Ketamine Could Help Treat Severe Traumatic Brain Injuries in Children

Ketamine could help to treat severe traumatic brain injuries in children, a preliminary study suggests.

The results of the study, published in the journal Critical Care Medicine, indicate a potential shift in a decades-old paradigm regarding our understanding of how ketamine affects increased pressure in the skull.

Increased intracranial pressure (ICP) is a potentially life-threatening condition that can result from head trauma, among other causes. Traumatic brain injury is any injury to the head. A TBI is considered severe if a person is comatose—meaning they are unable to wake up—soon after the injury occurs.

Children with severe traumatic brain injury are at risk of dying or having long-term neurologic impairment, such as difficulty walking and talking.

"In the critical days following their initial injury, our focus in the pediatric intensive care unit [PICU] is to minimize ongoing damage to their brains, with a focus on preventing and treating high pressure inside of the skull, known as intracranial pressure," Dr. Michael Wolf, an author of the study who is with Monroe Carell Jr. Children's Hospital at Vanderbilt, told Newsweek.

"Despite decades of research, our treatment options remain limited to a handful of medicines and techniques. Investigating new treatments, including repurposing existing medications, is a crucial effort for clinicians and clinical researchers hoping to improve outcomes for our patients," said Wolf. He is an assistant professor of pediatrics and neurological surgery and director of neurocritical care in the hospital's Division of Critical Care Medicine.

Ketamine is a versatile medicine and perhaps the most widely used anesthetic in the world. First marketed in the 1970s, the drug is also used for analgesia, or pain relief. The World Health Organization (WHO) lists ketamine as an essential medicine.

Ketamine is safer to administer than other anesthetics and pain relief drugs because it does not depress breathing or lower blood pressure. It also does not require expensive patient-monitoring equipment.

According to the WHO, the drug's high level of safety make it "indispensable" for surgery in low- and middle-income countries, disaster zones and conflict areas where anesthesiologists may not be available and where running water, electricity and oxygen supplies are not easily accessible.

In recent years, researchers have been investigating the drug's potential for the treatment of mental health conditions, such as depression, post-traumatic stress disorder and anxiety.

Ketamine induces a sense of disassociation and disembodiment. Given its dissociative effects, it is also a commonly abused recreational drug.

The side effects of ketamine depend on several factors, including the type of drug (medical or recreational) and the dose, as well as a person's age and health status. These side effects may include nausea or vomiting, dizziness, muscle spasms or stiffness, urinary problems, confusion, heart-related problems, seizures, hallucinations and difficulty breathing.

Clinicians have traditionally avoided administering ketamine to patients with traumatic brain injuries because early studies suggested that the drug could raise ICP. But recent research has begun to question this paradigm.

In the Critical Care Medicine study, Wolf and his colleagues examined the medical records of 33 children with severe TBI who were cared for in the PICU at Monroe Carell Jr. Children's Hospital.

The children's ages ranged from 1 month to 16 years old. Twenty-two of the children received ketamine as part of a treatment protocol informed by evidence-based guidelines.

The researchers analyzed measurements taken of these patients' ICP to look for differences before and after each dose of ketamine. The key finding of their analysis was that ketamine did not raise ICP and, in some cases, even lowered it.

Eighteen ketamine doses were administered during ICP crises in 11 of the patients. Among these cases, the researchers observed an overall decrease in ICP.

"These findings suggest a potential shift in a decades-old paradigm related to ketamine and ICP," Wolf said. "Not only might ketamine be an appropriate choice as a sedative medication in patients with severe TBI, in some cases it may be useful as a treatment to lower ICP when it is dangerously high."

He continued: "If we are able to improve our understanding of ketamine's effects in a larger study, we might find that ketamine represents another tool to provide the best possible treatment for children with traumatic brain injury."

Children with severe TBI are some of the "most vulnerable patients" in any hospital, requiring thoughtful management by a multidisciplinary team, Wolf said.

"The stakes are high for these children, and minutes count," he said. "Adding any tool to improve their care could ultimately be impactful, supporting the best possible outcomes."

Other groups have begun studying ketamine's effects on adults with TBI.

While the results of the latest study show promise, it is important to note that the research is preliminary and more investigations will be required before such treatments can be approved.

"As with any study performed at a single center, we will need to confirm our findings by partnering with colleagues at other children's hospitals," Wolf said.

"If a larger study confirms that ketamine seems to be safe and potentially effective, these efforts could culminate in a trial testing whether incorporating ketamine into the care of children with severe TBI results in better outcomes," he said. "The field of pediatric neurocritical care emphasizes collaboration, and we are eager to build a team to do this important work."

Correction, 04/13/23, 12:50 p.m. ET: This story was updated to correct the name of Monroe Carell Jr. Children's Hospital at Vanderbilt.

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