Clinical Survey and Predictors of Outcomes of Pediatric Out-of-Hospital Cardiac Arrest Admitted to the Emergency Department

Pediatric out-of-hospital cardiac arrest (OHCA) is a rare event with severe sequelae. Although the survival to hospital-discharge (STHD) rate has improved from 2–6% to 17.6–40.2%, only 1–4% of OHCA survivors have a good neurological outcome. This study investigated the characteristics of case management before and after admittance to the emergency department (ED) associated with outcomes of pediatric OHCA in an ED. This was a retrospective study of data collected from our ED resuscitation room logbooks dating from 2005 to 2016. All records of children under 18 years old with OHCA were reviewed. Outcomes of interest included sustained return of spontaneous circulation (SROSC), STHD, and neurological outcomes. From the 12-year study period, 152 patients were included. Pediatric OHCA commonly affects males (55.3%, n = 84) and infants younger than 1 year of age (47.4%, n = 72) at home (76.3%, n = 116). Most triggers of pediatric OHCA were respiratory in nature (53.2%, n = 81). Sudden infant death syndrome (SIDS) (29.6%, n = 45), unknown medical causes (25%, n = 38), and trauma (10.5%, n = 16) were the main causes of pediatric OHCA. Sixty-two initial cardiac rhythms at the scene were obtained, most of which were asystole and pulseless electrical activity (PEA) (93.5%, n/all: 58/62). Upon ED arrival, cardiopulmonary resuscitation (CPR) was continued for 32.66 ± 20.71 min in the ED and 34.9% (n = 53) gained SROSC. Among them, 13.8% (n = 21) achieved STHD and 4.6% (n = 7) had a favorable neurological outcome. In multivariate analyses, fewer ED epinephrine doses (p < 0.05), witness of OHCA (p = 0.001), and shorter ED CPR duration (p = 0.007) were factors that increased the rate of SROSC at the ED. A longer emergency medical service (EMS) scene interval (p = 0.047) and shorter ED CPR interval (p = 0.047) improved STHD.

improvement in pre-and in-ED care; improving survival with good neurological outcomes 20 . Identification and documentation of aspects other than epidemiological variables of pediatric OHCA are of great importance for developing a treatment plan and determining proper preventive measures. This study assessed the clinical characteristics, prior to and during admission to the ED, associated with clinical outcomes including sustained return of spontaneous circulation (SROSC), STHD, and neurological outcomes of pediatric OHCA in an ED.

Methods study setting and patient selection. This study was conducted in the ED of Chang Gung Hospital in
Taiwan. The setting of our study was a tertiary medical center that receives cases transferred from local clinics and regional hospitals. The data were collected from the ED resuscitation room logbooks from January 2005 to December 2016. All records of children under 18 years old who were pulseless on arrival and required cardiac pulmonary resuscitation (CPR) at the ED were reviewed. The study was approved by the Institutional Review Board of the Chang Gung Memorial Hospital (201701095B0). All methods were performed in accordance with the relevant guidelines and regulations.
The data were collected, reviewed, de-identified, and anonymously analyzed by the authors, and the ethics committee waived the requirement for informed consent because of the anonymized nature of the data and scientific purpose of the study. study design. Patients who were of gestational age of less than 21 weeks, had "do not resuscitate" orders, or were transferred from another ED after return of spontaneous circulation (ROSC) were excluded. Data collected included patient demographic profiles (i.e., age, sex), category of etiology, comorbidities, timing, initial heart rhythm, place, events, and history that involved the OHCA. Pre-ED information was obtained from the emergency medical services (EMS) records, including the time the call was received, the time of arrival and departure from the scene, the time the patient arrived at the ED, and the duration of pre-ED CPR. Places of OHCA were classified as home/residence, industrial/workplace, sports/recreation event, street/highway, public building, daycare/nursing home, educational institution, other, and unknown/not documented. Duration of transportation, timing of interventions by a bystander, EMS, and physicians were also recorded and analyzed. Response interval was defined as the time from incoming call to the time the first emergency response vehicle stopped at a point close to the patient's location 21 . The duration of ED CPR was defined as the time interval from the time CPR was initiated to the time it was stopped at the ED. Outcomes including SROSC, STHD, and pediatric cerebral performance category (PCPC) score were collected and analyzed 21 . SROSC was defined as restoration of perfusing and heart rhythm in the absence of external chest compressions for over 20 min 14 . The PCPC scores, ranging from 1 (normal) to 6 (brain dead), were validated to quantify a child's cognitive function after a critical illness or an injury. The investigators judged the PCPC score by reviewing the discharge summaries and outpatient records with the consensus of another investigator. Categories 1 to 3 were viewed as good neurological outcomes 22 . The American Heart Association (AHA) guidelines for CPR was updated to the chest compressions, airway, breathing/ventilations (CAB) sequence from the conventional airway, breathing/ventilations, chest compressions (ABC) sequence in 2010 23 . The trend of outcomes before and after this change was evaluated for a 5-year time span. statistical methods. Descriptive statistics are presented for most variables (i.e., demographics). Univariate summaries (means, standard deviations) were provided for continuous variables (e.g., age), whereas frequencies and percentages were used to summarize categorical variables (e.g., sex). SPSS ver. 21 software was used for all analyses and a p-value < 0.05 was considered to reflect statistical significance. Student t test and the χ 2 test with the Fisher exact test were used to test the significance of categorical and numerical variables, respectively. Multivariate logistic regression analyses were performed to determine the factors in regard to outcomes of pediatric OHCA. Variables were kept in the final model if the p value was <0.05.

Manner of pediatric OHCA Frequency
www.nature.com/scientificreports www.nature.com/scientificreports/ Factors of outcomes. After univariate analyses, significant variables for SROSC included witness of OHCA (p < 0.05), bystander CPR (p = 0.045), pediatrician (p = 0.041), ED epinephrine doses (p < 0.05), and ED CPR interval (p < 0.05) were entered into the logistic regression model. In multivariate analyses, fewer ED epinephrine doses (p < 0.05), witness of OHCA (p = 0.001), and shorter ED CPR duration (p = 0.007) were significant for SROSC (Table 4). For STHD, witness of OHCA (p < 0.05), pediatrician (p = 0.041), ED epinephrine doses (p < 0.05), ED CPR interval (p < 0.05), and EMS scene interval (p = 0.02) were entered into multivariate analyses and a longer EMS scene interval (p = 0.047) and shorter ED CPR interval (p = 0.047) were kept in the model (Table 5). Age, sex, preexisting condition, day or night OHCA, EMS transport, and EMS advanced airway management were not associated with the outcomes of interest. We could not determine predictors of neurological outcomes because of the small number of cases.

Discussion
Pediatric OHCA cases represented 23 of every 100,000 pediatric visits in our ED. The most common age was infancy 5,14,18 and the incidence was higher in males 1,5,13 . Medically fragile children (with preexisting conditions; 30.6%) were also at a high risk for OHCA 13 . The overall SROSC rate was 34.9%, higher than in an earlier report (a pooled study rate of 27.8%) 14 . The STHD rate was 13.8%, within the range of earlier studies (4.7-40.2%) 5,14,[16][17][18][24][25][26] . Of our patients, 4.6% had a good neurological outcome which matched our earlier figure of 1-4% 4,5,13-15 . The common causes of pediatric OHCA were consistent with previous reports: SIDS, airway-related causes, trauma, drowning, intoxication, and cardiac causes 5,10,27 most triggers were respiratory in nature 28,29 . The home/residence was the most common site of OHCA (76.3%, n = 116) (60% in a previous report) 4 and the rate was higher between 00:00 and 09:0029 in Spring. SIDS was the principal cause of pediatric OHCA; the rate was similar to those of other studies (18-60%) 2,10,13,25,26,30,31 . The high prevalence of SIDS at home in the   www.nature.com/scientificreports www.nature.com/scientificreports/ early morning must be recognized when seeking to prevent and monitor this phenomenon. Unknown medical causes were the second common OHCA trigger, rendering precise etiological diagnosis difficult. Notably, 63.2% of children had no preexisting condition and 44.4% did not undergo blood testing or imaging, indicating that OHCA etiologies were underexplored. If the clinical cause of OHCA is not that of the coroner's report 11 , autopsy might clarify the exact cause of death. Potentially preventable etiologies including trauma, suspected abuse, choking, drowning, poor ventilation, house fires, and hanging accounted for 35.5% of all OHCAs. Child death review seeking to improve strategies for preventing childhood deaths caused by preventable etiologies is imperative 32 .
The OHCA witness rate was earlier reported to be 30.8-34%, thus lower than in our study (42.1%) 1,13,14,18 . Witnessed arrest status was significantly associated with SROSC and STHD, as also reported in an earlier pooled study 14 , due to immediate emergency response when witnessing reduced the no-blood-flow time 1,14,33 . Although our witness rate was higher than those of other reports, the bystander CPR rate (9.9%) was lower than a previous report of 17-35% 1,2,5,10,13,25,26,30 . Our bystander CPR frequency was low even when OHCA was witnessed 13 , indicating that public resources on pediatric life support were insufficient and caretakers were unfamiliar with pediatric life support 13 . This emphasizes the need to the improve bystander CPR rate 5 through education or reachable instructions of pediatric life support, particularly for potential caregivers of medically high-risk children 13 .
Our results are consistent with the notion that bystander CPR is associated with SROSC but not STHD 14 . It cannot be assumed that bystander CPR will aid survival because the no-blood-flow time prior to CPR may be considerable, and many post-SROSC factors may affect STHD.
Nearly half (52.6%) of patients were transported by EMS, a much lower rate than that reported in previous study (81%) 5 . Our OHCA cases transported by EMS were all supported with oxygenation and chest compressions while en route to the ED. Surprisingly, the outcomes of those patients did not differ from those of children transported by caregivers, which suggests that pre-ED oxygenation and chest compression may be insufficient to improve outcomes of pediatric OHCA. The primary deficiency of EMS service in this study was a lack of or failure to procure IV access for epinephrine and fluid administration. Early epinephrine administration was associated with better survival and favorable neurological outcomes 34 and intraosseous administration is a safe and effective method for delivering drugs during CPR 35 .
EMS systems should consider strategies such as the use of IO for early epinephrine administration in pediatric OHCA whenever IV access cannot be rapidly obtained 34 . Our rate of advanced airway management (19.4%) was higher than that in a previous study (16.9%) 36 , but pre-ED EMS advanced airway management failed to increase both SRSC and STHD 36 . The most common presenting arrhythmia at the scene was asystole (68-92%) 5,13,14,37 because most arrests were due to asphyxiation and were unwitnessed, triggering progressive hypoxia and ultimately cardiac arrest with asystole 28 . Timely defibrillation of shockable rhythms (VT and VF) is critical in terms of survival 38 . Unfortunately, the rate of VT/VF at the scene was lower than that of previous pediatric studies (2-19%) 5,13,14,37 . Placement of defibrillators in public places and training of volunteers would promote earlier identification and defibrillation, and thus improve survival 39 . A longer EMS scene interval, which implies more resuscitation efforts at the scene rather than a "scoop and run" approach, was associated with STHD in this study 5 . This indicates that EMS resuscitation approaches for children at the scene are important and differences in EMS practice at the scene deserve more research to improve outcomes 5 .
Pediatricians achieved higher SROSC and STHD rates than non-pediatricians in univariate analyses. Michelson et al. also reported higher pediatric survival after non-traumatic OHCA when patients were in pediatric EDs rather than general EDs 40 . Although this item did not remain in the model of multivariate analyses, pediatricians whose resuscitation practice is constantly refreshed in real pediatric environments should improve the outcomes of pediatric OHCA and all emergency care providers should seek more training in real or simulated child resuscitation.
High-fidelity simulation (HFS), which replace real-life experiences with guided experience in realistic clinical situations, are routinely used to train professionals to cope with high-risk and/or lower-frequency pediatric events [41][42][43][44][45] . Deliberate and repetitive pediatric HFS that enhance skills, team spirit, and leadership for ED physicians will be helpful for the outcomes of pediatric OHCA 44,46 .
Fewer epinephrine doses, which augment coronary blood flow efficiently 47 , is associated with increased hospital survival for pediatric OHCA patients 27,48 . As the ED CPR duration decreased, the probabilities of SROSC and STHD increased. A short ED resuscitation time reduced the no-blood-flow time prior to SROSC, and improved outcomes. Thus, prolonged resuscitative efforts do not afford good neurological outcomes to survivors 13,26 .
In 2010, the PALS guideline substituted CPR ABC with CAB, and emphasized the importance of chest-compression-only CPR 23 . We found that the trend of SROSC and STHD rates were not significantly different. Most child OHCA is triggered by respiratory causes, not cardiac caused as in adult OHCA 28 Table 5. Multivariate analysis for factors associated with STHD. *Statistical significance was set at p < 0.05.