Question: In patients who are critically ill, does normalization of blood glucose levels with intensive insulin therapy reduce mortality and morbidity?
Design: Randomized (allocation concealed*), blinded (patients and outcome asessors),* controlled trial with {mean follow-up of 23 days}†.
Setting: Surgical intensive care unit (ICU) at a university hospital in Leuven, Belgium.
Patients: 1548 patients (mean age 63 y, 71% men) admitted to the ICU who were receiving mechanical ventilation. Patients were excluded if they were participating in another trial, were moribund, or had do-not-resuscitate orders. Follow-up was 100%.
Intervention: Patients were assigned to intensive (n = 765) or conventional (n = 783) insulin therapy. Intensive therapy was insulin infusion that was begun if the blood glucose level was > 6.1 mmol/L and adjusted to maintain normoglycemia (maximum insulin dose 50 IU/h). Conventional therapy was continuous insulin infusion by a pump that was begun if the blood glucose level was > 11.9 mmol/L and adjusted to maintain a blood glucose level between 10.0 and 11.1 mmol/L. All patients were given continuous intravenous glucose on ICU admission, and total enteral feeding was attempted as early as possible.
Main outcome measures: The primary outcome measure was all-cause mortality in the ICU. Secondary outcome measures included in-hospital mortality, duration of ICU stay, need for ICU care or ventilatory support for > 14 days, and various diseases.
Main results: Analysis was by intention to treat. Patients who received intensive insulin therapy had reduced rates of all-cause ICU mortality (P < 0.04), in-hospital mortality (P = 0.01), ICU care > 14 days (P = 0.01), ventilatory support > 14 days (P = 0.003), renal failure requiring dialysis or hemofiltration (P = 0.007), bloodstream infections in the ICU (P = 0.003), and critical-illness polyneuropathy (P < 0.001) (Table). The groups did not differ for duration of ICU stay (median 3 d in both groups, P = 0.2).
Conclusion: In patients who are critically ill, normalization of blood glucose levels with intensive insulin therapy reduced mortality and morbidity.
Intensive vs conventional insulin therapy in critically ill patients‡
| Outcomes at mean 23 d | Intensive | Conventional | RRR (95% CI) | NNT (CI) |
| All ICU mortality | 5% | 8% | 43% (15 to 62) | 29 (17 to 94) |
| All in-hospital mortality | 7% | 11% | 34% (9 to 52) | 27 (15 to 122) |
| ICU stay > 14 d | 11% | 16% | 28% (7 to 44) | 23 (13 to 108) |
| Ventilatory support > 14 d | 8% | 12% | 37% (14 to 54) | 23 (14 to 67) |
| Renal failure requiring dialysis or hemofiltration | 5% | 8% | 41% (13 to 60) | 30 (17 to 112) |
| Bloodstream infection | 4% | 8% | 46% (19 to 65) | 28 (17 to 79) |
| Critical-illness polyneuropathy | 29% | 52% | 45% (28 to 59) | 4 (3 to 8) |