Continuous regional arterial infusion of protease inhibitor and antibiotics in acute necrotizing pancreatitis

doi:10.1016/S0002-9610(97)89617-1

The American Journal of Surgery

Volume 171, Issue 4, April 1996, Pages 394-398

https://doi.org/10.1016/S0002-9610(97)89617-1 Get rights and content

Purpose

This study was conducted to determine whether continuous regional arterial infusion (CRAI) of the protease inhibitor, nafamostat mesylate, in acute necrotizing pancreatitis, would reduce mortality. In addition, the effectiveness of CRAI of the antibiotic imipenem in combination with nafamostat was investigated for its effect in preventing secondary infection of the pancreatic necrotic tissue.

Patients and Methods

Fifty-three patients with acute necrotizing pancreatitis were divided into

Three groups

Group I, 16 patients who were referred >8 days after disease onset, received intravenous nafamostat and antibiotics; Group II, 22 patients referred within 7 days, received nafamostat via CRAI, and antibiotics intravenously; GroupI, 1, 15 patients referred within 7 days, received both nafamostat and imipenem via CRAI.

Results

The mortality rates in group II (13.6%) and groupI (6 (6.7%) were significantly reduced, as compared with that in group I (43.8%). The incidence of infection of pancreatic necrosis in groupI (0 (0%) was significantly lower than those in group I (50%) and in group II (22.8%).

Conclusion

CRAI of nafamostat and imipenem in acute necrotizing pancreatitis was effective in reducing mortality and preventing the development of pancreatic infection.

