Taguchi A, Sharma N, Saleem R M, Sessler D I, Carpenter R L, Seyedsadr M, Kurz A
Department of Anesthesiology, Washington University, St Louis, MO 63110, USA.
N Engl J Med. 2001 Sep 27;345(13):935-40. doi: 10.1056/NEJMoa010564.
Postoperative recovery of gastrointestinal function and resumption of oral intake are critical determinants of the length of hospital stay. Although opioids are effective treatments for postoperative pain, they contribute to the delayed recovery of gastrointestinal function.
We studied the effects of ADL 8-2698, an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier, on postoperative gastrointestinal function and the length of hospitalization. We randomly assigned 79 patients--including 1 whose surgery was canceled--to receive one capsule containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule two hours before major abdominal surgery and then twice daily until the first bowel movement or until discharge from the hospital. Data were analyzed for 26 patients in each of the three groups; all received opioids for postoperative pain relief. Observers who were unaware of the group assignments evaluated the outcomes.
Fifteen patients underwent partial colectomy and 63 underwent total abdominal hysterectomy. Patients given 6 mg of ADL 8-2698 had significantly faster recovery of gastrointestinal function than those given placebo. The median time to the first passage of flatus decreased from 70 to 49 hours (P=0.03), the median time to the first bowel movement decreased from 111 to 70 hours (P=0.01), and the median time until patients were ready for discharge decreased from 91 to 68 hours (P=0.03). Effects in the group that received 1 mg of ADL 8-2698 were less pronounced.
Selective inhibition of gastrointestinal opioid receptors by an antagonist with limited oral absorption that does not readily cross the blood-brain barrier speeds recovery of bowel function and shortens the duration of hospitalization.
胃肠道功能的术后恢复及经口进食的恢复是住院时间长短的关键决定因素。尽管阿片类药物是术后疼痛的有效治疗方法，但它们会导致胃肠道功能恢复延迟。
我们研究了ADL 8-2698（一种口服吸收有限且不易透过血脑屏障的新型阿片类拮抗剂）对术后胃肠功能及住院时间的影响。我们将79例患者（包括1例手术取消者）随机分组，在腹部大手术前两小时给予1粒含1mg或6mg ADL 8-2698的胶囊或外观相同的安慰剂胶囊，之后每日两次，直至首次排便或出院。对三组中每组26例患者的数据进行分析；所有患者均接受阿片类药物缓解术后疼痛。不知道分组情况的观察者对结果进行评估。
15例患者接受了部分结肠切除术，63例接受了全腹子宫切除术。给予6mg ADL 8-2698的患者胃肠道功能恢复明显快于给予安慰剂的患者。首次排气的中位时间从70小时降至49小时（P=0.03），首次排便的中位时间从111小时降至70小时（P=0.01），患者准备出院的中位时间从91小时降至68小时（P=0.03）。给予1mg ADL 8-2698组的效果不那么明显。
一种口服吸收有限且不易透过血脑屏障的拮抗剂对胃肠道阿片受体的选择性抑制作用可加速肠功能恢复并缩短住院时间。
