Mild induced hypothermia and coagulation and platelet function in patients with septic shock: Secondary outcome of a randomized trial.


Journal

Acta anaesthesiologica Scandinavica
ISSN: 1399-6576
Titre abrégé: Acta Anaesthesiol Scand
Pays: England
ID NLM: 0370270

Informations de publication

Date de publication:
08 2023
Historique:
revised: 05 04 2023
received: 22 09 2022
accepted: 12 04 2023
medline: 14 7 2023
pubmed: 2 5 2023
entrez: 2 5 2023
Statut: ppublish

Résumé

Coagulation abnormalities and microthrombi contribute to septic shock, but the impact of body temperature regulation on coagulation in patients with sepsis is unknown. We tested the hypothesis that mild induced hypothermia reduces coagulation and platelet aggregation in patients with septic shock. Secondary analysis of randomized controlled trial. Adult patients with septic shock who required mechanical ventilation from eight intensive care units in Denmark were randomly assigned to mild induced hypothermia for 24 h or routine thermal management. Viscoelastography and platelet aggregation were assessed at trial inclusion, after 12 h of thermal management, and 24 h after inclusion. A total of 326 patients were randomized to mild induced hypothermia (n = 163) or routine thermal management (n = 163). Mild induced hypothermia slightly prolonged activated partial thromboplastin time and thrombus initiation time (R time 8.0 min [interquartile range, IQR 6.6-11.1] vs. 7.2 min [IQR 5.8-9.2]; p = .004) and marginally inhibited thrombus propagation (angle 68° [IQR 59-73] vs. 71° [IQR 63-75]; p = .014). The effect was also present after 24 h. Clot strength remained unaffected (MA 71 mm [IQR 66-76] with mild induced hypothermia vs. 72 mm (65-77) with routine thermal management, p = .9). The proportion of patients with hyperfibrinolysis was not affected (0.7% vs. 3.3%; p = .19), but the proportion of patients with no fibrinolysis was high in the mild hypothermia group (8.8% vs. 40.4%; p < .001). The mild induced hypothermia group had lower platelet aggregation: ASPI 85U (IQR 50-113) versus 109U (IQR 74-148, p < .001), ADP 61U (IQR 40-83) versus 79 U (IQR 54-101, p < .001), TRAP 108 (IQR 83-154) versus 119 (IQR 94-146, p = .042) and COL 50U (IQR 34-66) versus 67U (IQR 46-92, p < .001). In patients with septic shock, mild induced hypothermia slightly impaired clot initiation, but did not change clot strength. Platelet aggregation was slightly impaired. The effect of mild induced hypothermia on viscoelastography and platelet aggregation was however not in a range that would have clinical implications. We did observe a substantial reduction in fibrinolysis.

Identifiants

pubmed: 37129236
doi: 10.1111/aas.14254
doi:

Types de publication

Randomized Controlled Trial Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

909-917

Subventions

Organisme : Danmarks Grundforskningsfond
Organisme : Lundbeckfonden
ID : R54-A5342
Organisme : Region Hovedstaden
Organisme : TrygFonden
ID : 7-10-1301
Organisme : Danish National Research Foundation
ID : DNRF126
Organisme : The Research Foundation for the Capital Region of Denmark
ID : A6052

