Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
- Conditions
- Memory DisordersPerceptual DisordersIntellectual Disability
- Registration Number
- NCT02225041
- Lead Sponsor
- University of Pennsylvania
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 360
RESTORE subjects
- Age ≤8 years and PCPC=1 at RESTORE PICU admission
- PCPC ≤3 at RESTORE hospital discharge Sibling control subjects
Inclusion criteria:
- Age 4 to 17 years at time of testing
- PCPC=1
- Same biological parents as primary subject
- Lives with the primary subject
RESTORE subjects
- 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Neurocognitive function at 2.5 years post-ICU discharge, as assessed using standardized tests of attention, processing speed, learning and memory, visual-spatial skills, motor skills, language, executive function, IQ, and behavior 2.5 to 5 years post-discharge
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (31)
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Memorial Hospital, Chicago
🇺🇸Chicago, Illinois, United States
Johns Hopkins Children's Center
🇺🇸Baltimore, Maryland, United States
Advocate Hope Children's Hospital
🇺🇸Oak Lawn, Illinois, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
University of Maryland Hospital for Children
🇺🇸Baltimore, Maryland, United States
University Medical Center, The University of Arizona
🇺🇸Tucson, Arizona, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Lucile Salter Packard Children's Hospital at Stanford
🇺🇸Palo Alto, California, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
St. Louis Children's Hospital
🇺🇸Saint Louis, Missouri, United States
The Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
Nemours/Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
University of Massachusetts Memorial Children's Medical Center
🇺🇸Worcester, Massachusetts, United States
Children's Medical Center Dallas
🇺🇸Dallas, Texas, United States
Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
Medical City Children's Hospital
🇺🇸Dallas, Texas, United States
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Children's Hospital at University of California San Francisco Medical Center
🇺🇸San Francisco, California, United States
Yale-New Haven Children's Hospital
🇺🇸New Haven, Connecticut, United States
Holtz Children's Hospital
🇺🇸Miami, Florida, United States
Florida Hospital for Children
🇺🇸Orlando, Florida, United States
Duke Children's Hospital and Health Center
🇺🇸Durham, North Carolina, United States
Monroe Carell, Jr. Children's Hospital at Vanderbilt
🇺🇸Nashville, Tennessee, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
C. S. Mott Children's Hospital of the University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Children's Mercy Hospital, Kansas City
🇺🇸Kansas City, Missouri, United States
Doernbecher Children's Hospital
🇺🇸Portland, Oregon, United States