High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients.
BACKGROUND
Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that is implicated in the pathogenesis of several postoperative complications. Studies have shown that proinflammatory cytokines are increased by acute hyperglycemia. Recent evidence suggests that insulin has antiinflammatory properties. Therefore, we hypothesized that high-dose insulin therapy would attenuate the systemic inflammatory response to cardiopulmonary bypass and surgery in coronary artery bypass patients while maintaining normoglycemia.


METHODS
A total of 52 patients who presented for elective coronary artery bypass were randomized to receive intraoperative intravenous insulin infusion, titrated to maintain blood glucose concentrations less than 180 mg/dL (group I, n = 25), or receive intraoperative fixed high dose of intravenous insulin infusion (5 mU/kg/min) with dextrose 20% infused separately to maintain a blood glucose level between 70 and 110 mg/dL (group II, n = 27). Blood samples were collected at different time points to determine tumor necrosis factor alpha (TNFalpha), interleukin 6 and 8 (IL6 and IL8), and complement factor 3 and 4 (C3 and C4).


RESULTS
Patients in both groups had similar preoperative characteristics. Patients in the high-dose insulin group had higher blood insulin concentrations and tighter blood glucose control. There were lower levels of IL6 (150 pg/dL vs 245 pg/dL, p = 0.03), IL-8 (49 pg/dL vs 74 pg/dL, p = 0.05), and TNFalpha (2.2 pg/dL vs 3.0 pg/dL, p = 0.04) in group II in the early postoperative period.


CONCLUSIONS
High-dose insulin therapy blunts the early postoperative surge in inflammatory response to CPB as reflected by decreased levels of IL6, IL8, and TNFalpha.
Albacker
Turki
T
Division of Cardiothoracic Surgery, Department of Surgery, McGill University Health Center, McGill University, Montreal, Quebec, Canada. dr_turki@yahoo.com
Carvalho
George
G
Schricker
Thomas
T
Lachapelle
Kevin
K
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000379:methods; D003324:Coronary Artery Disease / Q000150:complications / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage*; D007430:Intraoperative Care / Q000379:methods; D008297:Male; D011183:Postoperative Complications / Q000503:physiopathology / Q000517:prevention & control; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014336:Troponin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D018836:Inflammation Mediators; D007328:Insulin; D014336:Troponin