Resuscitation 85 (2014) 762–768

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Clinical Paper

Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: A prospective observational study夽 Tetsuya Sakamoto, Naoto Morimura ∗ , Ken Nagao, Yasufumi Asai, Hiroyuki Yokota, Satoshi Nara, Mamoru Hase, Yoshio Tahara, Takahiro Atsumi, SAVE-J Study Group1 The Japanese Scientific Research Group of the Ministry of Health, Labour and Welfare for Extracorporeal Cardiopulmonary Resuscitation: Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J), Japan

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Article history: Received 21 August 2013 Received in revised form 27 January 2014 Accepted 30 January 2014 Keywords: Out-of-hospital cardiac arrest Ventricular fibrillation Cardiopulmonary resuscitation Extracorporeal cardiopulmonary resuscitation Advanced life support Percutaneous cardiopulmonary support

a b s t r a c t Background: A favorable neurological outcome is likely to be achieved in out-of-hospital cardiac arrest (OHCA) patients with ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) on the initial electrocardiogram (ECG). However, in patients without pre-hospital restoration of spontaneous circulation despite the initial VF/VT, the outcome is extremely low by conventional cardiopulmonary resuscitation (CPR). Extracorporeal CPR (ECPR) may enhance cerebral blood flow and recovery of neurological function. We prospectively examined how ECPR for OHCA with VF/VT would affect neurological outcomes. Methods and results: The design of this trial was a prospective, observational study. We compared differences of outcome at 1 and 6 months after OHCA between ECPR group (26 hospitals) and non-ECPR group (20 hospitals). Primary endpoints were the rate of favorable outcomes defined by the GlasgowPittsburgh Cerebral Performance and Overall Performance Categories (CPC) 1 or 2 at 1 and 6 months after OHCA. Based on intention-to-treat analysis, CPC 1 or 2 were 12.3% (32/260) in the ECPR group and 1.5% (3/194) in the non-ECPR group at 1 month (P < 0.0001), and 11.2% (29/260) and 2.6% (5/194) at 6 months (P = 0.001), respectively. By per protocol analysis, CPC 1 or 2 were 13.7% (32/234) in the ECPR group and 1.9% (3/159) in the non-ECPR group at 1 month (P < 0.0001), and 12.4% (29/234) and 3.1% (5/159) at 6 months (P = 0.002), respectively. Conclusions: In OHCA patients with VF/VT on the initial ECG, a treatment bundle including ECPR, therapeutic hypothermia and IABP was associated with improved neurological outcome at 1 and 6 months after OHCA. © 2014 Elsevier Ireland Ltd. All rights reserved.

1. Background A favorable neurological outcome is likely to be achieved in out-of-hospital cardiac arrest (OHCA) patients with ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) on the initial electrocardiogram (ECG). However, in patients without

夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.01.031. ∗ Corresponding author at: Department of Emergency Medicine, Yokohama City University Graduate School of Medicine, 4-57 Urafunecho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan. E-mail address: [email protected] (N. Morimura). 1 The members of SAVE-J Study Group, contributors, participating investigators and coordinators, and participating institutes of this study are listed in Acknowledgements section. http://dx.doi.org/10.1016/j.resuscitation.2014.01.031 0300-9572/© 2014 Elsevier Ireland Ltd. All rights reserved.

pre-hospital restoration of spontaneous circulation (ROSC) despite the initial VF/VT, the rate of favorable neurological outcome is extremely low by conventional cardiopulmonary resuscitation (CPR).1–5 In the metabolic phase after cardiac arrest, therapeutic hypothermia (TH) and assisted circulation are necessary because systemic ischemia progresses.6 Because cerebral blood flow is insufficient during CPR, the possibility of extracorporeal CPR (ECPR) using a cardiopulmonary support device, especially percutaneous cardiopulmonary support (PCPS), has been explored with the aim of achieving recovery of neurological function. ECPR was introduced in the 1960s,7 with the intention of improving neurological outcomes. Several recent studies have demonstrated better neurological preservation after cardiac arrest in patients receiving ECPR.8–11 Although ECPR has recently been reported to achieve better survival to discharge outcomes than conventional CPR in cases of in-hospital cardiac arrest,12 the effects on long-term neurological

T. Sakamoto et al. / Resuscitation 85 (2014) 762–768

outcomes in cases of OHCA are still unknown. Recently we conducted a retrospective case series study in Japan and demonstrated favorable neurological outcomes to be achieved by ECPR.13 In this study, we prospectively examined how ECPR performed for OHCA would affect neurological outcomes.

