修回日期: 2006-04-25
接受日期: 2006-04-30
在线出版日期: 2006-06-28
内镜逆行性胰胆管造影(ERCP)以及相关治疗技术已成为胆胰疾病的重要治疗手段, ERCP术后急性胰腺炎(AP)是常见且严重的并发症之一, 目前研究发现, 治疗性ERCP、Oddi括约肌运动功能障碍、Oddi括约肌压力检测、内镜下乳头括约肌气囊扩张术、插管困难与多次胰管注射、操作者的经验不足为ERCP术后急性胰腺炎的常见危险因素. 关于预防ERCP术后AP的药物研究被广泛开展, 生长抑素和加贝酯被多数学者认为对AP有显著的预防作用. 更广泛的药物研究其具体效果尚待进一步的研究证实. 在内镜技术方面, 选择性插管技术的改进、胰管支架和胆道引流技术被认为可有效地防止ERCP术后AP的发生.
引文著录: 韩兵, 王宝仁. ERCP术后急性胰腺炎并发症的危险因素及预防研究进展. 世界华人消化杂志 2006; 14(18): 1813-1818
Revised: April 25, 2006
Accepted: April 30, 2006
Published online: June 28, 2006
N/A
- Citation: N/A. N/A. Shijie Huaren Xiaohua Zazhi 2006; 14(18): 1813-1818
- URL: https://www.wjgnet.com/1009-3079/full/v14/i18/1813.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v14.i18.1813
内镜逆行性胰胆管造影(ERCP)以及相关治疗技术已成为胆胰疾病的重要治疗手段, 虽然此项技术临床应用日臻成熟, 但ERCP存在一定的并发症. ERCP术后急性胰腺炎(AP)是常见且严重的并发症之一, 发生率在1%-24.4%[1-4]. 探讨ERCP术后的危险因素及其预防, 对于提高ERCP诊断治疗水平及安全性有着重要的意义. 以下对ERCP并发症的危险因素、药物及内镜技术预防做一综述.
目前诊断性ERCP主要应用于组织标本的获取与Oddi括约肌运动功能失调的诊断, 其应用领域已部分为磁共振胆胰管造影(MRCP)所取代[5]. 多数学者认为治疗性ERCP急性胰腺炎发生率高于诊断性ERCP[6-7]. 主要与十二指肠乳头括约肌切开术(EST)相关. Cheng et al[8]收集美国中西部15个中心胰胆治疗组1115例ERCP资料, 分析EST行小切开为AP的独立危险因素, 而EST行大切开这种临床征象则很少出现. 考虑与切开不充分, 切开后乳头水肿, 胰液引流不畅有关. 关于EST切开使用切开与混合电流问题, Macintosh et al[9]研究认为电流类型的选择并不改变AP发生的风险, 选择何种电流, 取决于操作者的经验与习惯. 但在乳头开口处行切开操作时应避免使用高功率凝固电流, 以免热传导损伤导致胰管开口处凝固而增加AP发生的风险. 但也有学者认为诊断性ERCP与治疗性ERCP术后AP发生率无显著差异[10].
SOD是Oddi括约肌运动异常导致胆汁、胰液排出受阻, 使胆胰管内压升高, 临床上表现为胆源性腹痛、梗阻性黄疸、胰源性腹痛与AP. 多数学者认为对疑有SOD患者行ERCP, 术后有较高的AP发生率[8,11-13].
Oddi括约肌压力由包绕胆管、胰管开口处及胆管和胰管共同通道周围的括约肌组成, 起到调节胆道压力、胆汁流向作用. 目前, SOD已得到普遍认可. 而Oddi括约肌压力检测(SOM)作为SOD最有价值的诊断方法, 有助于选择适宜EST的SOD患者. 以往文献报道SOM为AP的危险因素, 而近期某些学者报道SOM并不作为AP的独立危险因素[8,11,14]. Wong et al[15]研究表明, SOM后AP发生率为9%, 其相关危险因素为既往ERCP急性胰腺炎史、括约肌基础压力增高(≥40 mmHg)、括约肌基础波频率增高(≥7次/min). Wehrmann et al[16]认为采用带有微型换能器测压法相比标准的灌注测压法, 发生AP的风险减少.
