Format

Send to

Choose Destination
Lancet Respir Med. 2018 Mar;6(3):183-192. doi: 10.1016/S2213-2600(18)30004-3. Epub 2018 Jan 8.

Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial.

Author information

1
Department of Anesthesia and Intensive Care, Nordsjællands Hospital, Hillerød, Denmark; Centre of Excellence in Immunity and Infection/Centre of Excellence for Personalised Medicine of Infectious Complications in Immune Deficiency, Department of Infectious Diseases, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
2
Centre of Excellence in Immunity and Infection/Centre of Excellence for Personalised Medicine of Infectious Complications in Immune Deficiency, Department of Infectious Diseases, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
3
Department of Anesthesia and Intensive Care, Nordsjællands Hospital, Hillerød, Denmark.
4
Department of Anesthesia and Intensive Care, Bispebjerg Hospital, Copenhagen, Denmark.
5
Department of Anesthesia and Intensive Care, Herlev and Gentofte Hospital, Hellerup, Denmark.
6
Department of Anesthesia and Intensive Care, Herlev and Gentofte Hospital, Herlev, Denmark.
7
Department of Anesthesia and Intensive Care, Zealand University Hospital, Køge, Denmark.
8
Department of Anesthesia and Intensive Care, Roskilde Hospital, Roskilde, Denmark.
9
Department of Intensive Care, Academic Medical Center, Amsterdam, Netherlands.
10
Department of Anesthesia and Intensive Care, Horsens Hospital, Horsens, Denmark.
11
Center for Critical Care, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA.
12
Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA.
13
Department of Anesthesia and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.
14
Department of Neuroanesthesiology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
15
Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, UK.
16
Centre of Excellence in Immunity and Infection/Centre of Excellence for Personalised Medicine of Infectious Complications in Immune Deficiency, Department of Infectious Diseases, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark; Respiratory Medicine Division, Department of Internal Medicine, Herlev and Gentofte Hospital, Hellerup, Denmark. Electronic address: jens.ulrik.jensen@regionh.dk.

Abstract

BACKGROUND:

Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock.

METHODS:

In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70 mm Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of stay in the ICU at least 24 h, and recruitment into the study within 6 h of fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding, clinically important bleeding disorder, recent open surgery, pregnancy or breastfeeding, or involuntary psychiatric admission. We randomly allocated patients 1:1 (with variable block sizes ranging from four to eight; stratified by predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II score, and study site) to routine thermal management or 24 h of induced hypothermia (target 32-34°C) followed by 48 h of normothermia (36-38°C). The primary endpoint was 30 day all-cause mortality in the modified intention-to-treat population (all randomly allocated patients except those for whom consent was withdrawn or who were discovered to meet an exclusion criterion after randomisation but before receiving the trial intervention). Patients and health-care professionals giving the intervention were not masked to treatment allocation, but assessors of the primary outcome were. This trial is registered with ClinicalTrials.gov, number NCT01455116.

FINDINGS:

Between Nov 1, 2011, and Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned 560 participants, the trial was terminated for futility (220 [50%] randomly allocated to hypothermia and 216 [50%] to routine thermal management). In the hypothermia group, 96 (44·2%) of 217 died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]).

INTERPRETATION:

Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce mortality. Induced hypothermia should not be used in patients with septic shock.

FUNDING:

Trygfonden, Lundbeckfonden, and the Danish National Research Foundation.

Comment in

PMID:
29325753
DOI:
10.1016/S2213-2600(18)30004-3
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center