Current best practices for refractory cardiac arrest
The American Heart Association estimates that in 2015, there were 350,000 out-of-hospital cardiac arrests (OHCAs).1 Survival rates vary widely, but the estimated overall survival rate in the United States is approximately 12%.1,2
All emergency medical systems occasionally see at least one subgroup with even less chance of survival, those that presented in ventricular fibrillation (v fib) but remain in refractory cardiac arrest, with v fib or other rhythms, after minutes of resuscitation efforts. Often, these are middle-aged individuals with seemingly less co-morbidities than expected.
Nonetheless, the typical approach to these refractory cardiac arrest patients is simply “more of the same;” typically this means continued CPR, repeated defibrillation attempts and administration of ACLS medications, the latter unproven at best, and thought by some to be of little value.3
What’s the expectation if such treatment hasn’t worked earlier? Certainly, there are rare cases with return of spontaneous circulation (ROSC) on the “nth” defibrillation attempt or after very lengthy ACLS efforts, but these seem to be the exception rather than the rule.
Though mistakenly attributed to Albert Einstein, the saying, “the definition of insanity is doing the same thing over and over again and expecting different results,” is particularly appropriate in this regard.4
It’s time to begin to think differently. The key question is why are the standard treatments, including defibrillation and ACLS therapies, not effective for this particular patient? In adult out-of-hospital refractory cardiac arrest, when the patient repeatedly reverts to, or stays in, v fib, the usual cause is a catastrophic coronary issue, i.e., acute closure of the left main coronary artery or its equivalent.
What’s needed in these cases is rapid reperfusion of the occluded coronary, while providing some systemic circulation to the central nervous system and the myocardium. Following reperfusion, defibrillation then has a real chance of success in restoring spontaneous circulation.
A new paradigm for those with v fib refractory out-of-hospital cardiac arrest is now on the horizon. Rather than the usual approach of “stay and play, … and play, … and play some more,” a better scenario appears to be to “load and go”-perhaps better described as “scoop and treat on the way” to the catheterization laboratory.
The concept is relatively simple. If an acutely occluded coronary is preventing any meaningful coronary blood flow from reaching the myocardium, the resultant ischemic myocardial milieu is preventing establishment of a sustained perfusing rhythm. Continued efforts to defibrillate will likely be futile until the occluded coronary is reperfused and the milieu changed.
Acute reperfusion of an occluded coronary during cardiac arrest is best accomplished by primary angioplasty in the catheterization laboratory as opposed to IV thrombolytics.
The European TROICA trial found no survival benefit when TNK was administered to refractory OHCA patients. Table 1, p. 4, summarizes both patient demographics and treatment results from this trial. The principal investigator suggested that elimination of those with suspected pulmonary emboli as the cause of their cardiac arrest may have eliminated an important subgroup for whom such a strategy might have been beneficial.5
PCI for Reperfusion
Just as primary percutaneous coronary intervention (PPCI) has become the preferred method of reperfusion in ST-segment elevation myocardial infarction (STEMI) patients, it also appears to be the best option for successful reperfusion during cardiac arrest, given the results of the TROICA study.
If timely reperfusion with PPCI is desirable for those with refractory OHCA, the next pragmatic question is how to get them to the hospital while providing systemic circulatory support to their brain and heart during transport? The answer: mechanical chest compression devices.
According to the few studies that have looked at their impact on resuscitation, such devices have failed to improve overall outcomes when used routinely for all OHCA patients.6,7 Nevertheless, the current cardiopulmonary guidelines recommend their consideration in some special circumstances, such as during transport when CPR is necessary.
The American Heart Association 2015 CPR and ECC guidelines note, “The use of mechanical piston devices may be considered in specific settings where the delivery of high-quality manual compressions may be challenging or dangerous for the provider (e.g., limited rescuers available, prolonged CPR, during hypothermic cardiac arrest, in a moving ambulance, in the angiography suite, during preparation for extracorporeal CPR [ECPR]), provided that rescuers strictly limit interruptions in CPR during deployment and removal of the devices (Class IIb, LOE C-EO).”8
Certainly, manual chest compressions in the patient compartment of a moving ambulance are problematic. Several reports suggest that allowing unrestrained rescuers to attempt manual CPR during transport is a definite safety hazard and puts the rescuer at risk.9,10
Others have shown that manual chest compressions during transport are frequently interrupted and often more shallow than recommended. However, mechanical compressions in a moving ambulance achieved the recommended rate and depth, while improving the CPR fraction compared to manual compressions.11,12
Determining When to Transport
When to load the patient and transport to the hospital with ongoing resuscitation efforts is an important question, and one that’s not yet fully answered. It’s clear that waiting until a lengthy resuscitation effort has failed in the field before transporting typically leaves a non-viable patient.
One study highlighted the importance of starting extracorporeal membrane oxygenation (ECMO) within 60 minutes of cardiac arrest onset, if meaningful survival is to be realized.13
On the other hand, transporting too early means some patients who would have been resuscitated with less invasive means are exposed to increased morbidity because of the invasive nature of introducing extracorporeal support.
So, how should refractory cardiac arrest be defined? Contemporary reports in the literature have generally used one of two methods. The first approach is to simply limit the time spent in the field attempting resuscitation. Three published reports have suggested three different time intervals in this regard: One using 5-10 minutes of resuscitation effort; the second using 10 minutes; and the third using 10-15 minutes.14-16
Using the passage of time to determine refractoriness of the cardiac arrest is complicated by the need to ensure that standard treatments are completed within that time period and by the difficulty of keeping track of time during the complex task of emergency cardiac care and resuscitation.
An alternate approach is to define a cardiac arrest as refractory if standard treatments are completed but cardiac arrest persists. One study used the completion of three defibrillation shocks without ROSC; another used three shocks and administration of IV or intraosseous (IO) amiodarone.15,17 If cardiac arrest continued they then transported to the hospital.17
This completion of treatment approach may still be impacted by the need for accurate time measurement. These therapies need to occur quickly and not be drawn out beyond reasonable expectations, or the intervention will again be adversely impacted and ineffective secondary to the extent of injury to both the central nervous system and the myocardium.
As these examples show, there’s currently no consensus on how to best define refractory cardiac arrest, which makes evaluating different therapeutic approaches difficult.
Candidates for ECPR
A major decision point in successfully applying this new paradigm is determining who should be included as candidates for this new, aggressive and hyper-invasive alternative.
Realistically, not all patients will respond well to extracorporeal CPR (ECPR), so choosing the optimal candidates may greatly influence the success of such a program, particularly in the early period of introducing this change in the EMS protocol. Table 2 summarizes clinical features known to negatively affect outcome from cardiac arrest.18 Such factors suggest that the ideal candidate for early transport from the field with ongoing CPR to an ECPR center should optimally have the following features:
• Younger age;
• Few co-morbid conditions;
• Witnessed v fib cardiac arrest;
• Immediate bystander CPR; and
• Likely cardiac etiology of the arrest.
The specifics regarding how old is too old, or how long before bystander CPR is begun is too long, aren’t yet clear, but certainly deserve careful consideration.
Providing chest compressions during transport of refractory cardiac arrest patients is critical to the success of an ECPR program. Manual chest compressions in a moving ambulance have been shown to be both difficult to perform and potentially unsafe for the rescuer.9-12
One report showed that more than 70% of manual chest compression were too shallow (< 2 inches).11 The other published report using a recording manikin in a moving ambulance, found that attempted manual chest compressions resulted in poor quality CPR and a decrease in CPR fraction. Changing to mechanical chest compressions improved the rate, CPR fraction and the depth of compressions.12
If mechanical CPR is either not available or not feasible (e.g., a very large patient won’t fit in the device), then perhaps a “load and go” strategy may not be the best option.
Systemic Circulatory Support
Extracorporeal circulation can be provided through a number of mechanical devices, including extracorporeal membrane oxygenation (ECMO), percutaneous cardiopulmonary bypass, and TandemHeart. TandemHeart is an extracorporeal circulatory pump that requires a trans-septal puncture to access the left atrium for the source of arterial circulation.
In addition, other technologies are currently in development currently as well, such as the TandemLife.19 TandemLife is an alternative extracorporeal pump that uses the femoral artery for access to the arterial circulation. This was developed for such true emergencies such as cardiac arrest, where a trans-septal approach isn’t feasible.
Each require large bore venous and arterial access, typically via the femoral vessels, though some have reported success via the axillary route.
The venous (withdrawal port) generally requires placement at the right atrial-inferior vena-caval junction, in order to ensure adequate volume to avoid collapse of the venous vessel from the suction action of withdrawal. Typically, a 22-25 F catheter is required. The arterial catheter is typically smaller, usually 15-17 F, and can be positioned in the iliac system for blood infusion.
The hope for such an invasive therapy as extracorporeal life support (ECLS) is that a reversible cause for the refractory arrest can be identified and corrected. Emergent cardiac catheterization and coronary angiography are the mainstays of this search/approach for remediable conditions.
An acute coronary issue is the easiest to correct of the reversible conditions, and usually responds well to primary percutaneous intervention and stenting.
