Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood



Status:Recruiting
Conditions:Cognitive Studies, Hospital, Neurology
Therapuetic Areas:Neurology, Psychiatry / Psychology, Other
Healthy:No
Age Range:Any - 13
Updated:10/17/2018
Start Date:August 2014
End Date:May 2019
Contact:Martha AQ Curley, RN, PhD
Email:curley@nursing.upenn.edu
Phone:215.573.9449

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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.

Inclusion Criteria:

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

Exclusion Criteria:

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.
We found this trial at
31
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Orlando, Florida 32803
Phone: 407-303-5600
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1600 7th Avenue
Birmingham, Alabama 35233
(205) 638-9100
Phone: 205-939-9387
Children's Hospital of Alabama Children
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282 Washington St
Hartford, Connecticut 06106
(860) 545-9000
Phone: 860-545-8737
Connecticut Children's Medical Center Connecticut Children’s Medical Center is a nationally recognized, 187-bed not-for-profit children’s...
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747 52nd St
Oakland, California 94609
(510) 428-3000
Phone: 510-428-3885
Children's Hospital and Research Center Oakland For nearly 100 years, Children's Hospital & Research Center...
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1201 W La Veta Ave
Orange, California 92868
(714) 997-3000
Phone: 714-509-8225
Children's Hospital of Orange County For more than 45 years, CHOC Children’s has been steadfastly...
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South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Principal Investigator: Athena Zuppa, MD
Phone: 215-898-4151
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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100 N Mario Capecchi Dr
Salt Lake City, Utah 84132
(801) 662-1000
Phone: 801-662-2442
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Ann Arbor, Michigan 48109
Phone: 734-763-7131
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Baltimore, Maryland 21201
Phone: 410-328-6957
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Baltimore, Maryland 21287
Principal Investigator: Cynthia Salorio, PhD
Phone: 443-923-4469
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Bronx, New York 10467
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2515 N Clark St
Chicago, Illinois 60614
(312) 227-6060
Principal Investigator: Scott Hunter, PhD
Phone: 773-702-7873
Children's Memorial Hospital, Chicago Ann & Robert H. Lurie Children
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7777 Forest Lane
Dallas, Texas 75230
Phone: 972-566-8340
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1935 Medical District Dr
Dallas, Texas 75235
(214) 456-7000
Principal Investigator: Lana Harder, PhD
Phone: 214-456-5877
Children's Medical Center of Dallas Children's Medical Center is private, not-for-profit, and is the fifth-largest...
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Durham, North Carolina
Phone: 919-681-5872
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Kansas City, Missouri 64108
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1 Medical Center Dr
Lebanon, New Hampshire 03756
 (603) 650-5000
Principal Investigator: Jonathan Lichtenstein, PsyD
Phone: 603-653-3658
Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock is a national leader in patient-centered health care and building...
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Miami, Florida 33136
Phone: 305-585-6051
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Nashville, Tennessee 37232
Phone: 615-936-3968
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New Haven, Connecticut 06511
Principal Investigator: Mary Best, PhD
Phone: 203-737-8378
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New Hyde Park, New York 11040
Phone: 718-470-3330
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Oak Lawn, Illinois 60453
Phone: 708-684-5685
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Emile St
Omaha, Nebraska 68198
(402) 559-4000
Phone: 402-955-4228
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Palo Alto, California 94304
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Portland, Oregon 97239
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2315 Stockton Blvd.
Sacramento, California 95817
(916) 734-2011
Phone: 916-734-2131
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Saint Louis, Missouri 63110
Phone: 314-454-2527
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San Francisco, California 94143
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Phone: 415-353-1946
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Tucson, Arizona 85724
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Wilmington, Delaware 19803
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Worcester, Massachusetts 01655
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