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• W2003753023 abstract "Study objectives: Acute organophosphate poisoning causes mortality by 2 discrete mechanisms: (1) peripheral cholinergic crisis; and (2) central respiratory depression. It has further been reported that the respiratory depressant diazepam paradoxically attenuates organophosphate-induced central respiratory depression; however, it is not known whether this is specifically caused by diazepam's actions on the γ-aminobutyric acid (GABA) receptor or a nonspecific effect on respiratory drive. We determine whether the respiratory depressant morphine also attenuates organophosphate-induced respiratory depression. Methods: Sprague-Dawley rats (n=34) weighing 200 to 250 g were randomized to receive treatment with nothing (controls), glycopyrrolate 3 mg/kg, diazepam 5 mg/kg, morphine 5 mg/kg, glycopyrrolate+diazepam or glycopyrrolate+morphine, 5 minutes before a single subcutaneous injection of the organophosphate dichlorvos (20 mg/kg). A reviewer blinded to the treatment group observed the animals for signs of peripheral cholinergic crisis (salivation, defecation, urination, and retractions) and respiratory arrest for up to 20 minutes after poisoning. Results: Fasciculations were seen within 3 minutes of dichlorvos injection in all animals, regardless of treatment group. In control animals and those treated solely with diazepam or morphine, fasciculations were followed by signs of severe peripheral cholinergic crisis and respiratory arrest within 6 minutes of poisoning. Rapid respiratory arrest (within 8 minutes of poisoning) also occurred in all animals treated with glycopyrrolate alone; however, it was not preceded by signs of peripheral cholinergic distress. Fifty percent of the animals treated with diazepam+glycopyrrolate survived to the 20-minute endpoint of the study (P≤.05 by χ2 analysis), suggesting that this combination treatment attenuated both the peripheral and central nervous system manifestations of the poisoning. The beneficial effects of combination treatment with a peripheral anticholinergic+a respiratory depressant were not seen in the cohort receiving morphine+glycopyrrolate (100% mortality by 8 minutes). Conclusion: These findings suggest that diazepam attenuates central respiratory depression by a GABA-dependent mechanism not related to its respiratory depressive effects. Study objectives: Acute organophosphate poisoning causes mortality by 2 discrete mechanisms: (1) peripheral cholinergic crisis; and (2) central respiratory depression. It has further been reported that the respiratory depressant diazepam paradoxically attenuates organophosphate-induced central respiratory depression; however, it is not known whether this is specifically caused by diazepam's actions on the γ-aminobutyric acid (GABA) receptor or a nonspecific effect on respiratory drive. We determine whether the respiratory depressant morphine also attenuates organophosphate-induced respiratory depression. Methods: Sprague-Dawley rats (n=34) weighing 200 to 250 g were randomized to receive treatment with nothing (controls), glycopyrrolate 3 mg/kg, diazepam 5 mg/kg, morphine 5 mg/kg, glycopyrrolate+diazepam or glycopyrrolate+morphine, 5 minutes before a single subcutaneous injection of the organophosphate dichlorvos (20 mg/kg). A reviewer blinded to the treatment group observed the animals for signs of peripheral cholinergic crisis (salivation, defecation, urination, and retractions) and respiratory arrest for up to 20 minutes after poisoning. Results: Fasciculations were seen within 3 minutes of dichlorvos injection in all animals, regardless of treatment group. In control animals and those treated solely with diazepam or morphine, fasciculations were followed by signs of severe peripheral cholinergic crisis and respiratory arrest within 6 minutes of poisoning. Rapid respiratory arrest (within 8 minutes of poisoning) also occurred in all animals treated with glycopyrrolate alone; however, it was not preceded by signs of peripheral cholinergic distress. Fifty percent of the animals treated with diazepam+glycopyrrolate survived to the 20-minute endpoint of the study (P≤.05 by χ2 analysis), suggesting that this combination treatment attenuated both the peripheral and central nervous system manifestations of the poisoning. The beneficial effects of combination treatment with a peripheral anticholinergic+a respiratory depressant were not seen in the cohort receiving morphine+glycopyrrolate (100% mortality by 8 minutes). Conclusion: These findings suggest that diazepam attenuates central respiratory depression by a GABA-dependent mechanism not related to its respiratory depressive effects." @default.
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• W2003753023 date "2004-10-01" @default.
• W2003753023 modified "2023-10-03" @default.
• W2003753023 title "γ-Aminobutyric acid, but not opiate receptor agonists attenuate organophosphate-induced central respiratory depression" @default.
• W2003753023 doi "https://doi.org/10.1016/j.annemergmed.2004.07.011" @default.
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