2. Subjects and methods The design of this clinical trial was a prospective, observational study registered on a public Web site of the trial registry named “UMIN-CTR” at the URL of https://upload.umin.ac.jp/ cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno= R000001692&type=summary&lang.uage=E. This study followed the description of observational study in the ethical guideline of epidemiological study. In participating hospitals, information concerning objective, method, data management and right to refuse registration of this study was disclosed to the individuals representing patients. Informed consent before introduction of ECPR was waived because of the life-threatening emergency situation. Information was delivered to the next of kin, and consent was obtained during or after the introduction of ECPR in the usual manner of each hospital. Offering participation with all facilities that were national or local government designated tertiary emergency medical centers or advanced cardiovascular centers or emergency departments of university hospital in Japan, forty-six facilities participated in this study with the approval of the ethical committee of each hospital. These facilities were assigned to the ECPR or non-ECPR group. Twenty-six hospitals were enrolled in the ECPR group and 20 hospitals in the non-ECPR group. The assignment to the two groups was due to their requests which were based on their usual operational strategy of CPR aggressively using PCPS or not. There were no facilities that chose the ECPR group in order to use this opportunity to introduce a new strategy of CPR using PCPS for OHCA. Every facility in both groups had a similar function of tertiary emergency medical care or advanced cardiovascular care, and they had the capability to perform an intra-aortic balloon pump (IABP), coronary angiography (CAG), percutaneous coronary intervention (PCI) and TH. We analyzed differences in neurological outcomes at 1 and 6 months after collapse in OHCA patients who met the following inclusion criteria between the ECPR group and the non-ECPR group. The study period was from September 8, 2008 to September 30, 2011. Inclusion criteria for this study were: (1) VF/VT on the initial ECG, (2) cardiac arrest on hospital arrival with or without pre-hospital ROSC, (3) within 45 min from reception of the emergency call (119) or the onset of cardiac arrest to the hospital arrival, and (4) no ROSC at least during the 15 min after hospital arrival (or after contact with a doctor) even though conventional CPR was performed. ROSC was defined as at least 1 min of continuing confirmation of pulsation, (5) and excluded patients with one or more of the following conditions: (a) under the age of 20 years or those aged 75 years or older, (b) poor level of activities of daily livings before the onset of cardiac arrest, (c) non-cardiac origin (e.g., external factors such as trauma and drug intoxication, primary cerebral disorders, acute aortic dissection diagnosed prior to the introduction of PCPS, and terminal phase of cancer), (d) core body temperature of less than 30 ◦ C, and (e) no informed consent from the individuals representing patients. The nationwide free emergency call number to dispatch an ambulance is 119, which is managed by the Fire Department (FD) at the 119 center in each area. The main pre-hospital provider of ambulances is the emergency medical technician (EMT), who belongs to the FD. They are classified as basic EMTs, intermediate EMTs, and paramedics. The pre-hospital CPR that was performed by EMS personnel was in compliance with the national guidelines of

