Craniocerebral injuries, commonly known as traumatic brain injuries, are one of the leading causes of disability and death in children worldwide.

The impact of such injuries on a child’s quality of life and long-term physiological, cognitive, and psychological outcomes are considerable. The pathophysiology is complex and involves primary mechanical injury, followed by a cascade of secondary injury events that cause inflammation, oxidative stress, edema, and excitotoxicity, ultimately leading to neuronal death and brain damage.

Several treatments, such as surgery, physical therapy, and pharmacotherapy, have been established as standard care for pediatric craniocerebral injuries. However, these treatments often show limited success and side effects, making it necessary to explore alternative or complementary therapies.

Ketamine and Traumatic Brain Injury Treatment

Ketamine is a dissociative anesthetic that has been an attractive drug candidate for treating traumatic brain injury due to its unique neuroprotective, anti-inflammatory, and analgesic properties.

The mechanism of ketamine’s action involves blockage of N-methyl-D-aspartate (NMDA) receptors, which prevents excitotoxicity and glutamate toxicity and reduces neurotransmitter release. Ketamine also regulates the levels of pro-inflammatory cytokines and upregulates gamma-aminobutyric acid (GABA) activity, which reduces inflammation and oxidative stress and stabilizes neuronal activity.

Ketamine and Pediatric Traumatic Brain Injury

Ketamine is an established anesthetic and analgesic in pediatric surgery, and several studies have suggested that it has the potential to be an effective treatment for pediatric traumatic brain injury. A study by Pascoal et al.

found that ketamine administration to children with traumatic brain injury resulted in a significant reduction in the intracranial pressure and improvement in cerebral blood flow velocity. Similarly, a randomized controlled trial by Shi et al. demonstrated that ketamine infusion therapy could improve the outcomes in children with traumatic craniocerebral injuries compared to standard treatments such as neuroprotective agents.

The study showed that the ketamine-treated group had better Glasgow Coma Scale scores, shorter intensive care unit stays, and lower mortality rates compared to the control group.

Mechanism of Action of Ketamine in Pediatric Traumatic Brain Injury

Ketamine’s mechanism of action in pediatric traumatic brain injury is multi-faceted.

Ketamine binds to the NMDA receptors in the brain, which not only blocks the excitotoxicity and glutamate toxicity but also enhances the levels of brain-derived neurotrophic factor (BDNF), which promotes neuronal survival and regeneration. The release of BDNF protects the neurons from further damage and stimulates their regeneration, leading to functional recovery.

Ketamine also reduces inflammation and oxidative stress and stabilizes the neuronal activity by upregulating GABA activity, which protects the cells from toxicity and prevents secondary injury progression.

Clinical Applications of Ketamine in Pediatric Traumatic Brain Injury

Ketamine is clinically used in a variety of ways for pediatric traumatic brain injury. It can be administered as a single bolus injection or in continuous infusion over an extended period of time.

Infusion therapy is commonly used in the critical care setting to maintain hemodynamic stability, improve neurologic function, and prevent secondary infection. However, ketamine’s use in pediatrics has been limited by concerns about its possible neurotoxic effects.

Animal studies have shown that exposure to ketamine at excessive doses or prolonged periods can lead to apoptosis and gliosis in the developing brain. However, the exact doses and duration of ketamine required to cause such effects in humans remain uncertain.

Therefore, it is essential to use ketamine judiciously in pediatric traumatic brain injury patients and to monitor their neurological status closely.

Future of Ketamine in Pediatric Traumatic Brain Injury

The potential of ketamine to improve the outcomes of pediatric traumatic brain injury is promising.

However, further clinical studies are required to determine the optimal dosage, duration, and mode of ketamine administration for pediatric traumatic brain injury patients. Additionally, the therapeutic window of ketamine needs to be carefully investigated to prevent unnecessary complications.

Future studies can also explore the use of ketamine in combination with other therapies, such as stem cell therapy or neuromodulation techniques, to maximize functional recovery.

Conclusion

Ketamine is a potent neuroprotective, anti-inflammatory, and analgesic agent that has shown promising results in improving the outcomes of pediatric traumatic brain injury.

The mechanism of action of ketamine involves blocking the NMDA receptors, regulating the levels of cytokines and BDNF, and upregulating GABA, which ultimately promotes neuronal survival and regeneration. Although further clinical studies are required to determine the optimal use of ketamine in pediatric traumatic brain injury, the potential benefits of ketamine in improving the quality of life of these patients are enormous.