SEOUL NATIONAL UNIVERSITY HOSPITAL

The research team headed by Professor Sang Hyub Lee (Department of Internal Medicine) in the Pancreatic and Biliary Cancer Center and Gastrointestinal internal medicine at the SNUH has elucidated for the first time worldwide that, even without using propofol, it is possible to improve the hypnotic-sedative effect during conscious sedation cholangiopancreatic endoscopy by twice or more.

For conscious sedation endoscopy, both hypnotic-sedatives and analgesic anesthetics are administered. As for hypnotic-sedatives, there are midazolam and propofol. Though the risk of side effects is small, midazolam is low in the hypnotic-sedative effect. While it boasts an outstanding hypnotic-sedative effect, propofol has a high risk of side effects such as respiratory distress.

In the clinical field, midazolam has been mainly used for safety. However, certain patients have experienced considerable trouble such as awakening during conscious sedation endoscopy.

According to recent studies, dexmedetomidine and midazolam, both hypnotic-sedatives, are known to improve the hypnotic-sedative effect when administered together. However, this has been determined through surgical operations and animal experiments and not confirmed through conscious sedation endoscopy tests.

For the first time around the world, the research team conducted prospective clinical tests on 110 patients awaiting endoscopic retrograde cholangiopancreatography (ERCP) to test the effectiveness of dexmedetomidine.

After administering midazolam and meperidine (a kind of analgesic anesthetic) to patients, the research team administered dexmedetomidine to the reference group (53 patients) and a physiological saline solution to the control group (57 patients), respectively. It then compared both the hypnotic-sedative effect and side effects of both groups during endoscopy.

The Ramsay sedation scale (RSS; 1-6 points) quantifies the hypnotic-sedative effect felt by patients. The RSS determines the grade based on patients’ reactions during tests, and the higher the points are, the greater the hypnotic-sedative effect is.

During conscious sedation endoscopy, when the RSS score is 3 points or more, the hypnotic-sedative effect is seen as appropriate. 3 points refer to patients simply responding only to the medical personnel’s orders in a sedate state.

Upon examination, the ratio of patients whose score on the RSS continued to be 3 points or more was 75.5% (40 patients) for the reference group but 36.8% (21 patients) for the control group, thus being low.

The dose of midazolam administered additionally for an appropriate hypnotic-sedative effect was smaller for the reference group than for the control group as well. This is because the combined administration of dexmedetomidine increased the hypnotic-sedative effect, thus decreasing the amount of additionally needed hypnotic-sedative (midazolam).

This also affected the recovery time after sedative anesthesia so that the recovery rate within 15 minutes after tests was 68% for the reference group but 32% for the control group. This is because the reference group used less hypnotic-sedative (midazolam) than did the control group.

There were differences in patients’ pain and satisfaction levels as well. On the survey conducted after endoscopy, the pain index (0-100 points) was 12 points for the reference group but was 32 points for the control group, thus being high. While the satisfaction index (0-100 points) was 82 points for the reference group, it was 59 points for the control group, thus being low.

While neither group suffered from serious side effects, oxygenation during tests was performed one time for the reference group but 11 times for the control group. The combined administration of midazolam and dexmedetomidine activated the gamma-aminobutyric acid (GABA) receptors (receptors of neurotransmitters) in the brain, thus increasing the sedative effect, the research team explained.

Saying, “Though excellent in the hypnotic-sedative effect, propofol has a very narrow therapeutic range so that even a slight overdose can be fatal,” Professor Lee stated, “I think the combined midazolam-dexmedetomidine treatment, which has been elucidated to have the greatest effect with the fewest side effects, will play a big role.”

This study was published as the cover paper in the April issue of Endoscopy, the most authoritative journal in gastrointestinal endoscopy.