Ketamine Use in Infants: Neurodevelopmental Concerns and Current Recommendations
Ketamine should be avoided in infants whenever possible due to potential adverse neurodevelopmental effects, particularly with repeated or prolonged exposure. If ketamine must be used, it should be limited to single doses and with careful monitoring.
Current Recommendations Regarding Neurodevelopmental Concerns
FDA Warnings and Evidence
- The FDA drug label for ketamine explicitly warns about potential neurodevelopmental risks, stating that studies in juvenile animals demonstrate that ketamine administration during periods of rapid brain growth can result in "widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis" 1
- The FDA specifically notes that this vulnerability window correlates with exposures from the third trimester through the first several months of life but may extend to approximately 3 years of age in humans 1
Clinical Evidence of Neurodevelopmental Impact
- A prospective clinical study found that infants who received three or more exposures to ketamine anesthesia showed lower neurodevelopmental scores on the Bayley Scales of Infant Development compared to their baseline assessments before ketamine exposure 2
- Elevated S-100β levels (a marker of neuronal damage) were observed after ketamine exposure in infants, suggesting potential neurological effects 2
Specific Recommendations for Different Clinical Scenarios
For Procedural Sedation in Infants
- Guidelines suggest that other induction agents should be used instead of ketamine whenever possible 3
- If ketamine must be used, the Association of Anaesthetists recommends careful monitoring and advising parents to observe the infant for signs of drowsiness and poor feeding 3
For Mechanical Ventilation in Neonates
- The American Academy of Pediatrics notes that ketamine was only "modestly effective" at reducing pain scores in ventilated preterm neonates and did not alter physiologic responses in heart rate and systemic blood pressure 3
- A recent prospective cohort study found that prolonged ketamine infusion (>24 hours) in critically ill children was associated with increased rates of adverse events, particularly delirium 4
Risk Factors and Special Considerations
Age-Related Concerns
- The period of greatest vulnerability appears to be during rapid brain development (third trimester through early infancy) 1
- Younger infants (<6 years) may be at higher risk for adverse effects such as laryngospasm (13.9% vs 3.6% in older children) 3
Dosing and Duration Considerations
- Single doses appear to have less neurodevelopmental impact than repeated exposures 2
- Prolonged infusions (>24 hours) should be particularly avoided due to increased risk of adverse events 4
Monitoring Recommendations When Ketamine Must Be Used
- Observe for signs of drowsiness and poor feeding after ketamine administration 3
- Monitor for potential adverse effects including:
Alternative Approaches
- For procedural sedation, consider alternative agents with better safety profiles in infants
- For pain management, consider opioids, which have been more extensively studied in neonates, though they also carry risks of respiratory depression 3
- For sedation in mechanically ventilated infants, propofol may be preferred as minimal amounts (0.025%) are transferred to breast milk 3
Conclusion
The current evidence strongly suggests caution with ketamine use in infants due to potential neurodevelopmental concerns. The FDA warning, clinical studies, and guidelines all point toward avoiding ketamine in this population when alternatives exist, particularly for repeated or prolonged use.