The technology, therapeutic agents, and strategies for treatment and life support in childhood critical illness and injury have evolved rapidly during the past 2 decades. Children with illnesses and injuries who were once thought to be beyond the reach of modern medicine now survive in large numbers in multidisciplinary pediatric intensive care units (PICUs). Although mortality in U.S. PICUs has fallen precipitously, survivors of childhood critical illness and injury remain at risk for morbidity and disability. Pediatric critical care practice has evolved rapidly, but most of this development has occurred without the benefit of descriptive studies that might enable translational understanding of the pathophysiology of life-threatening illnesses and injuries in childhood. The risks and benefits of much of pediatric critical care practice remain unquantified and poorly understood, particularly with regard to long-term outcomes.
The NICHD established the CPCCRN in 2005 as a national resource for studying the scientific bases of pediatric critical care medicine; the Network was renewed in 2009. The Network is a major priority of the NICHD Pediatric Trauma and Critical Illness Branch that supports it through the Cooperative Agreement mechanism (U10) in 5-year competitive cycles. For the 2009–2014 cycle, the CPCCRN comprises seven clinical sites with large PICUs and a Data Coordinating Center. The sites were selected for participation based on proposed scientific work, patient diversity, expertise of the investigative team, and concordance with NICHD programmatic and scientific objectives. The Data Coordinating Center supports the Network by using cutting-edge informatics to manage the complexities of the emerging collaborative research.
Focused on critically ill infants and children, the CPCCRN aims to reduce morbidity and mortality from pediatric critical illness and injury by enhancing knowledge of the scientific bases of pediatric critical care practice. The CPCCRN conducts a wide range of research activities, reaching across traditional disciplinary lines and transcending customary thinking and organizational structures to achieve innovative research in the care of critically ill and injured children.
Data from CPCCRN studies constitute an important scientific resource, and public use datasets are available to qualified researchers. These data sets are administered by the Data Coordinating Center on behalf of the CPCCRN. Learn more about the CPCCRN Public Use Datasets.
The 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.
CPCCRN research priorities reflect the four topic areas described below.
Bereavement and Grief
Intensive Care Clinical Processes and Protocols
Infection and Sepsis
Bereavement and Grief
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 anecdotal. Some bereaved parents are incapacitated for a prolonged period, a situation known as “complicated grief.” CPCCRN investigators explore whether a postmortem follow-up meeting with the child’s PICU physician helps decrease complicated grief in these bereaved parents. Completed in this area include:
- The Parents’ Opinions on Physician Conference study assessed whether bereaved parents would be interested in a follow-up conference with the physician following the child’s death and, if so, the desirable components and participants in the conference. This study indicated that the large majority of bereaved parents expressed an interest in such a conference and that there were consistent thematic suggestions for the potential content.
- The PICU Bereavement Study measured the incidence of complicated grief in bereaved parents at 6 and 18 months, using five previously validated survey instruments. The study demonstrated that a significant number of parents exhibit complicated grief at 6 months, and a smaller but still large number of parents have complicated grief at 18 months. These results substantiate the importance of an effective intervention to prevent complicated grief.
- The Physicians’ Perspectives on the Physician-Parent Follow-Up Conference study evaluated physicians’ perspectives on the follow-up conference, revealing that the majority of physicians agree with the concept. In addition, physicians provided information to help guide the formulation of a content and structure for such meetings.
- Following the previous study of physicians, CPCCRN investigators developed a structured framework for these meetings in the Pilot Study of a Framework for Physician-Parent Follow-Up Meetings. The framework was intended to enable physicians, and perhaps other clinical staff, to conduct the meetings in a predictable manner, with the ultimate goal being a randomized trial of the intervention. This pilot study evaluated the feasibility of using the framework that was developed.
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. The FSS was compared with the Adaptive Behavior Assessment System II (ABAS II).
- The Trichotomous Outcome Prediction in Critical Care (TOPICC) Study has enrolled more than 10,000 PICU patients and will attempt to predict the outcome of PICU admissions in a trichotomous manner, using the three outcomes of good survival, poor survival, and death. The FSS was used to assess the quality of survival. Subject accrual for this study is completed and the data are being analyzed. If a predictive model is successfully developed, this model could be used in future studies to assess the quality of care in different intensive care units, and it may also be a useful outcome measure for interventional PICU trials.
Intensive Care Clinical Processes and Protocols
To improve the evidence base for pediatric critical care practices, CPCCRN investigators selected four clinical processes that are either frequently used or very high risk and implemented the following studies.
- The Measuring Opioid Tolerance Induced by Fentanyl (MOTIF) Study to understand whether opioid tolerance and dependence is truly common in the PICU setting.
- The Hypothermia’s Impact on Pharmacology study is an R01 ancillary study to the ongoing Therapeutic Hypothermia after Pediatric Cardiac Arrest trials described below. This study will evaluate the metabolism of morphine and midazolam, agents that are commonly used in the critical care setting, within the context of hypothermia.
- The Pediatric Extracorporeal Membrane Oxygenation (ECMO) and Cefepime (PEACE) Study aims to enhance the knowledge base regarding the impact of ECMO on cefepime pharmacokinetics to help improve accurate dosing. This study is also evaluating piperacillin and tazobactam pharmacokinetics in ECMO patients when cefepime is not utilized. These pharmacokinetic data will be important in ECMO patients because therapeutic drug monitoring is not available for these three antibiotics.
- The Bleeding and Thrombosis During ECMO (BATE) Study aims to quantify the incidence of bleeding and thrombosis adverse events in 600 ECMO patients and to explore potential associations of complications with variations in anticoagulation protocols at different hospitals.
- The Variations in Pediatric Severe Asthma Care study gathered information from the Pediatric Hospital Information System (PHIS) database for hospitals that participate in the 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.
- In the Critical Asthma Mortality and Morbidity Planning (CAMMP) Study,CPCCRN investigators followed up on the PHIS analysis and conducted a retrospective medical record review of all asthmatics 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.
- Variation of management of mechanical ventilation in pediatric patients was observed in the CAMMP study, but adult ventilator computer protocols have been successful in reducing such variation in adult critical care. In the R21-funded Translating an Adult Ventilator Computer Protocol to Pediatric Critical Care study, CPCCRN investigators are evaluating the acceptability of computer support decisions to PICU physicians and nurses.
- The Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) Trials aim to determine whether therapeutic hypothermia, in which the body’s temperature is lowered and maintained several degrees below normal for a limited period of time, is as successful at treating children who experience cardiac arrest as it has been in treating adults. The THAPCA Trials were developed by CPCCRN investigators in collaboration with the Pediatric Emergency Care Applied Research Network (PECARN), which is funded by the Emergency medical services in Children program in the Maternal and Child Health Bureau at Health Resources Services Administration. The THAPCA Trials are funded by the National Heart, Lung, and Blood Institute. 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 completed for THAPCA-OH, but continues for the in-hospital trial.
- 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. This study is evaluating high-fidelity physiological data (arterial waveforms) in PICU patients during CPR. The goal is to identify areas for improving CPR performance in the PICU setting, in order to improve diastolic coronary perfusion and enhance return of spontaneous circulation.
Infection and Sepsis
The Network concentrates on several major critical illness burdens:
- The Critical Pertussis Study (PDF - 240 KB), the largest prospective cohort ever assembled for scientific study, is a prospective cohort project undertaken to characterize the acute course of critical pertussis in children.
- The project uses trans-federal partnerships and a unique research business plan to conduct enhanced passive and active surveillance of 33,000 PICU admissions annually.
- Study researchers are collecting detailed data on pertussis-related mortality, organ failure, level of support, disability, and the burden for families.
- The Study seeks evidence of associations between acute course characteristics, mortality, and long-term neurobehavioral outcomes for survivors and their families.
- The unique CPCCRN infrastructure has also led to a translational partnership with a basic science laboratory funded by the National Institute of General Medical Sciences to improve understanding of the genomic and biological contributions to this persistent and often lethal disease for children.
- The Critical Illness Stress-induced Immune Suppression (CRISIS) Prevention Trial was intended to evaluate "prophylaxis" strategies used to prevent stress-induced nosocomial infection and sepsis. The study used a double-blind, randomized, controlled trial design to test the hypothesis that daily prophylaxis with metoclopramide, zinc, selenium, and glutamine would reduce nosocomial infection and sepsis in critically ill children. The study was terminated for futility after enrollment of 293 subjects. This trial was registered in ClinicalTrials.gov (NCT00395161).
- The Cortisol Quantification Investigation (CQI) study addresses the task of studying 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. In the past, measurement of free cortisol has required 24-hour equilibrium dialysis. In this study, CPCCRN investigators developed and validated an ultracentrifugation method that enables free cortisol quantification within 2 hours. This method will enable rigorous study of adrenocortical function in future studies of pediatric sepsis.
- Children's Hospital Los Angeles
- Children’s Hospital of Philadelphia
- Children’s National Medical Center (Washington, D.C.)
- Phoenix Children’s Hospital
- Seattle Children's Hospital
- University of Michigan, Ann Arbor
- University of Pittsburgh
- University of Utah Health Sciences Center (Data Coordinating Center)
- Wayne State University, Detroit
In addition, previous sites within the Network include Arkansas Children's Hospital, Little Rock, and Seattle Children's Hospital.