Depression of ventilatory responses to hypoxia and hypercapnia after pentamorphone

Pentamorphone is a novel, potent opiate with rapid onset and short duration of action that has been reported to produce analgesia with limited depression of ventilation. We quantified the effects of pentamorphone (0.08, 0.24, and 0.60 μg/kg, IV) on ventilatory responses to hypercapnia and hypoxia in 12 healthy volunteers. Normoxic hypercapnia and isocapnic hypoxia were induced through a rebreathing method. During each test we recorded ventilation (V̇E), end tidal carbon dioxide tension (PETCO₂), and arterial oxygen saturation (SO₂) using a pulse oximeter. Using linear regression analysis of the relationships between V̇E and PCO₂ during hypercapnia and V̇E and SO₂ during hypoxia, we determined the slope (slope CO₂) and intercept (V̇₅₅), both at PCO₂ 55 mm Hg, and the slope (slope O₂) and intercept (V̇₈₀) at SO₂ 80%. Pentamorphine produced dose-related reductions in the ventilatory responses to both hypercapnia and hypoxia. Maximal depression occurred 15 min after injection of pentamorphone with all doses; the highest dose (0.60 μg/kg) produced 48% and 53% reductions in slope CO₂ and V̇₅₅, and 42% and 22% reductions in slope O₂ and V̇₈₀, respectively, relative to parallel saline controls. The respiratory depressant actions of pentamorphone were short-lived, as all parameters returned to baseline levels within 45 min. Testing was continued for 180 min after injection, but not delayed ventilatory effects were detected, and minimal side effects were reported, even at the highest dose. The findings confirm previous reports that pentamorphine has limited ventilatory depressant effects in humans in doses that (in other studies) have been associated with clinically effective analgesia.