Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Am J Gastroenterol. 2020 Mar;115(3):473-480. doi: 10.14309/ajg.0000000000000529.
Severe acute pancreatitis (SAP) is still a big challenge. Accumulated data showed that overexpression of cyclooxygenase-2 (COX-2) in acute pancreatitis and experimental pancreatitis could be attenuated with COX-2 inhibitors. This study was aimed to evaluate whether the occurrence of SAP could be prevented by selective COX-2 inhibitors.
A total of 190 patients with predicted SAP were randomized into convention group or convention plus COX-2 inhibitors (C+COX-2-Is) group. Besides conventional treatment to all patients in 2 groups, parecoxib (40 mg/d intravenous injection for 3 days) and celecoxib (200 mg oral or tube feeding twice daily for 7 days) were sequentially administrated to the patients in the C+COX-2-Is group. The primary outcome was predefined as the occurrence of SAP. The serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) for all of the patients were measured.
The occurrence of SAP in the C+COX-2-Is group was decreased 47.08% compared with the convention group, 21.05% (20/95) vs 39.78% (37/93), P = 0.005. A reduction of late local complications was also shown in the C+COX-2-Is group, 18.95% (18/93) vs 34.41% (32/95), P = 0.016. The serum levels of IL-6 and TNF-α were significantly lower in the C+COX-2-Is group than those in the convention group, P < 0.05. Parecoxib relieved abdominal pain more rapidly and decreased the consumption of meperidine. An incremental reduction of cost for 1% decrease of SAP occurrence was RMB475.
Sequential administration of parecoxib and celecoxib in patients with predicted SAP obtained about half-reduction of SAP occurrence through decreasing serum levels of TNF-α and IL-6. This regimen presented good cost-effectiveness.
重症急性胰腺炎(SAP)仍然是一个巨大的挑战。大量数据表明,在急性胰腺炎和实验性胰腺炎中,环氧化酶-2(COX-2)的过表达可以通过 COX-2 抑制剂得到缓解。本研究旨在评估选择性 COX-2 抑制剂的应用是否可以预防 SAP 的发生。
共有 190 例预测 SAP 的患者被随机分为常规组或常规加 COX-2 抑制剂(C+COX-2-Is)组。除了对两组患者进行常规治疗外,C+COX-2-Is 组患者还依次给予帕瑞昔布(40 mg/d 静脉注射,连用 3 天)和塞来昔布(200 mg 口服或管饲,每日 2 次,连用 7 天)。主要结局为预先设定的 SAP 发生情况。检测所有患者的白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)血清水平。
与常规组相比,C+COX-2-Is 组 SAP 的发生率降低了 47.08%,分别为 21.05%(20/95)和 39.78%(37/93),P=0.005。C+COX-2-Is 组晚期局部并发症也有所减少,分别为 18.95%(18/93)和 34.41%(32/95),P=0.016。C+COX-2-Is 组的 IL-6 和 TNF-α 血清水平明显低于常规组,P<0.05。帕瑞昔布能更快缓解腹痛,并减少哌替啶的消耗。SAP 发生率每降低 1%,成本增加 475 元人民币。
在预测 SAP 的患者中序贯给予帕瑞昔布和塞来昔布,通过降低 TNF-α 和 IL-6 的血清水平,使 SAP 的发生率降低了近一半。该方案具有良好的成本效益。