ECPR Bests Standard CPR in Neurologically Favorable Outcomes

Batya Swift Yasgur MA, LSW

April 09, 2020

Extracorporeal cardiopulmonary resuscitation (ECPR) is associated with improved neurological outcomes, compared with standard cardiopulmonary resuscitation (CPR), even with prolonged resuscitation and progressive metabolic derangement, new research suggests.

Investigators compared adult patients with refractory ventricular fibrillation/ventricular tachycardia (VF/VT) who received ECPR with patients who received standard CPR during out-of-hospital cardiac arrest (OHCA).

ECPR was associated with improved survival, compared with standard CPR, at all durations of professional CPR under 60 minutes, and with successful treatment of some patients receiving prolonged professional CPR up to 60 to 90 minutes.

"ECPR is a powerful tool that provides perfusion when CPR has failed," lead author Jason Bartos, MD, PhD, assistant professor of medicine and medical director, Cardiovascular Intensive Care Unit, University of Minnesota Medical School, Minneapolis, told theheart.org | Medscape Cardiology.

"While randomized controlled trials are needed to more conclusively demonstrate the benefit, these data suggest that ECPR significantly improves neurologically favorable survival for patients with refractory VF/VT cardiac arrest, and even very long durations of professional CPR — all the way out to 98 minutes — suggest that even very long durations of CPR are survivable in some cases," said Bartos, who is also the associate director, Center for Resuscitation Medicine, Intervention/Critical Care Cardiology.

The study was published online March 16 in Circulation.

Powerful Tool

ECPR, a technique that uses extracorporeal membrane oxygenation (ECMO) for hemodynamic support, is a "powerful tool that provides immediate blood flow, replacing the need for heart function," Bartos explained.

"When looking at cardiac arrest patients, approximately half of VF/VT patients will fail to achieve return of spontaneous circulation [ROTC], resulting in death," he said.

"ECPR eliminates the need for ROTC, providing time for patients to recover without accumulating further injury."

He noted that even if ROTC is achieved, 25% to 33% of patients will rearrest, which causes more injury and may lead to death, but ECPR "eliminates the concern for rearrest by providing blood flow independent of heart function."

Although case series and cohort studies have suggested that ECPR can increase survival, none have been completed, "therefore a comparison with a group of shock refractory VF/VT patients was desired, in particular, a patient cohort that was well treated by well-trained emergency medical services."

The investigators also set out "to understand the effects of duration of profession CPR preceding ECPR to further our understanding of the geographic limits of a hospital-based program," Bartos said. To do so, "we needed to assess the effect of transport time on outcomes to understand how far we could stretch our catchment area to optimize the patient population reached by our program."

Long Durations Survivable

The researchers compared two groups of patients with refractory VF/VT OHCA: 160 patients treated with the University of Minnesota refractory VF/VT ECPR (UMN-ECPR) protocol from December 2015 to February 2019; and a comparison cohort of 654 patients participating in the Amiodarone, Lidocaine, or Placebo (ALPS) trial.

Patients receiving ECPR were rapidly transported (<30 minutes) to the UMN cardiac catherization laboratory after undergoing prehospital screening. Patients were required to have an initial rhythm of VF/VT, to have received three direct current shocks without ROTC, to have pulseless electrical activity or asystole, and to have received amiodarone 300 mg.

Patients in the ALPS cohort, who had nontraumatic OHCA, shock-refractory VF, or pulseless VT after at least one shock, were treated with parenteral amiodarone, lidocaine, and saline placebo in addition to standard care.

The researchers defined "neurologically favorable outcome" as a Cerebral Performance Category (CPC) score of 1 to 2 for the UMN-ECPR cohort, or a modified Rankin Scale (mRS) score of 0 to 3 for the ALPS cohort.

The UMN-ECPR patients were significantly younger than the ALPS patients (57 ± 1.0 vs 59 ± .4 years; = .033), but men accounted for roughly the same proportion of each cohort (79% vs 81%).

