Patients
This retrospective study included OHCA patients who were treated with ECPR at the tertiary emergency care center of Tokyo Metropolitan Bokutoh Hospital between January 2011 and December 2018. Patients aged below 18 years were excluded from the study. The patients were classified into two groups according to the initial rhythm: the shockable rhythm group and the non-shockable rhythm group. Data of the baseline demographic and clinical characteristics of the patients were obtained from patient’s medical records, and the timing of pre-hospital events was recorded according to the reports of emergency medical service (EMS) personnel. The institutional review board of Tokyo Metropolitan Bokutoh Hospital approved the study (institutional approval reference number 02-003), which complied with the tenets of the Declaration of Helsinki. The requirement for informed consent was waived owing to the retrospective design of the study.
Protocol for ECPR and post-cardiac arrest care
In Japan, EMS personnel are required to transport every OHCA patient to a hospital performing cardiopulmonary resuscitation. They are permitted to perform defibrillation and advanced airway placement (e.g., use of tracheal intubation and supraglottic devices) and administer adrenaline, where indicated.
The indications for ECPR at our institution are as follows: (i) OHCA patients aged ≤65 years with an initial shockable rhythm and witness and (ii) OHCA patients aged ≤70 years with presumed reversible etiology who collapsed after the arrival of EMS personnel. In this case, any initial rhythm was acceptable, and the reversibility of the etiology was speculated based on the medical history and symptoms recorded by EMS personnel. Patients with very long transfer times and terminal illnesses were excluded. The implementation of ECPR was decided at the discretion of the individual emergency physician. Therefore, some cases did not meet the rigid indications.
ECPR was implemented immediately after the patients’ arrival at the emergency room. In all cases, we selected the ipsilateral or contralateral femoral vein and artery for insertion of venous and arterial cannulas. Further, 16-French (Fr) and 22-Fr cannulas were chosen for femoral artery and vein, respectively. Cannulation was performed percutaneously using the Seldinger technique under ultrasonic guidance. When our emergency room was renovated in August 2014, an interventional radiology-computed tomography (CT) system was installed [10]. Before this (until July 2014), a cannula was placed under ultrasonic guidance only, and after August 2014, cannulas were placed under both ultrasonic and fluoroscopic guidance. The extracorporeal membrane oxygenation (ECMO) circuit, consisting of a centrifugal pump, a hollow fiber oxygenator (MERA CPB circuit; Senko Medical Instrument Mfg. Co. Ltd., Tokyo, Japan, or Capiox EBS; Terumo Corporation, Tokyo, Japan), and a heparin-coated surface circuit, was primed using normal saline with 3,000 units of heparin. After the successful insertion of the venous and arterial cannulas, the ECMO circuit was connected and the ECMO pump flow was set at 4 L/min initially. After the initiation of ECMO, a 4-Fr sheath was placed in the superficial femoral artery to prevent distal limb ischemia. The conventional cardiopulmonary resuscitation was performed parallel to the cannulation until efficient ECMO pump flow was achieved.
After the initiation of ECMO, all patients were resuscitated according to the recommendations at each period [11,12,13,14]. They received appropriate amounts of fluid or vasopressors to maintain the mean blood pressure above 65 mmHg and were placed under ventilation to maintain normocarbia and adequate oxygenation. Patients in whom cardiac etiology was suspected underwent coronary angiography (CAG) and percutaneous coronary intervention, if indicated. Patients who remained comatose after ECMO initiation were treated with targeted temperature management at 34°C for 24 h and subsequently rewarmed to 36°C for the next 12 h using a heat exchanger in the circuit.
Neurological outcomes were predicted according to the results of clinical examinations performed at least 72 h after the return of spontaneous circulation (ROSC) and of brain CT. Neurological outcomes were predicted as poor when (1) a patient remained unconscious for at least 72 h post-ROSC with a Glasgow Coma Scale motor response score of ≤2; (2) there was no pupillary reflex; and (3) diffuse anoxic injury was recognized post-ROSC or during follow-up brain CT (on days 4–5) [12,14]. Even in these patients, we did not withdraw treatment, and ongoing life-sustaining measures were retained. However, additional aggressive treatment modalities such as hemodialysis and additional mechanical circulatory support devices were withheld.
Outcomes
The cerebral performance category (CPC) scale was used to assess the outcomes of neurological function at hospital discharge [15], and this was the primary outcome. The CPC scale ranges from 1 to 5 with 1 representing intact function and 5 representing brain death. The outcome of neurological function was considered good if the CPC score was 1 or 2, and poor if the CPC score was 3–5. The CPC scores were determined by reviewing the report from the rehabilitation department.
Statistical analysis
Continuous variables were reported as medians with interquartile ranges (IQRs), and dichotomous variables were reported as numbers with percentages. Univariate analysis was performed using Fisher’s exact test for categorical variables and the Mann-Whitney U test for continuous variables. All reported p-values were two-tailed, and values less than 0.05 were considered to indicate statistical significance.
First, the rate of good neurological outcome was compared between the shockable and non-shockable rhythm groups. A multivariate logistic regression analysis was then performed to evaluate the association between the initial rhythm and good neurological outcomes to control for potential confounders. We selected potential confounders that appeared to be clinically important by referring to those used in previous studies (age, bystander CPR, witness, low flow time, and transient ROSC) [16].
Second, the background characteristics of the patients were compared between those with good and poor neurological outcomes in the non-shockable group.
All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan) [17], which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).