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the Japan Resuscitation Council (JRC), which was based on Guidelines 2005 for CPR and emergency cardiovascular care during this study period. Moreover, the National Protocol for pre-hospital management of cardiac arrest for paramedics was basically assigned to paramedics, and each regional medical control council modified it as needed. According to the protocol established by the regional Medical Control Council, paramedics perform field triage and transport patients to an emergency hospital for definitive treatment. Most regional protocols ordered paramedics to transport cardiac arrest patients to the regional tertiary emergency centers. Treatment protocols for both groups were introduced in Appendix A.1–3,14–17 The endpoints of outcome measures were favorable neurologic status at 1 month and 6 months after cardiac arrest, defined as the Glasgow-Pittsburgh Cerebral Performance and Overall Performance Categories (CPC) score of 1 or 2. We collected data on patient demographics and pre/in-hospital variables listed in Appendix B. 3. Statistical analysis All analyses were performed using statistical software (Statistical Package for Social Sciences (SPSS) version 11.0; SPSS Japan Inc., Tokyo, Japan). Fisher’s exact test was used to compare proportions between both groups. Differences with a p value of 0.05 or less were defined as statistically significant. 4. Results Between October 2008 and March 31, 2012, a total of 454 patients, including 260 patients in the ECPR group and 194 in the non-ECPR group, were registered. Among these 454 patients, 234 in the ECPR group and 159 in the non-ECPR group were treated according to the protocols (Fig. 1 and Table 1). There were no differences in background factors between the 2 groups (Table 1). Based on the intention-to-treat analysis, the rate of favorable outcomes was 12.3% in the ECPR group and 1.5% in the non-ECPR group at 1 month after onset of cardiac arrest (P < 0.0001) and 11.2% and 2.6%, respectively, at 6 months after onset (P = 0.001). Moreover, based on the per protocol analysis, the rate of favorable outcomes were 13.7% in the ECPR group and 1.9% in the nonECPR group at 1 month after onset (P < 0.0001) and 12.4% and 3.1%, respectively, at 6 months after onset (P = 0.002) (Table 2). The contents of treatments given to 214 patients, who were alive at 24 h after cardiac arrest, were compared. The frequencies of introducing TH and performing IABP were significantly higher in the ECPR group, respectively (Table 3). 5. Discussion In the 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations (CoSTR 2010),20 the International Liaison Committee on Resuscitation (ILCOR) concluded that there was very little evidence as to whether the routine use of ECPR for cardiac arrest should be recommended. In the 2010 American Heart Association Guidelines (AHA-G2010),21 the term “extracorporeal life support (ECLS)” was used synonymously with ECPR. The AHA-G2010 recommends, based on previous reports,11,12,22–24 that a Class IIb procedure should be performed under the following conditions, ECPR can be quickly prepared for introduction; the duration of circulatory arrest due to cardiac arrest is short; and reversal of the causes of cardiac arrest can be expected. The 2010 European Resuscitation Council Guidelines (ERC-G2010)25 have no description of ECPR in the chapter on adult patients.

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Table 1 Demographic and pre-hospital data of study patients. ECPR group

non-ECPR group

n

n

Number of participating hospitals Number of hospitals with registered cases Number of cases Intention-to-treat Per protocol Age (years)

26 22

20 17

260 234

194 159

90.0%

NS

235, 25

90.4%

172, 22

88.7%

NS

186 73 1

71.5%

151 42 1

77.8%

NS

127 126 3 4

48.8%

90 96 5 3

46.4%

NS

29.8 Cause Acute coronary syndrome Arrhythmia Myocarditis Myopathy Unknown N/A Pre-hospital procedure by paramedics Number of shocks

82.0%

58.1

56.3 Gender M, F (Male %) Witnessed Yes No N/A Bystander CPR Yes No Unknown N/A Time from 119 call to hospital arrival (min)

P value %

30.5

165 42 2 17 27 7 n = 256 3.1 ± 1.9

63.5% 16.2% 0.8% 6.5% 10.4% 2.7%

NS

115 28

59.3% 14.4% 0.0% 3.6% 22.2% 0.5%

7 43 1 n = 190 2.9 ± 1.9

NS

NS

N/A: not applicable. NS: not significant.

Table 2 Neurological outcomes of ECPR and non-ECPR groups.

Intention-to-treat CPC at 1 month after cardiac arrest CPC 1 CPC 2 CPC 3 CPC 4 CPC 5 Unknown Favorable outcome (CPC 1 or 2) CPC at 6 month after cardiac arrest CPC 1 CPC 2 CPC 3 CPC 4 CPC 5 Unknown Favorable outcome (CPC 1 or 2) Per protocol CPC at 1 month after cardiac arrest CPC 1 CPC 2 CPC 3 CPC 4 CPC 5 Unknown Favorable outcome (CPC 1 or 2) CPC at 6 months after cardiac arrest CPC 1 CPC 2 CPC 3 CPC 4 CPC 5 Unknown Favorable outcome (CPC 1 or 2)

ECPR group

non-ECPR group

260

194

23 9 9 28 191 0 32

1 2 5 4 181 1 3

25 4 8 19 202 2 29 234 23 9 9 27 166 0 32 25 4 8 18 177 2 29

12.3%

P value

1.5%

Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: a prospective observational study.

A favorable neurological outcome is likely to be achieved in out-of-hospital cardiac arrest (OHCA) patients with ventricular fibrillation or pulseless...
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