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.