ArticleAnesthesiology2021
Dose-dependent Respiratory Depression by Remifentanil in the Rabbit Parabrachial Nucleus/Kölliker-Fuse Complex and Pre-Bötzinger Complex.
Article in Anesthesiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Respiratory depression in women receiving propofol/esketamine versus propofol/fentanyl for abortion surgery or curettage: a randomized clinical trial.Annals of medicine · 2025Trial
- High proportions of respiratory and non-respiratory modulated pre-Bötzinger complex neurons receive monosynaptic inputs from the pontine respiratory group in rabbit.Respiratory physiology & neurobiology · 2026Article
- Intranasal Naloxone Reversal of Opioid-induced Respiratory Depression in Opioid-naive Individuals and Self-reported Daily Opioid Users.Anesthesiology · 2026Article
- Review
- Endogenous opioids and the development of the mammalian respiratory control network.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Sudden Death Induced by Acute Inhalation of Aerosolized Carfentanil.Archives of clinical and biomedical research · 2025Article
- Opioid-induced respiratory depression.BJA education · 2024Review
- ECDrug design, development and therapy · 2024Article
- Article
- Clinical study of the combined use of dexmedetomidine and remifentanil in patients with coronary heart disease undergoing 3D laparoscopic surgery with EEG bispectral index monitoring.International journal of clinical and experimental pathology · 2023Article
- Editorial: Opioid-induced respiratory depression: neural circuits and cellular pathways.Frontiers in physiology · 2023Article
- Changes in pontine and preBötzinger/Bötzinger complex neuronal activity during remifentanil-induced respiratory depression in decerebrate dogs.Frontiers in physiology · 2023Article
- Are thyrotropin-releasing hormone (TRH) and analog taltirelin viable reversal agents of opioid-induced respiratory depression?Pharmacology research & perspectives · 2022Review
- Contribution of the caudal medullary raphe to opioid induced respiratory depression.Respiratory physiology & neurobiology · 2022Article
- L-cysteine methyl ester overcomes the deleterious effects of morphine on ventilatory parameters and arterial blood-gas chemistry in unanesthetized rats.Frontiers in pharmacology · 2022Article
- Mu-opioid receptor-dependent transformation of respiratory motor pattern in neonatesFrontiers in physiology · 2022Article
- Current research in pathophysiology of opioid-induced respiratory depression, neonatal opioid withdrawal syndrome, and neonatal antidepressant exposure syndrome.Current research in toxicology · 2022Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundRecent studies showed partial reversal of opioid-induced respiratory depression in the pre-Bötzinger complex and the parabrachial nucleus/Kölliker-Fuse complex. The hypothesis for this study was that opioid antagonism in the parabrachial nucleus/Kölliker-Fuse complex plus pre-Bötzinger complex completely reverses respiratory depression from clinically relevant opioid concentrations.
methodsExperiments were performed in 48 adult, artificially ventilated, decerebrate rabbits. The authors decreased baseline respiratory rate ~50% with intravenous, "analgesic" remifentanil infusion or produced apnea with remifentanil boluses and investigated the reversal with naloxone microinjections (1 mM, 700 nl) into the Kölliker-Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex. In another group of animals, naloxone was injected only into the pre-Bötzinger complex to determine whether prior parabrachial nucleus/Kölliker-Fuse complex injection impacted the naloxone effect. Last, the µ-opioid receptor agonist [d-Ala,2N-MePhe,4Gly-ol]-enkephalin (100 μM, 700 nl) was injected into the parabrachial nucleus/Kölliker-Fuse complex. The data are presented as medians (25 to 75%).
resultsRemifentanil infusion reduced the respiratory rate from 36 (31 to 40) to 16 (15 to 21) breaths/min. Naloxone microinjections into the bilateral Kölliker-Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex increased the rate to 17 (16 to 22, n = 19, P = 0.005), 23 (19 to 29, n = 19, P < 0.001), and 25 (22 to 28) breaths/min (n = 11, P < 0.001), respectively. Naloxone injection into the parabrachial nucleus/Kölliker-Fuse complex prevented apnea in 12 of 17 animals, increasing the respiratory rate to 10 (0 to 12) breaths/min (P < 0.001); subsequent pre-Bötzinger complex injection prevented apnea in all animals (13 [10 to 19] breaths/min, n = 12, P = 0.002). Naloxone injection into the pre-Bötzinger complex alone increased the respiratory rate to 21 (15 to 26) breaths/min during analgesic concentrations (n = 10, P = 0.008) but not during apnea (0 [0 to 0] breaths/min, n = 9, P = 0.500). [d-Ala,2N-MePhe,4Gly-ol]-enkephalin injection into the parabrachial nucleus/Kölliker-Fuse complex decreased respiratory rate to 3 (2 to 6) breaths/min.
conclusionsOpioid reversal in the parabrachial nucleus/Kölliker-Fuse complex plus pre-Bötzinger complex only partially reversed respiratory depression from analgesic and even less from "apneic" opioid doses. The lack of recovery pointed to opioid-induced depression of respiratory drive that determines the activity of these areas. EDITOR’S PERSPECTIVE:
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