The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
Condition: Anesthesia; Adverse Effect; Congenital Heart Disease; Neurodevelopmental Disorders
MeSH terms: Heart Diseases; Heart Defects, Congenital; Neurodevelopmental Disorders
Study type: Interventional

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.
    

Intervention name(s): Isoflurane; Fentanyl (high dose); Fentanyl (low dose)
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Isoflurane (volatile anesthesia) will be delivered at 1.5-2.0%% as required for anesthetic management.; Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr.; Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 2 mcg/kg/hr.
Intervention MeSH terms: Fentanyl; Isoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention