Rectal Diclofenac Research Articles

Anaesthetic management of robotic-assisted gynaecology surgery in the morbidly obese - A case series of 46 patients in a UK university teaching hospital.

Background and Aims:The evolution of robotic technology has enhanced the scope of laparoscopic surgery. Morbid obesity [body mass index (BMI) >40 kg/m2] due to significant physiological attributes presents a significant surgical and anaesthetic challenge. Robotic surgery in this subset of patients can present with its own problems due to surgical requirements of prolonged pneumoperitoneum and steep Trendelenburg position.Methods:We reviewed the anaesthetic management of 46 morbidly obese patients undergoing robotic-assisted laparoscopic gynaecology surgery. Patient characteristics, anaesthetic management, length of hospital stay (LOS), complications, and readmissions within 30 days were noted. Mean with standard deviation was used for statistical analysis.Results:The mean [standard deviation (SD)] weight and BMI were 121.2 (18.49) kg and 47.83 (7.89) kg/m2, respectively. The mean (SD) anaesthetic and surgical times were 229 (75.9) and 167.7 (62.7) min, respectively. The mean (SD) LOS was 1.57 (1.03) days. About 70% of patients were discharged on the first day after surgery. Six patients needed critical care support. There were two readmissions within 30 days.Conclusion:Good preparation, teamwork, and multidisciplinary input helped us to conduct complex robotic-assisted and long-duration surgery in morbidly obese patients with minimal complications.

The efficacy of diclofenac for post caesarean section analgesia: Comparison of rectal and intramuscular routes

Background: Despite advances in postoperative pain therapy, pain relief may still be inadequate for a substantial number of women.Aim: The aim was to compare the analgesic efficacy of rectal and intramuscular diclofenac for post Caesarean section analgesia.Materials and Methods: Following approval from the Hospital Ethics Committee 94 ASA I and II parturients aged 18 years and above scheduled for elective Caesarean section under spinal anaesthesia were recruited into the study. While one group of parturients received 100 mg Diclofenac suppository rectally (group R) those in the other group received 75 mg Diclofenac intramuscularly (group IM) immediately after surgery. The patients were instructed to request analgesic when they felt pain post-operatively. Pain scores were recorded using the VAS (0 to 10), (0 = no pain, 10 = the most severe pain), initially every 30 minutes for the first 2 hours, then every 2 hours from the 2nd hour to the 8th hour and every 4 hours after the 8th hour till the 24th hour.Results: The demographic data, BMI, PCV and ASA classification between the two groups of patients were comparable; the two groups were also comparable in the haemodynamic variables (mean systolic BP, mean diastolic BP, mean MAP and mean heart rate) and in the mean SpO2 recorded in the recovery room, p > 0.05 for all the variables. The time to first analgesic request in group IM was 313.2 ± 218.8 mins and in group R 314.1 ± 121.6 mins, p=0.98. There was no significant difference between the IM/R groups in the mean VAS scores of patients, the number of patients who received pentazocine at each time interval in the two groups, and the total pentazocine consumption in the two groups in 24 hours, p>0.05 in all the variables. There was no significant difference between the two groups in the mean satisfaction score in pain relief, p = 0.73, the mean satisfaction score with staff's response to patient's pain management needs, p = 0.85, and the mean acceptability score, p = 0.62.Conclusion: Suppository diclofenac administered through the rectal route is as efficacious as intramuscular diclofenac injection for post Caesarean section analgesia with equal levels of patient satisfaction and acceptability.Keywords: Post Caesarean section analgesia, diclofenac, rectal, intramuscular, spinal anaesthesia,

Use of rectal Diclofenac as an adjunct to spinal analgesia after caesarean section

Use of rectal Diclofenac as an adjunct to spinal analgesia after caesarean section

Combination of diclofenac and aggressive hydration for the prevention of post-ERCP pancreatitis.

