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Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control.
Crit Care Med. 2003 Feb; 31(2):359-66.CC

Abstract

OBJECTIVES

Maintenance of normoglycemia with insulin reduces mortality and morbidity of critically ill patients. Here we report the factors determining insulin requirements and the impact of insulin dose vs. blood glucose control on the observed outcome benefits.

DESIGN

A prospective, randomized, controlled trial.

SETTING

A 56-bed predominantly surgical intensive care unit in a tertiary teaching hospital.

PATIENTS AND INTERVENTION

A total of 1,548 patients were randomly assigned to either strict normalization of blood glucose (80-110 mg/dL) with insulin infusion or the conventional approach, in which insulin is only given to maintain blood glucose levels at 180-200 mg/dL.

MEASUREMENTS AND MAIN RESULTS

It was feasible and safe to achieve and maintain blood glucose levels at <110 mg/dL by using a titration algorithm. Stepwise linear regression analysis identified body mass index, history of diabetes, reason for intensive care unit admission, at-admission hyperglycemia, caloric intake, and time in intensive care unit as independent determinants of insulin requirements, together explaining 36% of its variation. With nutritional intake increasing from a mean of 550 to 1600 calories/day during the first 7 days of intensive care, normoglycemia was reached within 24 hrs, with a mean daily insulin dose of 77 IU and maintained with 94 IU on day 7. Insulin requirements were highest and most variable during the first 6 hrs of intensive care (mean, 7 IU/hr; 10% of patients required >20 IU/hr). Between day 7 and 12, insulin requirements decreased by 40% on stable caloric intake. Brief, clinically harmless hypoglycemia occurred in 5.2% of intensive insulin-treated patients on median day 6 (2-14) vs. 0.8% of conventionally treated patients on day 11 (2-10). The outcome benefits of intensive insulin therapy were equally present regardless of whether patients received enteral feeding. Multivariate logistic regression analysis indicated that the lowered blood glucose level rather than the insulin dose was related to reduced mortality (p <.0001), critical illness polyneuropathy (p <.0001), bacteremia (p =.02), and inflammation (p =.0006) but not to prevention of acute renal failure, for which the insulin dose was an independent determinant (p =.03). As compared with normoglycemia, an intermediate blood glucose level (110-150 mg/dL) was associated with worse outcome.

CONCLUSION

Normoglycemia was safely reached within 24 hrs and maintained during intensive care by using insulin titration guidelines. Metabolic control, as reflected by normoglycemia, rather than the infused insulin dose, was related to the beneficial effects of intensive insulin therapy.

Authors+Show Affiliations

Department of Intensive Care Medicine, Catholic University of Leuven, Belgium. greta.vandenberghe@med.kuleuven.ac.beNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12576937

Citation

Van den Berghe, Greet, et al. "Outcome Benefit of Intensive Insulin Therapy in the Critically Ill: Insulin Dose Versus Glycemic Control." Critical Care Medicine, vol. 31, no. 2, 2003, pp. 359-66.
Van den Berghe G, Wouters PJ, Bouillon R, et al. Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control. Crit Care Med. 2003;31(2):359-66.
Van den Berghe, G., Wouters, P. J., Bouillon, R., Weekers, F., Verwaest, C., Schetz, M., Vlasselaers, D., Ferdinande, P., & Lauwers, P. (2003). Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control. Critical Care Medicine, 31(2), 359-66.
Van den Berghe G, et al. Outcome Benefit of Intensive Insulin Therapy in the Critically Ill: Insulin Dose Versus Glycemic Control. Crit Care Med. 2003;31(2):359-66. PubMed PMID: 12576937.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control. AU - Van den Berghe,Greet, AU - Wouters,Pieter J, AU - Bouillon,Roger, AU - Weekers,Frank, AU - Verwaest,Charles, AU - Schetz,Miet, AU - Vlasselaers,Dirk, AU - Ferdinande,Patrick, AU - Lauwers,Peter, PY - 2003/2/11/pubmed PY - 2003/3/26/medline PY - 2003/2/11/entrez SP - 359 EP - 66 JF - Critical care medicine JO - Crit Care Med VL - 31 IS - 2 N2 - OBJECTIVES: Maintenance of normoglycemia with insulin reduces mortality and morbidity of critically ill patients. Here we report the factors determining insulin requirements and the impact of insulin dose vs. blood glucose control on the observed outcome benefits. DESIGN: A prospective, randomized, controlled trial. SETTING: A 56-bed predominantly surgical intensive care unit in a tertiary teaching hospital. PATIENTS AND INTERVENTION: A total of 1,548 patients were randomly assigned to either strict normalization of blood glucose (80-110 mg/dL) with insulin infusion or the conventional approach, in which insulin is only given to maintain blood glucose levels at 180-200 mg/dL. MEASUREMENTS AND MAIN RESULTS: It was feasible and safe to achieve and maintain blood glucose levels at <110 mg/dL by using a titration algorithm. Stepwise linear regression analysis identified body mass index, history of diabetes, reason for intensive care unit admission, at-admission hyperglycemia, caloric intake, and time in intensive care unit as independent determinants of insulin requirements, together explaining 36% of its variation. With nutritional intake increasing from a mean of 550 to 1600 calories/day during the first 7 days of intensive care, normoglycemia was reached within 24 hrs, with a mean daily insulin dose of 77 IU and maintained with 94 IU on day 7. Insulin requirements were highest and most variable during the first 6 hrs of intensive care (mean, 7 IU/hr; 10% of patients required >20 IU/hr). Between day 7 and 12, insulin requirements decreased by 40% on stable caloric intake. Brief, clinically harmless hypoglycemia occurred in 5.2% of intensive insulin-treated patients on median day 6 (2-14) vs. 0.8% of conventionally treated patients on day 11 (2-10). The outcome benefits of intensive insulin therapy were equally present regardless of whether patients received enteral feeding. Multivariate logistic regression analysis indicated that the lowered blood glucose level rather than the insulin dose was related to reduced mortality (p <.0001), critical illness polyneuropathy (p <.0001), bacteremia (p =.02), and inflammation (p =.0006) but not to prevention of acute renal failure, for which the insulin dose was an independent determinant (p =.03). As compared with normoglycemia, an intermediate blood glucose level (110-150 mg/dL) was associated with worse outcome. CONCLUSION: Normoglycemia was safely reached within 24 hrs and maintained during intensive care by using insulin titration guidelines. Metabolic control, as reflected by normoglycemia, rather than the infused insulin dose, was related to the beneficial effects of intensive insulin therapy. SN - 0090-3493 UR - https://www.unboundmedicine.com/medline/citation/12576937/Outcome_benefit_of_intensive_insulin_therapy_in_the_critically_ill:_Insulin_dose_versus_glycemic_control_ L2 - https://dx.doi.org/10.1097/01.CCM.0000045568.12881.10 DB - PRIME DP - Unbound Medicine ER -