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Intensive insulin therapy reduced mortality and morbidity in critically ill patients

Daniel L. Hurley, MD; and M. Molly McMahon, MD
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*See Glossary.

†Information provided by author.

Sources of funding: University of Leuven; Belgian Fund for Scientific Research; Belgian Foundation for Research in Congenital Heart Disease; Novo Nordisk.

For correspondence: Dr. G. Van den Berghe, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium. E-mail greta.vandenberghe@med.kuleuven.ac.be.

Ann Intern Med. 2002;136(3):81. doi:10.7326/ACPJC-2002-136-3-081
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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 dIntensiveConventionalRRR (95% CI)NNT (CI)
All ICU mortality5%8%43% (15 to 62)29 (17 to 94)
All in-hospital mortality7%11%34% (9 to 52)27 (15 to 122)
ICU stay > 14 d11%16%28% (7 to 44)23 (13 to 108)
Ventilatory support > 14 d8%12%37% (14 to 54)23 (14 to 67)
Renal failure requiring dialysis or hemofiltration5%8%41% (13 to 60)30 (17 to 112)
Bloodstream infection4%8%46% (19 to 65)28 (17 to 79)
Critical-illness polyneuropathy29%52%45% (28 to 59)4 (3 to 8)

‡Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data provided by author.





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