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

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.

Cytokine Profile Elevations on Admission Can Determine Risks of Severe Acute Pancreatitis in Children

“…Patients who received the investigational drug had significantly lower levels of IL-6, and the therapy was associated with an almost 50% reduction in the progression of patients to severe disease. (12) This suggests that although IL-6 is a general marker of inflammation in many different disease states, and while not pancreas-specific, suppressing IL-6 levels by targeting either IL-6 itself or the upstream inflammasome in AP may lead to improved outcomes. (13) The mechanism of IL-6 activation is multifold and leads to downstream upregulation of the neutrophil response.…”

Glucocorticoids in acute pancreatitis: a propensity score matching analysis

“…Second, a study showed that cyclooxygenase-2 (COX-2) inhibitors can prevent AP from becoming severe recently [ 37 ]. This is the first report to demonstrate the effect of COX-2 inhibitors on the treatment of AP in humans.…”

Severe acute pancreatitis concurrent with lethal rupture of cerebral aneurysm: A case report and review of the literature

“…In this case, an obvious pancreatic and peripancreatic necrotic region shown in CT image, combined with elevated WBC count and neutrophil percentage during his hospitalization jointly indicated necrotic tissues-induced SIRS. Meanwhile, a clinical trial points out that inhibiting the inflammatory cascade in predicted SAP is of cost-effectiveness to strikingly reduce concurrence and promote the prognosis of SAP [ 12 ].…”