Thrombolytic-Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest.
OBJECTIVE
To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest.


METHODS
Laboratory investigation.


METHODS
University laboratory.


METHODS
Pigs.


METHODS
Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation.


RESULTS
A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation 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 electroencephalogram 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, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.
1Extracorporeal Life Support Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI. 2Department of Anesthesia, Critical Care, and Pain Medicine, University of Milano, Milano, Italy. 3Department of Emergency Medicine, University of Michigan, Ann Arbor, MI. 4Michigan Center for Integrative Research in Critical Care (MCIRCC), University of Michigan, Ann Arbor, MI. 5Department of Pediatric Cardiology, University of Michigan, Ann Arbor, MI. 6Department of Neurology, University of Michigan, Ann Arbor, MI. 7Department of Neurosurgery, University of Michigan, Ann Arbor, MI. 8Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI. 9Department of Surgery, Section of Transplantation, University of Michigan, Ann Arbor, MI.
Elena
E
Spinelli
Ryan P
RP
Davis
Xiaodan
X
Ren
Parth S
PS
Sheth
Trevor R
TR
Tooley
Amit
A
Iyengar
Brandon
B
Sowell
Gabe E
GE
Owens
Martin L
ML
Bocks
Teresa L
TL
Jacobs
Lynda J
LJ
Yang
William C
WC
Stacey
Robert H
RH
Bartlett
Alvaro
A
Rojas-Peña
Robert W
RW
Neumar
D000818:Animals; D001831:Body Temperature; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D003131:Combined Modality Therapy; D004569:Electroencephalography; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods*; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006323:Heart Arrest / Q000188:drug therapy / Q000628:therapy*; D006439:Hemodynamics; D007427:Intracranial Pressure; D013300:Streptokinase / Q000008:administration & dosage* / Q000627:therapeutic use; D013552:Swine; D013997:Time Factors
D005343:Fibrinolytic Agents; D013300:Streptokinase