Adaptation of global hemostasis to therapeutic hypothermia in patients with out-of-hospital cardiac arrest: Thromboelastography study
Abstract
Background: The use of mild therapeutic hypothermia (MTH) in patients after out-of-hospital cardiac arrest (OHCA) who are undergoing primary percutaneous coronary intervention (pPCI) can protect patients from thromboembolic complications. The aim of the study was to evaluate the adaptive mecha- nisms of the coagulation system in MTH-treated comatose OHCA survivors.
Methods: Twenty one comatose OHCA survivors with acute coronary syndrome undergoing imme- diate pPCI were treated with MTH. Quantitative and qualitative analyses of physical clot properties were performed using thromboelastography (TEG). Two analysis time points were proposed: 1) during MTH with in vitro rewarming conditions (37°C) and 2) after restoration of normothermia (NT) under normal (37°C) and in vitro cooling conditions (32°C).
Results: During MTH compared to NT, reaction time (R) was lengthened, clot kinetic parameter (a) was significantly reduced, but no effect on clot strength (MA) was observed. Finally, the coagulation index (CI) was significantly reduced with clot fibrinolysis attenuated during MTH. The clot lysis time (CLT) was shortened, and clot stability (LY60) was lower compared with those values during NT. In vitro cooling generally influenced clot kinetics and reduced clot stability after treatment.
Conclusions: Thromboelastography is a useful method for evaluation of coagulation system dysfunc- tion in OHCA survivors undergoing MTH. Coagulation impairment in hypothermia was associated with a reduced rate of clot formation, increased weakness of clot strength, and disturbances of fibrinoly- sis. Blood sample analyses performed at 32°C during MTH, instead of the standard 37°C, seems to enhance the accuracy of the evaluation of coagulation impairment in hypothermia.
Keywords: coagulationhypothermiacardiac arrestthromboelastography
References
- Go A, Mozaffarian D, Roger V, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics—2013 Update: A Report From the American Heart Association. Circulation. 2013; 127: 6–245.
- Skowronski GA. Cardiac arrest survivors need proof of neurological function before percutaneous coronary intervention. Crit Care Resusc. 2007; 9(3): 297–298.
- Rudner R, Jalowiecki P, Karpel E, et al. Survival after out-of-hospital cardiac arrests in Katowice (Poland): outcome report according to the "Utstein style". Resuscitation. 2004; 61(3): 315–325.
- Herlitz J, Bång A, Gunnarsson J, et al. Factors associated with survival to hospital discharge among patients hospitalised alive after out of hospital cardiac arrest: change in outcome over 20 years in the community of Göteborg, Sweden. Heart. 2003; 89(1): 25–30.
- Freund B, Kaplan PW. A review of the utility of a hypothermia protocol in cardiac arrests due to non-shockable rhythms. Cardiol J. 2017; 24(3): 324–333.
- Nolana J, Soar J, Zideman D, et al. on behalf of the ERC Guidelines Writing Group1. European Council Guidelines for 2010 Section 1.Executive summary. Resuscitation. 2010; 81: 1219–1276.
- Field J, Hazinski M, Sayre M, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Circ. 2010; 122: 640–656.
- Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in Mammalian central nervous system. J Cereb Blood Flow Metab. 2003; 23(5): 513–530.
- Nakashima K, Todd MM. Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization. Stroke. 1996; 27(5): 913–918.
- Van Poucke S, Stevens K, Marcus AE, et al. Hypothermia: effects on platelet function and hemostasis. Thromb J. 2014; 12(1): 31.
- Dirkmann D, Hanke AA, Görlinger K, et al. Hypothermia and acidosis synergistically impair coagulation in human whole blood. Anesth Analg. 2008; 106(6): 1627–1632.
- Esmon CT. The interactions between inflammation and coagulation. Br J Haematol. 2005; 131(4): 417–430.
- Koch A, Meesters MI, Scheller B, et al. Systemic endotoxin activity correlates with clot formation: an observational study in patients with early systemic inflammation and sepsis. Crit Care. 2013; 17(5): R198.
- Adrie C, Laurent I, Monchi M, et al. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care. 2004; 10(3): 208–212.
- Douning LK, Ramsay MA, Swygert TH, et al. Temperature corrected thrombelastography in hypothermic patients. Anesth Analg. 1995; 81(3): 608–611.
- Durila M, Lukáš P, Astraverkhava M, et al. Evaluation of fibrinogen concentrates and prothrombin complex concentrates on coagulation changes in a hypothermic in vitro model using thromboelastometry and thromboelastography. Scand J Clin Lab Invest. 2015; 75(5): 407–414.
- Wolberg AS, Meng ZH, Monroe DM, et al. A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function. J Trauma. 2004; 56(6): 1221–1228.
- Dixon S, Safian R. The year in interventional cardiology. J Am Coll Cardiol. 2012; 59(17): 1497–1508.
