Clinical paperMinimal effects on ex vivo coagulation during mild therapeutic hypothermia in post cardiac arrest patients☆
Introduction
Mild therapeutic hypothermia (MTH) with body core temperatures between 32 and 34 °C is being used for many years to improve neurological outcome and survival in patients successfully resuscitated after cardiac arrest. The optimal target temperature for MTH is still controversial. Recently two large RCT's showed that hypothermia at a target temperature of 33 °C had no benefit compared to a target temperature of 36 °C in terms of survival or neurological outcome.1, 2 These findings were criticized, but a shared conclusion was that hyperthermia should be avoided and that more research is needed before abandoning any temperature management from daily care.
MTH may lead to alterations in hemostasis and coagulopathy. Hypothermia below 33 °C affects the synthesis and kinetics of clotting enzymes, thrombin generation, plasminogen activator inhibitors and is related to dysfunction of platelets.3, 4 A prolonged clotting time (CT) was observed in healthy cooled animals and in externally cooled blood of healthy volunteers.5, 6 In post cardiac arrest patients treated with MTH only a slightly prolonged CT was demonstrated (measured at 37 °C) after the induction of hypothermia with a maximum clot formation identical to normothermic baseline samples, measured before cooling.7 The risk of bleeding associated with MTH seems to be relatively small in patients after cardiac arrest even when these patients are treated with anticoagulants and infusion of cold crystalloids.8 This might be related to concomitant activation of coagulation. Post cardiac arrest patients typically receive MTH after a period of hypoperfusion and reperfusion, which causes a pro-inflammatory response and activation of coagulation.9 After regaining spontaneous circulation, tissue factor increases which leads eventually to increased thrombin and fibrin formation.10, 11 The real impact of hypothermia on coagulation however, may be difficult to assess since most coagulation parameters are routinely measured at 37 °C and not at the actual patients core temperature.6, 7 The aim of this study is to investigate the effects of MTH on coagulation parameters tested by thromboelastometry both at body core (target) temperature of 32 °C and at 37 °C.
Section snippets
Study design and population
We conducted a prospective non-interventional study in a tertiary care hospital mixed medical-surgical intensive care unit. Post cardiac arrest patients were enrolled when they were older than 18 years, comatose upon the admission to the hospital, and with a presumed cardiac etiology of the cardiac arrest and return of spontaneous circulation. Exclusion criteria were: pregnancy, non-cardiac causes of cardiac arrest, traumatic brain injury, use of coumarin derivates, pre-existing coagulopathy
Demographic and clinical data
From April 2011 until June 2012 during daytime, 22 patients with an out-of-hospital cardiac arrest were included. In four patients cardiac arrest appeared to be of non-cardiac origin (pneumosepsis) and one patient had an additional subarachnoidal bleeding. These patients were excluded from analysis. One patient died during the study, but the first two measurements were included in the analysis. In total 17 patients were used for analysis. Patient characteristics are presented in Table 1.
Influence of hypothermia on thromboelastometry parameters
MTH led
Discussion
In this study the effects of MTH on coagulation in post cardiac arrest patients during all phases of therapeutic hypothermia and rewarming were determined by using thromboelastometry measurements at both 32 °C and 37 °C. The optimal target temperature for MTH is still controversial. Recently, a large RCT comparing two target temperatures, both intended to prevent fever, showed that in 939 post cardiac arrest patients hypothermia at a target temperature of 33 °C had no benefit compared to a target
Conclusion
The effects of MTH on coagulation are underestimated when measurements are performed at 37 °C instead of the patients’ actual body temperature of 32 °C. However, the minimal changes in CT are within reference range and not likely to be of clinical relevance.
Conflict of interest statement
The authors have no conflicts of interest to declare.
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Is there a role for therapeutic hypothermia in critical care?
2019, Evidence-Based Practice of Critical CareProlonged targeted temperature management compromises thrombin generation: A randomised clinical trial
2017, ResuscitationCitation Excerpt :Both standard laboratory investigations, ROTEM® and thrombin generation analyses were performed at 37 °C regardless of core temperature. Previous studies have found that by running the APTT, INR and ROTEM® analyses on hypothermic patients at 37 °C, prolonged clot initiation and clot propagation were overseen [11,18,19,29–31]. Thus, the affected clot formation observed in hypothermic patients was probably underestimated in the present study.
Out-of-hospital cardiac arrest and stent thrombosis: Ticagrelor versus clopidogrel in patients with primary percutaneous coronary intervention under mild therapeutic hypothermia
2017, ResuscitationCitation Excerpt :MTH has been proposed to preserve neurological status in these patients.4 MTH has been associated with haemostasis and coagulopathy disorders.5,6 The relationship between a higher risk of stent thrombosis (ST) and OHCA is however very controversial.
Safety of glycoprotein IIb/IIIa inhibitors in patients under therapeutic hypothermia admitted for an acute coronary syndrome
2016, ResuscitationCitation Excerpt :However, post resuscitation syndrome and MTH may produce alterations in haemostasis and coagulopathy.4 Hypothermia below 33° affects the synthesis and kinetics of clotting enzymes, thrombin generation, and plasminogen activator inhibitors and is related to platelet dysfunction, and this may be associated with an increased risk of both thrombotic and bleeding events.5,6 In this regard, Orban et al. reported an increase in major bleeding in patients in cardiogenic shock treated with primary PCI and MTH compared to those without MTH.7
European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015. Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015.
2015, ResuscitationCitation Excerpt :Hypothermia decreases insulin sensitivity and insulin secretion, and causes hyperglycaemia,188 which will need treatment with insulin (see glucose control). Mild induced hypothermia impairs coagulation and may increase bleeding, although this effect seems to be negligible256 and has not been confirmed in clinical studies.7,31,187 In one registry study, an increased rate of minor bleeding occurred with the combination of coronary angiography and mild induced hypothermia, but this combination of interventions was the also the best predictor of good outcome.20
Targeted temperature management; review of literature and guidelines; a cardiologist’s perspective
2018, Current Cardiology Reviews
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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.06.009.
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These authors contributed equally to this work.