Society of Cardiovascular Anesthesiologists

April 2002 Newsletter

Intensive Insulin Therapy in Critically Ill Patients

G Van den Berghe, P Wouters, F Weekers, C Verwaest, F Bruyninckx, M Schetz, D Vlasselaers, P Ferdinande, P Lauwers, R Bouillon. N Engl J Med 2001; 345: 1359-67.

Reviewer: Rose Christopherson, MD, PhD
Portland VA Medical Center
Oregon Health Sciences University
Portland, OR

Background: It is unknown whether maintence of normal blood glucose levels using insulin therapy may improve the prognosis of critically ill patients. Such patients are often hyperglycemic and / or insulin resistant, regardless of whether they have had diabetes in the past.

Methods: A prospective randomized trial was performed to determine whether strict control of blood glucose in an ICU population would result in decreased mortality or morbidity. Adults admitted to the surgical intensive care unit of University Hospital Gasthuisberg, Leuven, Belgium, who required mechanical ventilation were studied. After informed consent was obtained from family members, the patients were randomized to receive either intensive or conventional insulin therapy. Blood glucose levels of those in the intensive group were maintained at 80-110 mg / dl. Those in the conventional group received insulin only if the blood glucose level exceeded 215 mg / dl, and their glucose levels were maintained between 180-200 mg / dl. Patients in both groups who required insulin received it by infusion.

Outcomes were diagnosed by clinicians blinded to the randomization group.

Results: The study was stopped at 12 months with a total enrollment of 1548 patients because of reduced mortality during ICU stay among the patients assigned to intensive therapy (4.6 % compared to 8.0 % in the conventional group, P < 0.04). Mortality was reduced most among patients who remained in the ICU for more than 5 days (10.6 % in the intensive group, 20.2 % in the conventional group, P = 0.005). Among patients who required ICU care for 5 or fewer days mortality rates were similar in the 2 groups (1.7 % in the intensive group, 1.8 % in the conventional group). Intensive insulin treatment was also associated with reduction in overall in-hospital mortality by 34 %, bloodstream infections by 46 %, and critical-illness polyneuropathy by 44 %. Patients in the intensive therapy were less likely to require mechanical ventilation for more than 14 days (7.5 % vs. 11.9 %, P = 0.003) or prolonged stays in the ICU lasting more than 14 days 11.4 % vs. 15.7 %, P = 0.01).

Conclusions: The authors concluded that, among critically ill patients in the surgical ICU, intensive insulin therapy to maintain blood glucose levels at or below 110 mg / dl is associated with reduced morbidity and mortality.

Comments: Most of the patients (62-63 %) admitted to this surgical ICU had undergone cardiac surgery. Another 8 % had undergone thoracic surgery, or had respiratory insufficiency at baseline. Another 4 % had undergone vascular surgery. Thus, this patient population includes many patients who are cared for by cardiac anesthesiologists. It is interesting that multiple morbidities, including polyneuropathy, prolonged ventilation, sepsis, and renal failure appear to be affected by tight control of blood sugar. The study was not designed to determine the mechanisms of reductions in these morbidities.

The authors pointed out that few interventions in intensive care, since the development of artificial ventilation, have been shown to improve survival. Tight control of blood sugar is a simple intervention which results in a reduction in mortality of 40 %, much more impressive than the 20 % reduction in mortality which has been shown with treatment of sepsis with activated protein C.

They did caution, however, that the results of this study cannot be generalized to a benefit for patients who do not require hospitalization in a surgical ICU. Hypoglycemia, defined as a glucose < 40 mg / dl, did occur in 39 of the 765 patients assigned to intensive treatment, and 6 patients in the conventional treatment group. In a less ill population, morbidities related to hypoglycemia may or may not outweigh benefits found in ventilated ICU patients.

Table of Contents:

Archived Newsletter Articles