Neurodevelopmental outcome following exposure to sedative and analgesic drugs for complex cardiac surgery in infancy

Paediatr Anaesth. 2011 Sep;21(9):932-41. doi: 10.1111/j.1460-9592.2011.03581.x. Epub 2011 Apr 21.


Objectives/aim: To determine whether sedation/analgesia drugs used before, during, and after infant cardiac surgery are associated with neurodevelopmental outcome.

Background: Animal models suggest detrimental effects of anesthetic drugs on the developing brain. Whether these results can be extrapolated to human neonates is unclear.

Methods/materials: This is a prospective follow-up project conducted in Western Canada. In all infants ≤6 weeks of age having surgery for congenital heart disease between April 2003 and December 2006, demographic and perioperative variables were collected prospectively. Sedation/analgesia variables were collected retrospectively. For each drug class (inhalationals, opioids, benzodiazepines, ketamine, and chloral hydrate), we calculated the cumulative dose received during hospitalization, average dose received per day, and cumulative number of days the patient received the drug. The outcomes at 18-24 months were as follows: General Adaptive Composite and motor scaled scores of the Adaptive Behavior Assessment System, significant mental, motor, and vocabulary delay. Multivariable logistic and linear regression was used to analyze the data.

Results: One hundred and thirty-five neonates underwent open heart surgery; 19 died, 16 had chromosomal abnormality, and five were lost to follow up, leaving 95 survivors for analysis. Multiple linear regression analysis found no evidence of an association between sedation/analgesia variables and ABAS-GAC score or motor scale score. Multiple logistic regression analysis found no evidence of an association between sedation/analgesia variables and significant mental, motor, or vocabulary delay.

Conclusion: We found no evidence of an association between dose and duration of sedation/analgesia drugs during the operative and perioperative period and adverse neurodevelopmental outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / adverse effects*
  • Cardiac Surgical Procedures / adverse effects*
  • Cohort Studies
  • Developmental Disabilities / chemically induced*
  • Developmental Disabilities / epidemiology
  • Female
  • Heart Defects, Congenital / surgery
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Infant
  • Infant, Newborn
  • Male
  • Nervous System / growth & development*
  • Neuropsychological Tests
  • Prospective Studies
  • Treatment Outcome


  • Analgesics
  • Hypnotics and Sedatives