Other critical cardiac conditions that can lead to refractory cardiac arrest detectable at catheterization include significant cardiomyopathies, aortic stenosis and myocardial rupture. Finding no coronary issues has been associated with a decrease in favorable outcomes.20
A study in Japan repeatedly shows the importance of simultaneously instituting therapeutic hypothermia when beginning ECPR. Their best results are seen when ECPR in begun within 55 minutes of initial cardiac arrest and a target temperature of 34 degrees C is accomplished within 22 minutes of starting ECPR.13
Profound myocardial “stunning” with decreased ejection fraction often occurs after prolonged cardiac arrest, but is reversible if adequate circulatory support is provided until left ventricular function can recover.21,22
Hence, caution should be exercised before attempting to wean patients from ECLS too quickly. Researchers have found this global stunning of left ventricular function usually recovers after 3-5 days of continuous ECLS support post cardiac arrest.20
Clinical Reports to Date
There are two recent clinical reports of implementing a strategy of “load and go” using mechanical CPR during transport to an ECLS-capable institution for treatment of refractory out-of-hospital v fib cardiac arrest.20,23 According to these early experiences, this new paradigm holds real promise for these very difficult-to-treat patients.
Australian researchers recently published their experience with 11 out-of-hospital patients with refractory arrest who were treated with this new paradigm.23 This observational study included patients who were unsuccessful in achieving ROSC, were 18-65 years of age, had chest compressions begun within 10 minutes of collapse, and had mechanical CPR during transport.
In addition, therapeutic hypothermia was also initiated in the field and continued at the hospital. Extracorporeal circulation was begun in the ED, then the patient was taken to the cardiac catheterization laboratory for emergent coronary angiography and possible PCI.
The primary endpoint was survival-to-discharge with a cerebral performance category (CPC) of 1 or 2. Secondary endpoints included ROSC, weaning from ECMO, and hospital length of stay. Five of 11 (45%) of the patients survived to discharge with favorable neurological function (CPC 1 or 2).
In 2017, a second report appeared from researchers at the University of Minnesota. This was also an observational study of 62 patients with refractory out-of-hospital cardiac arrest who presented with v fib/v tach, and hadn’t achieved ROSC after three shocks and administration of IV/IO amiodarone.20
Inclusion criteria included body size that could accommodate a LUCAS automated CPR device, and a transfer time from the scene to the cardiac catheterization lab of < 30 minutes.
Mechanical compressions were utilized during transport and, upon arrival, the patient was taken to the catheterization lab for insertion and use of the ECMO device. Routine femoral and iliac angiography was performed to ensure adequate size for ECMO insertion. Immediate coronary angiography and PCI, when indicated, were performed. ECMO support was continued post PCI for support of the left ventricular dysfunction known to occur after prolonged cardiac arrest. Survival to hospital discharge with CPC 1 or 2 was the primary outcome. Secondary outcome was 3-month survival with CPC 1 or 2 and protocol-based complications.
Twenty-six of 62 patients (42%) were discharged with favorable neurological function (CPC 1 or 2). Two of the 62 (3%) patients were discharged with unfavorable neurological function (CPC 3 and 4, respectively). At three months, 26 (42%) of the 62 patients were alive and all had normal neurological function (CPC 1), while two neurologically damaged individuals remained with CPC scores of 3 and 4.
Table 3 compares and summarizes the outcome results achieved from these two recent reports of a “scoop and treat on the way” approach in both Australia and the U.S.20,23
A new paradigm of early transport to an ECMO/PCI center with ongoing mechanical chest compressions may change how refractory cardiac arrest victims are treated.
Success of such programs, particularly in the beginning, will depend on careful selection of appropriate patients. This novel approach consists of rapid transport of refractory out-of-hospital v fib cardiac arrest patients with mechanical chest compressions in route to the destination of an ECLS-capable medical facility, where rapid introduction of circulatory support can be achieved in either the ED or catheterization lab.
Simultaneous induction of therapeutic hypothermia (34 degrees C) and coronary angiography and PPCI are crucial to correct the underlying cause of the refractory arrest, and to ensure optimal neurological function of survivors.
Continuing ECMO support for the profound post-resuscitation left ventricular dysfunction associated with prolonged cardiac arrest is also critical to achieve long-term positive outcomes with this approach.
Early reports, though admittedly containing small numbers, suggest significant improvements in neurologically intact survival can be achieved with this new paradigm of “load and go” or “scoop and treat on the way.”
EMS agencies and their medical directors are encouraged to work with their specialty hospital facilities, as they have in Alameda County, Calif., to ensure that ECMO capabilities are available and can be alerted similar to prehospital STEMI alerts, to be able to fulfil this new treatment paradigm in their EMS system.
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