Ampakine CX1942 attenuates opioid-induced respiratory depression and corrects the hypoxaemic effects of etorphine in immobilized goats (Capra hircus).

OBJECTIVES: To determine whether CX1942 reverses respiratory depression in etorphine-immobilized goats, and to compare its effects with those of doxapram hydrochloride. STUDY DESIGN: A prospective, crossover experimental trial conducted at 1753 m.a.s.l. ANIMALS: Eight adult female Boer goats (Capra hircus) with a mean ± standard deviation mass of 27.1 ± 1.6 kg. METHODS: Following immobilization with 0.1 mg kg(-1) etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials. Respiratory rate, ventilation and tidal volume were measured continuously. Arterial blood samples for the determination of PaO2 , PaCO2 , pH and SaO2 were taken 2 minutes before and then at 5 minute intervals after drug administration for 25 minutes. RESULTS: Doxapram corrected etorphine-induced respiratory depression but also led to arousal and hyperventilation at 2 minutes after its administration, as indicated by the low PaCO2 (27.8 ± 4.5 mmHg) and ventilation of 5.32 ± 5.24 L minute(-1) above pre-immobilization values. CX1942 improved respiratory parameters and corrected etorphine's hypoxaemic effects more gradually than did doxapram, with a more sustained improvement in PaO2 and SaO2 in comparison with the control trial. CONCLUSIONS: CX1942 attenuated opioid-induced respiratory depression and corrected the hypoxaemic effects of etorphine in immobilized goats. CLINICAL RELEVANCE: Ampakines potentially offer advantages over doxapram, a conventional treatment, in reversing etorphine-induced respiratory depression without causing unwanted side effects, particularly arousal, in immobilized animals.

Nalbuphine and butorphanol reverse opioid-induced respiratory depression but increase arousal in etorphine-immobilized goats (Capra hircus).

OBJECTIVES: To evaluate and compare the efficacy of two opioid agonist-antagonists, nalbuphine and butorphanol, in reversing etorphine-induced respiratory depression in immobilized goats. STUDY DESIGN: Prospective, crossover, experimental trial conducted at 1753 m.a.s.l. ANIMALS: Eight adult female Boer goats (Capra hircus). METHODS: Eight minutes following immobilization with an intramuscular injection of 0.1 mg kg(-1) etorphine, goats were given one of nalbuphine (0.8 mg kg(-1) ), butorphanol (0.1 mg kg(-1) ) or sterile water intravenously, in random order in three trials. Respiratory rate (fR ), ventilation, tidal volume, oxygen consumption (V˙O2 ) and carbon dioxide production (V˙CO2 ) were measured continuously. Arterial blood samples to determine PaO2 and PaCO2 were taken 2 minutes before and at 5 minute intervals after etorphine administration for 25 minutes. RESULTS: Both nalbuphine and butorphanol increased mean PaO2 from 44 mmHg (5.9 kPa) to 63 mmHg (8.4 kPa) after etorphine administration. Butorphanol, but not nalbuphine, also corrected hypopnea and hypoventilation such that fR increased from 13 ± 4 to 21 ± 7 breaths minute(-1) (compared with 16 ± 6 breaths minute(-1) following nalbuphine) and ventilation increased from 4.69 ± 3.04 to 6.91 ± 4.42 L minute(-1) following butorphanol administration. Despite decreases in PaCO2 following nalbuphine and butorphanol, PaCO2 remained elevated compared with pre-immobilization values [nalbuphine: 34 ± 3 mmHg (4.5 ± 0.3 kPa); butorphanol: 34 ± 2 mmHg (4.5 ± 0.3 kPa)] throughout the immobilization. Both agents also decreased the level of immobilization, and increased V˙O2 and V˙CO2 . CONCLUSIONS: Nalbuphine and butorphanol significantly improved respiratory function in immobilized goats, with butorphanol eliciting a greater positive response than nalbuphine. However, both opioid agonist-antagonists partly reversed etorphine-induced immobilization. CLINICAL RELEVANCE: Butorphanol and nalbuphine can be used to improve respiratory parameters in etorphine-immobilized wildlife, with butorphanol being more effective, but unwanted arousal can occur.