Emergency Resuscitative Endovascular Balloon Occlusion of the Aorta in Out of Hospital Cardiac Arrest

This study will assess the feasibility of performing pre-hospital resuscitative endovascular balloon occlusion of the aorta (REBOA) as an adjunct to conventional Advanced Life Support (ALS) in patients suffering from non-traumatic out of hospital cardiac arrest (OHCA). As well as providing valuable insights into the technical feasibility of performing this procedure as part of a resuscitation attempt, the study will also evaluate the physiological benefits of REBOA in this group of patients.Twenty patients will be enrolled in this study. The protocol is designed according to the IDEAL framework Stage 2a1 for evaluating surgical interventions, where a small prospective case series is used to test and stabilise the intervention. The study will help establish whether the technique is ready for evaluation in a prospective multi-centre randomised study.

Background

In England, the average overall survival to hospital discharge from Emergency Medical Service (EMS) treated OHCA is 8.6%. This is significantly lower than in other European, Scandinavian and North American settings, where survival rates range from 14-21%.

Improving survival rates from OHCA is a major priority for the Resuscitation Council (UK), the British Heart Foundation and National Health Service (NHS) England and was identified as a key area for improvement by the Department of Health. The most common cause of sudden OHCA is coronary artery disease.

The current goals for pre-hospital management of OHCA are to provide early effective CPR to provide brain and heart blood flow, early defibrillation to restart the heart, and to support the circulation with advanced life support once available. Minimising periods of "no-flow" or "low-flow" are key to setting the conditions for successful resuscitation, and avoiding irreversible damage to critical organs, in particular the brain.

Other adjuncts to Advanced Life Support

Other therapeutic modalities such as percutaneous coronary intervention (PCI) and thrombolysis are well-documented therapies included in current ALS guidelines, but these require the patient to have a stable return of spontaneous circulation, and they can only realistically be provided after the patient has been fully resuscitated and delivered to a hospital. Even where this is possible, when these treatments are provided during ongoing CPR they are usually futile. Extracorporeal membrane oxygenation (ECMO) CPR (ECPR - the provision of an emergency heart-lung bypass circuit) is a suggested intervention for patients in refractory cardiac arrest with encouraging data from some observational studies. However, ECPR is a complex intervention that requires considerable resources and training. It is not currently available in the majority of UK hospitals. No prehospital services can currently deliver ECPR, a situation which is likely to persist. A capability gap exists which this study aims to address.

Pre-Hospital REBOA: anticipated clinical benefits and challenges

REBOA is a technique used to provide temporary occlusion of the aorta by inflation of an intra-aortic balloon. REBOA has been used to manage haemorrhagic shock and traumatic cardiac arrest by controlling bleeding and allowing a patient's physiology to stabilize.

REBOA has been proposed as an adjunct treatment in managing non-traumatic cardiac arrest patients. Thoracic aortic occlusion with a balloon provides a redistribution of the cardiac output to organs proximal to the occlusion. The resultant effect increases the coronary perfusion pressure (CPP); the driving force of blood through the coronary arteries. CPP is calculated as the diastolic aortic pressure minus the right atrial pressure: higher aortic diastolic blood pressure results in higher coronary perfusion pressure. REBOA during resuscitation also increases blood flow to the carotid arteries, cerebral arteries and cerebral perfusion pressure. This improves blood flow to the brain, which may protect it from damage.

During cardiac arrest, brain tissue is especially susceptible to hypoxemia; improved peri-resuscitation blood pressure may improve brain perfusion. Cerebral oximetry, which measures regional cerebral oxygen saturation (rSO2) by near-infrared spectroscopy, has emerged as a potentially helpful marker of cerebral ischaemia during CPR. In preclinical and clinical studies, higher rSO2 values during CPR are associated with improved cardiac arrest survival and neurologic outcome. rSO2 could be used as a surrogate marker for cerebral perfusion.

It is anticipated that REBOA can improve the perfusion of the brain and heart during CPR. Moreover, improved aortic blood pressure will have the potential clinical benefit of improving rates of ROSC. REBOA could also provide bridging therapy for patients who are refractory to conventional CPR until the patient is transferred to a unit capable of providing ECPR. Thus, REBOA could equally offer a "bridge to ROSC" or a "bridge to ECPR" in suitable patients.

Preclinical data

Animal data confirm multiple haemodynamic and electrophysiological benefits to aortic balloon occlusion during cardiopulmonary resuscitation. In 1993, Tang et al used a porcine model of cardiac arrest to investigate the effects of aortic balloon occlusion during resuscitation of twenty anaesthetised, ventilated pigs. After inducing ventricular fibrillation, chest compressions were commenced, and the animals randomised to various intervention arms, including aortic balloon occlusion by means of a 10 French (F) device inserted via the left femoral artery. This study demonstrated that the efficacy of CPR was augmented by balloon occlusion, resulting in better coronary perfusion pressure, and strikingly improved both the likelihood of successful resuscitation and 48 hour survival compared with control groups.

Building on their previous animal studies showing improvements in coronary perfusion pressure associated with an endovascular resuscitation technique, in 1996 a US group led by Manning combined aortic balloon occlusion with retrograde aortic perfusion in a canine model of cardiac arrest. Eight dogs (including 4 control animals) were sedated, intubated, catheterized, and instrumented to record ECG, right atrial pressure, and aortic pressure during resuscitation after ventricular fibrillation (VF) induced cardiac arrest. After 10 minutes of VF-induced arrest, mechanical CPR was initiated. 2 minutes later, the 4 study animals received selective aortic arch perfusion (SAAP - a combination of aortic occlusion and retrograde aortic perfusion). Defibrillation was attempted after 3 minutes of CPR and every minute thereafter. Animals received standard-dose epinephrine every 3 minutes by means of an intra-aortic catheter. SAAP infusion resulted in significant increases in median frequency and peak amplitude of VF in the SAAP group compared with the control group, coupled with an improvement in coronary perfusion pressure. This method of resuscitation was reliable in allowing restoration of a stable perfusing rhythm after defibrillation. The authors comment that the changes in peak amplitude and median frequency of the underlying cardiac rhythm, induced by improved coronary perfusion during resuscitation were likely responsible for the increased likelihood of successful defibrillation.

Gedeborg and colleagues further investigated the role of aortic balloon occlusion in order to evaluate the effects of this intervention on haemodynamics and the frequency of restoration of spontaneous circulation. Ventricular fibrillation was induced in 39 anaesthetised piglets, followed by an 8-min non-intervention interval. In a haemodynamic study (n = 10), closed chest CPR was performed for 7 min before an intra-aortic balloon was inflated. This intervention increased mean arterial blood pressure by 20% and increased coronary artery blood flow by 86%. Common carotid artery blood flow also increased by 62%. All these changes were statistically significant. Interestingly, although administration of epinephrine further increased mean arterial blood pressure and coronary artery blood flow, a paradoxical decrease was seen in common carotid artery blood. In a study of short-term survival, nine out of 13 animals (69%) in the balloon group and in three out of 13 animals (23%) in the control group had spontaneous circulation restored.

In 2002, Sesma et al compared the effectiveness of CPR with and without balloon aortic occlusion balloon, monitoring capnography, coronary and cerebral perfusion pressure (CePP) in normothermic induced VF arrest in a crossover study of 14 pigs. Aortic balloon deployment resulted in significant circulatory improvements: End-tidal carbon dioxide (ETCO2) rose by 38%, and coronary perfusion pressure rose initially from 10 to 29 mm Hg - an increase of 150%. The CePP improved from 12 to 39 mm Hg after the balloon was inflated, representing an increase of 200%. In all cases, the differences were statistically significant (P \< .0001), although they diminished as the resuscitation progressed in time.

Most recently, Hutin's resuscitation research group in Paris reported on the use of REBOA as a potential alternative to epinephrine in the management of non-traumatic cardiac arrest, assessing the comparative effects of epinephrine vs. REBOA on ROSC, haemodynamics and cerebral circulation in a porcine model of cardiac arrest. After 4 min of cardiac arrest and 18 min of basic life support (BLS) using a mechanical CPR device, animals were randomised to receive either REBOA or epinephrine administration before defibrillation attempts. Six animals were included in each experimental arm. Haemodynamic parameters were similar in both groups during BLS. After epinephrine administration or REBOA, mean arterial pressure, coronary and cerebral perfusion pressures similarly increased in both groups. However, carotid blood flow (CBF) and cerebral regional oxygenation saturation were significantly higher with REBOA as compared to epinephrine administration (+ 125% and + 40%, respectively). ROSC was obtained in 5 animals in both groups. After resuscitation, CBF remained lower in the epinephrine group as compared to REBOA. This study confirms the beneficial haemodynamic effects of aortic balloon occlusion during cardiac arrest, and hints at a potential role in reducing the deleterious effects of bolus epinephrine on the cerebral circulation. This is in accordance with Gedeborg's findings with respect to post-epinephrine carotid flow.

Clinical data

Human data concerning the potential role of aortic balloon occlusion include a number of case reports of the use of transient aortic occlusion during refractory cardiac arrest in the setting of the cardiac catheter lab or cardiac operating theatre. Deakin and Barron describe two cases of severe haemodynamic instability and intermittent cardiac arrest where aortic balloon occlusion was used: In the first case, mean radial artery pressure rose from 71/14 mmHg (mean=33 mmHg) to 92/24 mmHg (mean=47 mmHg). In the second case, mean radial artery pressure rose from 48/21 mmHg (mean=25 mmHg) to 62/26 mmHg (mean=36 mmHg). Calculated coronary artery perfusion pressure in case 1 increased from -2 to 8 mmHg, and in case 2 increased from 15 to 18 mmHg, suggesting that occlusion of the descending aorta during cardiac massage may improve coronary and cerebral perfusion pressures.

Aslanger et al report on a patient with myocardial infarction and severe multivessel coronary artery disease undergoing coronary angiography who suffered severe hypotension during the procedure. Despite inotropic support, cardiac arrest ensued. CPR was initiated and advanced life support (ALS) was performed according to guidelines. A peak blood pressure of approximately 100 mmHg was observed during chest compressions. There were no arterial waveforms on the monitor between chest compressions throughout this period, and asystole developed. During ongoing CPR, the 7F femoral access sheath

• Haemodynamic and oxygenation responses [Срок оценки: Within 1 hour of initiation]
• Near Infra-Red Spectrometry [Срок оценки: Within 1 hour of initiation]
• End Tidal CO2 [Срок оценки: Within 1 hour of initiation]