Overall, the UMN-ECPR patients experienced significantly higher rates of neurologically favorable survival than the ALPS patients (33% vs 23%; P = .01), translating into an overall relative risk (RR) reduction for death or poor neurologic outcomes of 13% (95% CI, 2 - 22; < .001).

Patients in the UMN-ECPR group also experienced significantly longer mean duration of CPRthan those in the ALPS group (60 vs 35 minutes; P < .001).

Although patients in both groups experienced progressive decline in neurologically favorable outcomes with longer CPR duration (1.9% per minute in ALPS patients and 2.5% per minute in UMN-ECPR patients), those in the UMN-ECPR group experienced significantly greater neurologically favorable survival at each CPR duration interval less than 60 minutes than those in the the ALPS group (P < .001).

Neurologically Favorable Outcomes Each Group by Duration of CPR
Duration of CPR UMN-ECPR Group ALPS Group
20–29 minutes 100% 24%
50–59 minutes 25% 0%
≥60 minutes 19% 0%

The RR reductions for death or poor neurologic function for patients receiving 20 to 59 minutes of CPR and for patients receiving at least 60 minutes of CPR were 29% (95% CI, 18 - 41; P < .001) and 19% (95% CI, 10 - 27; < .001), respectively.

All patients in the UMN-ECPR group showed significant metabolic changes during prolonged resuscitation, including decline in arterial pH, increased lactic acid and arterial partial pressure of carbon dioxide, and increased left ventricular lateral wall thickness.

"The rate of neurologically favorable survival — no or minimal neurological deficit at hospital discharge — was 33%, and this was after 60 minutes of CPR on average," Bartos commented. "In most areas of the world, including many areas of the United States, this duration of CPR would be considered nonsurvivable."

"Importantly, survival remains approximately 15% to 20% out to 98 minutes of professional CPR, suggesting that even very long durations of CPR are survivable in some cases," Bartos emphasized, noting that the decline in survival was associated with the "progressive worsening of the metabolic state of the patient."

A Call to Explore ECPR

Commenting on the study for theheart.org | Medscape Cardiology, Aaron W. Calhoun, MD, professor of pediatric critical care, University of Louisville School of Medicine, Department of Pediatrics/Norton Children's Hospital, Kentucky, said that this study "raises new possibilities for saving the lives of adults suffering cardiac arrest due to dysrhythmias in the out-of-hospital setting that were not as clear before."

However, "the only cardiac arrest states looked at here are pulses VT and VF, so they cannot be applied to asystolic arrest or pulseless electric activity, [which] often have different causes than pulses VT and VF," cautioned Calhoun, who was not involved with the study.

He observed that centers with ECPR capacities "are not that common at present, and so most adult clinicians will likely not have access to one."

But for communities that do, "this should encourage them to explore what an out-of-hospital arrest to ECPR program to ECPR (for select cases) could look like, and those adult cardiac centers without ECPR capability may wish to consider this as a call to explore what would be needed to create, implement, and maintain an ECPR team," Calhoun said.

Bartos emphasized that the "system of care and chain of survival is absolutely critical; the prehospital system must be optimized to maximize the perfusion provided by CPR and minimize the time to ECPR initiation."

He concluded: "Multidisciplinary postresuscitation and critical care is necessary to reverse the severe metabolic derangement that accumulates during the period of ECPR."

In an accompanying editorial, Romain Sonneville MD, PhD, and Matthieu Schmidt, MD, PhD, both from Hôpital Bichat-Claude Bernard, Paris, emphasize that a "systematic multidisciplinary approach is needed to avoid continuing futile and expensive therapies when poor neurological are likely but also to avoid inappropriate withdrawal of life-sustaining therapies in patients who may otherwise have a chance of achieving meaningful neurological recovery."

The study had no source of funding. Bartos and coauthors declare no relevant financial relationships. Sonneville has received grants from the French Ministry of Health, the French Society of Intensive Care Medicine, and the European Society of Intensive Care Medicine; and lecture fees from Baxter. Schmidt has received lecture fees from Getinge, Draeger, and Xenios. Calhoun declares no relevant financial relationships.

Circulation. Published online March 16, 2020. Full text, Editorial

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