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Performance on the Operant Test Battery in young children exposed to procedures requiring general anaesthesia: the
David O Warner1, John J Chelonis2, Merle G Paule2
1Department of Anesthesiology and Perioperative Medicine, USA.
Insights
General anesthesia exposure in young children did not show significant neurodevelopmental deficits on the Operant Test Battery (OTB). Findings suggest anesthesia safety in pediatric patients, contrasting with animal study results.
Area of Science:
- Pediatric Anesthesiology
- Neurodevelopmental Toxicology
- Cognitive Psychology
Background:
- Concerns exist regarding potential neurotoxicity of anesthetics in young children, mirroring findings in animal models.
- Infant macaque exposure to ketamine has demonstrated impaired cognitive performance on the Operant Test Battery (OTB).
- This study investigates whether similar neurodevelopmental effects are observed in children exposed to general anesthesia before age three.
Purpose of the Study:
- To determine if children exposed to general anesthesia before age 3 exhibit similar neurodevelopmental deficits on the OTB as observed in infant macaques.
- To assess the long-term cognitive effects of early-life anesthesia exposure in humans.
Main Methods:
- Analysis of data from the Mayo Anesthesia Safety in Kids (MASK) study.
- Inclusion of unexposed, singly-exposed, and multiply-exposed children sampled via a propensity-guided approach.
- Prospective Operant Test Battery (OTB) testing at ages 8-12 or 15-20 years, utilizing five tasks yielding 15 OTB scores.
Main Results:
- Primary analysis revealed no significant differences in OTB test scores based on anesthesia exposure status after correcting for multiple comparisons.
- Cluster analysis did not identify any association between anesthesia exposure status and subject clusters based on OTB performance.
- Exploratory factor analysis indicated a potential, though not robust, association between multiple anesthesia exposures and one cognitive factor.
Conclusions:
- The study found minimal evidence supporting the hypothesis that anesthesia exposure in early childhood leads to OTB deficits comparable to those in non-human primates.
- Findings suggest that general anesthesia administered to young children may not produce the same neurodevelopmental impairments observed in animal models.
- Further research may be warranted to fully elucidate the long-term neurodevelopmental effects of pediatric anesthesia.
Background:
It is not known whether the neurotoxicity produced by anaesthetics administered to young animals can also occur in children. Exposure of infant macaques to ketamine impairs performance in selected domains of the Operant Test Battery (OTB), which can also be administered to children. This study determined whether a similar pattern of results on the OTB is found in children exposed to procedures requiring general anaesthesia before age 3 yr.
Methods:
We analysed data from the Mayo Anesthesia Safety in Kids (MASK) study, in which unexposed, singly-exposed, and multiply-exposed children born in Olmsted County, MN, USA, from 1994 to 2007 were sampled using a propensity-guided approach and prospectively underwent OTB testing at ages 8-12 or 15-20 yr, using five tasks that generated 15 OTB test scores.
Results:
In primary analysis, none of the OTB test scores depended upon anaesthesia exposure status when corrected for multiple comparisons. Cluster analysis identified four clusters of subjects, with cluster membership determined by relative performance on the OTB tasks. There was no evidence of association between exposure status and cluster membership. Exploratory factor analysis showed that the OTB scores loaded onto four factors. The score for one factor was significantly less in multiply-exposed children (mean standardised difference -0.28 [95% confidence interval, -0.55 to -0.01; P=0.04]), but significance did not survive a sensitivity analysis accounting for outlying values.
Conclusions:
These findings provide little evidence to support the hypothesis that children exposed to procedures requiring anaesthesia show deficits on OTB tasks that are similar to those observed in non-human primates.
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