Epidemiology of patients who died in the emergency departments and need of end-of-life care in Korea from 2016 to 2019

The need of palliative care at the end-of-life in the emergency departments (ED) is growing. The study aims to investigate the epidemiology of patients who died during care in ED using nationwide database, and to estimate the need for palliative care in the ED. A retrospective observational study was conducted using the National Emergency Department Information System (NEDIS) database. Patients who died during ED care between 2016 and 2019 were included. Palliative care-eligible disease was defined as cancer (C00–C99 of ICD-10), chronic respiratory disease (CRD, J44–J46), chronic liver disease (CLD, K70–K77), and heart failure (HF, I50). Among the 36,538,486 ED visits during 4 years, 34,086 ED deaths were included. The crude incidence rate of ED deaths per 100,000 person-year was steady between 16.6 in 2016 and 16.3 in 2019 (p-for-trend = 0.067). Only 3370 (9.9%) ED deaths were injury, while 30,716 (90.1%) deaths were related to diseases. The most common ED diagnosis was cardiac arrest (22.1%), followed by pneumonia (8.6%) and myocardial infarction (4.7%). In cases of disease-related ED deaths, about 34.0% stayed longer than 8 h in the ED (median (interquartile range): 4.5 (1.9–11.7) h) and 44.2% received cardiopulmonary resuscitation (CPR) at end-of-life time. A quarter of the disease-related ED deaths were diagnosed with palliative care eligible disease: cancer (16.9%), CLD (3.8%), HF (3.5%), and CRD (1.4%). Cancer patients received less CPR (23.4%) and stayed longer in the ED (median (interquartile range): 7.3 (3.2–15.9) h). Over the past 4 years, more than 30,000 patients, including 5200 cancer patients, died during care in the ED. A quarter of disease-related ED death were patients with palliative care-eligible condition and more than 30% of them stayed longer than 8 h in the ED before death. It is time to discuss about need of palliative care in the ED.

www.nature.com/scientificreports/ As prevalence of the advanced disease increases, there is an increase in ED visits at end-of-life for patients with terminal cancer or chronic illnesses 8,9,[11][12][13] . People in proximity to death use more acute healthcare services than people who are not 14 . Among them, patients diagnosed with cancer and respiratory diseases are more likely to use acute-based healthcare service such as ED 15 . More than half of elderly patients who passed away in the ED had serious chronic illnesses and required palliative care 16,17 . Many ED visits in these terminally ill patients are considered avoidable, therefore, the need for palliative care at the end-of-life in ED is emphasized in many countries 18,19 . In the Unites States, there is a guideline for hospice care-eligible patients who visit the ED, and ED-initiated palliative care is recommended for patients with advanced cancer to improve the patients' quality of life 20,21 . United Kingdom also reported end-of-life care recommendations for dying patients in the ED 22 . However, there is currently insufficient information on how patients who need end-of-life care are being treated in the ED and how many patients with incurable diseases received life-sustaining treatment such as cardiopulmonary resuscitation (CPR) in the ED before death. To improve the palliative care at end-of-life for terminally ill patients, it is necessary to understand the epidemiologic characteristics of patients who died in the ED 18,23 .
The purpose of this study is to investigate the epidemiologic characteristics of patients who died in the ED using representative nationwide database and to identify the reasons of ED visits of those patients. The study intends to estimate the need for palliative care at end-of-life in the ED and to accumulate the baseline data for future research.

