Building the pediatric targeted temperature management registry: initial experiences and insights
Article information
Abstract
Background
Pediatric cardiac arrest is linked to poor outcomes, such as low survival rates and significant neurological disabilities. Effective cardiopulmonary resuscitation and high-quality post-resuscitation care are crucial, with targeted temperature management (TTM) being a key intervention. However, the evidence supporting TTM in pediatric populations, particularly in South Korea, is limited.
Methods
We organized a multicenter initiative to establish a Pediatric TTM Registry, which collects comprehensive data on pediatric patients (aged 0–18 years) who underwent TTM following cardiac arrest. We are using the REDCap platform to gather information on patient demographics, clinical interventions, TTM protocols, and neurological outcomes. The development of the case report form involved regular meetings with representatives from the four participating centers.
Results
The established case report form is divided into four groups: patient demographics, resuscitation-related parameters, post-resuscitation care-related parameters, and patient outcomes. As of October 2024, data from 41 pediatric patients have been collected.
Conclusion
The Pediatric TTM Registry is dedicated to improving the management of pediatric cardiac arrest in Korea by collecting and analyzing data. This initiative will enable improvements in clinical practices, assist in the development of evidence-based TTM protocols specifically designed for pediatric patients, and ultimately improve outcomes for this vulnerable group.
INTRODUCTION
Pediatric cardiac arrest, while less frequent than in adults, is linked to significantly worse outcomes, including survival rates ranging from 8% to 45% and severe disabilities among survivors [1,2]. Furthermore, neurological outcomes are generally poor, with nearly half of those who survive experiencing permanent damage due to the increased vulnerability of the immature pediatric brain to neurological injuries compared to adults [3]. Research aimed at improving the prognosis of pediatric cardiac arrest has underscored the vital importance of effective cardiopulmonary resuscitation (CPR) and high-quality post-resuscitation care.
In adult post-resuscitation care, targeted temperature management (TTM) is a widely used therapeutic intervention for neurological protection and also plays a crucial role in pediatric post-resuscitation care [4]. However, the evidence supporting TTM in pediatric patients is limited, primarily originating from a small number of cases or extrapolated from studies conducted on adults [5-7]. Particularly in South Korea, research on pediatric TTM is almost nonexistent, which presents substantial challenges for clinicians attempting to apply TTM guidelines to pediatric post-cardiac arrest cases [6].
South Korea currently lacks a dedicated pediatric TTM registry, which is essential for tailoring clinical guidelines and improving outcomes in this vulnerable population. While the Korean Hypothermia Network has made strides in temperature control management by establishing a national registry that encompasses data from approximately 22 hospitals [8], this registry only includes adult patients aged 18 and older, thus excluding the pediatric population. Although there are existing pediatric TTM registry studies, such as the Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children (THAPCA-IH) and Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children (THAPCA-OH), these studies were conducted outside of South Korea. Consequently, there is a pressing need for region-specific research and data collection [9,10].
Given the emerging application of TTM in pediatric neuroprotection and the existing gaps in both global and regional data, we have initiated the development of a dedicated Pediatric TTM Registry in South Korea. This registry is designed to address the current research gap, provide critical data to guide clinical practice, and ultimately improve patient outcomes and support future research in this vital area of pediatric care.
METHODS
Given the retrospective nature of the study, the Institutional Review Board of Seoul National University Hospital approved this study (IRB No. H-2111-158-1276) and waived the requirement for informed consent for collecting anonymized data and information that does not affect treatment. In the future, all prospective data collection efforts in the later stages of the registry will strictly adhere to the principles of informed consent.
Registry Design
The initial phase of the registry was designed as a retrospective, multicenter registry to collect data on pediatric patients who underwent TTM following cardiac arrest. Initially, representatives from four centers capable of operating TTM devices convened regular meetings starting in May 2023 to develop the case report form (CRF). Utilizing the CRF crafted through these multicenter discussions, data collection commenced at the principal investigator’s affiliated hospital. This phase focused on comprehensive data collection, encompassing patient demographics, clinical interventions, TTM protocols, and outcomes. Parameters concerning the neurological outcomes of surviving patients will be further refined, allowing for a more in-depth analysis of the efficacy of TTM.
Study Population
The study population consisted of pediatric patients aged 0 to 18 years who experienced cardiac arrest and subsequently underwent TTM. To be eligible for inclusion, patients must have had a documented cardiac arrest and received TTM as part of their post-resuscitation care, utilizing a surface-based cooling system equipped with a computerized temperature management mechanism. Patients who were managed with ice packs, cooling pads, or antipyretics were excluded, as these methods do not reliably ensure effective temperature management and do not permit controlled rewarming [11].
Collaborative Framework
The Research Electronic Data Capture platform, commonly referred to as REDCap, is currently utilized for data recording (https://redcap.research.or.kr/). Developed by Vanderbilt University, REDCap is a secure, web-based software platform tailored to support research studies. Although REDCap is the initial platform for the registry, plans are in place to develop a custom-built web-based input system as the registry progresses [12,13].
Governance, Oversight, and Security
Representatives from each participating center will form a steering committee. To ensure data accuracy and reliability, ongoing quality control measures, including periodic audits, will be implemented. Access to the database will be restricted to authorized individuals only, and any modifications to the registry’s protocol, such as changes in data collection methods or the addition of new variables, will be subject to review and approval by the steering committee.
Outcomes
In this article, we discuss the development process of the CRF for the registry, the current status of the CRF including the types of parameters recorded, and the methods for data collection and usage. As the registry is still in its early stages, it is not yet feasible to conduct meaningful analysis. Therefore, we present the demographic characteristics of the cohort that has already been assembled.
RESULTS
The study was initially planned as a prospective registry in 2023. However, to address the selection bias stemming from only including patients with relatively favorable prognoses, the design was changed to a retrospective, multicenter approach in August 2024, following IRB approval. By October 2024, Seoul National University Children’s Hospital had gathered patient data spanning from January 2022 to July 2024. Meanwhile, Seoul National University Bundang Hospital, Chonnam National University Hospital, and Seoul St. Mary’s Hospital were still in the process of securing IRB approval. After five meetings, the CRF was finalized, outlining patient characteristics, resuscitation-related parameters, post-resuscitation parameters including TTM, and patient outcomes.
In assessing patient characteristics, factors such as the cause of cardiac arrest and underlying diseases were considered to determine how baseline characteristics influence outcomes. Parameters related to resuscitation efforts, including total CPR duration, the proportion of in-hospital CPR, and the performance of bystander CPR, were evaluated to understand how the duration and quality of resuscitation efforts impact outcomes. These data are manually entered into the REDCap environment after reviewing the hospital's electronic medical records. Most parameters for post-resuscitation, including TTM, are collected directly from the TTM machine. For instance, when using the Arctic Sun 5000 (Bard/Becton Dickinson) for temperature control, information such as the time of TTM initiation, target temperature, time of rewarming initiation, rewarming rate, and total duration of TTM is stored on the device. This data can be retrieved using a USB drive. By collecting these files, the burden of data entry on researchers is reduced, and the accuracy of the data is enhanced by eliminating human error.
Similarly, many of the parameters related to outcomes, particularly those concerning complications during TTM, are directly extracted and downloaded from the hospital electronic medical record. Parameters including serum electrolytes, glucose, and complete blood count are collected throughout the TTM period to monitor changes. Additionally, other variables such as transfusion frequency, seizure events, and the presence of pathogens are manually entered into the REDCap environment.
The neurological outcomes following TTM are evaluated using the Pediatric Cerebral Performance Category (PCPC) scale [14]. A post-discharge PCPC scale score of 1 or 2 is deemed favorable [15]. In this study, patients with cerebral palsy or other medical conditions that contribute to a higher initial PCPC scale score are also considered to have a favorable outcome if their score remains unchanged. The final version of the CRF can be found in Supplementary Tables 1-6. Additionally, monthly protocol meetings are conducted to refine data parameters. A total of 41 patients under the age of 18 underwent TTM as part of their post-resuscitation care at Seoul National University Children’s Hospital from January 2022 to July 2024. The demographics of these patients are outlined in Table 1.
Demographics of patients under the age of 18 years who received targeted temperature management as a part of post-resuscitation care in Seoul National University Children’s Hospital between January 2022 and July 2024
Reporting and Utilization of Data
Data collected in the registry will be analyzed regularly, and analysis reports will be published periodically. These reports will concentrate on the efficacy of TTM, patient outcomes, and any emerging trends or patterns associated with TTM clinical guidelines. The findings will be disseminated to the participating hospitals and utilized to update clinical practices and guidelines.
DISCUSSION
Pediatric cardiac arrest care presents unique challenges compared to adult cases, requiring specialized approaches tailored to the pediatric population [1,2,9,16]. The data collected from this registry will identify the demographic and clinical characteristics of pediatric cardiac arrest patients in South Korea who underwent TTM therapy. This analysis will help determine factors that may influence patient outcomes. The insights gained will provide a foundation for enhancing post-resuscitation techniques, ultimately improving survival rates and reducing long-term neurological complications.
