Clinical PaperHemostasis in cardiac arrest patients treated with mild hypothermia initiated by cold fluids☆
Introduction
Application of mild hypothermia (32–33 °C) improves neurological recovery and survival in patients with out-of-hospital cardiac arrest.1, 2 Based on the results of two large clinical trials the European Resuscitation Council recommends to cool all hospitalized survivors of cardiac arrest with shockable rhythms to 32–34 °C for 12–24 h.3
Infusion of 4 °C cold crystalloids is an appealing method to initiate therapeutic hypothermia: it is inexpensive, easy to perform and effective in lowering body temperature,4 even in an out-of-hospital setting.5 Most cardiac arrests are caused by acute coronary syndromes with pronounced activation of the coagulation system. The notion that hypothermia may impair hemostasis is especially relevant for these patients, as many of them are treated with anti-thrombotic drugs like heparins and aspirin. Even mild hypothermia is associated with bleeding and increased transfusion requirements in surgical patients.6 On the other hand, induction of hypothermia with large amounts (30 ml/kg) of crystalloids causes hemodilution. Acute hemodilution caused by crystalloid infusion induces a hypercoagulable state detectable by whole blood thrombelastography.7, 8 Thrombelastography yields information on the cumulative effects of various blood components (e.g., coagulation factors, hematocrit, platelets, leukocytes)9 involved in the coagulation process. It is also sensitive to the anti-coagulant effects of therapeutic hypothermia in surgery patients.10
Currently, it is unknown how induction of mild therapeutic hypothermia by infusion of cold saline solution affects coagulation in patients with cardiac arrest. We therefore conducted a prospective study in 18 cardiac arrest survivors and assessed hemostasis using heparinase-modified thrombelastography.
Section snippets
Study design and study subjects
This was a prospective pilot study in 18 patients after cardiac arrest admitted to the emergency department of a tertiary care hospital. The study procedures were approved by our local Ethics Committee. Patients were eligible if they were comatose upon admission with a spontaneous circulation after resuscitation from non-traumatic, normothermic cardiac arrest of presumed cardiac etiology. Patients with one of the following criteria were excluded: age <18 and >85 years, pregnancy, clinical signs
Data analysis
All data are expressed as means ± standard deviation (SD) unless otherwise stated. After repeated measures ANOVA, the Friedman ANOVA and the Wilcoxon signed rank test for post hoc comparisons were used. A two-tailed p < 0.05 was considered statistically significant. All statistical calculations were performed using commercially available statistical software (Statistica Version 6.1; Stat Soft, Tulsa, OK).
Results
Subject characteristics are presented in Table 1.
Most of our study subjects (78%) were male, and acute myocardial infarction was the predominant cardiac arrest cause (61%). Correspondingly, all patients received anti-coagulant therapy (Table 1). Seven patients (39%) received a primary percutaneous coronary intervention within the first 4 h after admission to the emergency room. None of the study patients received fibrinolytic therapy.
We administered a total volume of 2528 ± 52 ml crystalloid fluid
Discussion
We found that thrombelastographic parameters are only slightly affected during therapeutic hypothermia in cardiac arrest patients. The heparinase in this assay allows measurement of coagulation despite the presence of heparins in the samples. Solely, the time to clot formation (CT) was prolonged 1 h after induction of mild hypothermia. This finding is consistent with a prolonged clotting time observed in healthy volunteers13 as well as in surgical patients after induction of hypothermia.14
Conclusions
Mild hypothermia only slightly prolonged clotting time as measured by rotation thrombelastography. Therefore, therapeutic hypothermia initiated by cold crystalloid fluids has only minor overall effects on coagulation in patients with cardiac arrest.
Conflicts of interest
None.
Acknowledgment
None.
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Cited by (43)
Prolonged TTM – enhanced hypocoagulation and bleeding?
2017, ResuscitationChanges in coagulation during therapeutic hypothermia in cardiac arrest patients
2016, ResuscitationCitation Excerpt :Thromboelastometric studies with in vitro induced hypothermia on whole blood from healthy volunteers have shown an association between impairment of coagulation and decreasing temperatures.11,12 Only a few studies have investigated the effect of hypothermia on coagulation in cardiac arrest patients,13–15 and some of these indicated a prolonged clot initiation during hypothermia.13,15 To the best of our knowledge, no previous studies have investigated coagulation in cardiac arrest patients both during hypothermia and subsequent normothermia.
Heparin dose adjustment required to maintain goal-activated partial thromboplastin time during therapeutic hypothermia
2015, Journal of Critical CareCitation Excerpt :The likely explanations were blood loss from blood draws taken every 2 hours as required per protocol for laboratory monitoring and volume expansion from infusions. Although coagulation is known to decrease in profound hypothermia (< 28°C) [9], the patients in our study only underwent mild TH (target temperature, 33°C), which has not been associated with significant effects on anticoagulation or bleeding [10,11]. Although aPTT is commonly used and recommended in managing UFH, its reliability in TH has yet to be validated.
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A Spanish translated version of the summary of this article appears as Appendix in the online version at doi:10.1016/j.resuscitation.2009.03.026.