Rectal indomethacin versus placebo to reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography: results of a controlled clinical trial.

BACKGROUND: Acute pancreatitis is the most common major complication after endoscopic retrograde cholangiopancreatography (ERCP). Many drugs have been evaluated for prophylaxis, including nonsteroidal anti-inflammatory drugs (NSAIDs), which are potent inhibitors of phospholipase A2 and play a role in the pathogenesis of acute pancreatitis. Rectal NSAIDs have been shown in prospective studies to decrease the incidence of this complication, but the indication is not generalized in clinical practice. The aim of this study was to evaluate the efficacy of rectal administration of indomethacin in reducing the incidence of post-ERCP pancreatitis in high-risk patients. METHODS: This was a controlled clinical trial where patients with an elevated risk of developing post-ERCP pancreatitis were assigned to receive 100 mg of rectal indomethacin or a 2.6 g suppository of glycerin immediately after ERCP, without placement of a pancreatic stent. The patients were determined to be at high risk based on validated patient- and procedure-related risk factors. Post-ERCP pancreatitis was defined as the presence of new upper abdominal pain, hyperamylasemia/hyperlipasemia (at least three times the upper limit) 2 hours after the procedure and hospitalization at least 48 hours because of the complication. Pancreatitis severity was defined according to Cotton's criteria. RESULTS: One hundred sixty-six patients were included; 82 in the study group and 84 in the placebo group. Patients had at least one major and/or two minor risk factors for developing post-ERCP pancreatitis. The incidence of the complication was 4.87% (4/82) in the study group and 20.23% (17/84) in the placebo group; this difference was significant (P = 0.01). According to Cotton's criteria, 17 patients (80.9%) developed mild pancreatitis and 4 (19.1%) had moderate pancreatitis; 3 of these 4 patients belonged to the placebo group (P = 0.60). Based on these results, an absolute risk reduction of 0.15 (15%), a relative risk reduction of 0.75 (75%) and a number needed to treat of 6.5 patients were calculated to prevent an episode of post-ERCP pancreatitis. There was no mortality. CONCLUSIONS: Rectal indomethacin reduced the incidence of post-ERCP pancreatitis among patients at high risk of developing this complication. TRIAL REGISTRATION: National Clinical Trials NCT02110810. Date April 7, 2014.

Antioxidant drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis: What does evidence suggest?

AIM: To determine whether or not the use of antioxidant supplementation aids in the prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis. METHODS: A systematic review of randomized controlled trials (RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The inclusion criteria included: acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo, to reduce PEP. The outcome measure was the incidence and severity of PEP. Twelve RCTs involving 3110 patients since 1999 were included. The antioxidants used were selenite, ß-carotene, and pentoxifylline (each one in one trial), N-acetylcysteine (NAC) in three trials, and allopurinol in six trials. The group of patients treated with NAC received different doses; either oral or intravenous, and allopurinol-treated patients received five different oral doses in two different administration periods. The results are expressed with raw numbers, proportions, as well as mean and standard deviations. The incidence of pancreatitis between groups was analyzed with Pearson's χ(2) test or Fisher's exact test (F). The main outcome is expressed as relative risks and 95%CI. RESULTS: The incidence of pancreatitis in all antioxidant treatment groups was 8.6%, whereas it was 9.7% in the control group. The antioxidants used were selenite, ß-carotene, and pentoxifylline (each one in one trial), NAC in three trials, and allopurinol in six trials. In allopurinol trials, three different dosifications were used; two trials reported a low dosage (of less than 400 mg), two trials reported a moderate dose (600 mg) and the remaining two employed higher doses (more than 900 mg). Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk (RR) = 0.93; 95%CI: 0.82-1.06; P = 0.28]. In addition, the incidences of PEP in patients treated with allopurinol and those treated with other antioxidants were similar to that observed in patients who received the placebo (RR for trials with allopurinol, 0.92; 95%CI: 0.78-1.08; P = 0.31) and, with the use of other antioxidants, the incidence of PEP was 8.9%, whereas it was 9.7% in the control group (RR = 0.95; 95%CI: 0.77-1.18; P = 0.19). CONCLUSION: Antioxidant supplementation shows no beneficial effect on the incidence of PEP. There is a lack of robust trials to support the use of antioxidants for prevention.

Oral allopurinol to prevent hyperamylasemia and acute pancreatitis after endoscopic retrograde cholangiopancreatography.

