Data source and data collection
The Korean Cardiac Arrest Research Consortium (KoCARC), a multicenter collaborative research network of 55 participating institutions, was developed to understand various studies in the resuscitation field of patients with OHCA and strengthen cooperative efforts. The KoCARC registry includes patients with OHCA of medical etiology transported to a participating ED with resuscitation efforts. The registry excludes patients with OHCA with a documented terminal illness, those under hospice care, those currently pregnant, and those with a previously documented “Do Not Resuscitate” card . After 2018, advanced directives (AD) are able to guarantee the patient’s self-determination. When an AD is completed, it is registered with the National Agency for Management of Life-sustaining Treatment, and a registration card is issued . This registration card is recognized as a “Do Not Resuscitate” card because it includes the rejection of CPR. Patients with OHCA of definite non-medical etiology, including trauma, drowning, poisoning, burn, asphyxia, or hanging, were also excluded . Starting in October 2015, data were collected from EMS and hospital medical records via a standardized registry form and entered into a web-based electronic database registry according to Utstein style . A quality management committee comprising emergency physicians, statisticians, local research coordinators, and investigators in each ED regularly monitored and reviewed the data quality .
Study design and setting
This retrospective observational study used a prospective, multi-center registry of OHCA patients between October 2015 and June 2019 from KoCARC. Patients aged < 18 years, for whom information or medical record data were missing, who were transferred from other hospitals, or who received ECPR were excluded. We extracted all data including baseline characteristics, pre-hospital environmental factors, EMS characteristics, laboratory data, in-hospital therapeutic interventions, CPR duration, and clinical outcomes from the KoCARC registry.
Pre-hospital CPR duration was defined as the time from the initiation of CPR to the achievement of sustained pre-hospital ROSC or hospital arrival. In-hospital CPR duration was defined as the time from the initiation of CPR at the hospital to the achievement of sustained ROSC or discontinuation of CPR. Total CPR duration was defined as the time from CPR initiation by EMS to the achievement of sustained ROSC or discontinuation of resuscitation.
The primary endpoint was a favorable neurological outcome at hospital discharge as determined by the cerebral performance category (CPC) score . CPC scores of 1–2 were considered favorable, whereas those of 3–5 were considered poor neurological outcomes.
Korean EMS system
In the Republic of Korea, the EMS is a centralized governmental service provided by 16 provincial headquarters of the National Fire Department covering the entire nation . As of 2019, the total surface area of Korea is 100,401.3 km2, with a population of 51,927,000. There are 12,033 paramedics and 1474 ambulances nationwide . In Korea, there is no special team of doctors, and emergency medical technicians (EMTs) and nurses are in charge of dispatch. There are standard guidelines for on-site first aid from CPR in the field to hospital transportation. According to this guideline, an automated chest compression device can be used if one paramedic has to be in charge of CPR during the transfer. Additionally, the use of metronomes and chest compression quality measuring devices are recommended to monitor chest compression . Two or three emergency paramedics work together, including at least one level 1 EMT who can administer intravenous fluids, perform endotracheal intubation, and apply an automatic external defibrillator (AED) on board a departing ambulance. However, the use of intravenous adrenaline is permitted only under direct medical instructions in limited locations. Paramedics are not legally allowed to declare death or terminate resuscitation attempts in the field unless the patients show obvious signs of death (e.g., corruption, rigor mortis) and medical physicians have confirmed the declaration via telephone. Therefore, most EMS-treated OHCA patients are transported to hospitals.
Overall, no imputation method for missing data was used. The chi-squared test was used to compare categorical variables between groups with favorable and unfavorable neurological outcomes. Furthermore, since continuous variables were not normally distributed, the Mann–Whitney U test was performed to analyze continuous variables. Values are presented as median (interquartile range [IQR]) for continuous variables and as percentages for categorical variables. Multivariable logistic regression was conducted for selected variables related to favorable neurological outcomes. Variables including age, sex, witnessed arrest, bystander CPR, initial shockable pre-hospital rhythm, and total CPR duration were selected based on previous studies [2, 3, 16, 24]. There were no more extra variables added to the logistic regression model.
Model calibration was assessed using the Hosmer–Lemeshow goodness-of-fit test. As an estimate of effect size and variability, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. We stratified patients into four subgroups by combining important variables that showed a high association with favorable outcomes based on the multivariable logistic regression analysis results.
The dynamic probability and cumulative proportion of favorable neurological outcomes at discharge were calculated for all eligible participants stratified by significant variables. The dynamic probability of favorable neurological outcome at discharge < 1% in the selected group indicates the proportion of the favorable neurological outcome at discharge was less than 1% in all patients in the selected group. The cumulative proportion > 99% refers 99% of patients with favorable neurological outcomes were discharged in the selected group. We measured the optimal cut-off time of pre-hospital and total CPR duration, which is the time of CPR duration that has maximum sensitivity and specificity for favorable neurological outcomes at discharge. The shortest distance between each point on the receiver operating characteristic curve and the upper left corner was considered the optimal cut-off CPR duration for a favorable neurological outcome at discharge.
Analyses were performed using R-project version 3.6.2 (package “rms” version 5.1), SAS (version 9.4), and SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Statistical significance was set at P < 0.05.