Methods
Study design and data sources. This is a retrospective observational study using data from the National Emergency Department Information System (NEDIS) database. The Ministry of Health and Welfare constructed this nationwide ED-based database in 2013. NEDIS collected administrative and clinical information of all patients who visited EDs in real time from a total of 402 EDs across the country in 2019 [24][25][26] . The information includes patient demographics, prehospital, and ED treatment. All patient-related information was automatically transferred from each ED to a central government server within 14 days of discharge from the ED or hospital. The trained coordinators designated in each institution managed the data uploading process. The NEDIS data is updated by the National Emergency Medical Center and is approved annually by National Statistics for data quality management. Study setting. Korea has a total population of 50 million, while the annual death rate was about 0.3 million in 2019. More than 70% of deaths occurred in medical institutions, and 14% at homes. The most common causes of death were cancer, heart disease, and pneumonia 27 .
The National Health Insurance (NHI) of Korea covers the entire population for inpatient, outpatient, and ED treatment. EDs are classified into 3 levels according to resources and capacity (including facilities, equipment, and medical staff), which are defined by the Ministry of Health and Welfare: 38 Level 1 EDs, 125 Level 2 EDs, and 239 Level 3 EDs (a total of 402 EDs), that are operational as of 2020. Level 1 ED provide the highest level of emergency care services in the country, and is designed to accommodate and to provide definite care to critically ill and severe emergency patients. Level 1 and 2 are emergency centers which take charge of treating critical ill patients, and Level 3 is in charge of general urgent care and primary responses 24 h a day, 7 days a week. Under this healthcare system, EDs are open to all beneficiaries without restriction, and patients have high accessibility to the ED care 28 .
Hospice and palliative care was first introduced to Korea in 2015 with inpatient hospice beds. Consultationbased hospice care for non-hospice wards and outpatients started as a pilot project in 2017 and home-based hospice care was officially started in 2020 29 . The hospice act defined four disease groups as target disease for palliative care: cancer, Acquired Immunodeficiency Syndrome (AIDS), chronic respiratory disease, and chronic liver cirrhosis as target disease for palliative care 6 . However, it is still in the introductory stage; there are not many providers of hospice ward and home-based hospice. The consultation-based hospice is mainly for inpatients and outpatients, and rarely applied to patients in ED.

Study population.
The study subject were patients who died during care in the ED (hereafter, ED deaths) in Korea for 4 years from January 2016 to December 2019. Death on arrival (DOA), patients who had already had cardiac arrest at ED arrival and did not receive any resuscitation efforts, patients who visited ED for nonmedical reasons such as issuance of medical certificates, and patients who had unknown information of age or reason for ED visit were excluded.
Variables and measurements. Based on the reason for ED visit, all ED deaths were initially classified into a disease-related group and injury-related (injury) group. For disease-related ED deaths group, the specific reasons for ED visits were classified based on the ED diagnosis codes of the international classification of diseases, 10th edition (ICD-10) in the ED discharge records written by emergency physicians.
Palliative care-eligible disease was defined based on the hospice act and literature review: cancer, chronic respiratory disease, chronic liver disease, and heart failure 30 . Palliative care-eligible disease was defined based on the ED diagnosis: cancer (ICD-10 code, C00-C99), chronic respiratory disease (chronic obstructive pulmonary disease and asthma, J44-J46), chronic liver disease (K70-K77), and heart failure (I50).
The following variables were collected from the NEDIS database to investigate the characteristics of ED deaths: 1. patient demographics (age, sex, and insurance), 2. prehospital and ED information (date and time of ED visit, mode of ED visit (use of ambulance or not), route of ED visit (direct visit or transfer-in from other hospital), region of ED (metropolitan or urban/rural), and level of ED (level 1, 2 and 3)), 3

Statistical analysis.
A descriptive analysis was conducted to investigate epidemiologic characteristics of the study population. Categorical variables were presented as counts and proportions and differences across groups were tested by Chi-square test. Continuous variables were presented as medians and interquartile ranges (IQR) and differences across groups were tested by Wilcoxon rank-sum test. The characteristics were compared according to the reason for ED visit (disease-related and injury-related). The most common diagnoses were investigated for the disease-related ED deaths group and cancer-related ED deaths.
The epidemiologic trends of all ED deaths and ED deaths of patients with palliative care-eligible conditions were investigated. The crude and the age-and sex-standardized incidence rates per 100,000 person-years were calculated. Direct standardization method was used using the 2020 mid-year census population as the standard population 33 .
NEDIS database collected during 2016-2019 were analyzed in July 2021. All statistical analyses were conducted using SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA). Statistical significance was taken as P < 0.05. Ethical statement. This study was approved by the Institutional Review Boards of Seoul National University Hospital (approval No. SNUH-2012-104-1183), and the requirement for informed consent was waived due to the retrospective nature of this study. Patient information was anonymized prior to analysis. All methods were performed in accordance with relevant guidelines and regulations.