To investigate whether aggressive hydration can increase the efficacy of prophylactic non-steroid anti-inflammatory drugs (NSAIDs) in prevention of post-ERCP pancreatitis. NSAIDs are recommended for the prevention of PEP; however, whether aggressive hydration can have additional benefits in this regard is not known. Patients candidate for ERCP received either pre-procedural rectal diclofenac (100 mg) alone (n = 112) or in combination with aggressive hydration by lactate ringer's (n = 107) as prophylactic method. PEP was defined based on increase in serum levels of pancreatic enzymes (from baseline to 24 hours following the procedure) accompanied with symptoms. PEP was occurred in 3 patients in the diclofenac only group and in 1 patient in the diclofenac + hydration group with no significant difference (2.7% vs. 0.9%, P = 0.622). Serum amylase levels decreased over time in the diclofenac + hydration group but not in the diclofenac only group. Also, serum lipase levels decreased more rapidly over time in the diclofenac + hydration group compared to the diclofenac only group. Combination prophylactic therapy with NSAIDs plus aggressive hydration does not seem to have additional clinically important benefits in preventing PEP. Studies with larger sample of patients are required in this regard.

A review of ketorolac as a prehospital analgesic

Non-steroidal anti-inflammatory drugs (NSAIDs) can be used as part of a multimodal approach to managing acute pain. Administering NSAIDs by intramuscular (IM) or intravenous (IV) injection allows them to be used in patients who are nil-by-mouth, who cannot swallow, and to allow a more rapid onset compared to the oral route. Current paramedic practice in the UK does not generally allow for the use of an NSAID given by IM or IV injection for acute pain. While paramedics may administer paracetamol and morphine intravenously, the only option for an NSAID is oral ibuprofen, or rarely oral naproxen or rectal diclofenac. Ketorolac is an NSAID, which can be administered by IV or IM injection. It is an effective analgesic agent when used alone, or in conjunction with other agents as part of a multimodal approach to analgesia. This article reviews the evidence from peer-reviewed papers and current clinical guidelines surrounding the safety and efficacy of ketorolac as an analgesic agent for acute pain, and discusses its potential use in UK paramedic practice.

Does rectal diclofenac reduce post-ERCP pancreatitis? A district general hospital experience

IntroductionThere is controversy in the literature recently regarding the efficacy of rectal non-steroidal anti-inflammatory drugs (NSAID) to prevent post-ERCP pancreatitis (PEP). The aim of this study was to compare the...

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitrate as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis.

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography(ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitrate might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitrate for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitrate can prevent PEP.

Rectal nonsteroidal anti-inflammatory drugs administration is effective for the prevention of post-ERCP pancreatitis: An updated meta-analysis of randomized controlled trials

BackgroundAcute pancreatitis is one of the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Whether the prophylactic administration of rectal non-steroidal anti-inflammatory drugs (NSAIDs) peri-ERCP is effective in preventing post-ERCP pancreatitis (PEP) remains controversial. The aim of this study was to assess the effect of rectal NSAIDs on PEP. MethodsA systematic search of literature databases (Cochrane Library, PubMed, EMBASE, and Web of Science) was performed to identify eligible randomized controlled trials (RCTs). The Jadad score for assessing risk of bias was used to evaluate the quality of included studies. The primary endpoint of the study was efficacy for PEP prevention. Sub-analyses were performed to determine the risk reduction for different NSAID types, for general vs. high-risk patients, by timing of administration and for moderate to severe PEP. ResultsTwelve RCTs, including a total of 3989 patients, were identified and included in the analysis. The risk of PEP was lower in the NSAIDs group than in the placebo group (RR 0.52; 95% CI 0.43–0.64; P < 0.01). The risk of moderate to severe PEP was also lower in the NSAIDs group. (RR 0.44; 95% CI 0.28–0.69; P < 0.01). There was no difference in efficacy between rectal indomethacin and diclofenac, nor between pre-ERCP and post-ERCP administration timing of rectal NSAIDs. ConclusionsA single rectal dose of NSAIDs is effective in preventing PEP both in high-risk and in unselected patients, regardless of timing of administration (pre- or post-ERCP) and NSAID type (indomethacin or diclofenac).

