Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
- for people ages 30 months to 13 years
- Healthy Volunteers
- healthy people welcome
- at Oakland, California and other locations
- study startedestimated completion:
- Principal Investigator
- Natalie Cvijanovich
The purpose of this study is to determine the relationships between sedative exposure during pediatric critical illness and long-term neurocognitive outcomes. We will test for drug- and dose-dependent relationships between sedative exposure and neurocognitive outcomes along the early developmental spectrum and will control for baseline and environmental factors, as well as the severity and course of illness. Hypotheses: 1. Greater exposure to benzodiazepines and/or ketamine will be associated with lower IQ even when controlling for severity of illness, hospital course, and baseline factors. In addition, benzodiazepines and/or ketamine will negatively affect other aspects of neurocognitive function. 2. Younger children exposed to benzodiazepines and/or ketamine will have worse neurocognitive outcomes than older children with similar sedative exposure and severity of illness.
Ensuring the safety and comfort of the more than 100,000 critically ill infants and young children supported on mechanical ventilation in the US each year is integral to the practice of pediatric critical care. Humane care of these young patients requires the use of sedating medications, most commonly combinations of opioids and benzodiazepines. Unfortunately, sedative use also carries risk. Animal studies found that even transient administration of benzodiazepines and other sedatives during periods of developmental synaptogenesis caused widespread neuronal apoptosis and residual learning and memory deficits. Sedation is administered for days to weeks in>90% of acutely-ill, ventilated infants and children. Thus, a commonly used treatment in critically ill young children may itself have detrimental, age-dependent long-term effects.
An opportunity to increase the understanding of the long-term cognitive effects of sedation during critical illness in children has been provided by the cluster randomized, controlled trial of a sedation protocol, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE), U01 HL086622, PI Curley, 31 sites, n=2,816. This trial determined whether the trial's sedation protocol used at intervention sites decreased the duration of mechanical ventilation and sedative exposure among children with acute respiratory failure due to a primary pulmonary process. Control sites continued usual sedation practice. We collected detailed data on doses and durations of sedative medications, in-hospital course, and post-discharge quality of life.
The purpose of RESTORE-cognition is to determine the relationships between sedative exposure during pediatric critical illness and long-term neurocognitive outcomes. We will assess multiple domains of neurocognitive function 2.5-5 years post-discharge in 500 RESTORE subjects with normal baseline cognitive function aged 2 weeks to 8 years at pediatric intensive care unit admission. In addition, we will study 310 matched, healthy siblings of RESTORE subjects to provide data on an unexposed group with similar baseline biological characteristics and environment. Our goal is to increase our understanding of the relationships between sedative exposure, critical illness, and long-term neurocognitive outcomes in infants and young children.
Intellectual Disability Perceptual Disorders Memory Disorders intensive care critical care child family survivors
You can join if…
Open to people ages 30 months to 13 years
- Age ≤8 years and PCPC=1 at RESTORE PICU admission
- PCPC ≤3 at RESTORE hospital discharge Sibling control subjects
- Age 4 to 17 years at time of testing
- Same biological parents as primary subject
- Lives with the primary subject
You CAN'T join if...
- Hospital readmission that includes MV and sedation
- History of cardiac arrest, traumatic brain injury (TBI) with loss of consciousness,genetic disorder, premature birth <32 weeks gestational age, or birth weight <2500 g Sibling control subjects
- Adopted or step siblings
- History of MV and sedation, receipt of general anesthesia, cardiac arrest, TBI with loss of consciousness, genetic disorder, premature birth <32 weeks gestational age, or birth weight <2500 gm.
- Children's Hospital and Research Center at Oakland not yet accepting patients
Oakland, California, 94609-1809, United States
- Children's Hospital at University of California San Francisco Medical Center not yet accepting patients
San Francisco, California, 94143, United States
- Lucile Salter Packard Children's Hospital at Stanford not yet accepting patients
Palo Alto, California, 94304-0126, United States
- University of California Davis Medical Center accepting new patients
Sacramento, California, 95817, United States
- Children's Hospital of Orange County accepting new patients
Orange, California, 92868, United States
- accepting new patients
- Start Date
- Completion Date
- University of Pennsylvania
- Lead Scientist
- Natalie Cvijanovich
- Study Type
- Last Updated
- June 1, 2017
Please contact me about this study
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If you do not hear from the study team, please call 888-689-8273 and tell them you’re interested in study number NCT02225041.