Evidence Based Medicine Keith Golden Oct 12th, 2007 Clinical Question: Does tight blood glucose control improve the prognosis of patients in a medical ICU? nd Intensive Insulin Therapy in the Medical ICU. New England Journal of Medicine. Feb. 2 , 2006. Vol. 354, No. 3 Van den Berghe G, Wilmer A, Hermans G, et al. Background: The Van den Berghe et al. follows a previous study in a surgical ICU that examined intensive insulin therapy, using a similar insulin titration guideline. That study showed a 3.4% absolute reduction in mortality. Post Hoc analysis revealed that patients who stayed in the surgical ICU for > 5 days had a 48% relative (9.6% absolute) reduction in mortality and morbidity. Hypothesis For patients in the medical ICU, who were presumed to need intensive care for greater than 3 days, intensive insulin therapy will reduce morbidity and mortality. Design: Prospective Randomized Study Follow-up period: Until hospital discharge. Setting: A medical ICU in Leuven, Belgium Intervention: Intensive insulin therapy (n = 595) or conventional insulin therapy (n = 605). For intensive therapy, insulin was given via infusion when blood glucose levels were > 110 mg/dL, and then adjusted to maintain 80 to 110 mg/dL. For conventional therapy, insulin was given when blood glucose levels were > 215 mg/dL, and then adjusted to maintain 180 to 200 mg/dL. When blood glucose levels fell below 180 mg/dL, the infusion was tapered or stopped. Are the results valid? 1. Were patients randomized? Yes. 1200 medical patients selected from 2110 possible. (See Figure 1.) Inclusion criteria: Adult patients admitted to ICU who were presumed to require > 3 days of MICU care. Exclution criteria: Surgical ICU, medical patients able to take p.o. nutrition, and patients w/ DNR. 2. Was randomization concealed? Blinded (primary outcome assesors and data analysts) 3. Were patients analyzed in the groups to which they were randomized? Yes. 4. Were patients in the treatment groups similar with respect to known prognostic factors? Yes. See Table 1. 5. Were the groups treated equally, apart from the experimental treatment? Yes. 6. Was follow-up sufficiently long and complete? Yes. Patients observed throughout hospital course. What are the results? Primary Outcome: In-hospital mortality. Intention to treat group did not differ for in-hospital, ICU, or 90-day mortality. Sub Group analysis of patients in ICU 3 days showed significant decrease in in-hospital mortality (p=0.009). Outcomes Intensive Conventional RRR NNT insulin (Y) therapy (X) IT In-hospital 37% 40% 7.5% Not significant mortality (p=0.33) ICU 3 days 43% 52.5% 18% 10.5 mortality (p=0.009) • Relative Risk (RR) = risk of the outcome in the experimental group (Y) compared to the risk in the control group (X). RR = Y / X = .43/.525 = 0.82 • Relative Risk Reduction (RRR) = percent reduction in risk in the experimental group (Y) compared to the control group (X). RRR = X-Y / X x 100 = .525-.43/.525 x 100 = 18% • Absolute Risk Reduction (ARR) = difference in risk between the control group (X) and the treatment group (Y). (Can also be thought of us the “absolute benefit” of treating with MMF) ARR = X – Y = .525-.43 * 100 = 9.5% • Number Needed to Treat (NNT) = number of patients that must be treated over a given period of time to prevent one adverse outcome. NNT = 1 / (X – Y) = 1/(.525-.43) = 10.5 Secondary Outcomes included: ICU and 90-day mortality, new kidney injury (serum creatinine level > 2.5 mg/dL or 2 times baseline), days to weaning from mechanical ventilation, duration of ICU and hospital stay, readmission to ICU, presence of bacteremia, and prolonged (> 10 d) antibiotic use. The intensive insulin therapy group had: Fewer new kidney injuries (RRR 34%, p=0.04) Earlier weaning from mechanical ventilation (HR 1.21, CI 1.02 to 1.44) Earlier discharge from the ICU (HR 1.15, CI 1.01 to 1.32) Earlier discharge from hospital (HR 1.16, CI 1.00 to 1.35) How can I apply the results to patient care? Applying the results of this study is difficult because it was limited in many ways: 1. Inclusion criteria attempted to predict who would require > 3 days of ICU care (64%). 2. Subgroup who stayed in ICU < 3 days had higher mortality (p=31). 3. Single center study 4. Control group does not accurately represent our standard of care Overall provides additional support for the use of intensive insulin therapy in the ICU setting, but raises questions about appropriate time for initiation and generalizability.
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