PMID- 35120040
OWN - NLM
STAT- MEDLINE
DCOM- 20220527
LR  - 20240216
IS  - 1530-0293 (Electronic)
IS  - 0090-3493 (Print)
IS  - 0090-3493 (Linking)
VI  - 50
IP  - 6
DP  - 2022 Jun 1
TI  - Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile 
      Critically Ill Patients With Sepsis: A Pilot Randomized Trial.
PG  - 924-934
LID - 10.1097/CCM.0000000000005470 [doi]
AB  - OBJECTIVES: To test the hypothesis that forced-air warming of critically ill 
      afebrile sepsis patients improves immune function compared to standard 
      temperature management. DESIGN: Single-center, prospective, open-label, 
      randomized controlled trial. SETTING: One thousand two hundred-bed academic 
      medical center. PATIENTS: Eligible patients were mechanically ventilated septic 
      adults with: 1) a diagnosis of sepsis within 48 hours of enrollment; 2) 
      anticipated need for mechanical ventilation of greater than 48 hours; and 3) a 
      maximum temperature less than 38.3 degrees C within the 24 hours prior to enrollment. 
      Primary exclusion criteria included: immunologic diseases, immune-suppressing 
      medications, and any existing condition sensitive to therapeutic hyperthermia 
      (e.g., brain injury). The primary outcome was monocyte human leukocyte antigen 
      (HLA)-DR expression, with secondary outcomes of CD3/CD28-induced interferon gamma 
      (IFN-gamma) production, mortality, and 28-day hospital-free days. INTERVENTIONS: 
      External warming using a forced-air warming blanket for 48 hours, with a goal 
      temperature 1.5 degrees C above the lowest temperature documented in the previous 24 
      hours. MEASUREMENTS AND MAIN RESULTS: We enrolled 56 participants in the study. 
      No differences were observed between the groups in HLA-DR expression (692 vs 
      2,002; p = 0.396) or IFN-gamma production (31 vs 69; p = 0.678). Participants 
      allocated to external warming had lower 28-day mortality (18% vs 43%; absolute 
      risk reduction, 25%; 95% CI, 2-48%) and more 28-day hospital-free days 
      (difference, 2.6 d; 95% CI, 0-11.6). CONCLUSIONS: Participants randomized to 
      external forced-air warming did not have a difference in HLA-DR expression or 
      IFN-gamma production. In this pilot study, however, 28-day mortality was lower in the 
      intervention group. Future research should seek to better elucidate the impact of 
      temperature modulation on immune and nonimmune organ failure pathways in sepsis.
CI  - Copyright (c) 2022 by the Society of Critical Care Medicine and Wolters Kluwer 
      Health, Inc. All Rights Reserved.
FAU - Drewry, Anne M
AU  - Drewry AM
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, MO.
FAU - Mohr, Nicholas M
AU  - Mohr NM
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, MO.
AD  - Department of Emergency Medicine, University of Iowa Carver College of Medicine, 
      Iowa City, IA.
AD  - Division of Critical Care, Department of Anesthesia, University of Iowa Carver 
      College of Medicine, Iowa City, IA.
AD  - Department of Epidemiology, University of Iowa Carver College of Medicine, Iowa 
      City, IA.
AD  - Department of Emergency Medicine, Washington University School of Medicine, St. 
      Louis, MO.
AD  - Department of Medicine, Washington University School of Medicine, St. Louis, MO.
FAU - Ablordeppey, Enyo A
AU  - Ablordeppey EA
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, MO.
AD  - Department of Emergency Medicine, Washington University School of Medicine, St. 
      Louis, MO.
FAU - Dalton, Catherine M
AU  - Dalton CM
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, MO.
FAU - Doctor, Rebecca J
AU  - Doctor RJ
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, MO.
FAU - Fuller, Brian M
AU  - Fuller BM
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, MO.
FAU - Kollef, Marin H
AU  - Kollef MH
AD  - Department of Medicine, Washington University School of Medicine, St. Louis, MO.
FAU - Hotchkiss, Richard S
AU  - Hotchkiss RS
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, MO.
LA  - eng
SI  - ClinicalTrials.gov/NCT02706275
GR  - L30 GM134513/GM/NIGMS NIH HHS/United States
GR  - K08 HS025753/HS/AHRQ HHS/United States
GR  - K23 GM129660/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000448/TR/NCATS NIH HHS/United States
GR  - R35 GM126928/GM/NIGMS NIH HHS/United States
GR  - K12 HL137942/HL/NHLBI NIH HHS/United States
GR  - KL2 TR000450/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20220207
PL  - United States
TA  - Crit Care Med
JT  - Critical care medicine
JID - 0355501
RN  - 0 (HLA-DR Antigens)
SB  - IM
CIN - Crit Care Med. 2022 Jun 1;50(6):1015-1018. PMID: 35612441
CIN - Crit Care Med. 2022 Aug 1;50(8):e693-e694. PMID: 35838268
CIN - Crit Care Med. 2022 Sep 1;50(9):e734-e735. PMID: 35984070
CIN - Crit Care Med. 2022 Dec 1;50(12):e811-e812. PMID: 36394408
MH  - Adult
MH  - *COVID-19
MH  - Critical Illness/therapy
MH  - HLA-DR Antigens
MH  - Humans
MH  - *Hyperthermia, Induced
MH  - Pilot Projects
MH  - Prospective Studies
MH  - SARS-CoV-2
MH  - *Sepsis/therapy
PMC - PMC9133030
MID - NIHMS1770858
COIS- Drs. Drewry's and Hotchkiss's (R35GM126928) institutions received funding from 
      the National Institutes of Health (NIH). Drs. Drewry's and Mohr's (K08HS025753) 
      institutions received funding from the Agency for Healthcare Research and 
      Quality. Dr. Drewry was supported by the Washington University Institute of 
      Clinical and Translational Sciences (UL1TR000448, KL2TR000450) and the NIH 
      (K23GM129660). Dr. Ablordeppey was supported by the Department of Anesthesiology, 
      Division of Clinical and Translational Research at Washington University and the 
      K12 Mentored Training in Implementation Science award (K12HL137942). Drs. Drewry, 
      Mohr, Dalton, and Hotchkiss received support for article research from the NIH. 
      Dr. Hotchkiss's institution received funding from the National Institute of 
      General Medical Sciences; he disclosed that he holds a patent for the 
      Enzyme-Linked Immunospot assay, which was used for immune phenotyping in this 
      article. The remaining authors have disclosed that they do not have any potential 
      conflicts of interest.
EDAT- 2022/02/05 06:00
MHDA- 2022/05/28 06:00
PMCR- 2023/06/01
CRDT- 2022/02/04 17:11
PHST- 2022/02/05 06:00 [pubmed]
PHST- 2022/05/28 06:00 [medline]
PHST- 2022/02/04 17:11 [entrez]
PHST- 2023/06/01 00:00 [pmc-release]
AID - 00003246-202206000-00003 [pii]
AID - 10.1097/CCM.0000000000005470 [doi]
PST - ppublish
SO  - Crit Care Med. 2022 Jun 1;50(6):924-934. doi: 10.1097/CCM.0000000000005470. Epub 
      2022 Feb 7.