1、药源性食管损伤medication-induced esophageal injury,林道明 教授,药源性食管损伤(medication-induced esophageal injury,MIEI)是指某些药物在常规剂量吞服时,作用于食管黏膜而引起的食管损伤.,1970 年,Juncosa1首先报道了一例口服泼尼松引起食管溃疡的老年患者.纤维内镜广泛应用于临床之后,人们才逐渐认识MIEI。,流行病学,1978 年，Carlborg 等3 对瑞典某医疗机构700 000 人进行了4 年的观察研究，共发现患者109 例，发病率为每年3.9/100 000。,迄今发现，本病在589 岁之间均可发
2、病，男女比例为11.5溴化依米波宁（emepronium bromide）MIEI可能与之相关。,病因和发病机制,可引起食管损伤的药物有70 余种4抗生素类有强力霉素、四环素、土霉素、青霉素、利福平等5解热镇痛药有阿司匹林、吲哚美辛、布洛芬等,制酸剂兰索拉唑（lansoprazole）9抗骨质疏松药物阿仑膦酸钠（alendronate sodium，商品名曼克星）10阳离子交换树酯聚磺苯乙烯钠11膜酶制剂Pantozyme 12等,其他还有避孕药6、氯化钾7、奎宁、硫酸亚铁、溴化依米波宁、心得舒，镇静药氟哌啶醇8,动物实验证实，腐蚀性药物粘附于食管，与食管黏膜过长时间的直接接触是导致损伤的根本
3、原因13药物的酸性或碱性刺激导致食管黏膜的损伤,1、药物可能通过局部高渗性和抗胆碱作用，诱发病理性胃食管反流而发病,2、药物直接损伤食管黏膜氯化钾可引起黏膜干燥，血管破坏，以致食管损伤。强力霉素、心得舒和解热镇痛药可被食管黏膜吸收而引起毒性反应15。环氧合酶-2 抑制剂理论上不会刺激食管黏膜，但它们可以影响上皮细胞的再生和增殖。,病理生理,口服药粘附于食管较为常见1、 ：正常人平卧位时，药物在食管内存留时间超过5 分钟者占一半以上16。2、干咽胶囊时，药物在食管内常能粘附2 小时以上，难以清理。3、睡前服药也不利于食管排空。,4、缓释药物引起食管损伤的可能性更大，不适于食管机械性梗阻（如食管癌
4、，食管消化性狭窄等） 的患者17。5、药物的大小、形状、表面成份也影响在食管壁的粘附。,心脏外科手术后的患者易致食管损伤，而且往往出现严重并发症。1、药物局部存留192、刺激及腐蚀性药物，如氯化钾、奎宁等,老年人MIEI较青年人发病率为高20，65 岁以上有服药史的患者，如果出现吞咽困难、吞咽疼痛或非心源性胸痛，27为MIEI饮酒能影响食管排空，延长药物与食管黏膜的接触时间，引起食管损伤21。,以前的临床研究没有发现食管运动性疾病与MIEI的关系前瞻性研究发现食管排空功能障碍及食管裂孔疝患者均较正常人容易发病22。,病理改变,MIEI 最常发生的部位是主动脉弓水平左房增大时，MIEI 则常发生
5、在左心房压迫部位的食管。食管中段损伤占总人数的75.623。MIEI需与与胃食管反流病鉴别尚无食管下段贲门交界部受损的报道。,病理改变：空泡样细胞炎症反应食管气管瘘、纵隔炎食管狭窄,抗生素所致的食管损伤占已报道病例的57%，但出血、狭窄等并发症发生的机会较少狭窄、致命性出血、侵及胸部大血管等并发症的发生率却很高若形成明显的结节，可自行消退，内镜及造影检查时应与食管肿瘤鉴别。,临床表现,MIEI 患者多无食管疾病的病史突然出现胸骨后疼痛（61%），夜间疼醒，并于吞咽时加重，症状轻时可只有吞咽疼痛（50%），严重者可出现吞咽困难（40%），34 天后症状逐渐缓解,约20%的患者发病隐匿，只出现无痛
6、性的吞咽困难，常持续数周甚至数月其他症状有脱水、体重减轻、低热、呕血等，均较少见。,有睡前干咽药片史食管造影不如内镜检查敏感，可表现为食管受压或排空延迟，钡气双重对比造影可见多发性黏膜破坏和龛影30。,内镜检查：是诊断MIEI 的金标准，99% 患者内镜下可见异常，表现为食管糜烂、溃疡及增生性管壁增厚，偶尔可见溃疡周围有药片残留物。活检切片呈急性炎症改变。,诊断与鉴别诊断,诊断根据病史及常规查体即可确诊食管造影检查：临床症状不典型或疑有狭窄等并发症时内镜检查:有明显的吞咽困难及出血或保守治疗无效者,鉴别诊断MIEI 需与冠心病、食管癌、重度胃食管反流病、食管异物、感染性食管炎及免疫功能缺陷性疾
7、病鉴别。,治疗,多数患者无需特殊治疗，3 -数周内痊愈对于左心房扩大和心脏外科手术后的患者，一经诊断为MIEI，应立即停药或改用水剂；严重者，可用制酸剂、H2 受体拮抗剂和黏膜保护剂；,疼痛明显时，可服止痛药；不能进食者，需给予静脉高营养，23 天后，逐渐进食出血者，需输血、止血乃至手术，因为病变常常侵及大血管，故一般不经内镜止血；食管出现狭窄时，需行扩张术，扩张失败则需手术治疗。,预防,1. 尽量避免服用腐蚀性药物2. 养成良好的服药习惯3. 改进药物剂型,参考文献,1 Juncosa L. Latrogenic peptic ulcer of the esophagus. Rev Esp
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