Cavallini G, Tittobello A, Frulloni L, Masci E, Mariana A, Di Francesco V
Cattedra di Gastroenterologia, Università di Verona, Italy.
N Engl J Med. 1996 Sep 26;335(13):919-23. doi: 10.1056/NEJM199609263351302.
Endoscopic retrograde cholangiopancreatography (ERCP) is associated with elevated levels of pancreatic enzymes and pancreatitis. Gabexate, a protease inhibitor, has been used to prevent pancreatic damage related to ERCP.
We conducted a multicenter, double-blind comparison of gabexate (1 g given by intravenous infusion starting 30 to 90 minutes before endoscopy and continuing for 12 hours afterward) with placebo (mannitol and sodium chloride, administered in the same fashion). A total of 435 adults scheduled to undergo ERCP and, when indicated, endoscopic sphincterotomy underwent randomization; 17 were excluded from the final analysis for various reasons. The remaining 418 patients (mean age, 60.4 years)--208 in the gabexate group and 210 in the placebo group--were analyzed. Acute pancreatitis was considered to be present if serum amylase or lipase levels (or both) were five times greater than the upper limits of normal in association with the onset of pancreatic pain.
After the procedures, 276 patients (66 percent) had elevated pancreatic-enzyme levels; the frequency was similar in the two groups. Mean serum amylase values were higher in the placebo group than in the gabexate group through 24 hours of observation (P=0.03). Twelve patients in the gabexate group and 29 in the placebo group had abdominal pain (6 percent vs. 14 percent, P=0.009). Sixteen patients in the placebo group and five in the gabexate group had acute pancreatitis (8 percent vs. 2 percent, P=0.03). Two patients treated with gabexate and six given placebo had adverse events, all of which resolved. Two patients given placebo died of acute pancreatitis; one was excluded from the evaluation because pancreatitis was present before endoscopy. One patient in the gabexate group died, from a myocardial infarction.
Prophylactic treatment with gabexate reduced pancreatic damage related to ERCP, as reflected by reductions in the extent but not the frequency of elevated enzyme levels and in the frequency of pancreatic pain and acute pancreatitis.
内镜逆行胰胆管造影术（ERCP）与胰腺酶水平升高及胰腺炎有关。加贝酯，一种蛋白酶抑制剂，已被用于预防与ERCP相关的胰腺损伤。
我们进行了一项多中心、双盲比较，将加贝酯（在内镜检查前30至90分钟开始静脉输注1 g，并在之后持续12小时）与安慰剂（甘露醇和氯化钠，以相同方式给药）进行对比。共有435名计划接受ERCP且在必要时接受内镜括约肌切开术的成年人进行了随机分组；17人因各种原因被排除在最终分析之外。对其余418名患者（平均年龄60.4岁）进行了分析，其中加贝酯组208人，安慰剂组210人。如果血清淀粉酶或脂肪酶水平（或两者）比正常上限高五倍且伴有胰腺疼痛发作，则认为存在急性胰腺炎。
手术后，276名患者（66%）的胰腺酶水平升高；两组频率相似。在24小时观察期内，安慰剂组的平均血清淀粉酶值高于加贝酯组（P = 0.03）。加贝酯组有12名患者出现腹痛，安慰剂组有29名患者出现腹痛（6%对14%，P = 0.009）。安慰剂组有16名患者发生急性胰腺炎，加贝酯组有5名患者发生急性胰腺炎（8%对2%，P = 0.03）。两名接受加贝酯治疗的患者和六名接受安慰剂治疗的患者出现不良事件，所有不良事件均得到缓解。两名接受安慰剂治疗的患者死于急性胰腺炎；其中一名因在内镜检查前就存在胰腺炎而被排除在评估之外。加贝酯组有一名患者死于心肌梗死。
加贝酯预防性治疗减少了与ERCP相关的胰腺损伤，这体现在酶水平升高的程度而非频率以及胰腺疼痛和急性胰腺炎的频率降低方面。
