Response to Morphine in Children with SC Disease

描述（由申请人提供）：镰状细胞病（SCD）是一种遗传性疾病，其特征是慢性溶血性贫血，伴有急性和慢性并发症。由于血管闭塞引起的组织缺血引起的疼痛发作是SCD儿童入院的最常见原因。疼痛性血管闭塞发作（VOE）占急诊和住院治疗的相当数量。吗啡通过患者自控镇痛被广泛用于医院设置，以管理严重疼痛的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、从一次发作到另一次发作以及个体患者之间变化很大，并且一些患者没有得到充分的缓解。我们的假设是镰状细胞病患儿的血浆吗啡浓度不能达到治疗水平。我们建议检查是否缺乏反应，以吗啡有关的亚治疗吗啡浓度或其他因素。吗啡的药代动力学参数将与急性疼痛状态下的已知群体值进行比较。其中一份血样将用于基因分型（UGT 2B 7、MOR 1、COMT），这些基因可能影响对吗啡的反应。将使用疼痛强度和疼痛缓解评分、疼痛部位和疼痛质量以及副作用（如镇静/嗜睡、恶心、瘙痒、通气不足（氧饱和度、呼吸频率）或低血压（血压））评估对吗啡的反应。来自K23职业发展奖的数据将用于设计最佳的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的疼痛所造成的短期和长期后果。这些疼痛管理的进步将使Jacob博士成为一名独立的临床研究人员。

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.