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环氧化酶-2 抑制剂预防重症急性胰腺炎的随机对照临床试验。

Prevention of Severe Acute Pancreatitis With Cyclooxygenase-2 Inhibitors: A Randomized Controlled Clinical Trial.

机构信息

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.

出版信息

Am J Gastroenterol. 2020 Mar;115(3):473-480. doi: 10.14309/ajg.0000000000000529.

Abstract

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

DISCUSSION

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.

摘要

目的

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。

方法

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。

结果

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。

讨论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c37/7060052/d78d7b9fb833/acg-115-473-g001.jpg

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