The registry will provide a comprehensive evaluation of the TTM protocols used in various centers nationwide, facilitating a comparison of their effectiveness within the Korean pediatric population. Current pediatric TTM protocols are derived from adult studies, which may not adequately consider the physiological differences between children and adults [5,6]. Additionally, due to the limited number of studies focused on children, not all centers adhere to the same TTM protocol. Historically, targeted hypothermia was the primary approach in TTM protocols based on adult research. However, recent studies suggest that targeted hypothermia offers no survival benefits over targeted normothermia [17]. These developments and debates in adult research must also be examined and applied in pediatric contexts. By analyzing data on various aspects of TTM protocols, including initiation, duration, temperature targets, outcomes, and complications, the registry could aid in establishing more standardized, pediatric-specific TTM guidelines.
One of the most important concerns in post-resuscitation care is assessing neurological outcomes following cardiac arrest. Although the current registry employs the PCPC scale to evaluate the neurological status of survivors, its subjectivity may lead to inconsistent assessments. The lack of objectivity can introduce inconsistencies in evaluating neurological outcomes. Consequently, we are developing a standardized neurological assessment tool that incorporates well-established methods, including the Neurological Pupil Index, neuroimaging, and electroencephalogram. An accurate neurological assessment will enable us to better determine the efficacy of TTM protocols. In addition to evaluating the efficacy of TTM, the registry will also examine the safety profile of TTM interventions in pediatric patients. Potential complications associated with TTM, such as electrolyte imbalances, infections, and hematological impairments, will be analyzed [18]. Understanding the incidence and impact of these complications will help balance the benefits of TTM against the risks, aiding clinicians in managing pediatric post-cardiac arrest cases with TTM.
There are several limitations to the retrospective registry study. First, the study is currently limited to only four hospitals, which may restrict the generalizability of the findings to other healthcare settings. To enhance the diversity and applicability of the data, it is necessary to expand the registry to include additional centers. Furthermore, the retrospective design of the initial phase introduces potential limitations. Retrospective data collection often results in variability in the availability and quality of data across different institutions. These inconsistencies may hinder the ability to standardize analyses fully and draw definitive conclusions.
As the registry matures and more data becomes available, future research will enable us to focus on more long-term outcomes. Understanding the neurological and functional status of survivors months or even years after the initial event will be crucial in evaluating the true impact of TTM on quality of life [2,19]. This includes tracking survival rates, assessing neurodevelopmental outcomes, cognitive function, and overall well-being. Such long-term data will be invaluable for clinicians, researchers, and policymakers as they work to improve the long-term prognosis for pediatric cardiac arrest survivors [19]. We also believe that the collaborative nature of this registry sets the stage for future nationwide partnerships. By aligning efforts with other centers throughout the nation, this registry could contribute to a national body of evidence that supports the development of universally applicable guidelines. Those who wish to participate in the registry building process are welcome to contact the corresponding author via email.
The establishment of the Pediatric TTM Registry in South Korea marks a significant advancement in the management of pediatric cardiac arrest. By compiling and analyzing data specific to pediatric cardiac arrest patients, the registry aims to provide insights into coherent clinical practices tailored to the Korean pediatric population. Additionally, it will assist in the development of advanced intervention protocols to improve patient outcomes.
Notes
CONFLICT OF INTEREST
Hwa Jin Cho, Kyunghoon Kim, and Bongjin Lee are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
FUNDING
This study was funded by GEMS Korea. The funding body had no role in the design of the registry, data collection, or writing of the manuscript.
AUTHOR CONTRIBUTIONS
Conceptualization: BL. Funding acquisition: BL. Data curation: WJ, YJ. Methodology: WJ, YSK, YJ, JHK, HJC, IC, KK, IKL, KHL, BL. Supervision: BL. Writing – original draft: WJ. Writing – review & editing: YSK, YJ, JHK, HJC, IC, KK, IKL, KHL, JDP, BL. All authors read and agreed to the published version of the manuscript.
SUPPLEMENTARY MATERIALS
Supplementary materials can be found via https://doi.org/10.32990/apcc.2023.00031.
Patient characteristics
CPR related parameters
Post-resuscitation care related parameters
Outcome related parameters
TTM related parameters obtained directly from Arctic Sun
Outcome related parameter during TTM obtained directly from EMR