Target Temperature Management and Survival with Favorable Neurological Outcome After Out-of-Hospital Cardiac Arrest in Children: A Nationwide Multicenter Prospective Study in Japan

Abstract

To assess whether target temperature management (TTM) is effective for 1-month survival with favorable neurological outcome among pediatric patients who achieved return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). The Japanese Association for Acute Medicine-out-of-hospital cardiac arrest (JAAM-OHCA) Registry, a multicenter prospective observational registry in Japan, included OHCA patients aged ≤17 years who achieved ROSC between June 2014 and December 2017. The primary outcome was 1-month survival with favorable neurological outcomes, defined as pediatric cerebral performance category 1 or 2. We conducted a propensity score analysis with inverse-probability-of-treatment weighting (IPTW) and evaluated the effect of TTM using logistic regression models with IPTW. A total of 167 patients [120 in the non-TTM group (71.9%) and 47 in the TTM group (28.1%)] were eligible for our analysis. The proportion of patients demonstrating 1-month survival with favorable neurological outcomes was 25.5% (12/47) in the TTM group and 16.7% (20/120) in the non-TTM group; there were no significant differences in favorable neurological outcomes (odds ratio, 1.36; 95% confidence interval, 0.55–3.35) between the non-TTM and TTM groups after performing adjustments with IPTW. In our study population composed of pediatric patients who achieved ROSC after OHCA, we did not find a positive association between TTM implementation and 1-month survival with favorable neurological outcomes.

Introduction

Out-of-hospital cardiac arrest (OHCA) is one of the most serious problems in industrialized countries (Japanese Guidelines for Emergency Care and Cardiopulmonary Resuscitation, 2015; Hazinski et al., 2015; Monsieurs et al., 2015; Neumar et al., 2015), and pediatric patients having OHCA account for only a small proportion of the total cases of OHCA (Herlitz et al., 2007; Matsui et al., 2019). However, it has a significantly negative impact on the community in terms of life-years lost, health care costs for survivors, and the emotional burden of family members (Atkins and Berger, 2012). To achieve favorable outcomes in pediatric OHCA, it is important to establish multifactor evidence regarding prehospital interventions, as well as postcardiac arrest care after hospital arrival.

The proportion of survivors in children with OHCA is very low (Jayaram et al., 2015). Moreover, even if children survive OHCA, they often demonstrate poor neurological outcomes (Donoghue et al., 2005; Matsui et al., 2019). In addition, the neurological outcomes in pediatric OHCA patients who achieved return of spontaneous circulation (ROSC) after hospital arrival were extremely poor (Matsui et al., 2019). To improve the neurological outcomes, advancements in methods of brain resuscitation in advanced intensive care for pediatric OHCA patients achieving ROSC are needed. However, treatment methods targeting brain resuscitation in pediatric patients achieving ROSC are insufficiently established. For example, target temperature management (TTM) that has been shown to be effective in adult OHCA has not been well-established in pediatric OHCA (Moler et al., 2015, 2016; Buick et al., 2019), and TTM for pediatric OHCA is only a weak recommendation in the cardiopulmonary resuscitation (CPR) guidelines (de Caen et al., 2015). Therefore, further study on TTM in pediatric OHCA is necessary.

Using the Japanese Association for Acute Medicine (JAAM)-OHCA Registry, we aimed to assess the effect of TTM on 1-month survival with favorable neurological outcomes among pediatric OHCA patients.

Materials and Methods

Study design, population, and setting

The JAAM-OHCA Registry, which aims to improve survival following OHCA by providing an evidence-based therapeutic strategy and emergency medical system, has launched a multicenter prospective registry that enrolls OHCA patients transported to critical care medical centers (CCMCs) or hospitals with an emergency care department in Japan (Kitamura et al., 2018).

This study was a retrospective analysis of the JAAM-OHCA Registry. The study period was from June 2014 to December 2017. The inclusion criteria were patients aged ≤17 years for whom resuscitation was attempted by emergency medical service (EMS) personnel or bystanders and who were subsequently transported to participating institutions. This study excluded children with OHCA who did not receive any resuscitation, including CPR, as well as advanced procedures, because physicians judged that it was impossible to save their lives at the time of hospital arrival, those who did not achieve ROSC even after receiving CPR in hospital settings, and those who died before hospitalization.

The JAAM-OHCA registry

The JAAM-OHCA Registry is a nationwide hospital-based prospective observational data registry. The complete study methodology has been previously described (Kitamura et al., 2018). In brief, in Japan, there are 288 CCMCs certified by the Ministry of Health, Labour and Welfare that can provide highly specialized treatments such as extracorporeal cardiopulmonary life support (ECLS), TTM, or percutaneous coronary intervention, 24 hours a day. A total of 66 CCMCs and 21 non-CCMCs with an emergency care department participated in this registry. The registry is ongoing without having the end date of the registry period settled. The registry was approved by the Ethics Committee of Kyoto University and Hyogo Prefectural Kobe Children's Hospital; each participating hospital also approved the JAAM-OHCA Registry protocol as necessary.

The EMS system in Japan

Prehospital resuscitation data were obtained from the All-Japan Utstein Registry of the Fire and Disaster Management Agency (FDMA) of Japan. Details of the EMS system and the registry also have been previously described (Kitamura et al., 2018). Data were prospectively collected using the data form recommended by the Utstein-style international guideline of reporting OHCA (Jacobs et al., 2004; Perkins et al., 2015). Data on the following aspects were collected: witness status, bystander-initiated CPR, dispatcher instructions, first documented rhythm, application of advanced airway management, adrenaline administration, and resuscitation duration. A data form was completed by the EMS personnel collaborating with physicians in charge of the patient. The data were uploaded to the registry system of the FDMA database server and logically checked by the computer system.

In-hospital data collection and quality control

The JAAM-OHCA Registry collected substantial information on OHCA patients after hospital arrival. The details have been previously provided (Kitamura et al., 2018). During the study period, anonymized data were entered into either the online form or the fax—Optical Character Recognition (OCR) software by a physician or medical staff in cooperation with the physician in charge of the patient, were logically checked by the system, and were finally confirmed by the JAAM-OHCA Registry committee, which consists of specialists in emergency medicine and epidemiology. If there was something incomplete in the data form, a committee member returned it to each institution and the data form was reentered as completely as possible. In-hospital data were systemically combined with prehospital resuscitation data obtained from the All-Japan Utstein Registry of the FDMA, using the five key items in both datasets: prefecture, emergency call time, age, sex, and pediatric cerebral performance category (PCPC) 1 month after the OHCA.

In-hospital data of patients with OHCA were prospectively collected using a uniform data form: age, sex, cause of arrest, ROSC status (ROSC after hospital arrival, ROSC before hospital arrival, no ROSC), first documented rhythm, Glasgow coma scale (GCS), advanced treatments provided for OHCA (e.g., TTM and ECLS), and outcome data. The timing of GCS measurement depends on the first documented cardiac rhythm after hospital arrival. The target (maintenance) body temperature during TTM was also collected (33°C, 34°C, 35°C, and 36°C). In addition, we described TTM time course; for example, the time from emergency call to the start of TTM, the time from emergency call to the reach of the target body temperature, and the time from the start of TTM to the start of rewarming. The cause of arrest was classified into cardiac (acute coronary syndrome, other heart disease, presumed cardiac cause) and noncardiac (cerebrovascular diseases, respiratory diseases, malignant tumors, external causes) causes. The presumed cardiac cause category was determined by exclusion, that is, the diagnosis was made when there was no evidence of a noncardiac cause. The diagnosis of cardiac or noncardiac origin was clinically judged by the physician-in-charge. The PCPC scale was defined as follows: category 1, normal cerebral performance; category 2, mild cerebral disability; category 3, moderate cerebral disability; category 4, severe cerebral disability; category 5, coma or vegetative state; and category 6, death/brain death (Pollack et al., 2014).

Outcome measurements

The primary outcome of this study was 1-month survival with favorable neurological outcomes. The secondary outcome was 1-month survival. The neurological status of the survivors was evaluated by the medical staff at each institution 1 month after the event. Favorable neurological outcome was defined as a PCPC score of 1 or 2 (Lin et al., 2010).

Statistical analyses

Pre- and in-hospital data and outcomes were compared between the TTM and non-TTM groups. To reduce the impact of treatment bias and potential confounding factors in the direct comparisons between children with OHCA who received TTM and those who did not receive TTM, we conducted logistic regression models with inverse-probability-of-treatment weighting (IPTW) because of the observational nature of this study (Kuss et al., 2016). In this technique, the weights for patients who received TTM were the inverse of the propensity score (PS), and the weights for patients who did not receive TTM were the inverse of 1-PS. The probability of receiving TTM for each patient was calculated using multivariate logistic regression analysis based on the following 14 variables: year (2014, 2015, 2016, 2017), sex (male or female), age (continuous value), witness status (no, yes), bystander CPR (no, yes), dispatcher instruction (no, yes), first prehospital documented rhythm (shockable, nonshockable, other), prehospital adrenaline administration (no, yes), prehospital advanced airway management (no, yes), time from call to contact with patient by EMS personnel (continuous value), first documented rhythm after hospital arrival (shockable, nonshockable, presence of pulse), in-hospital adrenaline administration (no, yes), ECLS (no, yes), and cause of arrest (cardiac, noncardiac). We performed a receiver operating characteristic curve analysis with an area under the curve of PS for predicting the effect of TTM in pediatric patients with OHCA. To measure covariate balance, we checked the standardized mean difference (SMD) before and after IPTW. When the SMD was less than 0.25 (Stuart, 2010), it implied that there was negligible imbalance between the two groups. In addition, we performed PS matching for the two groups. One-to-one pair matching between the TTM and non-TTM groups was performed using nearest neighbor matching without replacement, using calipers of width equal to 0.2 of the standard deviation of the logit of the PS.

We investigated the association between TTM implementation and outcomes using univariate, IPTW, and PS matching analyses. Based on these analyses, we calculated the odds ratios (ORs) and their 95% confidence intervals (CIs). Moreover, we performed subgroup analyses by cause of arrest (cardiac, noncardiac), first documented rhythm assessed by EMS personnel (shockable, nonshockable), or age category (<1 year, 1–17 years) using univariate analysis to detect potential effective subgroups for the effect of TTM. All tests were two tailed, and p-values <0.05 when comparing outcomes between the two groups, and <0.10 when assessing the interaction in subgroup analyses, were considered statistically significant. All statistical analyses were carried out using STATA version 15.0 MP software (Stata Corp LP).

Results

During the study period, 34,754 OHCA patients were documented (Fig. 1). Of these, 33,921 patients received in-hospital resuscitation attempts, and prehospital data were available for 30,856 patients. Excluding 30,201 adult patients aged ≥18 years, 470 patients who did not achieve ROSC, and 18 patients who died before hospitalization, a total of 167 patients (non-TTM group, n = 120, 71.9%; TTM group, n = 47, 28.1%) were eligible for our analysis.

FIG. 1.

Overview of patient selection process. TTM, target temperature management.

Comparison of patient characteristics, prehospital data, and in-hospital data of pediatric patients who achieved ROSC after OHCA between the non-TTM and TTM groups before and after PS matching are shown in Table 1, along with the SMD after IPTW. Among all patients, the patients in TTM group were more likely to have a shockable rhythm as the first documented cardiac rhythm by EMS personnel before and after hospital arrival, to undergo ECLS, and to have a cardiac cause. The covariate balance between the groups after IPTW was well improved. After PS matching, 43 patients were selected from each group; the area under the receiver operating characteristic curve of PS was 0.738. However, shockable rhythm as the first documented rhythm after hospital arrival was not well balanced between the groups.

Table 1.

Characteristics of Pediatric Patients with Out-of-Hospital Cardiac Arrest Achieving Return of Spontaneous Circulation With or Without Target Temperature Management Implementation

	All patients					PS matched patients					IPTW
	Non-TTM		TTM		p	Non-TTM		TTM		SMD	SMD
	(n = 120)		(n = 47)		p	(n = 43)		(n = 43)		SMD	SMD
Year, n (%)					0.557
2014	12	(10.0)	5	(10.6)		3	(7)	4	(9)	0.084	0.190
2015	38	(31.7)	11	(23.4)		14	(33)	11	(26)	0.152	0.228
2016	41	(34.2)	15	(31.9)		13	(30)	14	(33)	0.050	0.107
2017	29	(24.2)	16	(34.0)		13	(30)	14	(33)	0.050	0.207
Age, median (IQR)	6.5	(1–14)	12	(1–15)	0.125	10	(2–15)	12.0	(1–15)	0.045	0.026
<1 year, n (%)	28	(23.3)	10	(21.3)	0.776	7	(16)	10	(23)
1–17 years, n (%)	92	(76.7)	37	(78.7)		36	(84)	33	(77)
Males, n (%)	79	(65.8)	33	(70.2)	0.588	30	(70)	30	(70)	0.000	0.027
Witnessed, n (%)	61	(50.8)	29	(61.7)	0.205	27	(63)	25	(58)	0.094	0.021
Bystander CPR, n (%)	81	(67.5)	28	(59.6)	0.333	22	(51)	27	(63)	0.234	0.091
Dispatcher instruction, n (%)	61	(50.8)	28	(59.6)	0.309	24	(56)	27	(63)	0.141	0.040
First documented cardiac rhythm by EMS, n (%)					0.066
Shockable	10	(8.3)	10	(21.3)		6	(14)	8	(19)	0.125	0.048
Nonshockable	84	(70.0)	29	(61.7)		27	(63)	28	(65)	0.048	0.076
Other	26	(21.7)	8	(17.0)		10	(23)	7	(16)	0.174	0.048
Adrenaline administration at prehospital, n (%)	8	(6.7)	5	(10.6)	0.389	5	(12)	5	(12)	0.000	0.105
AAM at prehospital, n (%)	17	(14.2)	10	(21.3)	0.262	12	(28)	9	(21)	0.161	0.026
Time from call to contact with patient by EMS, minutes, median (IQR)	8	(6–10)	8	(7–9)	0.566	8	(6–10)	8	(7–9)	0.242	0.050
First documented cardiac rhythm after hospital arrival, n (%)					0.049
VF or pulseless VT	3	(2.5)	4	(8.5)		1	(2)	4	(9)	0.298	0.058
PEA or Asystole	92	(76.7)	28	(59.6)		27	(63)	25	(58)	0.094	0.119
Presence of pulse	25	(20.8)	15	(31.9)		15	(35)	14	(33)	0.049	0.095
In-hospital adrenaline administration, n (%)	87	(72.5)	31	(66.0)	0.404	28	(65)	28	(65)	0.000	0.006
Extracorporeal membrane oxygenation, n (%)	5	(4.2)	8	(17.0)	0.005	4	(9)	5	(12)	0.075	0.020
Cardiac cause, n (%)	30	(25.0)	21	(44.7)	0.013	19	(44)	17	(40)	0.093	0.006
Time from emergency call to the start of TTM, minutes, median (IQR)			141	(64–184)				145	(88–184)
Time from emergency call to the reach of target body temperature, minutes, median (IQR)			304	(210–552)				303	(217–562)
Time from the start of TTM to the start of rewarming, minutes, median (IQR)			1640	(1500–1920)				1668	(1515–2085)
Targeted temperature, n (%)
33–34°C			32	(68.0)				28	(65.1)
35–36°C			15	(32.0)				15	(34.9)

The area under receiver operating characteristic curve of the logistic regression model to calculate the PS was 0.738.

AAM, advanced airway management; CPR, cardiopulmonary resuscitation; EMS, emergency medical service; IPTW, inverse-probability-of-treatment weighting; IQR, interquartile range; PEA, pulseless electrical activity; PS, propensity score; SMD, standardized mean difference; TTM, targeted temperature management; VF, ventricular fibrillation; VT, ventricular tachycardia.

Supplementary Table S1 shows GCS by the timing of ROSC with or without TTM implementation. The median at the timing of hospital arrival for cases who had already ROSC at hospital arrival was seven in the non-TTM group and three in the TTM group, whereas at the timing of ROSC for those who got ROSC after hospital arrival it was three in both groups.

Table 2 shows the comparison of outcomes of pediatric OHCA patients who achieved ROSC between the non-TTM and TTM groups. The proportion of 1-month survival with favorable neurological outcomes was 25.5% (12/47) in the TTM group and 16.7% (20/120) in the non-TTM group. The outcome of 1-month survival with favorable neurological outcomes did not significantly differ between the groups among all patients (OR, 1.71; 95% CI, 0.76–3.86) and among PS-matched patients (OR, 1.13; 95% CI, 0.42–3.04). After adjustments with IPTW, there were no significant differences in 1-month survival (OR, 1.07; 95% CI, 0.50–2.31) and favorable neurological outcomes (OR, 1.36; 95% CI, 0.55–3.35).

Table 2.

Outcomes of Pediatric Patients with Out-of-Hospital Cardiac Arrest Achieving Return of Spontaneous Circulation With or Without Target Temperature Management Implementation

	Total	Non-TTM	TTM	Crude OR (95% CI)	IPTW OR (95% CI)
All patients	n = 167	n = 120	n = 47
1-month survival	76 (45.5%)	51 (42.5%)	25 (53.2%)	1.54 (0.78–3.03)	1.07 (0.50–2.31)
PCPC 1 or 2	32 (19.2%)	20 (16.7%)	12 (25.5%)	1.71 (0.76–3.86)	1.36 (0.55–3.35)
PS-matched patients	n = 86	n = 43	n = 43
1-month survival	43 (50.0%)	20 (46.5%)	23 (53.5%)	1.32 (0.57–3.09)
PCPC 1 or 2	21 (24.4%)	10 (23.3%)	11 (25.6%)	1.13 (0.42–3.04)

ORs were calculated for TTM versus non-TTM groups.

CI, confidence interval; OR, odds ratio; PCPC, pediatric cerebral performance category.

Table 3 shows the results of the subgroup analyses. Considering the cause of cardiac arrest, favorable neurological outcomes were similar between the non-TTM and TTM groups irrespective of the cause. As for the first documented rhythm assessed by EMS personnel, patients with nonshockable rhythm tended to have better neurological outcomes in the TTM group than in the non-TTM group (10.3% vs. 2.4%; OR, 4.73; 95% CI, 0.75–29.87), and the p-value for interaction was 0.070. Considering the age category, there were no survivors in the TTM group among infants, but the TTM group tended to demonstrate better neurological outcomes than the non-TTM group among children aged 1–17 years (32.4% vs. 18.5%; OR, 2.12; 95% CI, 0.89–5.04).

Table 3.

Subgroup Analysis of Neurologically Favorable Outcomes Among Pediatric Patients with Out-of-Hospital Cardiac Arrest Achieving Return of Spontaneous Circulation With or Without Target Temperature Management

	Total	Non-TTM	TTM	Crude OR (95% CI)	p-for interaction
	n/N (%)	n/N (%)	n/N (%)	Crude OR (95% CI)	p-for interaction
Cause of cardiac arrest					0.669
Cardiac cause	25/51 (49.0)	15/30 (50.0)	10/21 (47.6)	0.91 (0.30–2.78)
Noncardiac cause	7/116 (6.0)	5/90 (5.6)	2/26 (7.7)	1.41 (0.26–7.76)
First documented cardiac rhythm assessed by EMS					0.070
Shockable	12/20 (60.0)	7/10 (70.0)	5/10 (50.0)	0.43 (0.07–2.68)
Nonshockable	5/113 (4.4)	2/84 (2.4)	3/29 (10.3)	4.73 (0.75–29.87)
Age category
<1 year	3/38 (7.9)	3/28 (10.7)	0/10 (0.0)	NA	NA
1–17 years	29/129 (22.5)	17/92 (18.5)	12/37 (32.4)	2.12 (0.89–5.04)

ORs were calculated for TTM versus non-TTM groups.

NA, not applicable.

Discussion

From a nationwide multicenter registry, we investigated whether TTM is effective as an advanced procedure for recovery after ROSC among pediatric OHCA patients using PS methods and found that there were no differences in 1-month survival with favorable neurological outcomes between the TTM and non-TTM groups. In the subgroup analysis, this study suggested that TTM might be effective for recovery in pediatric OHCA patients achieving ROSC who had nonshockable rhythm as the first documented rhythm or those aged 1–17 years. Thus, our findings provide useful implications for the CPR guidelines regarding the use of TTM in pediatric OHCA as a treatment for postcardiac arrest syndrome (PCAS).

In this study, we evaluated 1-month survival and favorable neurological outcomes using the IPTW method, but no significant differences in outcomes were observed between the non-TTM and TTM groups, which were different from the evidence in adults. Among adult OHCA patients, TTM was effective especially for patients with a shockable rhythm (Bernard et al., 2002; Hypothermia after Cardiac Arrest Study Group., 2002; Arrich et al., 2016), and the CPR guidelines therefore strongly recommend TTM (Panchal et al., 2020), whereas, among pediatric OHCA patients, CPR guidelines moderately recommended TTM (Topjian et al., 2021). One of the reasons for these differences in outcomes between children, including our study population and adults, could be explained by the difference in the mechanism of brain injury after cardiac arrest between them (Benedetti et al., 2018). However, further accumulation of evidence on the effect of TTM in pediatric OHCA patients is needed in the future.

A subgroup analysis of the first documented cardiac rhythm in this study showed that nonshockable patients achieving ROSC tended to have improved neurological outcomes in the TTM group than in the non-TTM group. In shockable patients, it was difficult to evaluate the effect of TTM due to the small number of patients and the high proportion of those patients having favorable neurological outcomes regardless of TTM implementation. Indeed, a previous randomized control trial comparing hypothermia and normothermia in pediatric OHCA was not able to evaluate the differences in outcomes based on the cardiac rhythm (Moler et al., 2015). In contrast, a recent study reported that hypothermia was more favorable than normothermia in recovery of nonshockable adult cardiac arrest patients (Lascarrou et al., 2019). Thus, our results suggest that TTM might be effective in children with nonshockable rhythm, who have poor neurological outcomes after OHCA, and provide insights for improving the treatment strategy of PCAS in children.

Moreover, our subgroup analysis showed that among pediatric OHCA patients aged 1–17 years, the TTM group tended to have improved neurological outcomes than the non-TTM group, which was similar to the effect of TTM in adult OHCA (Arrich et al., 2016). In contrast, in this study, the number of infant survivors achieving ROSC who had favorable neurological outcomes was small, and no infant had favorable neurological outcomes in the TTM group. Previous studies also reported poor outcomes in children with OHCA aged <1 year (López-Herce et al., 2005; Atkins et al., 2009; Nitta et al., 2011; Okamoto et al., 2013). The reason why infants with OHCA had poor outcomes might be due to the high proportion of sudden infant death syndrome (SIDS) (Nitta et al., 2011), and infants with SIDS usually have a long period of no blood flow before the caregiver recognizes cardiac arrest (Meert et al., 2016). Therefore, it is important to improve the treatment strategy in infant OHCA, although prevention of cardiac arrest in this population is more essential (Pease et al., 2017, 2018).

This study has several limitations. First, the protocol of introduction of TTM used in each participating institution was unknown, and there could be other biases between the hospitals. The decision to initiate TTM depends on the clinicians' judgment, which can be a surrogate of the outcomes. In this registry, we obtained GCS at the timing of hospital arrival for cases who had already ROSC at hospital arrival, whereas we did it at the timing of ROSC for those who got ROSC after hospital arrival. As shown in Supplementary Table S1, the time interval from GCS measurement to ROSC differed by the first documented cardiac rhythm after hospital arrival. However, GCS was not available at the timing of TTM implementation, which would affect the clinicians' decision to initiate TTM. Furthermore, “intention” is important; clinicians probably decide how to perform TTM, such as device, drugs, or duration, partially based on the ordered target temperature, which may affect the outcomes. Second, this hospital-based registry did not enroll all OHCA patients across Japan. However, in this study we registered all OHCA patients transported to the participating institutions; thus, the selection bias in this study would be small. Finally, there could be unmeasured confounding factors that could have affected the relationship between TTM and the outcomes in OHCA.

Conclusions

We did not find a positive association between TTM implementation and 1-month survival with favorable neurological outcomes in our study population of pediatric patients who achieved ROSC after OHCA.

Footnotes

Acknowledgments

The authors thank their colleagues from Osaka University Center of Medical Data Science and Advanced Clinical Epidemiology Investigator's Research Project for providing insight and expertise for our research. The authors also thank Editage () for English language editing.

Authors' Contributions

S.M., A.H., and T.K. conceptualized and designed the study, drafted the initial article, as well as reviewed and revised the article. T Sobue, T.H., H.T., N.T., Y.O., S.K., T.S., G.Y., H.K., and R.T. conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the article for important intellectual content. All authors approved the final article as submitted and agree to be accountable for all aspects of the work.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was supported by a scientific research grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (19K09393). Funding sources had no role in the study design, analysis and interpretation of the data, and writing of the article.

Supplementary Material

References

Arrich

, Holzer

, Havel

, et al. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database Syst Rev, 2016; 2:CD004128.

Atkins

, Berger

. Improving outcomes from out-of-hospital cardiac arrest in young children and adolescents. Pediatr Cardiol, 2012; 33:474–483.

Atkins

, Everson-Stewart

, Sears

, et al. Epidemiology and outcomes from out-of-hospital cardiac arrest in children: the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest. Circulation, 2009; 119:1484–1491.

Benedetti

, Silverstein

. Targeted Temperature Management in Pediatric Neurocritical Care. Pediatr Neurol, 2018; 88:12–24.

Bernard

, Gray

, Buist

, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med, 2002; 346:557–563.

Buick

, Wallner

, Aickin

, et al. Paediatric targeted temperature management post cardiac arrest: a systematic review and meta-analysis. Resuscitation, 2019; 139:65–75.

de Caen

, Maconochie

, Aickin

, et al. Part 6: Pediatric Basic Life Support and Pediatric Advanced Life Support: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation, 2015; 132:S177–S203.

Donoghue

, Nadkarni

, Berg

, et al. Out-of-hospital pediatric cardiac arrest: an epidemiologic review and assessment of current knowledge. Ann Emerg Med, 2005; 46:512–522.

Hazinski

, Nolan

, Aickin

, et al. Part 1: Executive Summary: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation, 2015; 132:S2–S39.

10.

Herlitz

, Svensson

, Engdahl

, et al. Characteristics of cardiac arrest and resuscitation by age group: an analysis from the Swedish Cardiac Arrest Registry. Am J Emerg Med, 2007; 25:1025–1031.

11.

Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med, 2002; 346:549–556.

12.

Jacobs

, Nadkarni

, Bahr

, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa). Circulation, 2004; 110:3385–3397.

13.

Japanese Guidelines for Emergency Care and Cardiopulmonary Resuscitation. Japan Resuscitation Council ed. Tokyo: Health Shuppansha, 2015.

14.

Jayaram

, McNally

, Tang

, et al. Survival after out-of-hospital cardiac arrest in children. J Am Heart Assoc, 2015; 4:e002122.

15.

Kitamura

, Iwami

, Atsumi

, et al. The profile of Japanese Association for Acute Medicine-out-of-hospital cardiac arrest registry in 2014–2015. Acute Med Surg, 2018; 5:249–258.

16.

Kuss

, Blettner

, Borgermann

. Propensity score: an alternative method of analyzing treatment effects. Dtsch Arztebl Int, 2016; 113:597–603.

17.

Lascarrou

, Merdji

, Le Gouge

, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med, 2019; 381:2327–2337.

18.

Lin

, Li

, Wu

, et al. Post-resuscitative clinical features in the first hour after achieving sustained ROSC predict the duration of survival in children with non-traumatic out-of-hospital cardiac arrest. Resuscitation, 2010; 81:410–417.

19.

López-Herce

, García

, Domínguez

, et al. Outcome of out-of-hospital cardiorespiratory arrest in children. Pediatr Emerg Care, 2005; 21:807–815.

20.

Matsui

, Kitamura

, Sado

, et al. Location of arrest and survival from out-of-hospital cardiac arrest among children in the public-access defibrillation era in Japan. Resuscitation, 2019; 140:150–158.

21.

Meert

, Telford

, Holubkov

, et al. Pediatric out-of-hospital cardiac arrest characteristics and their association with survival and neurobehavioral outcome. Pediatr Crit Care Med, 2016; 17:e543–e550.

22.

Moler

, Hutchison

, Nadkarni

, et al. Targeted temperature management after pediatric cardiac arrest due to drowning: outcomes and complications. Pediatr Crit Care Med, 2016; 17:712–720.

23.

Moler

, Silverstein

, Holubkov

, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med, 2015; 372:1898–1908.

24.

Monsieurs

, Nolan

, Bossaert

, et al. European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation, 2015; 95:1–80.

25.

Neumar

, Shuster

, Callaway

, et al. Part 1: executive summary. Circulation, 2015; 132:S315–S367.

26.

Nitta

, Iwami

, Kitamura

, et al. Age-specific differences in outcomes after out-of-hospital cardiac arrests. Pediatrics, 2011; 128:e812–e820.

27.

Okamoto

, Iwami

, Kitamura

, et al. Regional variation in survival following pediatric out-of-hospital cardiac arrest. Circ J, 2013; 77:2596–2603.

28.

Panchal

, Bartos

, Cabañas

, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 2020; 142:S366-S468.

29.

Pease

, Ingram

, Blair

, et al. Factors influencing maternal decision-making for the infant sleep environment in families at higher risk of SIDS: a qualitative study. BMJ Paediatr Open, 2017; 1:e000133.

30.

Pease

, Blair

, Ingram

, et al. Mothers' knowledge and attitudes to sudden infant death syndrome risk reduction messages: results from a UK survey. Arch Dis Child, 2018; 103:33–38.

31.

Perkins

, Jacobs

, Nadkarni

, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Circulation, 2015; 132:1286–1300.

32.

Pollack

, Holubkov

, Funai

, et al. Relationship between the functional status scale and the pediatric overall performance category and pediatric cerebral performance category scales. JAMA Pediatr, 2014; 168:671–676.

33.

Stuart

. Matching methods for causal inference: a review and a look forward. Stat Sci, 2010; 25:1–21.

34.

Topjian

, Raymond

, Atkins

, et al. Part 4: Pediatric Basic and Advanced Life Support 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics, 2021; 147:e2020038505D.

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