Disruption of the Rhythmic Activity of the Medullary Inspiratory Neurons and Phrenic Nerve by Fentanyl and Reversal with Nalbuphine

Tabatabai, M.; Kitahata, Luke M.; Collins, J. G.

doi:10.1097/00000542-198903000-00020

Cited by 28 publications

(12 citation statements)

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“…Opioids may also alter other neuronal mechanisms that promote chest wall rigidity, ones that have not yet been challenged with D 1 R agonists and that could be resistant. For example, Tabatabai et al (29) found that fentanyl induced tonic discharges of inspiratory neurons in the nucleus of the solitary tract in cats and suggested that the effect might lead to sustained contraction of inspiratory muscles.…”

Section: Discussionmentioning

confidence: 99%

D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Lalley¹

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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A previous study in this laboratory showed that dopamine-D1 receptor (D1R) agonists restored phrenic nerve activity after arrest by fentanyl in immobilized, mechanically ventilated cats. The reinstated phrenic nerve rhythm was slower than control, so it was not known whether D1R agonists can restore spontaneous breathing to levels that provide favorable alveolar gas exchange and blood oxygenation. It was also not known whether the agonists counteract opioid analgesia. In the present study, anesthetized, spontaneously breathing cats were given intravenous doses of fentanyl (18.0 Ϯ 3.4 g/kg) that severely depressed depth and rate of respiration, lowered arterial hemoglobin oxygenation (HbO2), elevated end-tidal carbon dioxide (ETCO2), and abolished the nociceptive hind limb crossed-extensor reflex. Fentanyl (30 g/kg) also evoked tonic discharges of caudal medullary expiratory neurons in paralyzed mechanically ventilated cats, which might explain decreased chest compliance. The selective D1R agonists 6-chloro APB (3 mg/kg) or dihydrexidine (DHD, 1 mg/kg) increased depth and rate of spontaneous breathing after opioid depression and returned HbO2 and ETCO2 to control levels. Opioid arrest of the nociceptive reflex remained intact. Pretreatment with DHD prevented significant depression of spontaneous breathing by fentanyl (17.5 Ϯ 4.3 g/kg). Tonic firing evoked by fentanyl in expiratory neurons was converted to rhythmic respiratory discharges by DHD (1 mg/kg). The results suggest that D1R agonists might be therapeutically useful for the treatment of opioid disturbances of breathing without impeding analgesia. expiratory neuron discharges; fentanyl; nociceptive reflex; phrenic nerve activity; respiration and ventilation OPIATES ARE AMONG THE OLDEST and most frequently used drugs for the alleviation of pain, coughing, and smooth muscle spasticity. However, their therapeutic effects are produced at a cost to breathing. Tidal volume and gas exchange are depressed, and respiration is slowed or arrested after an opiate overdose. Therapeutic doses of opiates blunt respiratory responsiveness to carbon dioxide (32,13,28,9), but normal breathing and ventilation are maintained in most individuals because carotid body and medullary chemoreceptors are further stimulated by elevated CO 2 and a consequent acid shift in pH of the arterial blood and extracellular fluid (27, 13). On the other hand, in some patients with renal, pulmonary and cardiac diseases, CO 2 desensitization predisposes them toward respiratory depression by normal doses of opiates (5, 6). In addition, fentanyl and its derivatives can impair ventilation during and after surgery by inducing chest wall rigidity (8a, 25)Opiate receptor antagonists such as naloxone counteract respiratory effects of opioids, but they also block analgesia (5a). They can also produce hypertension, tachycardia, ventricular arrhythmias, and pulmonary edema (9). Thus novel pharmacological approaches are sought that will preserve the therapeutic usefulness of opiates, particularly analgesia, wi...

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Section: Discussionmentioning

confidence: 99%

D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Lalley¹

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…; Tabatabai et al . ). Juxtacellular microiontophoresis of morphine evokes postsynaptic depression, whereas i.v.…”

Section: Medullary Neurons Distributed Throughout the Bulbar Respiratmentioning

confidence: 97%

CrossTalk opposing view: The pre‐Bötzinger complex is not essential for respiratory depression following systemic administration of opioid analgesics

Lalley

Pilowsky

Forster

et al. 2014

The Journal of Physiology

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“…The pH of the serum or plasma can markedly affect opioid plasma binding [8,9]. Therefore, we can assume that there was no change in the free probably involving a decrease in the sensitivity of the Discussion respiratory centre to CO 2 [10]. In the pethidine group pH was initially normal but decreased significantly during the trial, although the pH of arterial blood remained within the normal range.…”

Section: Haemodynamic Parametersmentioning

confidence: 99%

Comparison of respiratory effects of tramadol and pethidine

1998

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Tramadol is a centrally acting opioid with a low affinity for mu-opioid receptors, which has been claimed not to depress respiration as do the classic opioids. The respiratory effects of intravenous (i.v.) pethidine (0.6 mg kg-1) and tramadol (0.6 mg kg-1) were compared in 36 ASA Grade I-II patients in a placebo-controlled double-blind study. After induction of anaesthesia with propofol followed by suxamethonium-facilitated endotracheal intubation, the patients spontaneously breathed halothane in 70% nitrous oxide and oxygen via a non-rebreathing valve. Inspiratory and expiratory oxygen, and end-tidal carbon dioxide concentrations (PETCO2), tidal volume (VT), minute volume of ventilation (MV) and respiratory rate were monitored by a side-stream spirometry at an end-tidal halothane of 0.3%. The recordings were collected before surgery. Pethidine caused significant respiratory depression seen as an increase in fractional inspiratory-expiratory oxygen difference and PETCO2 and as a decrease in MV and respiratory rate. However, the effects of tramadol were similar to those of a placebo. Tidal volume was not affected by any study drug. In conclusion, tramadol 0.6 mg kg-1 was shown not to be associated with respiratory depression, unlike equipotent dose of pethidine in this setting.

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Disruption of the Rhythmic Activity of the Medullary Inspiratory Neurons and Phrenic Nerve by Fentanyl and Reversal with Nalbuphine

Cited by 28 publications

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D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

CrossTalk opposing view: The pre‐Bötzinger complex is not essential for respiratory depression following systemic administration of opioid analgesics

Comparison of respiratory effects of tramadol and pethidine

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Disruption of the Rhythmic Activity of the Medullary Inspiratory Neurons and Phrenic Nerve by Fentanyl and Reversal with Nalbuphine

Cited by 28 publications

References 0 publications

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

CrossTalk opposing view: The pre‐Bötzinger complex is not essential for respiratory depression following systemic administration of opioid analgesics

Comparison of respiratory effects of tramadol and pethidine

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D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

D₁-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat