Background
In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure.

Objectives
To assess the effects of different pharmacological interventions in people with acute pancreatitis.

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials.

Selection criteria
We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review.

Data collection and analysis
Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model.

Main results
We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials.

Source of funding: seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.

Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life.

Authors' conclusions
Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

Pharmacological interventions for acute pancreatitis

Background: Multi-organ dysfunction, and in particular lung injury, is often responsible for the unfavorable outcome of patients with severe acute pancreatitis Understanding of the mechanisms by w

From acute pancreatitis to end-organ injury: mechanisms of acute lung injury.

Patients who have been diagnosed as having acute pancreatitis should be, on principle, hospitalized. Crucial fundamental management is required soon after a diagnosis of acute pancreatitis has been made and includes monitoring of the conscious state, the respiratory and cardiovascular system, the urinary output, adequate fluid replacement and pain control. Along with such management, etiologic diagnosis and severity assessment should be conducted. Patients with a diagnosis of severe acute pancreatitis should be transferred to a medical facility where intensive respiratory and cardiovascular management as well as interventional treatment, blood purification therapy and nutritional support are available. The disease condition in acute pancreatitis changes every moment and even symptoms that are mild at the time of diagnosis may become severe later. Therefore, severity assessment should be conducted repeatedly at least within 48 h following diagnosis. An adequate dose of fluid replacement is essential to stabilize cardiovascular dynamics and the dose should be adjusted while assessing circulatory dynamics constantly. A large dose of fluid replacement is usually required in patients with severe acute pancreatitis. Prophylactic antibiotic administration is recommended to prevent infectious complications in patients with severe acute pancreatitis. Although the efficacy of intravenous administration of protease inhibitors is still a matter of controversy, there is a consensus in Japan that a large dose of a synthetic protease inhibitor should be given to patients with severe acute pancreatitis in order to prevent organ failure and other complications. Enteral feeding is superior to parenteral nutrition when it comes to the nutritional support of patients with severe acute pancreatitis. The JPN Guidelines recommend, as optional continuous regional arterial infusion and blood purification therapy.

/pdf/fundamental-and-intensive-care-of-acute-pancreatitis-usqxeri27b.pdf

Fundamental and intensive care of acute pancreatitis

Purpose To evaluate whether the annual number of pain relapses of chronic pancreatitis correlated with sex, type of pancreatitis, drinking and smoking, presence of intraductal calcifications, pancreaticojejunostomy, and length of follow-up in the first 10 years of follow-up. Methods The authors analyzed 205 nonobstructive chronic pancreatitis cases with at least a 10- year follow-up, for a total of 2,034 person/year observations. Data were recorded on the daily number of cigarettes smoked and grams of alcohol drunk, as well as the presence of intraductal calcifications, and performance of pancreaticojejunostomy. Results The model for multivariate autoregressive repeated measures analysis indicated that drinking ( P P P P P Conclusions Regardless of surgical treatment, patients should be advised to reduce both their alcohol intake and cigarette smoking.

Pain relapses in the first 10 years of chronic pancreatitis

The differential diagnosis between acute and chronic alcohol-associated pancreatitis is often difficult or impossible at onset of the disease. A study was conducted to determine possible relationships between patients suffering from a first episode of acute alcoholic pancreatitis and patients with unequivocal chronic alcoholic pancreatitis, comparing age, drinking and smoking habits, and body mass index (BMI). Two groups of men were considered. The first group consisted of 67 patients with a diagnosis of acute alcohol-associated pancreatitis in the absence of other potential pathogenic factors; in this group, 48 of the 56 patients surviving the acute attack were submitted to imaging studies for a median period of 9 years. The second group consisted of 396 patients with chronic alcoholic pancreatitis with a median follow-up period of 12 years. The variables that differed significantly in the two groups were BMI (p < 0.009) and number of smokers (p < 0.001). Logistic regression analysis selected only BMI with an odds ratio of 1.19 (95% CI, 1.07-1.33; p < 0.00015) in favor of acute alcoholic pancreatitis. In male patients, from an epidemiologic standpoint, only smoking habits and BMI are significant differences at clinical onset between the two types of pancreatitis.

