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Paediatr Anaesth. 2014 Mar;24(3):257-65. doi: 10.1111/pan.12257. Epub 2013 Sep 19.

Neurotoxicity of sedative and analgesia drugs in young infants with congenital heart disease: 4-year follow-up.

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Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.



To determine whether sedation/analgesia drugs used before, during, and after infant cardiac surgery are associated with neurocognitive and functional outcomes.


Some animal models suggest neurotoxic effects of anesthetic drugs on the developing brain; however, potential human effects are unknown. Whether these results can be extrapolated to humans is unknown.


Prospective follow-up project of all infants ≤6 weeks old having surgery for congenital heart disease between 04/03 and 12/06. Demographic, perioperative, and sedation/analgesia variables were collected. Outcomes at kindergarten age were Wechsler Preschool and Primary Scale of Intelligence-III, Beery-Buktenica Developmental Test of Visual Motor Integration (VMI-V), and General Adaptive Composite (GAC) of the Adaptive Behavior Assessment System-II. Multivariable linear regression was used to identify predictor variables.


From 135 infants who underwent heart surgery, 19 died, 17 were excluded, 8 were lost to follow-up, leaving 91 children for analysis. Multiple linear regression found days on chloral hydrate [3.5 (3.7) days] was associated with lower performance intelligence quotient (PIQ) (Effect size -1.03; 95% CI -1.96, -0.10; P = 0.03), and cumulative dose [54.2 (60.3) mg·kg(-1) ] of benzodiazepines was associated with lower VMI scores (Effect size -0.07; 95% CI -0.12, -0.01; P = 0.026). No other associations were found between sedation/analgesia variables and full-scale IQ, PIQ, Verbal IQ, VMI, or GAC.


Assessment of this cohort at kindergarten age found a small statistically significant association between days on chloral hydrate and PIQ, and benzodiazepine cumulative dose and lower VMI. No other association between sedation/analgesia drugs and outcomes was found.


analgesia; congenital heart disease; neonates; neurotoxicity; outcomes; sedation

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