Response to Morphine in Children with SC Disease

描述（由申请人提供）：镰状细胞病（SCD）是一种以慢性溶血性贫血为特征的遗传性疾病，伴有急性和慢性并发症。由血管闭塞引起的组织缺血引起的疼痛发作是SCD患儿入院的最常见原因。疼痛性血管闭塞发作（VOE）占急诊和住院人数的显著比例。吗啡通过病人控制的镇痛被广泛应用于医院设置管理严重疼痛SCD。然而，实现疼痛缓解所需的阿片类药物剂量在每次疼痛发作中、在一次发作到另一次发作之间以及在个体患者之间差异很大，并且一些患者没有得到足够的缓解。我们的假设是，患有镰状细胞病的儿童没有达到治疗水平的血浆吗啡浓度。我们建议研究对吗啡缺乏反应是否与亚治疗吗啡浓度或其他因素有关。在急性疼痛状态下，吗啡的药代动力学参数将与已知的人群值进行比较。其中一份血样将用于基因分型可能影响吗啡反应的基因（UGT2B7、MOR1、COMT）。对吗啡的反应将通过疼痛强度和疼痛缓解评分、疼痛位置和疼痛质量以及副作用(如镇静/嗜睡、恶心、瘙痒、低通气（氧饱和度、呼吸频率）或低血压（血压）来评估。该职业发展奖项K23的数据将用于设计最佳疼痛管理策略和临床方案，旨在最大限度地减少镰状细胞病儿童急性血管闭塞发作期间未经治疗或管理不当引起的疼痛的短期和长期后果。这些疼痛管理方面的进步将引导雅各布博士成为一名独立临床研究人员的长期职业目标。

DESCRIPTION (provided by applicant): Sickle cell disease (SCD) is an inherited disease characterized by chronic hemolytic anemia with acute and chronic complications. The painful episode that results from tissue ischemia due to vaso-occlusion is the most common reason for admission in children with SCD. Painful vaso-occlusive episodes (VOE) account for a significant number of emergency department and hospital admissions. Morphine via patient controlled analgesia is widely used in hospital settings to manage severe pain in SCD. However, the opioid dose required to achieve pain relief varies considerably within each painful episode, from one episode to another, and between individual patients, and some patients do not receive adequate relief. Our hypothesis is that children with sickle cell disease do not achieve plasma concentrations of morphine at therapeutic levels. We propose to examine whether the lack of response to morphine is related to subtherapeutic morphine concentrations or other factors. Pharmacokinetic parameters of morphine will be compared with known population values during acute painful states. One of the blood samples will be used for genotyping genes (UGT2B7, MOR1, COMT) that may affect response to morphine. Response to morphine will be assessed using pain intensity and pain relief scores, pain location and pain quality, and side effects such as sedation/drowsiness, nausea, itching, hypoventilation (oxygen saturation, respiratory rate), or hypotension (blood pressure). Data from this career development award K23 will be used to design optimal pain management strategies and clinical protocols that aim to minimize the short and long term consequences resulting from untreated or inadequately managed pain during acute vaso-occlusive episodes in children with sickle cell disease. These advancements in pain management will lead Dr. Jacob to her long term career goal as an independent clinical researcher.