Korsten Mark A, Rosman Alan S, Ng Anthony, Cavusoglu Erdal, Spungen Ann M, Radulovic Miroslav, Wecht Jill, Bauman William A
VA Medical Center, Bronx, New York, New York 10468, USA.
Am J Gastroenterol. 2005 Jul;100(7):1560-5. doi: 10.1111/j.1572-0241.2005.41587.x.
Defecatory complications are common after spinal cord injury (SCI) and have been attributed, in part, to an imbalance of the autonomic nervous system between parasympathetic and sympathetic effects on the colon. Because parasympathetic (i.e., cholinergic) input to the bowel may be downregulated after SCI, it was hypothesized that neostigmine, a medication that increases cholinergic tone by blocking the metabolism of acetylcholine, might promote bowel evacuation in these persons. Since neostigmine is known to cause bradycardia and bronchoconstriction, we also assessed whether these side-effects could be prevented by coadministration of neostigmine with glycopyrrolate, an anticholinergic agent that has limited activity on the muscarinic receptors of the colon. The hypothesis was tested in 13 persons with SCI in whom videofluoroscopy was carried out after instillation of a barium oatmeal paste into the rectum and descending colon. On separate days, subjects received, in a randomized, blinded design, one of three intravenous infusates (normal saline, 2 mg neostigmine, or 2 mg neostigmine + 0.4 mg glycopyrrolate). The effect of these infusates on bowel evacuation of the barium paste, heart rate, and airway resistance was determined. Both neostigmine and neostigmine + glycopyrrolate resulted in prompt bowel evacuation. The nadir heart rate was lower after neostigmine alone than with the combination. Neostigmine administration increased both total and central airway resistance, an effect that was not observed with the coadministration of glycopyrrolate. Other side-effects of neostigmine and the combination of drugs included muscle fasciculations and dry mouth, both of which were mild and short-lived. Abdominal cramping was noted in subjects with spinal cord lesions below thoracic level 10. These results indicated that neostigmine/glycopyrrolate administration is safe and well tolerated in persons with chronic SCI.
排便并发症在脊髓损伤(SCI)后很常见,部分原因是自主神经系统对结肠的副交感神经和交感神经作用失衡。由于SCI后肠道的副交感神经(即胆碱能)输入可能下调,因此推测新斯的明(一种通过阻断乙酰胆碱代谢来增加胆碱能张力的药物)可能促进这些患者的肠道排空。由于已知新斯的明会引起心动过缓和支气管收缩,我们还评估了新斯的明与格隆溴铵(一种对结肠毒蕈碱受体活性有限的抗胆碱能药物)联合使用是否可以预防这些副作用。在13名脊髓损伤患者中进行了该假设的测试,这些患者在将钡燕麦糊注入直肠和降结肠后进行了视频透视检查。在不同的日子里,受试者以随机、盲法设计接受三种静脉输注液之一(生理盐水、2毫克新斯的明或2毫克新斯的明+0.4毫克格隆溴铵)。确定了这些输注液对钡糊肠道排空、心率和气道阻力的影响。新斯的明和新斯的明+格隆溴铵均导致钡糊迅速排空。单独使用新斯的明后的最低心率低于联合使用时。使用新斯的明会增加总气道阻力和中心气道阻力,而联合使用格隆溴铵时未观察到这种效果。新斯的明和联合用药的其他副作用包括肌肉抽搐和口干,两者均轻微且持续时间短。在胸段10以下脊髓损伤的受试者中观察到腹部绞痛。这些结果表明,新斯的明/格隆溴铵给药对慢性脊髓损伤患者是安全的且耐受性良好。