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Pharmacological Management of Acute and Chronic Pancreatitis
2022, Comprehensive Pharmacology
Pancreatitis is often categorized as acute and chronic pancreatitis. Acute pancreatitis (AP) is an inflammatory condition that often results in a significant systemic inflammatory response; chronic pancreatitis (CP) is an ongoing inflammatory and fibrotic condition that often results in loss of exocrine and endocrine functions. Many pharmaceutical therapies have been trialed in pancreatitis. However, evidence based recommendations are limited by a paucity of large, randomized controlled studies and significant heterogeneity in available studies. In AP, early, aggressive fluid therapy is the most supported intervention. Therapies aimed at decreasing pancreatic stimulation (anti-secretory agents), inflammation (protease inhibitors, NSAIDs, glutamine), or oxidative stress (antioxidants, N-acetylcysteine, vitamin C, selenium) have also been used. Antibiotics and probiotics have also been used in AP. In CP, pharmaceutical therapies are often aimed at treating the resulting exocrine insufficiency, and there are several pancreatic enzyme replacement therapies (PERT) available. Pharmaceutical therapies are also used to treat the chronic pain that frequently accompanies CP. These therapies include non-opioid and opioid pain medications, along with adjuvant therapies (pregabalin, antidepressants, and ketamine) aimed at addressing the neuropathic component of CP pain. Therapies targeting decreasing pancreatic stimulation (PERT and octreotide) and inflammation (antioxidants) have also been used in CP.
Clinical practice of acute pancreatitis in Japan: An analysis of nationwide epidemiological survey in 2016
2020, Pancreatology
Citation Excerpt :
Although the guidelines do not recommend antibiotic administration in mild AP cases, 94.5% of mild AP cases received antibiotics. In Japan, CRAI of protease inhibitors such as nafamostat mesylate has been commonly used in severe AP patients presenting hypoenhanced areas of the pancreatic parenchyma to maintain the high intrapancreatic concentrations of this reagent [31]. In this survey, CRAI of nafamostat mesylate did not reduce the mortality rate of severe AP cases, even in cases with extended hypoenhanced lesion of the pancreatic parenchyma.
To provide updates on clinical practice of acute pancreatitis (AP) in Japan, we conducted a nationwide epidemiological survey.
This study consisted of a two-staged survey; the number of AP patients was estimated by the first-stage survey and their clinical features were examined by the second-stage survey. We surveyed AP patients who had visited hospitals in 2016.
The estimated number of AP patients in 2016 was 78,450, with an overall incidence of 61.8 per 100,000 persons. We obtained detailed clinical information of 2994 AP patients, including 706 (23.6%) severe cases classified according to the Japanese severity criteria. The male-to-female sex ratio was 2.0, and the mean age at onset was 59.9 years in males and 66.5 years in females. Alcohol was the most common etiology (42.8%) in males and gallstones in females (37.7%). The AP-associated mortality was 6.1% in severe AP cases, which was decreased by 40% compared to the 2011 survey. Antibiotics were administered to most cases, with carbapenem being frequently used. Enteral nutrition was given in 31.8% of severe cases, but majority cases received after 48 h. Among the 107 patients who received intervention for walled-off necrosis, five patients received surgery-first approach, 66 received endoscopic ultrasound-guided transluminal drainage, and 19 underwent step-up approach.
We clarified the current status of AP in Japan including the significant reduction of mortality in severe cases, shift to endoscopic approaches for walled-off necrosis, and poor compliance of the recommendations in the guidelines including management of enteral nutrition and antibiotic administration.
Efficacy of recombinant human soluble thrombomodulin in preventing walled-off necrosis in severe acute pancreatitis patients
2015, Pancreatology
Citation Excerpt :
Enrolled patients were treated based on the strategy recommended in the Japanese guidelines for early stage acute pancreatitis [39–42]: in brief, fasting, aggressive fluid therapy, and administration of a protease inhibitor (nafamostat mesilate: 0.06–0.20 mg/kg/hours infused continuously; gabexate mesilate: 20–39 mg/kg/day). Continuous regional arterial infusion of the protease inhibitor (nafamostat mesilate) and prophylactic antibiotics (CRAI) [43–45] was undertaken for patients with ischemic or necrotizing pancreatitis [46,47]. Intravenous antibiotics were admitted for patients suspected to have sepsis (high fever with shock-like states).
To investigate the efficacy of recombinant human soluble thrombomodulin (rTM) in preventing the development of walled-off necrosis (WON) in severe acute pancreatitis (SAP) patients.
We retrospectively analyzed 54 SAP patients divided into two groups: SAP patients treated by rTM (rTM group, 24 patients) and not treated by rTM (control group, 30 patients). rTM was administered to patients with disseminated intravascular coagulation (DIC). Initially, on the admission day, we recorded patient severity and pancreatic necrosis/ischemia positive or negative. Then we investigated development of WON using 4 weeks later CT/MRI. Finally we compared the proportions of patients developing WON in the rTM group and the control group.
On the admission day, the condition of patients treated by rTM was significantly worse than patients in the control group; rTM group vs. control: 71.8 ± 13.9 vs. 59.8 ± 15.3 years for age, 10.7 ± 3.5 vs. 8.0 ± 4.4 for Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and 3.3 ± 1.8 vs. 2.2 ± 1.8 for sequential organ failure assessment (SOFA) score (p < 0.05). We found no significant differences on the admission day in rate of pancreatic necrosis/ischemia between patients treated by rTM and controls (58.3% vs. 63.3%, p = 0.71). Nevertheless, the proportion of patients developing WON was significantly lower among those administered rTM than in those not administered rTM {29.2% (7/24 patients) vs. 56.7% (17/30 patients), p < 0.05}.
Treatment of SAP patients treated by rTM may prevent progression from pancreatic necrosis/ischemia to WON.
Continuous regional arterial infusion for the treatment of severe acute pancreatitis: A meta-analysis
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Continuous regional arterial infusion (CRAI) is a drug delivery system, which dramatically increases the drug concentration in the pancreas. Previous clinical and basic studies have demonstrated the possible therapeutic efficacy of CRAI for severe acute pancreatitis (SAP). This meta-analysis of all published randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of CRAI for the treatment of SAP.
Up to August 10, 2014, RCTs comparing CRAI with intravenous infusion for SAP in PubMed, Embase, EBSCO, MEDLINE, Science Citation Index Expanded, Cochrane Library, China Academic Journals Full-Text Database, Chinese Biomedical Literature Database, and Chinese Scientific Journals Database were selected by two independent reviewers. The relative risk (RR) and their 95% confidence intervals (CI) for duration of elevated serum amylase and urine amylase, duration of abdominal pain, infection rate, incidence of complication, overall mortality, curative rate, hospital stay and details of subgroup analysis were extracted. Meta-analyses were made using the software Review Manager (RevMan version 5.10).
Six RCTs with 390 patients meeting the inclusion criteria were included in the final analysis. Compared with intravenous infusion route, CRAI significantly shortened the duration of elevated urine amylase (MD=-2.40, 95% CI=-3.20, −1.60; P<0.00001) and the duration of abdominal pain (MD=-1.46, 95% CI=-1.94, −0.98; P<0.00001), decreased the incidence of complication (RR=0.35, 95% CI=0.15, 0.81; P=0.01) and overall mortality (RR=0.25, 95% CI=0.08, 0.78; P=0.02), shortened the duration of hospital stay (MD=-10.36, 95% CI=-17.05, −3.68; P=0.002), and increased the curative rate (RR=1.66, 95% CI=1.13, 2.46; P=0.01). No mortality and catheter-related infections due to CRAI administration was reported in these studies. Subgroup analysis showed that the combination of drug administration via CRAI did not significantly improve the outcomes.
CRAI is effective for the treatment of SAP, and the combination of drug administration via CRAI did not have a significant effect on the improvement of the outcomes.
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View full text

Continuous regional arterial infusion of protease inhibitor and antibiotics in acute necrotizing pancreatitis

Purpose

Patients and Methods

Three groups

Results

Conclusion

Am J Surg

Gastroenterology

Treatment of acute pancreatitis with Trasyrol: report of a controlled trial

Br Med J

A single-centre double-blind trial of Trasyrol therapy in primary acute pancreatitis

Br J Surg

Morbidity of acute pancreatitis: the effect of aprotinin and glucagon

Gut

A controlled trial of Trasyrol in the treatment of acute pancreatitis

Br J Surg

Vascular changes of pancreatic ducts and vessels in acute necrotizing and in chronic pancreatitis in humans

Int J Pancreatol

Contrast-enhanced computed tomography and microangiography of the pancreas in acute human hemorrhagic/necrotizing pancreatitis

Pancreas

Effects of continuous arterial infusion of protease inhibitor on experimental acute pancreatitis induced by closed duodenal loop obstruction

Jpn J Gastroent