Alcohol intake, cigarette smoking, and body mass index in patients with alcohol-associated pancreatitis.

Despite controversial experimental and clinical findings, the use of Aprotinin (A) in the treatment of acute pancreatitis (AP) is still widespread in our country. Compared to A, Gabexate Mesilate (FOY) should have the following advantages: lack of antigenicity, low molecular weight with better cellular penetrance, wide inhibitory spectrum (against phospholipase A2 too) and good tolerability. In order to verify the efficacy of FOY versus, we decided to carry out a prospective multicenter (34 centers) randomized double blind trial in moderate-severe AP with FOY 3g/day versus A 1,500,000 U.I.K./day infused for 7 days with central venous line. Based on standard clinical, biochemical and radiological data, 199 patients suffering from AP were enrolled to the study from January 1989 to December 1990. The main admission criteria were: onset of the disease from no more than 72 hours, at least 2 Ranson positive criteria and C.T. evidence of acute pancreatic damage. Seventeen no protocol patients were excluded. The Etiology in the 182 analyzed patients (106 male, 76 female; mean age 57.6 years, range 21-91) were: biliary 102 (56%), alcohol 47 (25.8%), post-operative 13 (7.1%), unknown causes 13 (7.1%) and others 7 (3.8%). Median Ranson's Score was 3. CT examination showed 66 AP with edema, while 116 cases (63.7%) were recognized as severe forms with pancreatic necrotic involvement of 30% of the gland in 71 (61.2%), 50% in 31 (26.7%), and more than 50% in 14 (12.1%). Out of 182 patients, 91 were treated with A and 91 with FOY. The two groups were comparable regarding the main prognostic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Gabexate mesilate in the treatment of acute pancreatitis.

Most patients suffering from chronic pancreatitis are referred to the surgeon for the presence of disabling pain which fails to respond to conservative medical therapy [1]. In most medico-surgical patient series, from 30 % to 60 % of patients with chronic pancreatitis are treated surgically for this indication at some time in the course of the disease. Other indications for surgical treatment include pseudocysts, mechanical jaundice, bleeding oesophageal varices, duodenal stenosis, pancreatic ascites and suspected presence of carcinoma [2].

Derivative Surgical Treatment

I tumori cistici del pancreas

Naturally occurring somatostatin and, even more so, its analogue, octreotide, by virtue of its greater manageability, are used extensively today in various pancreatic and gastrointestinal disorders, where their potent secretion-inhibiting capacity is exploited. In a number of conditions such as pancreatic fistulas the beneficial efficacy of the hormone is now definitely established both for therapeutic and for prophylactic purposes, whereas, in the other disease areas analyzed here, its use appears to be as an adjuvant to more specific and more radical procedures. Future clarification as to indications, dosage regimens and treatment times may reveal more strictly curative uses of octreotide in its own right, though, even as things stand at present, its efficacy as a complementary measure is so self-evident as to prompt its inclusion in treatment schedules both for enterocutaneous fistulas and for ascites and pancreatic pseudocysts.

Role of Somatostatin and Its Analogues in Gastrointestinal Fistulas, Ascites and Pancreatic Pseudocysts

To date, gabexate mesilate, a synthetic protease inhibitor, has been used in the prophylaxis and treatment of acute pancreatitis, but has yet to be tested in preventing the postoperative complications of pancreatic surgery. For this purpose we planned a pilot study based on two treatment groups, each numbering 25 patients, submitted to high-risk pancreatic resection. In the first group, all patients received a continuous infusion of gabexate mesilate 1 g/day up to postoperative day 4; the second group of patients received the same treatment plus octreotide 0.1 mg every 8 hours for 5 days after surgery. All patients were followed until discharge with clinical and instrumental investigations to detect the onset of postoperative complications. The overall incidences of an uneventful course were 40% (10/25) and 32% (8/25), respectively. We found 12 complications closely related to pancreatic surgery in the former and 8 in the latter group. In the combined treatment group therefore we observe a 33% reduction in the incidence of related abdominal complications (12 vs 8). This favourable trend, however, needs to be confirmed in a larger multicentre trial.

[Gabexate mesilate vs gabexate mesilate combined with octreotide in the prevention of postoperative complications of pancreatic surgery: preliminary results].

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