Patient and public involvement statement. The National Emergency Medical Center under the Min-
istry of Health and Welfare was involved in the design and conduct of this research, but it was not possible to involve patients in our research.

Results
Study population. Between 2016 and 2019, the total number of ED visits was 36,538,486 of which total death toll was 117,256 (0.3%). Among them, 34,086 ED deaths were included as a study population, excluding cases that were already in cardiac arrest at the ED entrance (n = 81,222) and cases with unknown information on age (n = 3) and reason for ED visit (n = 1945) (Fig. 1). Approximately 8500 patients per year died in the ED during the ED care.
Characteristics of the disease-related ED deaths. Among 30,716 disease-related ED deaths, 7855 (25.6%) were ED deaths of patients with palliative care-eligible: 16.9% (n = 5187) was related with cancer, 1.4% (n = 416) with chronic respiratory disease, 3.8% (n = 1176) with chronic liver disease, and 3.5% (n = 1076) with heart failure. The ED deaths of patients with palliative care-eligible conditions had longer median ED-LOS, compared to ED deaths of patients without palliative care-eligible conditions (p < 0.01). Regarding life-sustaining treatment, 2327/7855 (29.6%) received CPR and 2707/7855 (34.5%) received endotracheal intubation before death. Cancer patients received relatively less life-sustaining treatment: 23.4% received CPR and 27.1% received endotracheal intubation (Table 3). Demographics according to the ED-LOS are presented in Supplementary  Table S1. www.nature.com/scientificreports/ Regarding provision of CPR, 55.8% (n = 17,154) of the 30,716 disease-related ED deaths did not receive CPR prior to death. Patients who did not receive CPR had longer ED-LOS than those who received CPR (6.5 (2.6-16.0) vs. 3.0 (1.6-6.8) h, p < 0.01). Of the ED deaths that received CPR, 17.2% were diagnosed with palliative care-eligible diseases (cancer 9.0%, chronic respiratory disease 1.1%, chronic liver disease 3.6%, and heart failure 3.5%). (Table 4). The provision of CPR for the ED deaths of patients with palliative care-eligible diseases are presented in Supplement Table S2.
Epidemiologic trends of ED deaths. The crude incidence rate of ED deaths per 100,000 person-years was  (Fig. 2). ED deaths with cancer were slightly increased with crude rate from 2.3 to 2.7 and standardized rate from 2.7 to 2.9 (Fig. 3).

