Clinical Trial to Examine Ketamine as an Alternative to Morphine to Treat Pain in Children

Whether it’s from a broken bone or abdominal issues, many children’s visits to the emergency room are associated with pain. At Children’s Wisconsin and many other treatment centers, these bouts of moderate or severe pain in children are commonly treated with intravenous morphine.

However, Amy L. Drendel, DO, professor of pediatrics and division chief of pediatric emergency medicine at the Medical College of Wisconsin (MCW), sees great promise in a different drug to treat pain in children: ketamine. Ketamine is a non-opioid dissociative anesthetic used medically for induction and maintenance of anesthesia.

“With the opioid crisis, we're looking for alternatives and ketamine shows promise as an option,” says Dr. Drendel, a world-renowned expert in pain research in children and medical director of emergency medicine at Children’s Wisconsin. “Low-dose ketamine can be effective at reducing pain and may be associated with fewer side effects and lower risk of addiction.”

A $16 million grant from the National Institutes of Health’s (NIH) National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Human Development as part of the Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, will allow Dr. Drendel and colleagues to test that theory.

Dr. Drendel will join Daniel S. Tsze MD, professor of pediatrics in the Department of Emergency Medicine at the Columbia University Irving Medical Center, as the primary investigators of a new study that will compare the outcomes of ketamine versus morphine as part of a five-year clinical trial. Terri A. deRoon-Cassini, PhD, professor of surgery and director of the Comprehensive Injury Center at MCW is a co-investigator.

Morphine has been associated with adverse events such as hypotension and respiratory depression. Because it’s an opioid, there is some hesitation among caregivers to administer the drug to children and among parents to allow their children to be treated with it.

Ketamine has the potential to improve short- and long-term treatment of pain in children, lower rates of cardiorespiratory events, and positively impact other outcomes, such as anxiety, post-traumatic stress and depression.

In the study, the investigators aim to determine whether ketamine is more effective than morphine in decreasing pain intensity in children treated at the emergency department, compare adverse events in both treatments, and examine the relationship between ketamine and the aftereffects of acute pain.

“We'll be able to evaluate the role of these emergency department interventions to treat acute pain and then follow patients longitudinally over six months to evaluate for these other outcomes and determine whether there is impact,” Dr. Drendel says.

The study will be conducted as a randomized clinical trial at eight sites within the Pediatric Emergency Care Applied Research Network (PECARN), including Children's Wisconsin. Information will eventually be collected from 1,010 children aged 6-17 with moderate to severe acute pain and require IV morphine for analgesia. The goal is to begin enrolling patients by September 2025.

The findings of the study have the potential to change how acute pain is managed in children, improving their short- and long-term health. It could result in a transition from morphine, an opioid, to sub-dissociative ketamine as the primary pain treatment tool for children with moderate to severe acute pain.

“It would be great if ketamine was either as good or better at controlling pain than the opioid morphine, have less side effects, and help with other outcomes associated with pain, including post-traumatic stress disorder, anxiety and depression,” Dr. Drendel says. “If I can more effectively treat pain in the emergency department and the child continues to have better outcomes once they go home, that would be a real win.”