Children undergoing complex cardiac surgery are exposed to substantial cumulative doses of sedative medications and volatile anesthetics and are more frequently anesthetized with ketamine, compared with healthy children. This study hypothesized that greater exposure to sedation and anesthesia in this population is associated with lower neurodevelopmental scores at 18 months of age.


A secondary analysis was conducted of infants with congenital heart disease who participated in a prospective observational study of environmental exposures and neurodevelopmental outcomes to assess the impact of cumulative volatile anesthetic agents and sedative medications. Cumulative minimum alveolar concentration hours of exposure to volatile anesthetic agents and all operating room and intensive care unit exposures to sedative and anesthesia medications were collected before administration of Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley III), at 18 months of age.


The study cohort included 41 (37%) single-ventricle and 69 (63%) two-ventricle patients. Exposures to volatile anesthetic agents, opioids, benzodiazepines, and dexmedetomidine were not associated with abnormal Bayley III scores. At 18-month follow-up, after adjusting for confounders, each mg/kg increase in ketamine exposure was associated with a 0.34 (95% CI, −0.64 to −0.05) point decrease in Bayley III motor scores (P = 0.024).


Total cumulative exposures to volatile anesthetic agents were not associated with neurodevelopmental impairment in infants with congenital heart disease undergoing various imaging studies and procedures, whereas higher ketamine doses were associated with poorer motor performance.

Editor’s Perspective
What We Already Know about This Topic
  • Preclinical data suggest that cumulative exposure to general anesthetics in the early postnatal period can induce lasting impairment of neurodevelopment
  • Children with congenital cardiac abnormalities undergo prolonged diagnostic and surgical procedures requiring multiple anesthetic exposures early in life
  • The question of whether greater exposure to general anesthesia in children with congenital heart disease is associated with worse neurodevelopmental outcomes is incompletely explored
What This Article Tells Us That Is New
  • In this secondary analysis of a prospective study evaluating neurodevelopmental outcomes of pediatric patients with congenital heart disease, no association was found between total cumulative exposures to volatile anesthetics and Bayley III scores assessed at 18 months of age, whereas higher ketamine doses were associated with poorer motor performance