The analgesic effects of rectal diclofenac versus rectal paracetamol following caudal-bupivacaine for pediatric day-case inguinal herniotomies: a randomized controlled prospective trial

BackgroundPostoperative pain is a common complaint in day-case inguinal herniotomy, thus there is a need to provide effective analgesia. This study compared the postoperative analgesic effects of the combinations of caudal-bupivacaine and rectal diclofenac with caudal-bupivacaine and rectal-paracetamol in children scheduled for daycase inguinal-herniotomy. MethodsNinety children of ASA I scheduled for elective day-case inguinal-herniotomy were randomly assigned into Group A (1ml/kg of 0.25% caudal-bupivacaine and 1mg/kg rectal-diclofenac), Group B (1ml/kg of 0.25% caudal-bupivacaine and 30mg/kg rectal paracetamol) and Group C (1ml/kg of 0.25% caudal-bupivacaine). The duration of analgesia, pain scores, postoperative analgesic consumption and side effects were assessed and recorded. Data collected was analyzed with the statistical package for social sciences 17 for windows. ResultsEighty-seven children completed the study, and it was found that the duration of analgesia was prolonged in Group A compared to Groups B and C (p<0.01). ConclusionCaudal-bupivacaine and rectal-diclofenac combination provides a more prolonged postoperative analgesia, and lower pain score compared to caudal-bupivacaine and rectal-paracetamol combination or caudal-bupivacaine alone. Level of evidenceLevel 1 evidence treatment study. Randomized controlled trials with adequate statistical power to detect differences (narrow confidence intervals) and follow up >80%.

Rectal diclofenac as acute pancreatitis prophylaxis post endoscopic retrograde cholangiopancreatography

Objective: To determine whether the use of rectal diclofenac decrease the incidence of post-ERCP pancreatitis. Methods: Serie of cases between January 2015 and June 2016 in which two groups were analyzed. Group A: ERCP without prophylactic rectal diclofenac and group B: use of 100 mg of rectal diclofenac 20–30 minutes before procedure. Biodemographic variables, technical variables of ERCP and mortality were recorded. Analytical and descriptive statistics were used measures of central tendency and dispersion. Results: 116 patients were included. Group A: 48 patients, Group B: 68 patients. Mean of age of group A and B: 53.1±12.6 and 55.3±11.9 years, respectively (p=0.670). Of the total group of patients, five (4.3%) developed post-ERCP pancreatitis, 6.2% (3/48) in group A and 2.9% (2/68) in group B (p=0.021). The main indication for ERCP in group A and group B was choledocholithiasis (44/48 and 61/68, respectively). Sphincterotomy was performed in 71 patients (61.2%), 3 developed post-ERCP pancreatitis, all of them of group A. Difficult cannulation of the bile duct in 13 patients and one of them (group B) developed pancreatitis post- ERCP. There was cannulation of pancreatic duct in 12 patients (10.3%) and three of them developed post-ERCP pancreatitis, two in group A and one in group B (p=0.804). There was no mortality and no adverse reactions to diclofenac. Conclusion: The results in this group of patients support the use of diclofenac as prophylaxis for post-ERCP pancreatitis.

Rectal NSAIDs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in unselected patients: Systematic review and meta-analysis.

Efficacy of rectal non-steroidal anti-inflammatory drugs (NSAIDs) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prophylaxis in unselected patients remained controversial. The aim of the present study was to evaluate the efficacy of rectal NSAIDs in the prevention of PEP in unselected patients. An electronic literature search in the Cochrane Library, Embase, and PubMed was carried out for randomized controlled trials comparing rectal indomethacin or diclofenac with placebo in the prevention of PEP in unselected patients. Cochrane risk of bias tool was used to evaluate methodological quality. The data were carried out in forest plots using fixed-effect methods, and random-effect methods were used when heterogeneity was significant. A total of nine trials were included in our final analysis. Rectal NSAIDs were effective to reduce the incidence of PEP in unselected patients (RR, 0.61; 95% CI, 0.46-0.79), especially for moderate-to-severe PEP (RR, 0.37; 95% CI, 0.17-0.79). Both indomethacin (RR, 0.67; 95% CI, 0.50-0.88) and diclofenac (RR, 0.29; 95% CI, 0.12-0.69) were significantly efficacious. Rectal NSAIDs given pre-ERCP showed significant efficacy (RR, 0.53; 95% CI, 0.39-0.71), whether when given within 30 min pre-ERCP (RR, 0.62; 95% CI, 0.42-0.92) or not (RR, 0.43; 95% CI, 0.28-0.67). Rectal NSAIDs are effective in the prevention of PEP in unselected patients.

Comparative Study of Rectal Tramadol versus Diclofenac in Post Cesarean Section Pain Management

Comparative Study of Rectal Tramadol versus Diclofenac in Post Cesarean Section Pain Management

Effect of diclofenac suppository on pain control during flexible cystoscopy-A randomized controlled trial

TRIAL DESIGN: To compare the difference in pain score during flexible cystoscopy between patients undergoing the procedure with plain lubricating gel only and plain gel with diclofenac suppository in a randomized control trial. METHODS: A total of 60 male patients with an indication of flexible cystoscopy were enrolled in a prospective, randomized controlled study. Patients were randomized in two groups. In group “A”, patients received diclofenac suppository one hour prior to the procedure while group “B” did not receive diclofenac suppository. Both groups received 10 ml of intra-urethral plain gel for lubrication during flexible cystoscopy. Pain score was recorded immediately after the procedure using the visual analogue scale (VAS). Pre- and post-procedure pulse rate and systolic blood pressure was also recorded. Statistical analyses were performed using chi-square test and student t-test. Regression analysis was performed to address the confounding variables. RESULTS: Both groups were comparable for variables including age, duration of procedure, level of operating surgeon and indication of procedure. Most common indication for flexible cystoscopy was removal of double J stent. There was a statistically significant difference in the mean pain score between two groups ( p = 0.012). The difference in post-procedure mean pulse rate in the two groups was statistically significant ( p= 0.01) however there was no difference observed in mean post procedure systolic blood pressure. Regression analysis showed that none of the confounding variables were significantly affecting pain perception. CONCLUSIONS: Intra rectal diclofenac suppository is simple and effective pre-emptive analgesia. We recommend its routine use during flexible cystoscopy for better pain control.

Effect of diclofenac suppository on pain control during flexible cystoscopy-A randomized controlled trial.

TRIAL DESIGN: To compare the difference in pain score during flexible cystoscopy between patients undergoing the procedure with plain lubricating gel only and plain gel with diclofenac suppository in a randomized control trial. METHODS: A total of 60 male patients with an indication of flexible cystoscopy were enrolled in a prospective, randomized controlled study. Patients were randomized in two groups. In group "A", patients received diclofenac suppository one hour prior to the procedure while group "B" did not receive diclofenac suppository. Both groups received 10 ml of intra-urethral plain gel for lubrication during flexible cystoscopy. Pain score was recorded immediately after the procedure using the visual analogue scale (VAS). Pre- and post-procedure pulse rate and systolic blood pressure was also recorded. Statistical analyses were performed using chi-square test and student t-test. Regression analysis was performed to address the confounding variables. RESULTS: Both groups were comparable for variables including age, duration of procedure, level of operating surgeon and indication of procedure. Most common indication for flexible cystoscopy was removal of double J stent. There was a statistically significant difference in the mean pain score between two groups ( p= 0.012). The difference in post-procedure mean pulse rate in the two groups was statistically significant ( p= 0.01) however there was no difference observed in mean post procedure systolic blood pressure. Regression analysis showed that none of the confounding variables were significantly affecting pain perception. CONCLUSIONS: Intra rectal diclofenac suppository is simple and effective pre-emptive analgesia. We recommend its routine use during flexible cystoscopy for better pain control.

Endoscopic and pharmacological treatment for prophylaxis against postendoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis and systematic review.

Postendoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP) is the most common complication following ERCP. We carried out a systematic review and meta-analysis of the global literature on PEP prevention to provide clinical guidance and a framework for future research in this important field. PubMed, Embase, Science Citation Index, Ovid, and the Cochrane Controlled Trials Register were searched by two independent reviewers to identify full-length, prospective, randomized controlled trials (RCTs) published up until March 2016 investigating the use of pancreatic duct stents and pharmacological agents to prevent PEP. Twelve RCTs comparing the risk of PEP after pancreatic duct stent placement (1369 patients) and 30 RCTs comparing pharmacological agents over placebo (10251 patients) fulfilled the inclusion criteria and were selected for final review and analysis. Meta-analysis showed that prophylactic pancreatic stents significantly decreased the odds of post-ERCP pancreatitis [odds ratio (OR), 0.28; 95% confidence interval (CI), 0.18-0.42]. Significant OR reduction of PEP was also observed in relation to rectal administration of diclofenac (OR, 0.24; 95% CI, 0.12-0.48) and rectal administration of indometacin (OR, 0.59; 95% CI, 0.44-0.79) compared with placebo. Subgroup analysis showed a significant reduction with bolus-administered somatostatin (OR, 0.23; 95% CI, 0.11-0.49). Subgroup analysis showed a significant reduction with bolus-administered somatostatin (OR, 0.23; 95% CI, 0.11-0.49). Pancreatic stent placement, rectal diclofenac, and bolus administration of somatostatin appear to be most effective in preventing post-ERCP pancreatitis.

