van der Schrier Rutger, Roozekrans Margot, Olofsen Erik, Aarts Leon, van Velzen Monique, de Jong Merijn, Dahan Albert, Niesters Marieke
From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Anesthesiology. 2017 Mar;126(3):534-542. doi: 10.1097/ALN.0000000000001505.
Respiratory depression is a potentially fatal complication of opioid use, which may be exacerbated by simultaneous ethanol intake. In this three-way sequential crossover dose-escalating study, the influence of coadministration of oral oxycodone and intravenous ethanol was assessed on resting ventilation, apneic events and the hypercapnic ventilatory response in healthy young and older volunteers.
Twelve young (21 to 28 yr) and 12 elderly (66 to 77 yr) opioid-naive participants ingested one 20 mg oxycodone tablet combined with an intravenous infusion of 0, 0.5, or 1 g/l ethanol. Resting respiratory variables and the primary outcome, minute ventilation at isohypercapnia (end-tidal partial pressure of carbon dioxide of 55 mmHg or VE55), were obtained at regular intervals during treatment.
Oxycodone reduced baseline minute ventilation by 28% (P < 0.001 vs. control). Ethanol caused a further decrease of oxycodone-induced respiratory depression by another 19% at 1 g/l ethanol plus oxycodone (P < 0.01 vs. oxycodone). Ethanol combined with oxycodone caused a significant increase in the number of apneic events measured in a 6-min window with a median (range) increase from 1 (0 to 3) at 0 g/l ethanol to 1 (0 to 11) at 1 g/l ethanol (P < 0.01). Mean (95% CI) VE55 decreased from 33.4 (27.9 to 39.0) l/min (control) to 18.6 (15.6 to 21.6) l/min (oxycodone, P < 0.01 vs. control) and to 15.7 (12.7 to 18.6) l/min (oxycodone combined with ethanol, 1 g/l; P < 0.01 vs. oxycodone).
Ethanol together with oxycodone causes greater ventilatory depression than either alone, the magnitude of which is clinically relevant. Elderly participants were more affected than younger volunteers.
呼吸抑制是阿片类药物使用的一种潜在致命并发症，同时摄入乙醇可能会使其加重。在这项三阶段序贯交叉剂量递增研究中，评估了口服羟考酮与静脉注射乙醇联合用药对健康年轻和老年志愿者静息通气、呼吸暂停事件及高碳酸通气反应的影响。
12名年轻（21至28岁）和12名老年（66至77岁）未使用过阿片类药物的参与者服用一片20毫克羟考酮片剂，并静脉输注0、0.5或1克/升乙醇。在治疗期间定期获取静息呼吸变量及主要结局指标，即等容高碳酸血症时的分钟通气量（呼气末二氧化碳分压为55毫米汞柱时的分钟通气量或VE55）。
羟考酮使基线分钟通气量降低28%（与对照组相比，P<0.001）。在1克/升乙醇加羟考酮组，乙醇使羟考酮所致的呼吸抑制进一步降低19%（与羟考酮组相比，P<0.01）。乙醇与羟考酮联合用药导致在6分钟时间段内测量的呼吸暂停事件数量显著增加，中位数（范围）从0克/升乙醇时的1次（0至3次）增加到1克/升乙醇时的1次（0至11次）（P<0.01）。平均（95%可信区间）VE55从33.4（27.9至39.0）升/分钟（对照组）降至18.6（15.6至21.6）升/分钟（羟考酮组，与对照组相比，P<0.01），并降至15.7（12.7至18.6）升/分钟（羟考酮与1克/升乙醇联合用药组；与羟考酮组相比，P<0.01）。
乙醇与羟考酮联合用药导致的通气抑制比单独使用两者时更严重，其程度具有临床相关性。老年参与者比年轻志愿者受影响更大。
