PANDA (Pediatric Anesthesia & NeuroDevelopment Assessment) Study

NCT ID: NCT00881764

Last Updated: 2023-02-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 369 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2016-01-31

Brief Summary

The purpose of this study is to determine whether the use of anesthetic agents in infants and children have long term adverse effects on neurocognitive development. According to the National Hospital Discharge Survey, around 2.5 million children have surgical procedures requiring anesthesia each year in the US. Recent animal studies have suggested that the exposure of the immature organism to a variety of commonly used anesthetic agents may lead to neurobehavioral functional deficits in vivo and to neuronal apoptosis in vitro. While the relevance of these findings on children exposed to anesthetics remains to be determined, it is clearly critically important to public health that this issue is resolved quickly and clearly.

Hypothesis: Exposure to anesthetic agents within the first three years of life will not significantly impair cognitive functions at ages 8 yr, 0 mo to 15 yr, 0 mo.

Detailed Description

The purpose of our study is to compare neurocognitive functions in sibling pairs: one of whom had exposure to anesthesia during surgery before 36 months of age (exposed sibling cohorts) and who would be from ages 8yr, 0 mo to15 yr, 0 mo at the time of the study; and the other who never had anesthesia or surgery less than 36 months of age, is from ages 8yr, 0mo to 15 yr, 0 mo at the time of the study, and is within 36 months of age range from the exposed sibling(unexposed sibling cohort).

Neuropsychological assessments are administered to the sibling cohorts prospectively and parents of the siblings will complete parental interviews/questionnaires. We assess individually neurocognitive, behavioral and emotional function for both exposed and unexposed siblings. Family function will also be evaluated. We will also obtain complete medical history for each participant, including significant perinatal events and social history. We also review medical records when appropriate.

All testing are performed during a one day site visit.

Conditions

Cognition - Other

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: OTHER

Study Groups

Exposed Cohort

Children who had inguinal hernia surgery and general anesthesia before 36 months of age (n=500). These children should be ages 8 yr, 0 mo to 15 yr, 0 mo at the time of the study period.

Inguinal hernia surgery

Intervention Type: PROCEDURE

Non-experimental procedure

General anesthesia

Intervention Type: PROCEDURE

Non-experimental procedure/treatment

Unexposed Cohort

Children who are siblings of the exposed children (inguinal hernia surgery and general anesthesia) and differ in age from the exposed children by less than 36 months and have no history of surgery or exposure to volatile and intravenous anesthetics or sedatives including barbiturates, benzodiazepines and chloral hydrate less than 36 months of age. These children should also be ages 8 yr, 0 mo to 15 yr, 0 mo at the time of the study period.

No interventions assigned to this group

Interventions

Inguinal hernia surgery

Non-experimental procedure

Intervention Type: PROCEDURE

General anesthesia

Non-experimental procedure/treatment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

Exposed cohort:

1. Subjects who had inguinal hernia surgery before 36 months of age

2. Ages 8 yr, 0 mo to 15 yr, 0 mo

3. Gestation age greater or equal to 36 weeks

4. Categorized as ASA I or ASA II

5. English speaking

6. Biologically related to the unexposed sibling

Unexposed cohort:

1. Sibling within 36 months of age of the exposed cohort

2. Never had surgery or exposure to anesthesia prior to 36 months of age

3. Ages 8 yr, 0 mo to 15 yr, 0 mo

4. Gestation age greater or equal to 36 weeks

5. Categorized as ASA I or ASA II

5. English speaking 6. Biologically related to the exposed sibling

Exclusion Criteria

Exposed cohort:

1. Gestational age less than 36 weeks at birth

2. No exposure to surgery or anesthesia prior to 36 months of age

3. Surgery/Anesthesia other than index hernia repair prior to 36 months of age

4. Not categorized as ASA I or ASA II

5. Not ages 8 yr, 0 mo to 15 yr, 0 mo

6. Not English speaking

7. Not biologically related to the unexposed sibling

Unexposed cohort:

1. Gestational age under 36 weeks at birth

2. Any exposure to surgery or anesthesia prior to 36 months of age

3. Not categorized as ASA I or ASA II

4. Not ages 8 yr, 0 mo to 15 yr, 0 mo

5. Not English speaking

6. Not biologically related to the unexposed sibling

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

NIH

Sponsor Role: collaborator

Office of Acquisitions and Grants Services (OAGS)

UNKNOWN

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Lena S. Sun

Emanuel M. Papper Professor of Anesthesiology and Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lena S Sun, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Children's Hospital Boston

Boston, Massachusetts, United States

Columbia University, 622 W. 168th St.

New York, New York, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999 Jan 1;283(5398):70-4. doi: 10.1126/science.283.5398.70.

Reference Type: BACKGROUND

PMID: 9872743 (View on PubMed)

Anand KJ, Soriano SG. Anesthetic agents and the immature brain: are these toxic or therapeutic? Anesthesiology. 2004 Aug;101(2):527-30. doi: 10.1097/00000542-200408000-00033. No abstract available.

Reference Type: BACKGROUND

PMID: 15277935 (View on PubMed)

Anand KJ. Anesthetic neurotoxicity in newborns: should we change clinical practice? Anesthesiology. 2007 Jul;107(1):2-4. doi: 10.1097/01.anes.0000268484.05444.35. No abstract available.

Reference Type: BACKGROUND

PMID: 17585205 (View on PubMed)

Olney JW, Young C, Wozniak DF, Jevtovic-Todorovic V, Ikonomidou C. Do pediatric drugs cause developing neurons to commit suicide? Trends Pharmacol Sci. 2004 Mar;25(3):135-9. doi: 10.1016/j.tips.2004.01.002. No abstract available.

Reference Type: BACKGROUND

PMID: 15019268 (View on PubMed)

Walden M, Carrier CT. Sleeping beauties: the impact of sedation on neonatal development. J Obstet Gynecol Neonatal Nurs. 2003 May-Jun;32(3):393-401. doi: 10.1177/0884217503253454.

Reference Type: BACKGROUND

PMID: 12774882 (View on PubMed)

Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children. Anesth Analg. 2007 Mar;104(3):509-20. doi: 10.1213/01.ane.0000255729.96438.b0.

Reference Type: BACKGROUND

PMID: 17312200 (View on PubMed)

Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, Olney JW, Wozniak DF. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci. 2003 Feb 1;23(3):876-82. doi: 10.1523/JNEUROSCI.23-03-00876.2003.

Reference Type: BACKGROUND

PMID: 12574416 (View on PubMed)

Slikker et al. FDA science 2005 Forum

Reference Type: BACKGROUND

Slikker W Jr, Zou X, Hotchkiss CE, Divine RL, Sadovova N, Twaddle NC, Doerge DR, Scallet AC, Patterson TA, Hanig JP, Paule MG, Wang C. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci. 2007 Jul;98(1):145-58. doi: 10.1093/toxsci/kfm084. Epub 2007 Apr 10.

Reference Type: BACKGROUND

PMID: 17426105 (View on PubMed)

Olney at al. FDA symposium. 2002:12:488-498

Reference Type: BACKGROUND

Jevtovic-Todorovic V. General anesthetics and the developing brain: friends or foes? J Neurosurg Anesthesiol. 2005 Oct;17(4):204-6. doi: 10.1097/01.ana.0000178111.26972.16. No abstract available.

Reference Type: BACKGROUND

PMID: 16184065 (View on PubMed)

Other Identifiers

R34HD060741

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HHSF223200810036C

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SmartTots

Identifier Type: OTHER

Identifier Source: secondary_id

AAAC8756

Identifier Type: -

Identifier Source: org_study_id