Rectal Diclofenac Along with Intravenous Infusion of Ringer Lactate and Dextrose Saline Is Highly Effective in Preventing Post ERCP Pancreatitis

Rectal Diclofenac Along with Intravenous Infusion of Ringer Lactate and Dextrose Saline Is Highly Effective in Preventing Post ERCP Pancreatitis

Comparison of Role of Different Doses of Rectal Paracetamol with Rectal Diclofenac as Pre-emptive Analgesics for Postoperative Pain Relief in Paediatric Surgeries

Background: Post operative pain is a major concern in children particularly in developing countries were opioids are not freely available. Use of opioids is associated with side effects increasing patient discomfort and delaying patient discharge from hospital. We conducted a study comparing the use of different doses of rectal paracetamol with rectal diclofenac when used as pre-emptive analgesics on postoperative pain and recovery in paediatric patients considering the relative risk of diclofenac to increase bleeding in surgeries like tonsillectomy, cleft lip and cleft palate. Methods: Study groups included 20 patients in each. Group P40 receiving 40 mg/kg rectal paracetamol, Group P20 receiving 20 mg/kg rectal paracetamol, Group D receiving rectal diclofenac 1 mg/kg. Pain scoring was done by TPPPS (Toddler Pre-schooler postoperative pain scale) time to first need of analgesia and total dose of analgesia was noted. The rates of recovery were evaluated by using “Modified Steward Coma Scale”at 5 and 10 minutes after extubation. Results: Time of first demand of analgesic was delayed in Group-P40 as compared to Group-D and Group-P20 and difference was statically significant. TPPPS of the three studied groups varied significantly at different time intervals in favour of Group-P40. Total duration of analgesia in Group- P40 was (646±9.94) min Group- D (501±10.63) min and in Group-P20 (294±23.17) min Total analgesic requirement was also low in Group P40 and the difference between groups was significant. Conclusion: Pre-emptive high dose rectal paracetamol appears to be more effective than rectal diclofenac sodium suppository for postoperative analgesia in children without additional risk of bleeding in surgeries like tonsillectomy and cleft lip and cleft palate repair. Hence, high dose rectal paracetamol can be used as an alternative to diclofenac sodium due to higher risks of bleeding with diclofenac sodium in surgeries with increased risk of bleeding.

No Benefit of Oral Diclofenac on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a serious complication. Rectal diclofenac (100mg) has been shown to reduce the incidence of pancreatitis; however, this dosage form is unavailable in several countries. We aimed to investigate the preventive effect of oral diclofenac on pancreatitis after ERCP in a multicenter, randomized, prospective, placebo-controlled, double-blind trial. Patients undergoing a first ERCP in seven high-volume centers between July 2012 and August 2014 were considered eligible. Participants were administered oral diclofenac (50mg) or placebo before and after ERCP. The primary endpoint was the incidence of pancreatitis. A subgroup analysis was performed for patients at high or low risk of pancreatitis. Secondary endpoints were pancreatic enzyme levels (amylase and lipase). We initially enrolled 430 patients (216 in the diclofenac and 214 in the placebo group), and 23 were excluded after randomization. The overall incidence of pancreatitis was 9.8% (20/205) and 9.4% (19/202) in the diclofenac and placebo groups, respectively (p=0.90). The incidence of pancreatitis was 20.3% (13/64) and 21.3% (13/61) in patients at high risk of pancreatitis (p=0.78) and 5.0% (7/141) and 4.3% (6/141) in patients at low risk of pancreatitis in the diclofenac and placebo groups (p=0.94), respectively. There were no significant differences in serum amylase and lipase levels between the two groups before and 24h after ERCP. Oral administration of diclofenac before and after ERCP showed no benefit in the prevention of pancreatitis. UMIN000008109.

