Osterlund Modalen A, Arlander E, Eriksson L I, Lindahl S G
Department of Anesthesiology and Intensive Care, Karolinska Hospital and Institute, Stockholm.
Anesth Analg. 2001 Feb;92(2):529-34. doi: 10.1097/00000539-200102000-00046.
Sameridine, a novel molecule, has both local anesthetic and partial mu-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% CO(2) 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 = Delta VE/Delta ETCO(2)) 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 mu-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.
沙美替定是一种新型分子，兼具局部麻醉和部分μ-阿片受体特性。这项单盲、随机、四向交叉研究的目的是调查12名健康志愿者的高碳酸通气反应（HCVR）。将两剂0.15mg/kg（小剂量沙美替定，S-Small）和0.73mg/kg（大剂量沙美替定，S-Large）的沙美替定静脉输注20分钟，并与0.10mg/kg的吗啡和安慰剂进行比较。通过呼吸流速描记法和在线二氧化碳描记法对通气情况进行了2小时的反复研究。在向吸入空气中添加4%二氧化碳直至达到稳定状态后，测量高碳酸通气反应。用视觉模拟量表评估镇静程度。在输注药物后，大剂量沙美替定组的通气反应曲线（HCVR = ΔVE/ΔETCO₂）出现显著右移（平均4.5mmHg）。其他组的HCVR没有变化。按摩尔计算，大剂量沙美替定的剂量是吗啡剂量的6.5倍，预计这样的剂量会导致右移12mmHg。这种效应上的差异很可能是沙美替定部分μ-激动剂作用的结果。大剂量沙美替定和吗啡输注后的镇静作用最为明显。作者得出结论，大剂量静脉注射沙美替定会抑制高碳酸通气反应，而较小的临床剂量则不会。