应用内镜下乳头括约肌气囊扩张术(EPBD)可有效减少EST所致出血的风险, 并可保留Oddi括约肌功能[17], 对于治疗10 mm以下的胆总管结石有满意的效果. 有学者研究认为, EPBD较EST有较高的AP发生率[18-20]. 主要是扩张气囊反复多次对乳头括约肌及胰管开口部位的机械性刺激及损害, 造成胰液引流不畅发生胰腺炎. 但也有作者认为EPBD术后AP主要与患者年龄、术前高淀粉酶血症以及胆道巨大/多发结石等因素相关[21]. Lin et al[22]对104例胆总管结石患者进行了EPBD与EST对照研究, 结果显示两组患者在术后淀粉酶水平及AP发生率方面无显著差异.
ERCP操作过程中因插管困难而多次插管易造成乳头水肿, 伴有导丝引导插管可能造成乳头部损伤, 导致胰液引流不畅; 胰管多次注射, 特别是胰腺显影及造影附件导致胰管损伤, 与ERCP术后AP相关, 已得到公认[23-25].
近年来, 关于预防ERCP术后AP的药物研究被广泛开展, 生长抑素(somatostatin)和加贝酯(gabexate)被多数学者认为对AP有显著的预防作用[1,31-33]. Poon et al[34]对270例施行ERCP患者进行了前瞻性对照研究. 在研究组于ERCP后立即给予somatostatin 250 mg iv. 在实验组与对照组高淀粉酶血症发生率为26.0% vs 38.5%, P = 0.036; AP发生率为4.4% vs 13.3%, P = 0.010, 显示有显著差异. 认为ERCP术后即刻给予单剂量静脉途径somatostatin可明显降低高淀粉酶血症和AP的发生率. Arvanitidis et al[35]对372例ERCP进行了随机双盲对照研究, 实验组一在ERCP前30 min开始给予somatostatin行持续12 h静脉滴注; 实验组二在乳头插管同时予somatostatin单剂量静脉注射. 结果实验组与对照组AP发生率为1.7% vs 9.8%(P<0.05), 且血清淀粉酶在实验组明显低于对照组, 显示有显著差异. 认为somatostatin可明显降低高淀粉酶血症和AP的发生率, 对于药物使用的成本核算与用药剂量、用药途径的研究应进一步开展. Tsujino et al[36]对406例施行ERCP患者进行了多中心随机双盲对照研究, 实验组在ERCP开始前10 min给予乌司他丁(ulinastatin) 15万U静脉滴注. 随后在ERCP后4和18 h采取血清胰腺生化酶学检测. 结果显示, 实验组与对照组相比高血清酶血症发生率明显降低(淀粉酶P = 0.011; 脂肪酶P = 0.008), AP发生率为2.9% vs 7.4%, P = 0.041. 认为ulinastatin 短期用药可明显降低高血清酶血症和AP发生率. Fujishiro et al[37]研究139例ERCP患者, 认为低剂量(15万U)与高剂量(45万U) ulinastatin和高剂量gabexate (900 mg)在预防ERCP后AP方面同样有效. Xiong et al[38]对193例ERCP患者进行对照研究. 实验组于ERCP开始前0.5 h开始静脉点滴gabexate维持至术后4 h, 总剂量为300 mg. 结果显示, 实验组与对照组高淀粉酶发生率为33.7% vs 43.7% (P = 0.133); AP发生率为3.1% vs 10.5% (P = 0.040); 胰源性腹痛发生率为15.3% vs 29.5% (P = 0.018). 认为4.5 h的加贝酯静脉滴注可能可以防止ERCP术后AP和胰源性腹痛. Masci et al[39]比较了gabexate在剂量与给药持续时间的不同与AP的关系. 在434例患者, 实验组与对照组均在ERCP开始前30 min予gabexate静脉点滴, 共维持6.5 h(总剂量500 mg), 此后实验组给予安慰剂, 对照组继续予gabexate 500 mg静脉点滴维持至13 h(总剂量1000 mg). 结果表明, 在术后腹痛发生、血清酶血症和AP发生率均无显著差异. Testoni et al[40]认为静脉途径使用1000 mg gabexate可明显减少ERCP术后AP发生率, 尤其对于存在高危因素的患者, 但gabexate不能减少重型胰腺炎的发生率. 然而部分学者对于生长抑素和加贝酯对ERCP术后AP的预防意义提出不同意见. Andriulli et al[41-42]对somatostatin和gabexate在ERCP短期用药(somatostatin 750 mg, gabexate 500 mg, 于术前开始持续静脉点滴2 h)与长期用药(somatostatin 750 mg, gabexate 500 mg, 于术前开始持续静脉点滴6.5 h)进行研究, 认为均对ERCP术后AP无预防作用. Vila et al[43]也认为在乳头插管前给予somatostatin 250 mg iv对AP无预防作用.
硝酸甘油(glyceryl trinitrate)可以降低Oddi括约肌压力, 增加经乳头的胆汁引流, 研究认为, 可以预防ERCP术后AP[44]. Moreto et al[45]在ERCP前经皮使用glyceryl trinitrate 15 mg进行对照研究, 结果实验组与对照组AP发生率为4.2% vs 15.1% (P<0.05), 显示有明显差异. 皮质类固醇具有减轻组织水肿和抑制炎症反应作用, 被用于AP的治疗, Kwanngern et al[46]报道单剂量corticosteroid可预防ERCP术后AP. 但近期多数学者研究表明其对ERCP术后AP并无预防作用[47-50]. 口服别嘌呤醇(allopurinol)的预防作用存在争议, 有研究报道大剂量allopurinol (ERCP前15 h, 3 h口服600 mg)可降低AP发生率, 但尚需更广泛的研究观察[51-52]. Fan et al[53]在一组160例ERCP患者对照研究中, 证明5-fluorouracil组与对照组AP发生率为2.5% vs 10.0%, 有显著差异, 提示5-fluorouracil对ERCP术后AP有预防意义.
近年开展更广泛的药物研究, 多种药物用于临床研究, 但具体效果尚待进一步的研究证实. 目前, 多数学者认为低分子肝素(low-molecular-weight heparin)、乙酰半胱氨酸(N-acetylcysteine)、硝苯地平(nifedipine)、β-胡萝卜素(beta-carotene)、利多卡因(lidocaine)对ERCP术后AP无预防作用[54-59].
选择性胆管插管在一些情况下是困难的, 多次插管造成乳头水肿, 伴有导丝引导插管可能造成乳头部损伤, 导致胰液引流不畅, 因此, 插管困难可能引发ERCP术后AP. 在近年的文献中, 许多学者对因插管困难的病例将传统的插管技术进行了改进, 以减少ERCP术后AP的发生. Goldberg et al[60]采用胰管支架协助选择性胆管插管. 对此报道2004例ERCP中选择性胆管插管困难39例患者, 行胰管支架置入, 引导选择性胆管插管的成功率为97.4%, 术后仅两例发生轻型AP(5.3%). 认为该技术安全有效. 乳头旁憩室, 尤其乳头完全进入憩室内, 通常认为选择性胆管插管困难. Fogel et al[61]报道, 采用主胰管支架结合胆管括约肌预切开技术, 提高选择性胆管插管成功率, 减少反复插管的次数. Lella et al[24]分析了一种新的插管方法: 采用带有尖端柔软的Teflon踪迹导丝(0.035英寸)的6 F双腔括约肌切开刀行插管、注射造影剂和括约肌切开术, 以区别传统方法的对照研究. 结果显示, 实验组和对照组的AP发生率为0% vs 4% (P<0.01), ERCP后24 h血清淀粉酶大于正常五倍的发生率为4.5% vs 19.5% (P<0.001). 这种方法主要避免了反复多次插管对乳头的影响. Lella et al[23]报道, 在胆囊结石合并胆总管结石的病例, 在腹腔镜胆囊切除术(LC)中采用"会师技术"协助内镜行胆管插管, 并与传统的先行ERCP而后行LC的治疗方式进行对照研究. 结果显示,实验组和对照组的AP发生率为0% vs 10% (P = 0.0274), 认为该项技术可明显降低ERCP术后AP的发生率. 考虑与顺行置入的导丝使选择性胆管插管易于完成, 避免了乳头水肿和胰管损伤有关. 对于选择性胆管插管失败患者, 有学者研究证明, 采用针型切开刀行乳头上括约肌切开术安全可靠[62-64].
