Controlled automated reperfusion of the whole body after cardiac arrest

Abstract

Background: Sudden circulatory arrest (CA) requiring cardiopulmonary resuscitation (CPR) has for decades been associated with high mortality and frequent neurological sequelae in the rarer survivors. The high mortality and morbidity are potentially related to a severe and global ischemia/reperfusion injury (IRI) of the whole body, especially the brain. Consequently, strategies to counteract this severe IRI may improve survival and neurological recovery of affected patients. Methods: Based on the target to limit IRI in single organs, suitable parameters and methods were composed to form a global treatment concept, the CARL method (controlled automated reperfusion of the whole body). The concept centers on extracorporeal circulation, enhanced with readily available online monitoring. It allows for targeted adaption of different parameters (i.e., blood pressure and flow, temperature, oxygen content, electrolytes) during the reperfusion process, in the sense of a controlled reperfusion. Parameters and elements of the CARL method were extensively tested in a chronic animal model. An appropriate medical device, the system configuration "CIRD 1.0" (Controlled Integrated Resuscitation Device) is approved to be applied to patients. Results: A set of parameters that support a limitation of a global IRI have been identified in over 250 animal experiments. Their specific targets and surveillance using adequate monitoring features are described. Using the CIRD in a single center, 14 patients with witnessed, but extremely prolonged CPR (51-120 minutes) have been treated with CARL. The outcome of these patients was favorable, with 7 of 14 patients regaining full consciousness and 6 of 7 allocated to Cerebral Performance Class (CPC) "1". Conclusions: CA followed by CPR is associated with a very high mortality and frequent neurological sequelae. Limiting the occurring severe and global IRI may be a key to an improved survival and neurological recovery. Therefore, the therapeutic approach of CARL, which stands for a personalized, comprehensive therapy based on a readily available set of monitoring data and diagnostic findings, has been developed. First experience in patients indicates beneficial effects that call for further studies in the field of CARL.

European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post-resuscitation care

“…controlled reperfusion of the whole body) have also demonstrated good neurological survival following 15 À20 min of experimental cardiac arrest and in humans. 260,261 These concepts are currently also undergoing further clinical evaluation. 262…”

Postreanimationsbehandlung

“…In jüngster Zeit wurde gezeigt, dass isolierte Schweinehirnzellen länger als 4-6 h überleben und elektrische Aktivität zeigen können, wenn eine Reperfusion des Gehirns unter Laborbedingungen durchgeführt wurde [262]. Sehr spezifische extrakorporale lebenserhaltende Konzepte (kontrollierte Reperfusion des gesamten Körpers) haben auch nach 15 bis 20 min experimentellen Kreislaufstillstands und auch beim Menschen gutes neurologisches Überleben gezeigt [263,264]. Diese Konzepte werden derzeit ebenfalls klinisch evaluiert [265].…”

Neurologic recovery after ten minutes of absent cerebral blood flow at normothermia

“…Thirty minutes of cooling to approximately 33°C in conjunction with "controlled automated reperfusion of the whole body" (CARL) following 20 minutes of normothermic cardiac arrest was sufficient to significantly improve survival and neurologic outcome in a porcine model. 1,2 In the clinical case presented above, the patient was rapidly cooled to a nadir temperature of 18°C. This strategy was partially neuroprotective following normothermic arrest as well as providing sufficient time to address the arch as the full extent of the tear was not initially evident.…”