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Dose-dependent Respiratory Depression by Remifentanil in the Rabbit Parabrachial Nucleus/Kölliker-Fuse Complex and
Barbara Palkovic1, Jennifer J Callison2, Vitaliy Marchenko2
1From the Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin; the Faculty of Medicine, University of Osijek, Osijek, Croatia.
Anesthesiology
|August 5, 2021
Summary
Opioid antagonism in key brainstem areas partially reversed respiratory depression in rabbits. This suggests that opioid-induced depression of respiratory drive significantly impacts these centers, limiting reversal effects.
Area of Science:
- Neuroscience
- Respiratory Physiology
- Pharmacology
Background:
- Opioid-induced respiratory depression is a significant clinical concern.
- Previous studies indicated partial reversal of opioid effects in specific brainstem nuclei.
Purpose of the Study:
- To test the hypothesis that combined opioid antagonism in the parabrachial nucleus/Kölliker-Fuse complex and pre-Bötzinger complex completely reverses opioid-induced respiratory depression.
- To investigate the efficacy of naloxone in reversing respiratory depression at clinically relevant opioid concentrations.
Main Methods:
- Experiments were conducted on artificially ventilated, decerebrate rabbits.
- Respiratory rate was decreased using remifentanil infusion or boluses.
- Naloxone microinjections were administered into the Kölliker-Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex.
Main Results:
- Naloxone microinjections into the Kölliker-Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex individually increased respiratory rate.
- Combined injections into the parabrachial nucleus/Kölliker-Fuse complex and pre-Bötzinger complex only partially reversed respiratory depression.
- Opioid agonist injection into the parabrachial nucleus/Kölliker-Fuse complex decreased respiratory rate.
Conclusions:
- Combined opioid antagonism in the parabrachial nucleus/Kölliker-Fuse complex and pre-Bötzinger complex did not fully reverse respiratory depression.
- The findings suggest that opioid-induced depression of respiratory drive limits the effectiveness of antagonism in these areas.
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