The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)

NCT ID: NCT03882788

Last Updated: 2022-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-22
• Study Completion Date: 2020-11-19

Brief Summary

The purpose of this study is to assess whether the type of anesthesia, narcotic-based versus inhalational anesthesia administered during cardiopulmonary bypass (CPB) surgery contributes to the wide variation in neurologic recovery and developmental outcome after surgery in infants with congenital heart disease.

Detailed Description

All subjects will be consented prior to participation in this study and prior to randomization.

All the subjects enrolled in the study will receive a preoperative assessment by one of the cardiac anesthesiologists and receive standardized induction with sevoflurane up to 2%, 2 mcg/kg of fentanyl and 1 mg/kg of rocuronium. The anesthetic maintenance will be determined using a computer- generated randomization table and assigning each patient to one of the two anesthetic regimens. Both of these anesthetic techniques are standard of care and are commonly used for these procedures.

Anesthetic Technique:

Volatile anesthetic:

In volatile anesthetic technique, maintenance of anesthesia will be standardized to the volatile anesthetic isoflurane. Isoflurane will be used for the study since this is what is presently available on the CPB machines. Anesthesia at 1.0 minimum anesthetic concentration (MAC) indicates that at this concentration 50% of the patients will not move when surgically stimulated. Anesthesiologists commonly use about 1.2-1.4 MAC in neonates, since the MAC value in infants is higher than that of children and adults. Isoflurane will be delivered at 1.5-2.0%% as required for anesthetic management.

Rocuronium or pancuronium will be used for muscle relaxation. Narcotic, fentanyl will be administered at no greater than 2 mcg/kg/hr.

Narcotic-based anesthetic:

In narcotic based anesthetic technique, no volatile anesthetics will be used except during induction.

Maintenance of anesthesia will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr.

The anesthetic may be supplemented with dexmedetomidine 0.05 mcg/kg/hr but not to exceed 1.0 mcg/kg/hr. Narcotic-based anesthetic will be used by the cardiac anesthesia team and the CPB technician throughout the operative case. 5 mcg/kg/hr of fentanyl is felt to represent 0.6 MAC of anesthesia.

Postoperative Sedative and Analgesic Care:

As per institutional standard of care, postoperative sedation will consist of fentanyl infusions of 2-4 mcg/kg/hr for the first 48 hours postoperatively.

A total of 9 Blood samples will be collected at different time points throughout the entire study for metabolomics determination (NAA/Cr and Chol/Cr)

EEG monitoring will be done for baseline in the pre-operative period for 15-20 minutes, during surgery and post-operatively up to 48 hours and prior to discharge for 15-20 minutes. Neurological and behavioral testing including Bayley Exam III will be done at 18-48 months.

Conditions

Anesthesia; Adverse Effect; Congenital Heart Disease; Neurodevelopmental Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Volatile Anesthesia

In volatile anesthetic technique, maintenance of anesthesia will be standardized to the anesthesia will be standardized to the volatile anesthetic isoflurane.

Rocuronium or pancuronium will be used for muscle relaxation. Additionally, narcotic fentanyl will be administered at no greater than 2 mcg/kg/hr (low dose). However, the primary anesthetic during CPB will be isoflurane with no narcotic administered during CPB.

Group Type: ACTIVE_COMPARATOR

Isoflurane

Intervention Type: DRUG

Isoflurane (volatile anesthesia) will be delivered at 1.5-2.0%% as required for anesthetic management.

Fentanyl (low dose)

Intervention Type: DRUG

Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 2 mcg/kg/hr.

Narcotic based anesthesia

In narcotic based anesthetic technique, no volatile anesthetics will be used past induction.

Maintenance of anesthesia will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr (high dose).

Group Type: ACTIVE_COMPARATOR

Fentanyl (high dose)

Intervention Type: DRUG

Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr.

Interventions

Isoflurane

Isoflurane (volatile anesthesia) will be delivered at 1.5-2.0%% as required for anesthetic management.

Intervention Type: DRUG

Fentanyl (high dose)

Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr.

Intervention Type: DRUG

Fentanyl (low dose)

Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 2 mcg/kg/hr.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Neonates of at least 32 weeks of gestation, infants and children up to 2 years of age admitted to The Children's Hospital for treatment of cyanotic or non-cyanotic heart disease requiring surgical intervention.
• Admitting diagnosis of cyanotic or non-cyanotic heart disease

Exclusion Criteria

• Neonates less than 32 weeks of gestational age, and children more than 2 years of age.
• Any documented central nervous system malformations.
• Any potential subject requiring unexpected postoperative Extracorporeal membrane oxygenation (ECMO) support

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 36 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Gerber Foundation

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa W Faberowski, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford Childrens hospital

Palo Alto, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NDO

Identifier Type: -

Identifier Source: org_study_id