Using isovaline in combination with anesthetic drugs may avoid the need for opioids and thus avoid the risk of potentially serious complications—especially opioid-related respiratory depression, according to the study by Dr. Bernard A. MacLeod of and colleagues of The University of British Columbia, Vancouver.
Isovaline Is Safe and Effective for Sedation and AnesthesiaIsovaline is a unique type of analgesic (pain-reducing) drug that acts on one specific type of neuroceptor: the GABAB receptors. Because it doesn't cross the "blood-brain barrier," isovaline acts only on peripheral neuroreceptors outside the central nervous system.
Dr. MacLeod and colleagues performed a series of studies in mice to see if isovaline could be used instead of opioids (morphine and related drugs) for anesthesia. Animals received the "hypnotic" anesthesia drug propofol, along with either isovaline or the opioid drug fentanyl.
The goal was to evaluate isovaline as a potentially safer alternative to opioids for use in anesthesia. Because opioids act on GABAA receptors while isovaline acts on GABAB receptors, the combination of the two might have synergistic effects in achieving general anesthesia.
Given together with an effective dose of propofol, isovaline produced both general anesthesia and conscious sedation. Propofol alone produced hypnosis, but didn't block pain responses; adding isovaline to propofol "resulted in loss of consciousness and immobility to noxious stimuli."
The combination of propofol and fentanyl also resulted in general anesthesia, but with an increased risk of respiratory depression. Even at the maximum dose, isovaline caused no apparent respiratory depression or other adverse effects. "The margin of safety for propofol-isolvaline was considerably higher than for propofol-fentanyl," Dr. MacLeod and coauthors write.
"Combinations of hypnotics and potent analgesics have been commonly used for procedural sedation and intravenous anesthesia," explains Dr. Steven L. Shafer of Stanford University, Editor-in-Chief of Anesthesia & Analgesia. "This procedure carries a risk of severe opioid-induced respiratory depression."
The results suggest that isovaline might be a useful new alternative for general anesthesia and procedural sedation. Because it doesn't have significant central nervous system effects, isovaline could improve the effectiveness of both types of anesthesia, without increasing the risk of serious adverse effects.
"This study in rodents provides a novel concept that may improve safety of intravenous anesthesia and procedural sedation in clinical settings," Dr. Shafer adds. While the experimental results support the concept of combining isovaline with anesthetics, more research will be needed to see how they translate to clinical anesthesia in humans.
Anesthesia & Analgesia is published by Wolters Kluwer.
Read the article in Anesthesia & Analgesia.
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About Anesthesia & AnalgesiaAnesthesia & Analgesia was founded in 1922 and was issued bi-monthly until 1980, when it became a monthly publication. A&A is the leading journal for anesthesia clinicians and researchers and includes more than 500 articles annually in all areas related to anesthesia and analgesia, such as cardiovascular anesthesiology, patient safety, anesthetic pharmacology, and pain management. The journal is published on behalf of the IARS by Lippincott Williams & Wilkins (LWW), a division of Wolters Kluwer Health.
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