[IPu] Tight Glucose Control in Medical ICU has Mixed Results (From MedPage)
Tight Glucose Control in Medical ICU Has Mixed Results
By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the
University of Pennsylvania School of Medicine.
February 01, 2006
MedPage Today Action Points
a.. Understand that this study found that intensive
glucose control reduces morbidity and mortality among patients who stay at
least three days in a medical intensive care unit, but suggests that intensive
insulin therapy could be harmful in patients with shorter ICU stays.
b.. Understand that although this study was randomized, it
was conducted in a single center, and investigators were not blinded to
patients' glycemic status at admission.
Review
Renee Meadows, M.D., Hospitalist at Ochsner Clinic
Foundation
LEUVEN, Belgium, Feb.1 - Patients who stay at least three days in
a medical ICU and get intensive insulin therapy have lower death rates than
patients who are treated just to bring down glucose spikes, researchers here
found.
In 2001, the same researchers here showed that intensive insulin
therapy to control hyperglycemia significantly reduce both morbidity and
mortality among patients in surgical intensive care units.
But this new study suggested that among patients in medical ICUs,
tight glycemic control reduces morbidity, but only reduces the death rate
among patients treated for three days or more, reported Greet Van den Berghe,
M.D., of the Catholic University of Leuven, and colleagues in the Feb. 2 issue
of the New England Journal of Medicine.
In fact, intensive insulin therapy may be associated with a higher
mortality rate among patients treated in the medical ICU for less than 72
hours, and there is no reliable way to predict which patients might benefit
or, possibly be harmed by the focus on glycemic control, they wrote.
The researchers were at a loss to explain why only patients with
longer ICU stays had lower death rates when treated with intensive insulin
therapy.
"In our previous study, brief exposure to insulin therapy had no
significant effect on the risk of death," they wrote. "Why 48 hours or less of
insulin therapy would cause harm, whereas sustained treatment would be
beneficial, is unclear."
An intensive care specialist who was not involved in the study
said that while the study data make it hard to draw inferences about when
intensive insulin therapy should be used in ICU patients, one message comes
through clearly.
"No matter how you take this specific article, it contributes to
the growing body of evidence that supports that hyperglycemia should be
controlled in the acutely ill and severely ill, " said Renee Y. Meadows, M.D.,
a hospital-based internist at the Ochsner Clinic in New Orleans.
"The days of just letting glucoses go above 250 and hang there,
because we're presuming it's of some physiologic benefit, are over," Dr.
Meadows said in an interview.
Pending the outcome of two large-scale randomized trials exploring
the benefits or drawbacks of glycemic control in the ICU, intensive care
physicians might try the middle ground, suggested Atul Malhotra, M.D., of
Boston's Brigham and Women's Hospital, in an accompanying editorial.
"In my opinion, a reasonable approach would be to provide adequate
exogenous insulin to achieve target glucose values of less than 150 mg/dL (8.3
mmol/L), at least during the first three days in the ICU," he wrote. "If
critical illness persists beyond three days despite the provision of other
proven therapies and resuscitation, a goal of normoglycemia (80 to 110 mg/dL
[4.4 to 6.1 mmol/L]) could then be considered, to maximize the potential
benefits."
The Belgian researchers conducted a prospective, randomized,
controlled study of adult patients admitted to the medical ICU. The patients
in the study were judged to need at least three days of intensive care.
Patients were randomly assigned on admission to either intensive
insulin therapy with the goal of normoglycemia (glucose 80 to 110 mg/dL [4.4
to 6.1 mmol/L]), or to conventional therapy, in which insulin would be
administered only when the blood glucose level exceeded 215 mg/dL [12 mmol/L],
with the infusion tapered when the level fell below 180 mg/dL [10 mmol/L]).
A total of 1,200 patients were enrolled, of whom 16.9% had
diabetes. Analysis was by intention-to-treat.
The investigators found that intensive insulin therapy reduced
blood glucose levels but did not significantly reduce in-hospital mortality
among all patients (40.0% in the conventional-treatment group vs. 37.3% in the
intensive-treatment group, P = 0.33).
"However, morbidity was significantly reduced by the prevention of
newly acquired kidney injury, accelerated weaning from mechanical ventilation,
and accelerated discharge from the ICU and the hospital," Dr. Van den Berghe
and colleagues wrote.
Among 433 patients whose ICU stays were less than three days, the
mortality rate was higher in those receiving intensive insulin therapy. There
were 56 deaths among the intensive-treatment group, compared with 42 in the
conventional treatment group, but the statistical significance of this finding
depended on the test used, the authors noted.
In contrast, among 767 patients who stayed in the ICU for three or
more days, in-hospital mortality in the 386 who received intensive insulin
therapy was reduced from 52.5% to 43.0%, and this difference was statistically
significant (P = 0.009). Morbidity was also in these patients, the authors
noted.
The investigators acknowledged that the study results were limited
by the fact that it was a single-center study and that it was not strictly
blinded because the presence of patients with diabetes required clinician
awareness of glycemic status for some patients.
"Because patients who will have a prolonged stay in the ICU cannot
be identified with certainty on admission, adequately powered trials are
needed to address his important issue," they wrote.
Primary source: New England Journal of Medicine
Source reference:
Van den Berghe et al. Intensive Insulin Therapy in the Medical
ICU. N Engl J Med 2006;354:449-61.
Additional source: New England Journal of Medicine
Source reference:
Malhotra A. Intensive Insulin in Intensive Care. N Engl J Med
2006;354:516-18.
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