6-o-monoacetylmorphine and Respiratory-Insufficiency

Opioids are known to induce respiratory depression. We aimed to characterize in rats the effects of four opioids on arterial blood gases and plethysmography after intraperitoneal administration at 80% of their LD(50) in order to identify opioid molecule-specific patterns and classify response severity. Opioid-receptor (OR) antagonists, including intravenous 10 mg kg(-1)-naloxonazine at 5 min [mu-OR antagonist], subcutaneous 30 mg kg(-1)-naloxonazine at 24 h [mu1-OR antagonist], subcutaneous 3 mg kg(-1)-naltrindole at 45 min [delta-OR antagonist], and subcutaneous 5 mg kg(-1)-Nor-binaltorphimine at 6 h [kappa-OR antagonist] were pre-administered to test the role of each OR. Methadone, morphine, and fentanyl significantly decreased PaO(2) (P<0.001) and increased PaCO(2) (P<0.05), while buprenorphine only decreased PaO(2) (P<0.05). While all opioids significantly increased inspiratory time (T(I), P<0.001), methadone and fentanyl also increased expiratory time (T(E), P<0.05). Intravenous 10 mg kg(-1)-naloxonazine at 5 min completely reversed opioid-related effects on PaO(2) (P<0.05), PaCO(2) (P<0.001), T(I) (P<0.05), and T(E) (P<0.01) except in buprenorphine. Subcutaneous 30 mg kg(-1)-naloxonazine at 24 h completely reversed effects on PaCO(2) (P<0.01) and T(E) (P<0.001), partially reversed effects on T(I) (P<0.001), and did not reverse effects on PaO(2). Naltrindole reversed methadone-induced T(E) increases (P<0.01) but worsened fentanyl's effect on PaCO(2) (P<0.05) and T(I) (P<0.05). Nor-binaltorphimine reversed morphine- and buprenorphine-induced T(I) increases (P<0.001) but worsened methadone's effect on PaO(2) (P<0.05) and morphine (P<0.001) and buprenorphine's (P<0.01) effects on pH. In conclusion, opioid-related respiratory patterns are not uniform. Opioid-induced hypoxemia as well as increases in T(I) and T(E) are caused by mu-OR, while delta and kappa-OR roles appear limited, depending on the specific opioid. Regarding severity of opioid-induced respiratory effects at 80% of their LD(50), all drugs increased T(I). Methadone and fentanyl induced hypoxemia, hypercapnia, and T(E) increases, morphine caused both hypoxemia and hypercapnia while buprenorphine caused only hypoxemia.

Topics: Animals; Blood Gas Analysis; Buprenorphine; Catheterization; Fentanyl; Lactic Acid; Male; Methadone; Morphine; Morphine Derivatives; Naltrexone; Narcotic Antagonists; Narcotics; Plethysmography, Whole Body; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Respiratory Insufficiency; Respiratory Mechanics