Endoluminal Pancreatic Duct Lidocaine for Prevention of Post-ERCP Pancreatitis

描述（由申请人提供）：急性胰腺炎是内镜逆行胰胆管造影术（ERCP）最常见的严重并发症，发生率在5 - 15%之间。这些事件中约55%为中度至重度，构成了发病率、死亡率和医疗事故索赔的巨大负担。ERCP后胰腺炎的机制是多因素的，涉及局部神经弧通路、胰腺酶和炎症级联的激活。利多卡因是一种常用的廉价麻醉剂和抗心律失常药物，对这些神经弧通路和磷脂酶A2有抑制作用，并在动物模型中显示出减轻或预防急性胰腺炎的作用。尽管有人建议使用利多卡因导管内预防ercp后人类胰腺炎的具体指征，但迄今为止尚无研究。我们假设，当利多卡因加入造影剂并在ERCP时注入胰管时，可以通过抑制局部神经反射弧和磷脂酶A2来减少ERCP诱导的胰腺炎的发生率，这两种酶都是通过操纵和胰管炎症激活的。该项目的目标是开展一项随机、双盲、对照试验，纳入宾夕法尼亚州立好时医学中心的ERCP患者，每组570名患者，研究功率为80%。患者将按1:1的比例随机分为对照组或研究组。对照组接受生理盐水稀释至50%的造影剂（标准护理），实验组接受利多卡因（100mg）稀释至50%的造影剂。主要终点是手术后24小时内急性胰腺炎的发生率（临床和生化定义），次要终点是手术后2小时的血清淀粉酶水平。最近完成了一项10例患者的安全性试验，未发生并发症或胰腺炎。这项研究的结果将阐明利多卡因是否有助于预防胰腺炎，并可能进一步阐明其机制。

DESCRIPTION (provided by applicant): Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP) and occurs with an incidence between 5 and 15%. Approximately 55% of these occurrences are moderate to severe in magnitude, representing an enormous burden of morbidity, mortality and malpractice claims. The mechanisms of post- ERCP pancreatitis are multifactorial and involve activation of local neural arc pathways, pancreatic enzymes, and the inflammatory cascade. Lidocaine, a commonly used and inexpensive anesthetic and antiarrhythmic, has an inhibitory effect on these neural arc pathways as well as on phospholipase A2, and has been shown to attenuate or prevent acute pancreatitis in animal models. Although it has been suggested, to date there have been no studies performed using intraductal lidocaine for the specific indication of preventing post-ERCP pancreatitis in humans. We hypothesize that lidocaine, when added to the contrast material and infused into the pancreatic duct at the time of ERCP, can reduce the incidence of ERCP-induced pancreatitis by inhibiting local neural reflex arcs and phospholipase A2, both of which are activated by manipulation and inflammation of the pancreatic duct. The goal of this project is to launch a randomized, double-blind, controlled trial of patients referred to Penn State Hershey Medical Center for ERCP with a goal of 570 patients in each arm for a study power of 80%. Patients will be randomized in a 1:1 ratio to control or study group. The control arm will receive contrast dye diluted to 50% with normal saline (standard of care) and the study arm will have contrast dye diluted to 50% with lidocaine (100mg). The primary outcome will be the incidence of acute pancreatitis, defined clinically and biochemically, within 24 hours post procedure with a secondary outcome of serum amylase levels 2 hours post procedure. A safety trial of 10 patients has recently been completed without complication or incident pancreatitis. The results of this study will elucidate if lidocaine is useful in preventing pancreatitis and may shed additional light onto its mechanisms. PUBLIC HEALTH RELEVANCE: Pancreatitis is the most common serious complication of endoscopic retrograde pancreato- cholangiography (ERCP), occurring in 5-15% of patients, with 55% of these cases being considered moderate to severe in magnitude. The goal of this study is to determine if lidocaine is effective in diminishing the risk of post-ERCP pancreatitis, and to further the understanding of the safety and usefulness of lidocaine when used in ERCP.