According to the results of a recent study published in The Lancet Respiratory Medicine, patients with septic shock and respiratory failure did not have improved outcomes after induced hypothermia compared with routine thermal management, leading to early trial termination.
In this randomized controlled trial (ClinicalTrials.gov identifier: NCT01455116), researchers enrolled patients meeting the following inclusion criteria: severe sepsis or septic shock, mean arterial pressure <70 mm Hg, receiving mechanical ventilation in 1 of 10 intensive care units in Europe and North America, age ≥50 years, predicted length of stay ≥24 hours, and recruitment into the study within 6 hours of fulfilling inclusion criteria. Patients with uncontrolled bleeding or bleeding disorders were excluded from the study. Participants were randomly assigned to receive routine thermal management or induced hypothermia for 24 hours (target 32°C-34°C) followed by normothermia for 48 hours (target 36°C-38°C). All-cause mortality within 30 days was the primary outcome.
Of the planned 560 patients to be enrolled in the trial, 436 participants were enrolled before the trial was closed for futility.
Most of the 220 patients in the hypothermia group underwent external pad-based induction (n=202), and 15 patients received cooling by intravenous catheter. The target temperature was achieved by a median of 3.2 hours.
The 30-day all-cause mortality rate was not significantly different between the induced hypothermia group (44.2%) and the routine thermal management group (35.8%; relative risk 1.2; P =.07). Mortality rates were similar between patients cooled with intravenous catheters (47%) and those cooled with external pads (44%).
Compared with the routine thermal management group, patients in the induced hypothermia group had fewer days alive without mechanical ventilation (P =.03), fewer days alive without vasoactive therapy (P =.006), and fewer days alive without renal replacement therapy (P =.04) within the first 30 days.
The study authors concluded that, “hypothermia delayed recovery of several key organ functions. Our findings do not support use of induced hypothermia in patients with septic shock.”
Itenov TS, Johansen ME, Bestle M, et al; for the Cooling and Surviving Septic Shock (CASS) Trial Collaboration. Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial [published online January 8, 2018]. Lancet Respir Med. doi: 10.1016/S2213-2600(18)30004-3