Deborah Cook, MD; Lauralyn McIntyre, MD
In critically ill patients with severe sepsis or septic shock, how does intensive insulin therapy (IIT) compare with conventional therapy for mortality? How does fluid resuscitation with hydroxyethyl starch (HES) compare with Ringer's lactate (RL)?
Randomized, 2 × 2 factorial design, controlled trial (Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis [VISEP] study).
18 intensive care units (ICUs) in Germany.
537 patients (mean age 65 y, 60% men) with severe sepsis or septic shock developing < 24 hours before ICU admission or < 12 hours after admission if condition developed in the ICU. Exclusion criteria included receipt of HES > 1000 mL in the 24 hours before randomization.
IIT (n = 247) or conventional therapy (n = 290) and fluid resuscitation with HES (n = 262) or RL (n = 275). IIT consisted of insulin infusion when plasma glucose levels were > 110 mg/dL, then adjusted to maintain euglycemia (80 to 110 mg/dL). Conventional therapy consisted of continuous insulin infusion when glucose levels were > 200 mg/dL, then adjusted to maintain levels at 180 to 200 mg/dL.
All-cause mortality and Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes included length of ICU stay, acute renal failure, renal replacement therapy (RRT), hypoglycemia (≤ 40 mg/dL), and development of ≥ 1 adverse event and ≥ 1 serious adverse event.
89% (intention-to-treat analysis).
The trial was stopped early by the safety committee. More patients in the IIT group had hypoglycemia, ≥ 1 adverse event, and ≥ 1 serious adverse event than the conventional therapy group (Table), but groups did not differ for all-cause mortality (Table), SOFA scores, length of ICU stay, acute renal failure, or RRT. Cumulative median dose of HES was 70.4 mL/kg; 38% of patients in the HES group exceeded the maximum dose of 20 mL/kg/d. HES led to more acute renal failure and RRT than RL (Table); groups did not differ for mortality (Table), SOFA scores, length of ICU stay, hypoglycemia, or adverse events.
Intensive insulin therapy increased hypoglycemia and adverse events compared with conventional therapy. Fluid resuscitation with hydroxyethyl starch increased acute renal failure and renal replacement therapy compared with Ringer's lactate.
Intensive insulin therapy (IIT) vs conventional insulin therapy (CIT) and fluid resuscitation with hydroxyethyl starch (HES) vs Ringer's lactate (RL) in severe sepsis or septic shock‡
‡Abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from data in article.
Cook D, McIntyre L. Intensive insulin therapy and starch (HES 200/0.5) had some risk and no clear benefit in severe sepsis. Ann Intern Med. 2008;148:JC4–4. doi: 10.7326/0003-4819-148-12-200806170-02004
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Published: Ann Intern Med. 2008;148(12):JC4-4.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism, Multi-Organ Failure and Sepsis.
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