Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm.
Intensive insulin therapy (IIT) improves the outcome of prolonged critically ill patients, but concerns remain regarding potential harm and the optimal blood glucose level. These questions were addressed using the pooled dataset of two randomized controlled trials. Independent of parenteral glucose load, IIT reduced mortality from 23.6 to 20.4% in the intention-to-treat group (n = 2,748; P = 0.04) and from 37.9 to 30.1% among long stayers (n = 1,389; P = 0.002), with no difference among short stayers (8.9 vs. 10.4%; n = 1,359; P = 0.4). Compared with blood glucose of 110-150 mg/dl, mortality was higher with blood glucose >150 mg/dl (odds ratio 1.38 [95% CI 1.10-1.75]; P = 0.007) and lower with <110 mg/dl (0.77 [0.61-0.96]; P = 0.02). Only patients with diabetes (n = 407) showed no survival benefit of IIT. Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly <110 mg/day, but this level carried the highest risk of hypoglycemia. Within 24 h of hypoglycemia, three patients in the conventional and one in the IIT group died (P = 0.0004) without difference in hospital mortality. No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units (ICUs). We conclude that IIT reduces mortality of all medical/surgical ICU patients, except those with a prior history of diabetes, and does not cause harm. A blood glucose target <110 mg/day was most effective but also carried the highest risk of hypoglycemia.
Van den Berghe
Greet
G
Department of Intensive Care Medicine, University Hospital Gasthuisberg, University of Leuven, B-3000 Leuven, Belgium. greta.vandenberghe@med.kuleuven.be
Wilmer
Alexander
A
Milants
Ilse
I
Wouters
Pieter J
PJ
Bouckaert
Bernard
B
Bruyninckx
Frans
F
Bouillon
Roger
R
Schetz
Miet
M
D018806:APACHE; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016638:Critical Illness; D004334:Drug Administration Schedule; D002149:Energy Intake; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin