Pediatric critical care, or the effective and efficient care of children with critical or unstable conditions, is an important and growing subspecialty in pediatrics. The number of pediatric intensivists, pediatric intensive care units (PICUs), and PICU beds in the United States has increased dramatically in recent years. Mortality in U.S. PICUs has fallen precipitously, yet survivors of childhood critical illness and injury remain at risk for morbidity and disability.
Much of the technology and many therapies in pediatric critical care have evolved without adequate study or have been adopted uncritically from adult, neonatal, or anesthetic practice. As a result, the risks and benefits of much of intensive care practice remain largely unknown. Research is needed to make optimal decisions regarding effective critical care practices. Rigorous use of appropriate scientific methodology, deployed across a network structure, achieves the numbers of patients required to provide answers more rapidly than individual sites acting alone.
In April 2004, NICHD published a request for applications to establish CPCCRN. Clinical sites and a data coordinating center (DCC) were identified through a competitive application process. The network was renewed by the same process in 2009 and 2014.
The network is a major priority of NICHD's Pediatric Trauma and Critical Illness Branch and is supported through the cooperative agreement mechanism (UG1 for clinical sites, and U01 for the DCC) in 5-year competitive cycles. The latest cycle includes seven clinical sites with large PICUs and a DCC.
The network’s goal is to develop an infrastructure to pursue well-designed collaborative clinical trials and meaningful descriptive studies in pediatric critical care medicine. The network seeks to reduce morbidity and mortality in pediatric critical illness and injury, and to provide a framework for the development of the scientific basis of pediatric critical care practice.
Data from CPCCRN studies constitute an important scientific resource, and public use datasets are available to qualified researchers. Learn more about the CPCCRN Public Use Datasets .
CPCCRN conducts controlled observations and objective evaluations of pediatric critical care practices, including new management and technology methodologies, in children with complex critical illnesses and injuries. The resulting data will help to balance prompt implementation of new technologies and treatments with effective evaluation of their safety, efficacy, cost/risk/benefit ratios, and effects on long-term outcomes for children and their families. Additional information on all active and completed CPCCRN studies, including links to study publications, is available at https://www.cpccrn.org .
CPCCRN research priorities reflect the following topic areas.
Following the death of a child in the PICU, all parents grieve. Guidance for communicating about and considering the family's grief, emotional burden, and difficult decision-making remains largely anecdotal. Some bereaved parents are incapacitated for a prolonged period, a situation known as "complicated grief." CPCCRN investigators explore whether a follow-up meeting with the child's PICU physician after a child's death helps decrease complicated grief in these bereaved parents. Completed projects in this area include:
- Bereavement I: Parents' Perspective. The objective of the first phase of the CPCCRN bereavement studies was to investigate parents’ perspectives on the desirability, content, and conditions of a physician-parent conference after their child’s death in the PICU. This study has been completed and the results have been published.
- Bereavement II: PICU Study. This study was designed to investigate the extent of complicated grief symptoms and associated risk factors among parents whose child died in a PICU. This study has been completed and the results have been published.
- Bereavement III: Physicians' Perspective. The objective of this study was to describe physicians’ experiences with and attitudes toward follow-up meetings after a child’s death. This study has been completed and the results have been published.
- Bereavement IV: Pilot Study of a Framework for Physician-Parent Follow-Up Meetings. This study was a multicenter pilot study of video-recorded physician-parent follow-up meetings using the framework developed from the previous CPCCRN bereavement studies. This study has been completed and the results have been published.
Two continuing priorities of the CPCCRN Advisory Committee, especially the parents who serve on the committee, are to improve processes of care and concentrate on functional outcomes of children requiring critical care. To provide a mechanism for measuring functional outcome, CPCCRN has undertaken the following studies:
- In the Development of a Quantitative Functional Status Scale (FSS) for Pediatric Patients study, CPCCRN investigators tested a new functional status scoring system that had been developed with 500 initial patients and validated with a test set of 250 additional patients. Visit https://www.cpccrn.org/network-projects/ for more information about this project. The FSS resulted in a functional status outcome measure for large outcome studies that is well-defined, quantitative, rapid, reliable, minimally dependent on subjective assessments, and applicable to hospitalized pediatric patients across a wide range of ages and inpatient environments, making it well suited for large outcome studies (Pollack, et al.; 2009; PMC3191069).
- The Trichotomous Outcome Prediction in Critical Care study has enrolled more than 10,000 PICU patients and aims to predict the outcome of PICU admissions in a trichotomous manner, using the three outcomes of good survival, poor survival, and death. Visit https://www.cpccrn.org/network-projects/ for more information about this project.
To improve the evidence base for pediatric critical care practices, CPCCRN investigators selected clinical processes that are either frequently used or high-risk and implemented the following studies .
- The Pediatric Intensive Care Quality of CPR (PICqCPR) study is studying whether American Heart Association guidelines for proper performance of cardiopulmonary resuscitation (CPR) are utilized in the hospital setting, particularly within the PICU. The goal is to identify areas for improving CPR performance in the PICU setting to improve diastolic coronary perfusion and enhance return of spontaneous circulation.
- The Bleeding and Thrombosis During ECMO study aimed to quantify the incidence of bleeding and thrombosis adverse events in pediatric patients requiring extracorporeal membrane oxygenation (ECMO) and to explore potential associations of complications with variations in anticoagulation protocols at different hospitals. The goal of this research is to eliminate bleeding and thrombotic complications during ECMO and to improve outcomes for these patients. Study recruitment is complete, and data analyses have begun.
- The Pediatric ECMO and Cefepime (PEACE) study enhanced the knowledge base regarding the impact of ECMO on cefepime pharmacokinetics to help improve accurate dosing. This study has been completed and the results are being published.
- The Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) Trials aim to determine whether therapeutic hypothermia is as successful at treating children who experience cardiac arrest as it has been in treating adults. The trials were developed in concert with the Pediatric Emergency Care Applied Research Network, funded by the Emergency Medical Services in Children program in the Maternal and Child Health Bureau at the Health Resources Services Administration. THAPCA Trials are funded by the National Heart, Lung, and Blood Institute with CPCCRN sites serving as vanguard sites for the initial phase of the trial. The trials evaluate therapeutic hypothermia's efficacy at increasing survival rates and reducing the risk of brain injury in infants and children who experience a cardiac arrest while out of the hospital (THAPCA-OH, ClinicalTrials.gov NCT00878644) or in the hospital (THAPCA-IH, ClinicalTrials.gov NCT00880087). Subject accrual is complete for THAPCA-OH, but continues for the in-hospital trial.
- The Measuring Opioid Tolerance Induced by Fentanyl (MOTIF) study to examine the clinical factors associated with increased opioid analgesia dose among mechanically ventilated children in the PICU.
- The Variations in Pediatric Severe Asthma Care study gathered information from the Pediatric Hospital Information System (PHIS) database for hospitals that participate in CPCCRN and analyzed the data to evaluate variation of management of critical asthma. Large variations were found between sites within the network, as well as between overall CPCCRN sites and the nation.
- Critical Care for Pediatric Asthma: Wide Care Variability and Challenges for Study (Bratton, et al.; 2012; PMC3298633)
- In the Critical Asthma Mortality and Morbidity Planning study, CPCCRN investigators followed up on the PHIS analysis and conducted a retrospective medical record review of all patients admitted to CPCCRN PICUs during a 5-year period. The results confirmed significant variability of asthma management between individual sites participating in CPCCRN. The results from this and the Variations in Pediatric Severe Asthma Care study indicate areas for further research concerning drug therapy and mechanical ventilation strategies for children with critical, near-fatal asthma.
- In the R21-funded Translating an Adult Ventilator Computer Protocol to Pediatric Critical Care study, CPCCRN investigators evaluated the acceptability of computer support decisions to PICU physicians and nurses.
- The CPCCRN Core Data Project obtains descriptive information about all PICU discharges from the network clinical sites, based primarily on clinical site hospital administrative databases. The data provides a valuable resource to CPCCRN by helping to stimulate new research protocols, identify potential need for non-network partners to access additional patient populations, and provide a descriptive understanding of the critically ill infants and children cared for within the network.
The network concentrates on several major critical illness burdens through the following studies :
- GM-CSF for Immunomodulation Following Trauma (GIFT-1 Study). This is being conducted as a dose-finding study to determine the lowest tolerable dose of GM-CSF that will reverse trauma-induced immune suppression in high-risk, critically injured children. The study uses highly standardized, generalizable, rapid functional immune monitoring in a CPCCRN laboratory to determine those children at highest risk for the development of nosocomial infection. This study is currently enrolling patients.
- GM-CSF for Reversal of immmunopAralysis in pediatriC sEpsis-induced MODS (GRACE). This open-label interventional trial seeks to identify the optimal dose and route of delivery (intravenous or subcutaneous) for GM-CSF in children with sepsis-induced MODS, with reversal of immunoparalysis as the primary outcome variable. The study hopes to demonstrate the role of patient-specific immunomodulation in promoting resolution of organ failure and reducing mortality from pediatric sepsis-induced MODS.
- Microbiome, Virome, and Host Responses Preceding Ventilator-Associated Pneumonia (VAP). This is a prospective longitudinal observational study of high-risk mechanically ventilated children with systematic bacterial and viral analyses of the respiratory tract, along with proteomic evaluation of the host response. VAP seeks to determine whether specific taxa and patterns of bacterial microbiota contribute to VAP risk and whether bacterial communities are modulated by viral infection and host immune responses to increase the risk of VAP in critically ill children. Enrollment in this study is complete and data are being analyzed.
- Sepsis Induced Red Cell Dysfunction (SiRD). This study is built on the infrastructure from the PHENOMS study (discussed in the next bullet point) and is aimed at characterizing red cell dysfunction that impairs oxygen delivery in septic children.
- Biomarker Phenotyping of Pediatric Sepsis and Multiple Organ Failure (PHENOMS) study. This prospective observational cohort study enrolled more than 400 children with severe sepsis and tested the hypothesis that children with inflammation pathobiology phenotypes have increased mortality, predisposing genotype and environmental risk factors, and increased C-reactive protein and ferritin levels that correlate with clinical outcomes. This study has been completed and the results have been published.
- Life After Pediatric Sepsis Evaluation (LAPSE) study. This prospective observational study aims to describe the post-sepsis illness trajectory through serial measurements of Health-Related Quality of Life, subject functional status, and examination of organ dysfunction, as well as individual and environmental characteristics that may influence these outcome measures. Enrollment in this study is complete and the data are being analyzed.
- The Critical Pertussis study, the largest prospective cohort ever assembled for scientific study of critical pertussis, aims to characterize the acute course of critical pertussis in children. The project established trans-federal partnerships as well as partnerships with non-CPCCRN sites to conduct enhanced passive and active surveillance of 33,000 PICU admissions annually. This study has been completed and the results have been published.
- The Critical Illness Stress-induced Immune Suppression (CRISIS) Prevention trial evaluated "prophylaxis" strategies used to prevent stress-induced nosocomial infection and sepsis. The study was terminated for futility after enrolling 293 subjects. Despite the early termination of this study, important information was gleaned, and the results have been published.
- The Cortisol Quantification Investigation study studied adrenocortical function in children with sepsis and septic shock, commonly difficult to study because total cortisol measurements include protein-bound cortisol, which is not active. This study has been completed and the results have been published.