Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood

NCT ID: NCT02225041

Last Updated: 2019-06-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 360 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2018-12-31

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.

Conditions

Intellectual Disability; Perceptual Disorders; Memory Disorders

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Eligibility Criteria

Inclusion Criteria

RESTORE subjects

• 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
• 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.

• Minimum Eligible Age: 30 Months
• Maximum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martha AQ Curley, RN, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

R. Scott Watson, MD

Role: PRINCIPAL_INVESTIGATOR

Seattle Childrens Hospital

Locations

Children's Hospital of Alabama

Birmingham, Alabama, 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

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

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Yale-New Haven Children's Hospital

New Haven, Connecticut, United States

Nemours/Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Holtz Children's Hospital

Miami, Florida, United States

Florida Hospital for Children

Orlando, Florida, United States

Children's Memorial Hospital, Chicago

Chicago, Illinois, United States

Advocate Hope Children's Hospital

Oak Lawn, Illinois, United States

University of Maryland Hospital for Children

Baltimore, Maryland, United States

Johns Hopkins Children's Center

Baltimore, Maryland, United States

University of Massachusetts Memorial Children's Medical Center

Worcester, Massachusetts, United States

C. S. Mott Children's Hospital of the University of Michigan

Ann Arbor, Michigan, United States

Children's Mercy Hospital, Kansas City

Kansas City, Missouri, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

The Children's Hospital at Montefiore

The Bronx, New York, United States

Duke Children's Hospital and Health Center

Durham, North Carolina, United States

Doernbecher Children's Hospital

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Monroe Carell, Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

Medical City Children's Hospital

Dallas, Texas, United States

Children's Medical Center Dallas

Dallas, Texas, United States

Primary Children's Medical Center

Salt Lake City, Utah, United States

Countries

United States

References

Curley MAQ, Watson RS, Cassidy AM, Burns C, Delinger RL, Angus DC, Asaro LA, Wypij D, Beers SR; RESTORE-cognition Study Investigators. Design and rationale of the "Sedation strategy and cognitive outcome after critical illness in early childhood" study. Contemp Clin Trials. 2018 Sep;72:8-15. doi: 10.1016/j.cct.2018.07.004. Epub 2018 Jul 11.

Reference Type: DERIVED

PMID: 30017814 (View on PubMed)

Other Identifiers

1R01HD074757-01A1

Identifier Type: NIH

Identifier Source: secondary_id

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1R01HD074757-01A1

Identifier Type: NIH

Identifier Source: org_study_id

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