Feasibility of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in Patients Suffering From Refractory Cardiac Arrest: a Pilot Study

Background and Rationale Outcome after non-traumatic cardiac arrest remains poor despite many efforts in improving immediate advanced life support (ALS) and post-arrest therapy. Preserving myocardial and cerebral perfusion in the event of cardiac arrest by the means of effective cardio-pulmonary resuscitation (CPR) is of utmost importance. During CPR, coronary perfusion pressure is a significant predictor of increased rates of return of spontaneous circulation (ROSC) and survival to hospital discharge, while cerebral perfusion pressure is crucial for good neurologic outcome. The absence of ROSC despite prolonged high quality and efficient initial basic life support (BLS) followed by traditional ALS ends finally in neuronal damage and death. Occlusion of the aorta using a REBOA catheter in the management of non-compressible abdominal or pelvic haemorrhage has shown improvements in hemodynamic profiles and has proved to be feasible in a preclinical setting for trauma patients in haemorrhagic shock. Animal models of continuous balloon occlusion of the aorta in non-traumatic cardiac arrest have shown meaningful increases in coronary artery blood flow, coronary artery perfusion pressure and carotid blood flow leading to improved rates of ROSC, 48h-survival and neurological function. These promising data provide an opportunity to improve outcome after cardiac arrest in humans too. Before testing such an approach in humans, the safe and reliable placement procedure of the catheter-balloon in humans after cardiac arrest needs to be established under ongoing CPR.

Investigational Product (treatment, device) and Indication The ER-REBOA™ Catheter, Prytime Medical, 229 North Main Street, Boerne, TX 78006, USA, has a CE Declaration of Conformity and is intended, as defined in the instruction manual, for temporary occlusion of large vessels and blood pressure monitoring. The ER-REBOA™ Catheter is specifically designed for use in the emergency and critical care environment and was developed to support rapid and immediate haemorrhage control in trauma patients but can also be used in patients with ruptured aneurysms of the abdominal aorta. Importantly, the ER-REBOA™ Catheter is indicated to be safely and effectively placed with or without the aid of medical imaging if none is available. The device will be placed via femoral artery directly in the thoracic part of the aorta, with the aid of a standard 7-F introducer sheath. For blood pressure monitoring standard equipment (transducer and 0.9% saline flush unit) are required.

Puncture of the femoral artery to gain access to the arterial system is a standard procedure in the emergency and critical care area, as well as in cardiology, interventional radiology, angiology/vessel surgery and anaesthesiology. Puncture itself can be difficult or impossible, even with the aid of ultrasonography, especially in an emergency. Nevertheless, even prehospital puncture of the femoral artery during cardiac arrest in order to obtain hemodynamic monitoring and guide CPR has shown feasible. Handling the balloon catheter requires a short introduction and some mannequin training before first use.

Preclinical Evidence Several studies have examined the effect of continuous balloon occlusion of the aorta during non-traumatic cardiac arrest in animal models. Occlusion of the aorta with and without selective aortic arch perfusion was shown to increases coronary artery blood flow and perfusion pressure as well as carotid perfusion pressure and blood flow, thus leading to improved rates of ROSC, 24h- and 48hsurvival and neurological function in animals. To the investigators' knowledge, no conflicting data failing to show the described effects has been published, leading to the suggestion that further research should concentrate on the question whether these promising findings apply for humans, too.

Clinical Evidence to Date Recent advances in technology have led to the endovascular approach to the aorta being no longer exclusively the domain of cardiology, angiology and vascular surgery, but emergency and critical care physicians and surgeons using the technique in the emergency and critical care setting as well as in a prehospital setting to control major pelvic and abdominal hemorrhage in trauma victims. Therefore, regarding the use of the ER-REBOA catheter, available literature reports mainly trauma victims, where endovascular occlusion of the aorta was used to control exsanguinating hemorrhage but was also shown to lead to meaningful increases of mean arterial blood pressure immediately following occlusion of the aorta. A recent study examining the outcome of trauma victims with severe hemorrhage also included patients in traumatic cardiac arrest and showed a neurological intact survival rate of 10%, whereas survival of cardiac arrest due to massive hemorrhage treated with emergency department thoracotomy with aortic cross-clamp is known to be dismal. Similarly, patients with non-traumatic hemorrhage mainly from intraabdominal aneurysmal rupture received REBOA until definitive hemorrhage control, with 7 of 11 patients being in cardiac arrest at the time of insertion and a high survival rate of 57%. Regarding cardiac arrest not associated with hemorrhage and/or trauma, for humans only case reports exist, describing neurological intact survival in one case of refractory cardiac arrest with PEA/Asystole during coronary angiography, where after 20 minutes of futile ALS an intra-aortal balloon pump (IABP) was inserted, with detection of ROSC 30seconds after occlusion of the descending aorta. Importantly, the estimated benefit of increased mean arterial pressure and coronary perfusion pressure even with intermittent occlusion of the aorta has led to the recommendation to use the IABP (after switching to a pressure-triggered mode) in patients with cardiac arrest after heart surgery and IABP in place.