Thrombolytic-Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest

Abstract

Objective To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation (ECPR) and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest. Design Laboratory investigation Setting University Laboratory Subjects Pigs Interventions Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation (ECPR) for 6 hours. Animals were allocated into two experimental groups: t-ECPR, which received Streptokinase 1 MU and c-ECPR which did not receive Streptokinase. In both groups the resuscitation protocol included the following physiologic targets: mean arterial pressure (MAP) > 70 mmHg, Cerebral perfusion pressure (CerPP) > 50 mmHg, PaO2 150 ± 50 mmHg, PaCO2 40 ± 5 mmHg and core temperature 33 ± 1 °C. Defibrillation was attempted after 30 minutes of ECPR. Measurements and Main Results A cardiac resuscitability score was assessed on the basis of: success of defibrillation; return of spontaneous heart beat; weanability form ECPR; and left ventricular systolic function after weaning. The addition of thrombolytic to ECPR significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40 ± 15% VS 18 ± 21 %). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of EEG signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages. Conclusions In a porcine model of prolonged cardiac arrest, thrombolytic-enhanced ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early EEG recovery and ischemic neuronal injury were not improved.

Early Coronary Reperfusion Facilitates Return of Spontaneous Circulation and Improves Cardiovascular Outcomes After Ischemic Cardiac Arrest and Extracorporeal Resuscitation in Pigs

“…In addition, it was progressively impossible to maintain high ECPR flow given that venous return was insufficient. This could be related to a progressive no reflow that seems to occur after prolonged cardiac arrest given that thrombolytic drugs were shown to improve the outcome in pigs during ECPR . This shows that cardiovascular recovery was not possible in our study with late reperfusion, despite successful defibrillation after ECPR.…”

“…External defibrillation was attempted every 5 minutes during the first 15 minutes of ECPR and then every 15 minutes until successful defibrillation. As previously described, return of spontaneous heart beat (ROSB) was defined as successful defibrillation with organized ventricular contraction . ROSC was defined as an organized ECG rhythm with a systolic blood pressure above 80 mm Hg until the end of the protocol.…”

“…As previously described, return of spontaneous heart beat (ROSB) was defined as successful defibrillation with organized ventricular contraction . ROSC was defined as an organized ECG rhythm with a systolic blood pressure above 80 mm Hg until the end of the protocol. ECPR blood flow was maintained as high as possible to avoid hypotension, whereas it was progressively decreased if ROSC occurred.…”

Therapeutic Effect of Argatroban During Cardiopulmonary Resuscitation and Streptokinase During Extracorporeal Cardiopulmonary Resuscitation in a Porcine Model of Prolonged Cardiac Arrest

“…The primary cardiac recovery outcome was assessed 8 hours after ECPR using the cardiac resuscitability score (CRS) adapted from Spinelli et al ( 11 ). CRS is scored from 0 to 6 based on defibrillation (Yes = 1 or No = 0), ROSB (Yes = 1 or No = 0), weanability from ECPR (Yes = 1 or No = 0), and left ventricular systolic function after weaning (Normal or mildly depressed = 3, Moderately depressed = 2, Severely depressed = 1) ( Supplemental Table 1 , http://links.lww.com/CCX/B183 ).…”

“…We chose ARG as the anticoagulant because it directly inhibits both circulating and clot-bound thrombin without the requirement of cofactors to exert its antithrombotic action ( 9 , 10 ). We chose streptokinase (STK) for thrombolysis based on our previous study demonstrating that STK added to the ECPR prime circuit improved recovery of cardiac function in swine after prolonged CA ( 11 ).…”