Discussion
During the 4 years between 2016 and 2019, a total of 34,086 patients died in the ED during care, approximating to 2.9% of all deaths in Korea. Among those ED deaths, 90% were disease-related death. Patients stayed for a median 4.4 h before death in the ED, of which only 45.4% received CPR. A quarter of disease-related ED deaths had a condition eligible for palliative care. They stayed in the ED longer while receiving less life-sustaining treatment (29.6% received CPR) before death, compared to other patients. Cancer-related ED deaths accounted for 16% of disease-related ED deaths: half of them died after staying for more than 8 h in the ED and a quarter of them received CPR before death. This study found that nearly 8500 patients die in the ED every year and the annual incidence rate of ED deaths was about 17 per 100,000 person-year in Korea. To the best of current knowledge, it is the first study to investigate the magnitude of ED deaths nationwide.
In Korea, the death rates per 100,000 person-years in 2019 were 574.8 for all cause of death and 158.2 due to cancer, accounting for 27.5% of all deaths 27 . Since the ED is for providing acute care for critically ill patients, death in the ED is unavoidable. However, not much is known about patients who die in an ED 13,34 . In this study, only 10% of the ED deaths were caused by injuries such as traffic accidents or falls. This was smaller than a single center study done in Switzerland 10 . 90% of the ED deaths were disease-related patients, and one quarter of them had diagnosis codes subject to palliative care. Previous studies have reported that 30 ~ 50% of death in the ED were related to serious chronic illnesses or palliative care needs 16,17,35 . Since this study classified only four representative diseases as palliative care-eligible diseases, size of the palliative care subjects may be smaller than other studies. Theoretically, all patients with imminent death are eligible for palliative care, including those who die in the ED 2 .
In this study, ED deaths happened after a median 4.4 h in the ED, and 30% of disease-related ED deaths occurred after 8 h in the ED. It was previously reported in US that all ED visit patients stayed for median 4 h in the ED, and that more than 8 h of stay is defined as a long stay 31,32 . Other studies reported that, among ED visits, discharged patients stayed for median 2.5 h and hospitalized patients stayed for 4 h 36,37 . Patients who die in ED may stay for relatively longer periods of time in the ED and utilize more resources than patients who survived. Among all ED deaths, about half of ED deaths received CPR (45.4%) and endotracheal intubation (48.6%) before  [38][39][40] . Moreover, 30% of ED deaths with palliative care-eligible diseases and a quarter of cancer-related ED deaths received CPR before death, which is 4-7 times higher than that of a German study 41 . CPR is a life-saving treatment for acute stage patients, but it could be a life-sustaining treatment with little meaning for incurable and terminally ill patients. A hospital-level study or qualitative study is needed to know how life-sustaining treatment is provided in individual patients. The results of this study show the possibility that there still is a substantial unmet need for palliative care in the ED and the need for follow-up studies 42,43 . In this study, about half of ED deaths with palliative care-eligible diseases and cancer-related ED deaths stayed over 8 h before death in the ED. During ED care, 30% of ED deaths with palliative care-eligible diseases and a quarter of cancer-related ED deaths received CPR before death. More attention would be needed on how to provide end-of-life care in times of expected death in the ED. This discussion encompasses not only which care should be provided for dying patients, but also whether it would be suitable for such patients to stay in ED for such long times. This study showed overall epidemiologic characteristics of ED deaths using a nationally representative emergency database. Considering that patients who died within 72 h after visiting the ED, as well as ED death, are also eligible for palliative care, the need for palliative care at the end-of-life in the ED would Table 4. Demographics of disease-related deaths in the emergency department according to the provision of cardiopulmonary resuscitation. CPR cardiopulmonary resuscitation, IQR interquartile range, ED emergency department.  Table S3). Based on the need for palliative care at end-of-life in the ED in this study, it is necessary to develop a strategy for improving end-of-life care in the ED. This study has several limitations. First, the NEDIS database does not collect information on whether the patients have previously completed advance directives or physician orders for life-sustaining treatment (POLST). Further study is needed to determine whether patients with palliative-care eligible conditions have a plan before visiting the ED and can receive proper end-of-life care through this. As a limitation of the studies using a large database, it is necessary to comprehensively interpret the results of this study by referring to the results of studies focusing on individual patients. Second, whether the patient had a disease subject to palliative care was determined based on the diagnosis codes in the ED medical records. Whether that disease was previously diagnosed or first diagnosed in the ED is unknown. Third, the NEDIS data does not collect information of test results and medication prescription. It is difficult to know whether the dying patient received sufficient supportive care in  www.nature.com/scientificreports/ the ED before death, such as pain control. Fourth, Korea has the NHI service is implemented, and palliative care services are in the introduction stage. It is difficult to generalize the result to other countries with different healthcare system and accessibility to palliative care.
In conclusion, more than 30,000 people died during care in the ED over the past four years. At least a quarter of disease-related ED deaths were owed to palliative care-eligible diseases. More than 30% of disease-related ED deaths and 40% of cancer-related ED deaths happened at least 8 h after arrival in the ED. About half of disease-related ED deaths and 30% of ED deaths with palliative care-eligible diseases received CPR before death. Increased efforts to understand death in the ED may improve end-of-life care in the ED.

Data availability
The data of this study were obtained from the National Emergency Medical Center under the Ministry of Health and Welfare in Korea but restrictions apply to the availability of these data and so are not publicly available, but are available from the corresponding author on reasonable request.