- Cundrle I, Sramek V, Pavlik M, et al. Temperature corrected thromboelastography in hypothermia: is it necessary? Eur J Anaesthesiol. 2013; 30(2): 85–89.
- 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.
- Nielsen AK, Jeppesen AN, Kirkegaard H, et al. Changes in coagulation during therapeutic hypothermia in cardiac arrest patients. Resuscitation. 2016; 98: 85–90.
- Gurbel PA, Bliden KP, Guyer K, et al. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study. J Am Coll Cardiol. 2005; 46(10): 1820–1826.
- Khurana S, Mattson JC, Westley S, et al. Monitoring platelet glycoprotein IIb/IIIa-fibrin interaction with tissue factor-activated thromboelastography. J Lab Clin Med. 1997; 130(4): 401–411.
- Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975; 1(7905): 480–484.
- Watts DD, Trask A, Soeken K, et al. Hypothermic coagulopathy in trauma: effect of varying levels of hypothermia on enzyme speed, platelet function, and fibrinolytic activity. J Trauma. 1998; 44(5): 846–854.
- Nielsen N, Hovdenes J, Nilsson F, et al. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand. 2009; 53(7): 926–934.
- Kander T, Brokopp J, Friberg H, et al. Wide temperature range testing with ROTEM coagulation analyses. Ther Hypothermia Temp Manag. 2014; 4(3): 125–130.
- Shimokawa M, Kitaguchi K, Kawaguchi M, et al. The influence of induced hypothermia for hemostatic function on temperature-adjusted measurements in rabbits. Anesth Analg. 2003; 96(4): 1209–13, table of contents.
- Jeppesen AN, Kirkegaard H, Ilkjær S, et al. Influence of temperature on thromboelastometry and platelet aggregation in cardiac arrest patients undergoing targeted temperature management. Crit Care. 2016; 20(1): 118.
- Meyer MAS, Ostrowski SR, Sørensen AM, et al. Fibrinogen in trauma, an evaluation of thrombelastography and rotational thromboelastometry fibrinogen assays. J Surg Res. 2015; 194(2): 581–590.
- Kettner SC, Sitzwohl C, Zimpfer M, et al. The effect of graded hypothermia (36 degrees C-32 degrees C) on hemostasis in anesthetized patients without surgical trauma. Anesth Analg. 2003; 96(6): 1772–1776.
- Viuff D, Lauritzen B, Pusateri AE, et al. Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven). Br J Anaesth. 2008; 101(3): 324–331.
- Kahn HA, Faust GR, Richard R, et al. Hypothermia and bleeding during abdominal aortic aneurysm repair. Ann Vasc Surg. 1994; 8(1): 6–9.
- Gibbs NM. The effect of anaesthetic agents on platelet function. Anaesth Intensive Care. 1991; 19(4): 495–505.
- Bro-Jeppesen J, Kjaergaard J, Horsted TI, et al. The impact of therapeutic hypothermia on neurological function and quality of life after cardiac arrest. Resuscitation. 2009; 80(2): 171–176.
- Schefold JC, Storm C, Joerres A, et al. Mild therapeutic hypothermia after cardiac arrest and the risk of bleeding in patients with acute myocardial infarction. Int J Cardiol. 2009; 132(3): 387–391.
- Hoffmeister KM, Felbinger TW, Falet H, et al. The clearance mechanism of chilled blood platelets. Cell. 2003; 112(1): 87–97.
- Ao H, Moon JK, Tashiro M, et al. Delayed platelet dysfunction in prolonged induced canine hypothermia. Resuscitation. 2001; 51(1): 83–90.
- de Vrij EL, Vogelaar PC, Goris M, et al. Platelet dynamics during natural and pharmacologically induced torpor and forced hypothermia. PLoS One. 2014; 9(4): e93218.
- Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009; 37(7 Suppl): S186–S202.
- Tang XN, Liu L, Koike MA, et al. Mild hypothermia reduces tissue plasminogen activator-related hemorrhage and blood brain barrier disruption after experimental stroke. Ther Hypothermia Temp Manag. 2013; 3(2): 74–83.
- Hamann GF, Burggraf D, Martens HK, et al. Mild to moderate hypothermia prevents microvascular basal lamina antigen loss in experimental focal cerebral ischemia. Stroke. 2004; 35(3): 764–769.
- Forman KR, Wong E, Gallagher M, et al. Effect of temperature on thromboelastography and implications for clinical use in newborns undergoing therapeutic hypothermia. Pediatr Res. 2014; 75(5): 663–669.
- Lilja G, Nielsen N, Friberg H, et al. Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33°C versus 36°C. Circulation. 2015; 131(15): 1340–1349.
- Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33degreeC versus 36degreeC after cardiac arrest. N Engl J Med. 2013; 369(23): 2197–2206.