1. Induced hypothermia in patients with septic shock and respiratory failure (CASS):a randomised, controlled, open-label trial
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Theis Skovsgaard Itenov, Maria Egede Johansen, Morten Bestle, Katrin Thormar, Lars Hein, Louise Gyldensted, Anne Lindhardt, Henrik Christensen, Stine Estrup, Henrik Planck Pedersen, Matthew Harmon, Uday Kant Soni, Silvia Perez-Protto, Nicolai Wesche, Ulrik Skram, John Asger Petersen, Thomas Mohr, Tina Waldau, Lone Musaeus Poulsen, Ditte Strange, Nicole P Juffermans, Daniel I Sessler, Else Tønnesen, Kirsten Møller, Dennis Karsten Kristensen, Alessandro Cozzi-Lepri, Jens D Lundgren, Jens-Ulrik Jensen, Jens-Ulrik Stæhr Jensen, Jens Lundgren, Susanne Illkjær, Henry Masur, Christian Torp-Pedersen, Andrew Copas, Birgit Riis Nielsen, Jesper Grarup, Jette Hansen, Kim Nielsen, Lone Valbjørn, Sanne Lauritzen, Tina Kold, Kathrine Grundahl, Rikke Hein Rasmussen, Nikolaj Wesche, Hasse Blom, Peer Eske Jensen, Tina Galle, Bente Thaarslund, Camilla Skandov, Iben Langholz, Rasmus Ehrenfried Berthelsen, Dorthe Kjær, Merete Uldbjerg, Lily Lipsius, Magaly Engsig, Rikke Helsted, Birgitte Andersen, Eigil Nygaard, Søren Strande, Aimal Khan Bangash, Peter Søe-Jensen, Hamid Tousi, Malene Tangager, Daniel Hagi-Pedersen, Rainer Karl-Heinz Gatz, Marte Kaasen Engen, Christian Åge Wamberg, Bo Westergaard, Stine Stoktoft, Rebecca Scherwin, Finn Bærentzen, Marlene Lauritzen, Frank Pott, Christina Bruun, Christian Meyhoff, Ditte Gry Strange, Dorthe Fris Palmqvist, Claus Hemmingsen, Rune Gärtner, Kai Dieter Jung, Louise La Porte, Mette Viuf, Johannes Troglauer, Silva Borovnjak, Nina Strandkjær, Claus Bretlau, Marianna Hansen, Lea Kielsgaard Zaulich, Christian Overgaard, Katja Bergenholtz, Tejs Jansen, Mette Astrup Bæk-Jensen, Monika Detlefsen, Tannie Lund Albrechtsen, Birgitte Margareta Sode, Hans Christian Boesen, Maria Thostrup, Torben Mogens Andersen, Katrine Kjelsteen, Cilia Klara Winther Kjær, Elsebeth Haunstrup, Ole Christensen, Lone Spliid, Birgitte Rasmussen, Henriette Jejlskov, Søren Borchorst, Akil Walli Raad Abdel-Wahab, Marianne Brysting, Jette Victor, Anette Stensbirk, Karen Bjerregaard, Anne Poulsen, Annette Brix Roed, Bianca Bech, Oguz Yilmaz, Sanchit Ahuja, Iman Suleiman, Rodrigo Iglesias, Olena Breum, Intensive Care Medicine, AII - Amsterdam institute for Infection and Immunity, and AII - Infectious diseases
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Pulmonary and Respiratory Medicine ,Male ,Shock, Septic/complications ,Population ,Respiration, Artificial/methods ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Hypothermia, Induced ,law ,Intensive care ,medicine ,Clinical endpoint ,Journal Article ,Humans ,Respiratory function ,030212 general & internal medicine ,Respiratory Insufficiency/etiology ,education ,Aged ,APACHE ,education.field_of_study ,Septic shock ,business.industry ,Hypothermia, Induced/methods ,030208 emergency & critical care medicine ,Hypothermia ,medicine.disease ,Respiration, Artificial ,Shock, Septic ,Europe ,Intensive Care Units ,Treatment Outcome ,Respiratory failure ,Anesthesia ,North America ,Female ,medicine.symptom ,Respiratory Insufficiency ,business - 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.
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- 2018
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