Dohar Joseph E
Voice Resonance and Swallowing Center UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, University of Pittsburgh School of Health & Rehabilitation, 4401 Penn Ave., Pittsburgh, PA, 15224, United States.
Int J Pediatr Otorhinolaryngol. 2019 Jan;116:97-101. doi: 10.1016/j.ijporl.2018.10.035. Epub 2018 Oct 24.
Sialorrhea complicated by aspiration is a primary source of morbidity and mortality in neurologically impaired children. Anticholinergics are an effective treatment option, but have traditionally been considered only adjuncts due to tachyphylaxis and drug tolerance. Similarly, Botox-A salivary gland injections are also considered adjunctive due to the need to repeat treatment every 3 months. This retrospective case series assessed these two adjunctive strategies used in combination as definitive minimally invasive primary treatment.
112 subjects diagnosed with sialorrhea and treated at UPMC Children's Hospital of Pittsburgh between 2004 and 2011 were identified. Charts were carefully reviewed for pertinent information regarding the treatment of their sialorrhea and related outcomes.
Over half of the subject undergoing BTX-A injections were able to reduce their dosage of anticholinergics after receiving injection (58%, n = 28 for glycopyrrolate users and 61%, n = 20 for scopolamine users). Subjects experienced a significant reduction in days spent in the hospital in the year following Botox-A injection (P-Value = 0.03), and the number of pneumonia episodes in the year following injection (P-Value = 0.04).
Patients treated effectively with both BTX-A injections into their salivary glands and anticholinergics developed neither tachyphylaxis nor drug tolerance with up to 9.6 years of continuous treatment. During the year following combined therapy, patients' average length hospital stay was reduced by a full week and the number of pneumonia episodes was statistically decreased. The failure rate of combined therapy was below that reported for any other intervention or combination of interventions in the literature. Finally, patients did not require BTX-A re-injection at the reported frequency. We hypothesize that anticholinergic medications competitively block acetylcholine attachment to post-synaptic receptors while BTX-A inhibits acetylcholine release at the pre-synaptic terminal, tachyphylaxis/drug tolerance mechanisms resulting in up-regulation of post-synaptic receptors are disrupted. Although salivary production may increase in the year following BTX-A injection, there is enough remaining activity at a molecular level to inhibit release of acetylcholine allowing salvage with anticholinergic medications at tolerable dosages.
伴有误吸的流涎是神经功能受损儿童发病和死亡的主要原因。抗胆碱能药物是一种有效的治疗选择,但由于快速减敏和药物耐受性,传统上仅被视为辅助治疗。同样,肉毒杆菌毒素A唾液腺注射也因需要每3个月重复治疗而被视为辅助治疗。本回顾性病例系列评估了这两种辅助策略联合使用作为确定性微创主要治疗方法的效果。
确定了2004年至2011年期间在匹兹堡大学医学中心儿童医院诊断为流涎并接受治疗的112名受试者。仔细查阅病历以获取有关其流涎治疗及相关结果的相关信息。
超过一半接受肉毒杆菌毒素A注射的受试者在接受注射后能够减少抗胆碱能药物的用量(使用格隆溴铵的受试者中为58%,n = 28;使用东莨菪碱的受试者中为61%,n = 20)。受试者在接受肉毒杆菌毒素A注射后的一年中住院天数显著减少(P值 = 0.03),且注射后一年中肺炎发作次数也显著减少(P值 = 0.04)。
接受唾液腺肉毒杆菌毒素A注射和抗胆碱能药物联合有效治疗的患者,在长达9.6年的持续治疗中既未出现快速减敏也未出现药物耐受性。在联合治疗后的一年中,患者的平均住院时间减少了整整一周,肺炎发作次数在统计学上有所减少。联合治疗的失败率低于文献中报道的任何其他干预措施或干预措施组合的失败率。最后,患者无需按报道的频率再次注射肉毒杆菌毒素A。我们推测,抗胆碱能药物竞争性阻断乙酰胆碱与突触后受体的结合,而肉毒杆菌毒素A抑制突触前终末乙酰胆碱的释放,导致突触后受体上调的快速减敏/药物耐受机制被破坏。尽管在肉毒杆菌毒素A注射后的一年中唾液分泌可能会增加,但在分子水平上仍有足够的剩余活性来抑制乙酰胆碱的释放,从而允许使用可耐受剂量的抗胆碱能药物进行挽救治疗。