Coagulopathy during cardiac arrest and resuscitation in a swine model of electrically induced ventricular fibrillation

Abstract

Aims: Coagulopathy is often present after resuscitation from cardiac arrest but plays an undefined role in the post cardiac arrest syndrome. The aim of this study was to characterize coagulation changes during cardiac arrest and post-resuscitation care in order to direct further focused study.

Methods: Ventricular fibrillation (VF) was induced electrically in immature male swine, followed by normothermic American Heart Association Advanced Cardiac Life Support and a uniform post-resuscitation goal-directed resuscitation protocol. PT, aPTT, fibrinogen, Thrombelastography (TEG), platelet contractile force (PCF), clot elastic modulus (CEM), and collagen-induced platelet aggregation were compared at baseline, at 8 min of VF, during the 3rd round of chest compressions (CPR), and at 15, 90, 180, and 360 min after return of circulation using repeated measures ANOVA.

Results: 8/18 (44%) animals were resuscitated after 10.9 ± 0.9 min of VF and 7.6 ± 3.4 min of CPR. TEG revealed a significant impairment in clot strength (MA) and clot formation kinetics (K, alpha angle) arising during CPR, followed by a brief prolongation of clot onset times (R) after return of circulation. Both PCF and CEM fell significantly during CPR (PCF by 50%, CEM by 47% of baseline) and platelet aggregation was significantly decreased during CPR. Coagulation changes were partially recovered by 3h of post-resuscitation care.

Conclusion: Whole blood coagulation was rapidly impaired during CPR after electrically induced VF in this swine model by impaired platelet aggregation/contractile function and clotting kinetics. Further platelet-specific study is indicated.

Figure 1

Schematic representation of cardiac arrest protocol. CPR= cardiopulmonary resuscitation, ACLS= Advanced Cardiac Life Support, ROSC= return of spontaneous circulation. Blood was sampled described under Methods.

Figure 2

Summary of Thrombelastography (TEG) results in whole blood sampled as described under Methods. An aliquot of 340 μL of citrated whole blood was recalcified with 20 μL of 0.2M calcium chloride to initiate coagulation. Reaction time= time to onset of clot formation, Kinetics time= estimate of speed of clot buildup/polymerization, Clotting Angle= estimate of clot polymerization rate, Maximal Amplitude= estimate of clot strength. *= significantly different than baseline value by repeated measure ANOVA with Tukey HSD.

Figure 3

Representative TEG clot formation curves for a single subject at various times during the experimental protocol as described under Methods.

Figure 4

Summary of platelet-induced clot contraction and clot elastic modulus during cardiac arrest and resuscitation. Mean platelet contractile force (PCF) on the left axis and clot elastic modulus (CEM) on the right axis measured before, during and after cardiac arrest and resuscitation as described in Methods. *= significantly different than baseline value by one way ANOVA with Tukey HSD.

Figure 5

Average Collagen-induced platelet aggregation in whole blood by impedance performed as described in Methods. *= significantly different than baseline value by one way ANOVA with Tukey HSD. Error bars = SE.