Door-to-Needle Time for Extracorporeal Cardiopulmonary Resuscitation and Neurological Outcomes in Out-of-Hospital Cardiac Arrest: A Nationwide Study

Abstract

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is an option for refractory cardiac arrest, and immediate initiation after indication is recommended. However, the practical goals of ECPR preparation (such as the door-to-needle time) remain unclear. This study aimed to elucidate the association between the door-to-needle time and neurological outcomes of out-of-hospital cardiac arrest.

Methods and results: This is a post hoc analysis of a nationwide multicenter study on out-of-hospital cardiac arrest treated with ECPR at 36 institutions between 2013 and 2018 (SAVE-J [Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan] II study). Adult patients without hypothermia (≥32 °C) in whom circulation was not returned at ECPR initiation were included. The probability of favorable neurological function at 30 days (defined as Cerebral Performance Category ≤2) was estimated using a generalized estimating equations model, in which institutional, patient, and treatment characteristics were adjusted. Estimated probabilities were then calculated according to the door-to-needle time with 3-minute increments, and a clinical threshold was assumed. Among 1298 patients eligible for this study, 136 (10.6%) had favorable neurological function. The estimated probability of favorable outcomes was highest in patients with 1 to 3 minutes of door-to-needle time (12.9% [11.4%-14.3%]) and remained at 9% to 10% until 27 to 30 minutes. Then, the probability dropped gradually with each 3-minute delay. A 30-minute threshold was assumed, and shorter door-to-extracorporeal membrane oxygenation/low-flow time and fewer adverse events related to cannulation were observed in patients with door-to-needle time <30 minutes.

Conclusions: The probability of favorable functions after out-of-hospital cardiac arrest decreased as the door-to-needle time for ECPR was prolonged, with a rapid decline after 27 to 30 minutes.

Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.

Keywords: Cerebral Performance Category; cardiopulmonary resuscitation; extracorporeal cardiopulmonary resuscitation.

Figure 1. Patient flow diagram.

Of the 2157 patients treated with ECPR in the Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE‐J) II study, 1298 adults were not hypothermic on hospital arrival and did not obtain ROSC at the time of ECMO cannulation; therefore, they were eligible for this study. In total, 136 patients (10.6%) had favorable neurological function (CPC ≤2) 30 days after admission. CPC indicates Cerebral Performance Category; ECMO, extracorporeal membrane oxygenation; ECPR, extracorporeal cardiopulmonary resuscitation; OHCA, out‐of‐hospital cardiac arrest; ROSC, return of spontaneous circulation; and VA‐ECMO, veno‐arterial extracorporeal membrane oxygenation.

Figure 2. Number of patients treated with ECPR.

The number of patients treated with ECPR decreased as the door‐to‐needle time increased, and it rapidly decreased particularly after 12 to 15 minutes. The number of patients who had favorable functions was also reduced over time. There was a paucity of patients with CPC ≤2 30 days after admission after 27 to 30 minutes of door‐to‐needle time. CPC indicates Cerebral Performance Category; and ECPR, extracorporeal cardiopulmonary resuscitation.

Figure 3. Probability of favorable neurological outcomes.

The estimated probabilities of favorable functions in each door‐to‐needle time category are shown (dashed lines) with 95% CIs (error bars) along with the number of patients (stacked bar). The estimated probability was highest in patients with 1 to 3 minutes of door‐to‐needle time (12.9% [95% CI, 11.4%–14.3%]) and remained 9% to 10% until 27 to 30 minutes. Then, the probability of favorable neurological function sharply decreased to approximately 7.0% and further dropped gradually with each 3‐minute delay in door‐to‐needle time for ECMO cannulation. ECMO indicates extracorporeal membrane oxygenation.

Figure 4. Boxplots of the door‐to‐ECMO and low‐flow time.

The door‐to‐ECMO time (A) and low‐flow time (B) in each door‐to‐needle time category are shown in boxplots. The door‐to‐ECMO time increased linearly with the door‐to‐needle time. Conversely, the low‐flow time either remained constant or only slightly increased until 30 minutes after hospital arrival (door‐to‐needle time <30 minutes), and then rapidly rose with a steep incline. ECMO indicates extracorporeal membrane oxygenation.