . Setting We performed the study at St. Marys Hospital , Rochester , Minnesota , which is a tertiary care teaching hospital with 1157 beds and an average of more than 41000 admissions per year . Participants Adults undergoing elective cardiac surgery between July 2004 and April 2005 were eligible for enrollment in our study . We excluded patients who had off-pump cardiopulmonary bypass procedures . The Mayo Foundation Institutional Review Board , Rochester , Minnesota , approved the protocol . R and omization and Interventions Before we enrolled patients in our r and omized trial , we enrolled 20 patients in a 2-week pilot trial to ensure that the anesthesiologists in the operating room and the nursing staff in the intensive care units ( ICUs ) had adequate experience with the study insulin infusion algorithm . The 20 patients received intensive insulin therapy during surgery and for 24 hours after surgery . The pilot period data allowed us to modify the grade d insulin infusion to achieve desired glucose concentration goals . We built safety features into our infusion protocol to minimize hypoglycemia . We discontinued the infusion when glucose levels were less than 4.4 mmol/L ( < 80 mg/dL ) and initiated dextrose infusion . When glucose levels decreased to less than 3.3 mmol/L ( < 60 mg/dL ) , we treated hypoglycemia according to a st and ardized hypoglycemia protocol . Per protocol , patients treated in the pilot phase were not included in the analyzed cohort . Study coordinators obtained written informed consent from all patients who met eligibility criteria . We r and omly assigned patients to receive intensive or conventional intraoperative insulin therapy . R and omization was computer-generated with permuted blocks of 4 , with stratification according to surgeon , surgical procedure ( coronary artery bypass grafting [ CABG ] with or without other procedures and no CABG ) , and diabetes . The r and omization assignments were concealed in opaque , sealed , tamper-proof envelopes that were opened sequentially by study personnel after participants signed the patient consent form . We could not possibly know , before obtaining consent , the few patients who would not have intraoperative hyperglycemia ( glucose concentration of 5.6 mmol/L or more [ 100 mg/dL ] ) . Therefore , per protocol , patients who gave consent were r and omly assigned , and those whose glucose levels were less than 5.6 mmol/L ( < 100 mg/dL ) during surgery were not included in the final analyses . Intraoperative Period Intensive Treatment Patients in the intensive treatment group received a continuous intravenous insulin infusion , 250 units of NovoLin R ( Novo Nordisk , Princeton , New Jersey ) in 250 mL of 0.45 % sodium chloride , when their blood glucose levels exceeded 5.6 mmol/L ( > 100 mg/dL ) . We adjusted the infusions to maintain blood glucose levels between 4.4 ( 80 mg/dL ) and 5.6 mmol/L ( 100 mg/dL ) . We adjusted the dose according to a st and ardized algorithm used by anesthesiologists ( Appendix Table 1 ) . Appendix Table 1 . Insulin Infusion Protocol * Conventional Treatment Patients in the conventional treatment group did not receive insulin during surgery unless their glucose levels exceeded 11.1 mmol/L ( 200 mg/dL ) . If glucose concentration was between 11.1 ( 200 mg/dL ) and 13.9 mmol/L ( 250 mg/dL ) , patients received an intravenous bolus of 4 units insulin every hour until the glucose concentration was less than 11.1 mmol/L ( < 200 mg/dL ) . If the intraoperative glucose concentration was greater than 13.9 mmol/L ( > 250 mg/dL ) , patients received an intravenous infusion of insulin that was continued until the glucose level was less than 8.3 mmol/L ( < 150 mg/dL ) . In both study groups , we measured arterial plasma glucose concentration every 30 minutes , starting just before anesthetic induction by using hexokinase method on a Double P Modular System ( Roche Diagnostics , Indianapolis , Indiana ) . Intraoperative procedures , including cardiopulmonary bypass , monitoring , laboratory testing , and treatment , were left to the discretion of anesthesiologists and cardiac surgeons . There was no st and ard protocol for monitoring and managing intraoperative potassium levels . Postoperative Period Intravenous insulin infusion was started in patients in the conventional treatment group on their arrival in the ICU . Thereafter , both study groups were treated identically , with the intravenous insulin infusion rates adjusted by a nursing staff that was not involved with the study according to a st and ard protocol . The target blood glucose range was 4.4 ( 80 mg/dL ) to 5.6 mmol/L ( 100 mg/dL ) ( Appendix Table 1 ) . Arterial blood glucose levels were measured every 1 to 2 hours by using the Accu-Check Inform blood glucose monitoring system ( glucometer ) ( Roche Diagnostics ) . During the first 24 hours after surgery , patients were given only clear liquids by mouth ; we did not administer subcutaneous insulin or oral diabetic medications during this time . Thereafter , the hospital diabetes consulting service saw all patients and provided individualized recommendations for ongoing care . Outcomes and Measurements The primary outcome variable was a composite of death , sternal wound infections , prolonged pulmonary ventilation , cardiac arrhythmias ( new-onset atrial fibrillation , heart block requiring permanent pacemaker , or cardiac arrest ) , stroke , and acute renal failure within 30 days after surgery . Secondary outcome measures were length of stay in the ICU and hospital . Trained study personnel identified the occurrence of a complication through chart abstract ion by using confirmable , objective criteria in accordance with st and ardized definitions from the Society of Thoracic Surgeons ( STS ) data base committee ( 17 ) . Personnel who assessed outcomes were not aware of patient treatment assignment or of the study hypothesis . Follow-up Procedures We contacted patients by telephone and used a st and ardized telephone survey at 30 days after surgery to assess outcomes that occurred after discharge . We considered
None of the trials examined the effects of the interventions in terms of costs .
AUTHORS ' CONCLUSIONS The included trials did not demonstrate significant differences for most of the outcomes when targeting intensive perioperative glycaemic control compared with conventional glycaemic control in patients with diabetes mellitus .
However , posthoc analysis indicated that intensive glycaemic control was associated with an increased number of patients experiencing hypoglycaemic episodes .
BACKGROUND Patients with diabetes mellitus are at increased risk of postoperative complications .
Data from r and omised clinical trials and meta-analyses point to a potential benefit of intensive glycaemic control , targeting near-normal blood glucose , in patients with hyperglycaemia ( with and without diabetes mellitus ) being su bmi tted to surgical procedures .
However , there is limited evidence concerning this question in patients with diabetes mellitus undergoing surgery .
OBJECTIVES To assess the effects of perioperative glycaemic control for diabetic patients undergoing surgery .