目前普遍认为胰管支架对ERCP术后AP有预防作用, 尤其是对于具有AP高危因素的ERCP者[65-66]. 疑有SOD的患者行ERCP, 术后AP发生率明显高于无SOD者, SOD患者中约有75%存在胰管括约肌基础压力增高, 在施行胆管括约肌切开术时, 由于胰管括约肌未被完全切开而导致暂时性水肿, 使原来基础上的胰管括约肌压力进一步升高, 导致胰液引流不畅而发生AP. Fogel et al[13]认为对此类患者单独行胆管括约肌切开术具有很高的AP发生率, 而采用胰管支架, 并行胰胆管括约肌联合切开术, 可有效地降低AP的发生率. Tarnasky[67]认为ERCP术后AP病理生理中最重要的是胰腺引流不畅. 胰管支架可以降低AP的发生率和AP的严重程度. 胰管支架适用于疑有SOD的年轻者、先前有AP病史者、插管困难者、乳头预备切开者和胰管括约肌切开术者. 支架可以在1 wk内移除. 胰管支架可以降低AP的发生率, 但由于胰管狭小、曲折而使导丝或支架置入失败, 则大大地提高了AP的发生率. Freeman et al[68]报道了一种改良的支架置入技术, 以解决由于胰管解剖原因造成的支架置入的技术困难. 这种改良技术, 采用短小支架(2-3 cm, 3-5 F), 以0.018英寸镍钛合金尖端的导丝引导, 支架远端越过胰管括约肌1-2 cm, 可明显提高困难的胰管支架置入成功率, 从而避免了因支架置入失败造成的风险. Rashdan et al[69]认为3-4 F胰管支架与传统使用的5-6 F的胰管支架相比, 对于预防ERCP术后AP更为有效. EPBD较EST有较高的AP发生率, 主要是扩张气囊反复多次对乳头括约肌及胰管开口部位的机械性刺激及损害, 造成胰液引流不畅发生胰腺炎. Sato et al[20]在34例胆总管结石行EPBD术后行经内镜鼻胆管引流术(ENBD), 无一例AP发生, EPBD术后ENBD可有效减少AP的发生率, 推测是由于ENBD防止了因残余结石或乳头水肿所致胰管梗阻而起到预防作用.
内镜逆行性胰胆管造影以及相关治疗技术已成为胆胰疾病的重要治疗手段, ERCP术后急性胰腺炎是常见且严重的并发症之一, 探讨ERCP术后的危险因素及其预防, 对于提高ERCP诊断治疗水平及安全性有着重要的意义.
对于ERCP术后急性胰腺炎的预防, 目前较为一致的观点是, 对于存在高危因素的患者, 提倡预防性胰管支架的应用, 文章从这个角度出发, 分析了技术上的要点, 以及胰管支架的类型和多位学者的创新方法.
目前, ERCP技术已在国内县级以上医院普遍开展, 而急性胰腺炎作为ERCP术后常见、严重的并发症, 探讨ERCP术后的危险因素及其预防, 对于提高ERCP诊断治疗水平及安全性有着重要的意义. 文章通过对ERCP术后急性胰腺炎的危险因素及其预防的研究综述, 对ERCP的临床应用有一定的指导作用.
本文系统总结了ERCP及其相关治疗术后AP发生的危险因素及预防, 引用文献较新, 有一些新的观点, 对临床有较好的指导作用.
电编:张敏 编辑:潘伯荣
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