NEW UNIVERSITY

By: Karen Zhou
February 22, 2011

UC Irvine’s very own Dr. Zeev Kain has been dedicating his career to finding ways to reduce a child’s pain from surgery. With millions of dollars of funding from the National Institutes of Health (NIH), he continues to conduct studies and publish papers that will alter the way clinicians and anesthesiologists treat children.

One topic he has researched revolves around relieving children’s anxiety before surgery and reducing their delirium after the operation.

“These are two different phenomena that occur before and after a child undergoes surgery,” Kain said. “Midazolam is routinely given every day to help decrease anxiety, but we have found that melatonin works to reduce emergence delirium post-anesthesia.”

Midazolam is made chemically in a laboratory and works on the GABA receptors in the body, which respond to the primary inhibitory neurotransmitter in the vertebrate central nervous system. Used as a controlled agent, it is commonly given to surgery patients under the watchful eye of a health care provider in a setting that can provide immediate care should anything go wrong.

Regardless of how commonly it is administered, midazolam remains a drug, and all drugs come with inherent side effects. If the dose is too high, the patient may become extremely agitated and can even stop breathing.

“We are moving toward more behavioral studies,” Kain said. “Obviously, the best thing would be to find a natural alternative.”

While that substitute has not been found yet, Kain has found a way for a natural substance to relieve a child’s post-op delirium, which doctors refer to as emergence delirium.

Secreted in the brain, melatonin is continuously being produced in the body, and is often referred to as the “hormone of darkness.” It causes humans to sleep and Kain has found that orally administering melatonin significantly reduces the incidence of emergency delirium.

Studies had already been conducted in adults, showing that melatonin reduces their delirium levels. Research done on children was very limited, so Kain and his team decided to take the on the challenge.

After testing 148 children between the ages of 2 to 8 years, Kain’s results showed that melatonin triggered a similar response. However, because adults basically experience less severe anxiety, melatonin is administered right before surgery, sometimes by injecting straight in the vein. With children, it is given half an hour before surgery by the form of a syrup or oral supplement.

“There are a certain percentage of kids that cry, flail and scream after surgery. They look at you, but they don’t really see you and you just cannot comfort them. The fact that melatonin can ease this is really great, but this phenomenon is still very poorly understood and we have yet to find out exactly how it works,” Kain said.

Finishing training as a pediatrician, Kain has always enjoyed working with children. After completing a second residency at Yale University for anesthesiology, he devoted his research to taking care of children and trying to make their lives a little bit better.

After the melatonin and midazolam studies, Kain is focusing more on pain and what happens to children at home, before and after surgery.

He takes more of a behavioral approach, developing a web-based management system to reduce a child’s pain.

“It is an intervention that the child and parents take five days prior to surgery and 10 days after. It’s tailored specifically to them and their means, including their personalities, coping styles, belief systems and culture,” Kain said.

The group even hired a company that works with Nickelodeon to create unique characters. It teaches children what is going to happen during surgery and how they can manage the pain. For parents, the program offers relaxation and coping techniques.

Focus groups will soon be tested on how the system works. Once it passes that stage, which Kain is very positive that it will, it will go through trials to test how efficient it is.

Complementing this study, Kain is also researching how changing or modifying the behavior of the anesthesiologist can directly increase or decrease the pain a child experiences.

Kain began by videotaping over 300 children, parents and anesthesiologists when a child undergoes surgery. When the anesthesiologist provides empathy and reassurance, it is clearly seen that the child’s pain increases. However, when they provide distractions and offer children information, their pain actually decreases, during sleep and when they wake up.

“Changing the behavior of the anesthesiologist and nurses may be more effective than administering drugs,” Kain said. “We are trying to make a comprehensive strategy with two different modalities – one that treats the child at home on the Web and another that changes the behavior of anesthesiologists.”

Kain, who has studied anxiety and delirium, is redirecting his focus specifically to pain in children, something that he feels is really important.

“This is incredibly great in the clinician’s community because we are giving tools for them to use in order to reduce anxiety and pain,” Kain said. “There is nothing sadder than seeing a child screaming and now we are developing tools to put in their arsenals to prevent just that.”