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Contribution of the caudal medullary raphe to opioid induced respiratory depression. Respir Physiol Neurobiol 2022 May;299:103855

Date

02/07/2022

Pubmed ID

35124284

Pubmed Central ID

PMC8897277

DOI

10.1016/j.resp.2022.103855

Scopus ID

2-s2.0-85124754852 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

BACKGROUND: Opioid-induced respiratory depression can be partially antagonized in the preBötzinger Complex and Parabrachial Nucleus/Kölliker-Fuse Complex. We hypothesized that additional opioid antagonism in the caudal medullary raphe completely reverses the opioid effect.

METHODS: In adult ventilated, vagotomized, decerebrate rabbits, we administrated remifentanil intravenously at "analgesic", "apneic", and "very high" doses and determined the reversal with sequential naloxone microinjections into the bilateral Parabrachial Nucleus/Kölliker-Fuse Complex, preBötzinger Complex, and caudal medullary raphe. In separate animals, we injected opioid antagonists into the raphe without intravenous remifentanil.

RESULTS: Sequential naloxone microinjections completely reversed respiratory rate depression from "analgesic" and "apneic" remifentanil, but not "very high" remifentanil concentrations. Antagonist injection into the caudal medullary raphe without remifentanil independently increased respiratory rate.

CONCLUSIONS: Opioid-induced respiratory depression results from a combined effect on the respiratory rhythm generator and respiratory drive. The effect in the caudal medullary raphe is complex as we also observed local antagonism of endogenous opioid receptor activation, which has not been described before.

Author List

Palkovic B, Cook-Snyder D, Callison JJ, Langer TM 3rd, Nugent R, Stuth EAE, Zuperku EJ, Stucke AG

Authors

Denise R. Cook-Snyder PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Astrid G. Stucke MD Professor in the Anesthesiology department at Medical College of Wisconsin
Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin
Edward J. Zuperku PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analgesics, Opioid
Animals
Apnea
Medulla Oblongata
Naloxone
Narcotic Antagonists
Rabbits
Respiratory Insufficiency