Clinical trial NCT03882788: The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
Official title: Anesthesia and the Developing Brain: a Comparison of Two Anesthetic Techniques
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anesthesia; Adverse Effect
Congenital Heart Disease
Neurodevelopmental Disorders
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: The Gerber Foundation
First posted: 2019-03-20
Enrollment: 153
Sex: ALL
Minimum age (years): 1
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Bayley III
timeFrame: Assessed once between age 18 to 48 months (approximately 2 hours to assess), up to 48 months from study start
measure: Electroencephalogram
timeFrame: EEG taken immediately prior to surgery, during surgery, during cardiovascular intensive care unit (CVICU) stay (up to 48 hours after surgery), and immediately prior to discharge (between 5 to 20 minutes to assess EEG at each time point)
Secondary outcomes:
measure: Choline
timeFrame: 0-72 hours
measure: Glutamate
timeFrame: 0-72 hours
measure: N-acetylaspartate (Naa)
timeFrame: 0-72 hours
measure: Lactate
timeFrame: 0-72 hours
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Childrens hospital
state: California
Study officials:
affiliation: Stanford University
name: Lisa W Faberowski, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: