Trial reportThe Lancet. Respiratory medicine2018
Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial.
Trial report in The Lancet. Respiratory medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01455116 (Randomized Trial to Determine Whether Mild Induced Hypothermia Can Reduce Mortality in Adult Patients With Septic Shock), which is not on this map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized Trial to Determine Whether Mild Induced Hypothermia Can Reduce Mortality in Adult Patients With Septic Shock
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Neurological Outcome Following Newborn Encephalopathy With and Without Perinatal Infection: A Systematic Review.Frontiers in pediatrics · 2021Pooled it
- Core Warming of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study.Therapeutic hypothermia and temperature management · 2023Trial
- Hypothermia is not therapeutic in a neonatal piglet model of inflammation-sensitized hypoxia-ischemia.Pediatric research · 2022Trial
- Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature.Critical care (London, England) · 2021Trial
- The poikilothermic hypothesis of sepsis.Critical care (London, England) · 2026Review
- Sepsis in the absence of fever: Determining the criteria for and feasibility of future therapeutic temperature management trials.Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2025Article
- Spontaneous and pharmacologically induced hypothermia protect mice against endotoxic shock.British journal of pharmacology · 2025Article
- Investigation into the influence of mild hypothermia on regulating ferroptosis through the P53-SLC7A11/GPX4 signaling pathway in sepsis-induced acute lung injury.Intensive care medicine experimental · 2025Article
- Association between body temperature and all-cause mortality in patients with sepsis: analysis of the MIMIC-IV database.European journal of medical research · 2024Article
- Modern CRRT systems are associated with lower risk of hypothermia.Scientific reports · 2024Observational
- Article
- Moderate Hypothermia Alleviates Sepsis-Associated Acute Lung Injury by Suppressing Ferroptosis Induced by Excessive Inflammation and Oxidative Stress via the Keap1/GSK3β/Nrf2/GPX4 Signaling Pathway.Journal of inflammation research · 2024Article
- Management of spontaneous septic hypothermia in intensive care. A national survey of French intensive care units.Frontiers in medicine · 2024Article
- Design and rationale of the CHILL phase II trial of hypothermia and neuromuscular blockade for acute respiratory distress syndrome.Contemporary clinical trials communications · 2023Article
- Ten tips on fever.Intensive care medicine · 2023Article
- Temperature control in sepsis.Frontiers in medicine · 2023Review
- Therapeutic hyperthermia for the treatment of infection-a narrative review.Frontiers in physiology · 2023Review
- Hibernation and hemostasis.Frontiers in physiology · 2023Review
- Therapeutic hypothermia attenuates physiologic, histologic, and metabolomic markers of injury in a porcine model of acute respiratory distress syndrome.Physiological reports · 2022Article
- Microcirculation during surgery.Anesthesia and pain medicine · 2022Review
Corrections and comments
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Authors and funding
29 authors at 14 institutions in 4 countries.
Funding
Abstract
backgroundAnimal 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.
methodsIn 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.
findingsBetween 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]).
interpretationAmong 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.
fundingTrygfonden, Lundbeckfonden, and the Danish National Research Foundation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.