AIM: To assess the efficacy of allopurinol to prevent hyperamylasemia and pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). METHODS: One hundred and seventy patients were enrolled and randomized to two groups: a study group (n = 85) who received 300 mg of oral allopurinol at 15 h and 3 h before endoscopic retrograde cholangiopancreatography (ERCP) and a control group (n = 85) receiving an oral placebo at the same times. Main Outcome Measurements included serum amylase levels and the number severity of the episodes of pancreatitis. Serum amylase levels were classified as normal (< 150 IU/L) or hyperamylasemia (> 151 IU/L). Episodes of PEP were classified following Ranson's criteria and CT severity index. RESULTS: Gender distribution was similar between groups. Mean age was 53.5 +/- 18.9 years for study group and 52.8 +/- 19.8 years for controls. Also, the distribution of benign pathology was similar between groups. Hyperamylasemia was more common in the control group (P = 0.003). Mild PEP developed in two patients from the study group (2.3%) and eight (9.4%) from control group (P = 0.04), seven episodes were observed in high-risk patients of the control group (25%) and one in the allopurinol group (3.3%, P = 0.02). Risk factors for PEP were precut sphincterotomy (P = 0.02), pancreatic duct manipulation (P = 0.002) and multiple procedures (P = 0.000). There were no deaths or side effects. CONCLUSION: Oral allopurinol before ERCP decreased the incidences of hyperamylasemia and pancreatitis in patients submitted to high-risk procedures.

End-stage renal disease and hepatitis C infection: comparison of alanine aminotransferase levels and liver histology in patients with and without renal damage.

BACKGROUND AND AIM: To what extent the serum levels of alanine aminotransferase (ALT) are related to histological characteristics of liver damage caused by hepatitis C virus (HCV) infection among patients with end-stage renal disease (ESRD) remains unclear. METHODS: Patients with a positive anti-HCV antibody titer confirmed by supplemental tests were evaluated by liver biopsy. We compared ALT levels in patients with and without renal damage, with similar histological grades and stages of inflammation and fibrosis. Results: Patients were divided into two groups: patients with ESRD (n = 25) and patients without ESRD renal damage (n = 39). RESULTS: The ALT level was 42.1 +/- 24.3 IU/L for the ESRD group, compared with 109.9 +/- 55.8 IU/L for the non-ESRD group (P < 0.001). Liver inflammation (modified Knodell grade) was 4.0 +/- 2.1 in the ESRD group versus 5.2 +/- 2.4 in the non- ESRD group; fibrosis (6-point scale) was 1.1 +/- 1.2 versus 1.7 +/- 1.5, respectively. CONCLUSIONS: Despite histological evidence of liver inflammation, ALT levels in the ESRD group were normal, while ALT levels were significantly higher in the non-ESRD group with similar levels of liver inflammation. In conclusion, ALT levels are not a useful indicator of HCV infection in patients with ESRD and liver biopsies should be recommended for kidney transplant candidates.

[Prevention of hyperamilasemia and pancreatitis after endoscopic retrograde cholangiopancreatography with rectal administration of indomethacin]. / Prevención de hiperamilasemia y pancreatitis posterior a la colangiopancreatografia retrógrada endoscópica con la administración rectal de indometacina.

BACKGROUND: Acute pancreatitis (AP) represents the main complication after endoscopic retrograde cholangiopancreatopgraphy (ERCP) and appears in 1% to 10% of the cases. The incidence increases in patients with opacification and instrumentation of pancreatic duct and it varies according to the indications of the procedure and the intervention performed. Risk factors for this complication include history of pancreatitis, difficult canulation, pancreatic acinar opacity, Oddi sphincter hypertension and sphincterotomy. OBJECTIVE: Evaluate the efficacy of rectal indometacine to reduce the incidence of hyperamylasemia and AP post-ERCP. METHODS AND MATERIALS: Control clinical trial simple blind perfomed between June and December of 2004. One hundred seventeen patients were included in the study. They were randomly assigned in two groups: 1) study group (n = 61, 52%), 100 mg of rectal indomethacin was administered 2 hours previous to the procedure and, 2) control group (n = 56, 47.8%) received placebo (glycerine suppository). Hyperamylasemia was diagnosed with levels > 151 U/L and AP with levels > 600 U/L and characteristically abdominal pain. RESULTS: Gender distribution was of 79 (67.5%) women and 38 (32.5%) men. Mean age was of 54.2 +/- 18.8 years for the study group and 50.1 +/- 18.1 years for the control group. After ERCP, 12 patients (10.2%) of the study group and 19 (16.2%) of control group presented hyperamylasemia (p = 0.09). AP was present in 3 patients (2.5%) in the study group and 8 patients (6.8%) of the control group (p = NS). There was no mortality in our study. CONCLUSION: The use of 100 mg of rectal indomethacine previous to ERCP decreases the risk of hyperamylasemia and AP. However, these differences did not reach statistical significance, probably because a greater sample of patients was needed.