Dershwitz M, Di Biase P M, Rosow C E, Wilson R S, Sanderson P E, Joslyn A F
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
Anesthesiology. 1992 Sep;77(3):447-52. doi: 10.1097/00000542-199209000-00007.
Ondansetron is a selective 5-hydroxytryptamine type 3 receptor antagonist effective as an antiemetic in patients experiencing post-operative or cancer chemotherapy-induced nausea and vomiting. Currently, no information is available regarding the interaction of ondansetron with opioids, although a serotonin antagonist might be expected to modify some opioid actions. This study was designed to measure the effects of ondansetron on alfentanil-induced ventilatory depression and sedation in healthy male volunteers. Ventilatory drive (measured as the end-tidal CO2 necessary to produce a minute ventilation of 15 l/min) was determined in 29 subjects using a modification of the Read rebreathing technique. Sedation was measured by asking the subjects to complete visual analog scales. Alfentanil was administered as a bolus (5 micrograms/kg) followed by a continuous infusion (0.25-0.75 micrograms.kg-1.min-1) for at least 90 min. Study medication (ondansetron 8 or 16 mg or vehicle placebo) was then administered in a randomized, double-blind manner, and the alfentanil was infused for an additional 15 min. Measurements of ventilatory drive and sedation were made at baseline, during alfentanil infusion, after study medication, and at 30-min intervals after alfentanil was discontinued. Alfentanil produced significant ventilatory depression (P less than 0.001) and sedation (P less than 0.001) in all three groups. Neither placebo nor ondansetron produced further change in the intensity of either alfentanil effect. After discontinuation of the opioid, both ventilatory depression and sedation decreased, and the rate of recovery was not significantly different between groups. The data indicate that alfentanil-induced sedation and ventilatory depression are not significantly affected by the subsequent administration of ondansetron.
昂丹司琼是一种选择性5-羟色胺3型受体拮抗剂，对术后或癌症化疗引起的恶心和呕吐患者有止吐作用。目前，关于昂丹司琼与阿片类药物的相互作用尚无相关信息，尽管人们预期血清素拮抗剂可能会改变某些阿片类药物的作用。本研究旨在测量昂丹司琼对健康男性志愿者中阿芬太尼引起的通气抑制和镇静作用的影响。采用改良的Read重复呼吸技术，对29名受试者测定通气驱动（以产生每分钟15升通气量所需的呼气末二氧化碳来衡量）。通过让受试者完成视觉模拟量表来测量镇静程度。先静脉推注阿芬太尼（5微克/千克），然后持续输注（0.25 - 0.75微克·千克⁻¹·分钟⁻¹）至少90分钟。然后以随机、双盲的方式给予研究药物（昂丹司琼8毫克或16毫克或赋形剂安慰剂），并再输注阿芬太尼15分钟。在基线、阿芬太尼输注期间、给予研究药物后以及停用阿芬太尼后每隔30分钟测量通气驱动和镇静程度。在所有三组中，阿芬太尼均产生了显著的通气抑制（P < 0.001）和镇静作用（P < 0.001）。安慰剂和昂丹司琼均未使阿芬太尼任何一种作用的强度进一步改变。停用阿片类药物后，通气抑制和镇静作用均减弱，且各组间恢复速率无显著差异。数据表明，随后给予昂丹司琼对阿芬太尼引起的镇静和通气抑制无显著影响。
