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GENERAL ARTICLES

The Effects on Hypercarbic Ventilatory Response of Sameridine Compared to Morphine and Placebo

Department of Anesthesiology and Intensive Care, Karolinska Hospital and Institute, Stockholm

Address correspondence and reprint requests to Åsa Österlund Modalen, MD, Department of Anesthesiology and Intensive Care, Karolinska Hospital and Institute, SE-171 76 Stockholm, Sweden.

Sameridine, a novel molecule, has both local anesthetic and partial µ-opioid receptor properties. The aim of this single, blinded, randomized, four-way cross-over study was to investigate the hypercarbic ventilatory response (HCVR) in 12 healthy volunteers. A 20-min IV infusion of two doses of sameridine 0.15 mg/kg (S-Small) and 0.73 mg/kg (S-Large) were compared with 0.10 mg/kg of morphine and placebo. Ventilation was studied repeatedly for 2 h by pneumotachography and inline capnography. The hypercarbic ventilatory response was measured after addition of 4% CO₂ to inspired air until steady state. A visual analog scale followed sedation. After drug infusion there was a significant rightward shift (on average 4.5 mm Hg) of the ventilatory response curve (HCVR = &OV0312;E/ETCO₂) in the S-Large group. There were no changes of HCVR in the other groups. On a molar basis, the S-Large dose was 6.5 times the morphine dose, and such a dose would have been expected to cause a 12 mm Hg rightward shift. This discrepancy in effect is most likely a result of the partial µ-agonist effect of sameridine. Sedation was most pronounced after S-Large and morphine infusions. The authors concluded that a large IV dose of sameridine depressed the hypercarbic ventilatory response, whereas a smaller, clinical dose did not.

Implications: A novel molecule, sameridine, produces both a local anesthetic blockade and a partial µ-agonist action. In large doses, the ventilatory CO₂ response was depressed, which was not the case when the recommended clinical dose was used.

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