Informations de copyright

© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

Références

Adamzik M, Görlinger K, Peters J, Hartmann M. Whole blood impedance aggregometry as a biomarker for the diagnosis and prognosis of severe sepsis. Crit Care. 2012;16:R204.
Daudel F, Kessler U, Folly H, Lienert JS, Takala J, Jakob SM. Thromboelastometry for the assessment of coagulation abnormalities in early and established adult sepsis: a prospective cohort study. Crit Care. 2009;13:R42.
Sivula M, Pettilä V, Niemi TT, Varpula M, Kuitunen AH. Thromboelastometry in patients with severe sepsis and disseminated intravascular coagulation. Blood Coagul Fibrinolysis. 2009;20:419-426.
Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369:840-851.
Afshari A, Wetterslev J, Brok J, Moller A. Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis. Br Med J. 2007;335:1248-1251.
Martí-Carvajal AJ, Salanti G, Cardona AF, Cardona-Zorrilla AF. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev. 2012;12(12):CD004388. doi:10.1002/14651858.CD004388.pub2
Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med. 2010;38:S26-S34.
Schouten M, Wiersinga WJ, Levi M, van der Poll T. Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol. 2008;83:536-545.
De Robertis E, Kozek-Langenecker SA, Tufano R, et al. Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding. Minerva Anestesiol. 2015;81:65-75.
Cavallini M, Preis FWB. Effects of mild hypothermia on blood coagulation in patients undergoing elective plastic surgery. Plast Reconstr Surg. 2005;116(1):316-321.
Rundgren M, Engström M. A thromboelastometric evaluation of the effects of hypothermia on the coagulation system. Anesth Analg. 2008;107:1465-1468.
Rohrer MJ, Natale AM. Effect of hypothermia on the coagulation cascade. Crit Care Med. 1992;20(10):1402-1405.
Jacob M, Hassager C, Bro-Jeppesen J, et al. The effect of targeted temperature management on coagulation parameters and bleeding events after out-of-hospital cardiac arrest of presumed cardiac cause. Resuscitation. 2015;96:260-267.
Kander T, Schött U. Effect of hypothermia on haemostasis and bleeding risk: a narrative review. J Int Med Res. 2019;47:3559-3568.
Huet O, Kinirons B, Dupic L, et al. Induced mild hypothermia reduces mortality during acute inflammation in rats. Acta Anaesthesiol Scand. 2007;51:1211-1216.
L'Her E, Amerand A, Vettier A, Sebert P. Effects of mild induced hypothermia during experimental sepsis. Crit Care Med. 2006;34:2621-2623.
Léon K, Pichavant-Rafini K, Ollivier H, Monbet V, L'Her E. Does induction time of mild hypothermia influence the survival duration of septic rats? Ther Hypothermia Temp Manag. 2015;5:85-88.
Schwarzl M, Seiler S, Wallner M, et al. Mild hypothermia attenuates circulatory and pulmonary dysfunction during experimental endotoxemia. Crit Care Med. 2013;41:e401-e410.
Scumpia PO, Sarcia PJ, Kelly KM, DeMarco VG, Skimming JW. Hypothermia induces anti-inflammatory cytokines and inhibits nitric oxide and myeloperoxidase-mediated damage in the hearts of endotoxemic rats. Chest. 2004;125:1483-1491.
Beurskens CJP, Aslami H, Kuipers MT, et al. Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover*. Crit Care Med. 2012;40:919-926.
Kluger MJ, Vaughn LK. Fever and survival in rabbits infected with Pasteurella multocida. J Physiol. 1978;282:243-251.
Vaughn LK, Veale WL, Cooper KE. The effect of venous blood stream cooling on survival of bacterially infected rabbits. Pflugers Arch. 1987;409:635-637.
Itenov TS, Johansen ME, Bestle M, et al. Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial. Lancet Respir Med. 2018;6:183-192.
Johansen ME, Jensen JU, Bestle MH, et al. Mild induced hypothermia: effects on sepsis-related coagulopathy - results from a randomized controlled trial. Thromb Res. 2015;135:175-182.
Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165-228.
Soliman M, Hartmann M. Multiplate® platelet aggregation findings are dependent on platelet count but can be corrected by use of a ratio. Appl Sci. 2020;10:7971.
Stissing T, Dridi NP, Ostrowski SR, Bochsen L, Johansson PI. The influence of low platelet count on whole blood aggregometry assessed by multiplate. Clin Appl Thromb Hemost. 2011;17:E211-E217.
Hanke AA, Roberg K, Monaca E, et al. Impact of platelet count on results obtained from multiple electrode platelet aggregometry (multiplate). Eur J Med Res. 2010;15:214-219.
Dirkmann D, Hanke AA, Görlinger K, Peters J. Hypothermia and acidosis synergistically impair coagulation in human whole blood. Anesth Analg. 2008;106:1627-1632.
Reed RL 2nd, Bracey AW Jr, Hudson JD, Miller TA, Fischer RP. Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels. Circ Shock. 1990;32:141-152.
Yazar H, Özdemir F, Köse E. Effect of centrifuge temperature on routine coagulation tests. Acta Haematol. 2018;139:158-163.
Kander T, Ullén S, Dankiewicz J, Wise MP, Schött U, Rundgren M. Bleeding complications after cardiac arrest and targeted temperature management, a post hoc study of the targeted temperature management trial. Ther Hypothermia Temp Manag. 2019;9:177-183.
Spiel AO, Kliegel A, Janata A, et al. Hemostasis in cardiac arrest patients treated with mild hypothermia initiated by cold fluids. Resuscitation. 2009;80:762-765.
Rajagopalan S, Mascha E, Na J, Sessler DI. The effects of mild perioperative hypothermia on blood loss and transfusion requirement. Anesthesiology. 2008;108:71-77.
Ferrara A, MacArthur JD, Wright HK, Modlin IM, McMillen MA. Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion. Am J Surg. 1990;160:515-518.
Watts DD, Trask A, Soeken K, Perdue P, Dols S, Kaufmann C. Hypothermic coagulopathy in trauma: effect of varying levels of hypothermia on enzyme speed, platelet function, and fibrinolytic activity. J Trauma. 1998;44:846-854.
Müller MC, Meijers JCM, Vroom MB, Juffermans NP. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care. 2014;18:R30.
Ostrowski SR, Windeløv NA, Ibsen M, et al. Consecutive thrombelastography clot strength profiles in patients with severe sepsis and their association with 28-day mortality: a prospective study. J Crit Care. 2013;28(317):e1-e11.
Schmitt FCF, Manolov V, Morgenstern J, et al. Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care. 2019;9:1-15.
Panigada M, Zacchetti L, L'Acqua C, et al. Assessment of fibrinolysis in sepsis patients with urokinase modified thromboelastography. PLoS One. 2015;10:e0136463.
Adamzik M, Eggmann M, Frey UH, et al. Comparison of thromboelastometry with procalcitonin, interleukin 6, and C-reactive protein as diagnostic tests for severe sepsis in critically ill adults. Crit Care. 2010;14:R178.
Hoshino K, Kitamura T, Nakamura Y, et al. Usefulness of plasminogen activator inhibitor-1 as a predictive marker of mortality in sepsis. J Intensive Care Med. 2017;5:42.
Devereaux PJ, Marcucci M, Painter TW, et al. Tranexamic acid in patients undergoing noncardiac surgery. N Engl J Med. 2022;386:1986-1997.

Auteurs

Theis S Itenov (TS)

CHIP/PERSIMUNE, Department of infectious diseases, Rigshospitalet, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Department of Anesthesiology, Copenhagen University Hospital - Bispebjerg, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health sciences, University of Copenhagen, Copenhagen, Denmark.

Maria E Kromann (ME)

CHIP/PERSIMUNE, Department of infectious diseases, Rigshospitalet, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Sisse R Ostrowski (SR)

Department of Clinical Medicine, Faculty of Health sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Immunology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Morten H Bestle (MH)

Department of Clinical Medicine, Faculty of Health sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Anesthesia and Intensive Care, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark.

Thomas Mohr (T)

Department of Anesthesiology, Copenhagen University Hospital - Herlev-Gentofte, Copenhagen, Denmark.

Louise Gyldensted (L)

Department of Anesthesiology, Copenhagen University Hospital - Herlev-Gentofte, Copenhagen, Denmark.

Anne Lindhardt (A)

Department of Anesthesia and Intensive Care, Copenhagen University Hospital - North Zealand, Copenhagen, Denmark.

Katrin Thormar (K)

Department of Anesthesiology, Copenhagen University Hospital - Bispebjerg, Copenhagen, Denmark.

Daniel I Sessler (DI)

Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Nicole P Juffermans (NP)

Department of Intensive Care, OLVG Hospital, Amsterdam, the Netherlands.
Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam University Medical Center, Amsterdam, the Netherlands.

Jens D Lundgren (JD)

CHIP/PERSIMUNE, Department of infectious diseases, Rigshospitalet, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health sciences, University of Copenhagen, Copenhagen, Denmark.

Jens-Ulrik Jensen (JU)

CHIP/PERSIMUNE, Department of infectious diseases, Rigshospitalet, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health sciences, University of Copenhagen, Copenhagen, Denmark.
Respiratory Section, Department of Internal Medicine, Copenhagen University Hospital - Gentofte, Copenhagen, Denmark.
Outcomes Research Consortium, Cleveland, Ohio, USA.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH