NICE SUGAR

NEJM

March 26, 2009

Intensive versus Conventional Glucose Control in Critically Ill Patients.

What was the research question?

  • In critically ill patients who are expected to stay 3 days or more in the ICU, does intensive control of blood glucose reduce mortality at 90 dayscompared to conventional controlled blood?


How did they do it?

  • A multicenter, randomized trial in 42 centers in Australia, New Zealand, and Canada.

  • 6104 patients who are expected to stay 3 days or more in the ICU were randomized to have an intensive control of blood glucose (81-108 mg/dL) or a conventional control of blood glucose of less than 180 mg/dL (3054 vs 3050 Patients).

  • Patients were stratified for the type of admission (operative vs non-operative) and geographical region.

  • The primary outcome was 90-day mortality, and the secondary outcomes included the number of days without need for organ support and the occurrence of adverse events.


What did they find?

  • 90-day mortality was significantly higher in the intensive group compared to the conventional group (27.5% vs. 24.9%, P-0.02).

  • No significant mortality difference between operative (surgical) patients and nonoperative (medical) patients (P=0.10).

  • Severe hypoglycemia (blood glucose level ≤40 mg/dL) was significantly higher in the intensive group compared to the conventional group (6.8% vs 0.5%, P<0.001).

  • No significant difference in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39).


Are there any limitations?

  • Possibility of bias as the clinicians were unblinded and the treatment was discontinued prematurely in 10.0% of patients in the intensive group and 7.4% in the conventional group.

  • Outcome may have been affected with a higher corticosteroid use in the intensive group compared to the control group (34.6% vs 31.7%; p=0.02).

  • The median blood sugar level was 6.4 mmol/liter (115 mg/dL) in the intensive control group which was above the target blood sugar levels, demonstrating difficulty in achieving the target range and it may have reduced the observed difference between the two groups.

  • Reduced generalizability to patients who are on parenteral nutrition as most patients were fed enterally.

  • It is not clear why mortality at 90 days is higher with intensive control but not at 28 days!


What does it mean?

  • Intensive control of blood glucose is associated with a higher 90-day mortality and a higher rate of severe hypoglycemia.

  • This study changed our practice to aim for blood sugar level of less than 180 in all ICU admitted patients.

NICE SUGAR