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No Benefits to Therapeutic Hypothermia for Severe Bacterial Meningitis


Clinical question

Can therapeutic hypothermia improve functional outcomes in comatose patients with severe bacterial meningitis?

Bottom line

For critically ill patients with severe bacterial meningitis, induced hypothermia using intravascular cooling or other cooling techniques does not improve outcomes and may lead to increased mortality. This trial was stopped early and thus lacked the statistical power to make definitive conclusions about the potential harmful effects of this intervention. (LOE = 1b-)


Mourvillier B, Tubach F, van de Beek D, et al. Induced hypothermia in severe bacterial meningitis: A randomized clinical trial. JAMA 2013;310(20):2174-2183.

Study design

Randomized controlled trial (nonblinded)

Funding source

Industry + govt




Inpatient (ICU only)


Adult patients with suspected or confirmed bacterial meningitis who had a Glasgow Coma Scale (GCS) score of less than 8 for fewer than 12 hours were randomized, using concealed allocation, into the induced hypothermia group or to usual care. All patients received appropriate antimicrobial therapy. In the hypothermia group, intravascular cooling was achieved by a loading dose of 1500 mL 40C saline over 30 minutes, and additional 500 mL boluses over 10 minutes as needed, to achieve a temperature of 33.50C or lower. Other cooling techniques, including ice packs, cooling air, and cooling pads, were also used. Temperatures were maintained between 32C and 34C for 48 hours, and the rewarming phase was passive. Baseline characteristics in the intervention group and control group were similar: mean age was 59 years, median GCS score was 7, all patients were mechanically ventilated, and the causative organism was identified as Streptococcus pneumoniae in the majority of patients. Analysis was by intention to treat. The primary outcome was the score on the Glasgow Outcome Scale. A favorable outcome was a score of 5, indicating mild or no disability; an unfavorable outcome was any score 1 through 4, with 1 indicating death. At 3 months, there was a trend toward unfavorable outcomes in the hypothermia group (86% vs 73% in the control group; relative risk = 1.17; 0.95-1.43; P = .13), as well as a trend toward increased mortality (hazard ratio = 1.76; 0.89-3.45; P = .10). The trial was stopped early because of the higher mortality in the hypothermia group.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

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