PTH-019 Does Rectal Diclofenac Reduce Post ERCP Pancreatitis in The UK?

Introduction Post ERCP pancreatitis(PEP) occurs in up to 10% of unselected cases and carries significant morbidity. PEP is significantly higher in certain patient groups, for example females, young age, Sphincter of Oddi dysfunction, previous pancreatitis and following pancreatic duct cannulation. There is a growing body of evidence that NSAIDS should be used in PEP prophylaxis but use is still uncommon in the UK. The 2010 European Society for Gastrointestinal Endoscopy Guidelines on PEP recommends routine use of rectal NSAIDs in all patients. There is only one published RCT from the UK demonstrating the efficacy of NSAIDS in reducing PEP. Rectal diclofenac was introduced into ERCP practice at the RUH in two phases. Firstly, a selective use in patients determined to be at high risk as determined by criteria above. Secondly diclofenac was used routinely in all patients without contraindication. Methods A retrospective analysis of 5 years ERCP data was performed using readmission data, blood results, radiology reports and discharge summaries to identify patients with PEP from August 2010 – December 2015. The administration of rectal diclofenac post procedure was recorded from the endoscopy reporting system. Fisher’s exact test was used to statistically analyse categorical data. Results 1318 ERCPs were performed by 4 endoscopists during the study period with 66 (5.0%) cases of pancreatitis. 445 ERCPs were performed prior to the introduction of NSAID use during which time there were 35 (7.9%) episodes of PEP. During the selective period of NSAID use (only used if patient deemed high risk by endoscopist) 539 ERCPs were performed and 72 (13.4%) patients received NSAIDS. 17 (3.2%) developed PEP. 334 ERCPs were performed when NSAIDS were given to all patients without contraindication. 289 (86.5%) of patients received rectal diclofenac and 13 (3.9%) developed pancreatitis. There is a statistically significant decrease in PEP comparing the groups of patients receiving NSAIDS selectively (p = 0.0009) or routinely (p = 0.0172) when compared with none. There is no difference between the selective and routine group (p = 0.571). Conclusion The use of rectal diclofenac post ERCP decreases the rate of PEP when used in a selective or routine protocol. Despite a growing body of evidence for NSAIDS use routine administration is used by the minority of endoscopists in the UK. The evidence for use of NSAIDS in PEP is heterogeneous a number of factors including diagnostic criteria for pancreatitis, type and route of NSAID and selective high risk or routine use. We believe that this heterogeneity and lack of UK evidence accounts for the slow uptake of NSAIDS for PEP. Our data demonstrates that the introduction of a selective or routine use of NSAIDS for PEP in a DGH significantly decreases the risk of pancreatitis (RR 43.7%). Disclosure of Interest None Declared

Early precut sphincterotomy for difficult biliary access to reduce post-ERCP pancreatitis: a randomized trial.

Precut sphincterotomy is a technique usually employed for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of bile duct disease. It is a validated risk factor for post-ERCP pancreatitis (PEP), but it is not clear whether the risk is related to the technique itself or to the repeated biliary cannulation attempts preceding it. The primary aim of the study was to assess the incidence of PEP in early precut compared with the standard technique in patients with difficult biliary cannulation. Secondary aims were to compare complications and cannulation success. In this prospective, multicenter, randomized, clinical trial, patients who were referred for therapeutic biliary ERCP and difficult biliary cannulation were randomized to early precut (Group A) or repeated papillary cannulation attempts followed, in cases of failure, by late precut (Group B). PEP was defined as the onset of upper abdominal pain associated with an elevation in serum pancreatic enzymes of at least three times the normal level at more than 24 hours after the procedure. No rectal indomethacin or diclofenac was used for prevention of PEP. A total of 375 patients were enrolled. PEP developed in 10 of the 185 patients (5.4 %) in Group A and 23 of the 190 (12.1 %) in Group B (odds ratio [OR] 0.35; 95 % confidence interval [CI] 0.16 - 0.78). The incidence of PEP was significantly lower in the early precut group (10/185, 5.4 %) than in the delayed precut subgroup (19/135 [14.1 %]; OR 0.42, 95 %CI 0.17 - 1.07). There were no differences in biliary cannulation success rates, bleeding, perforation, and cholangitis. In patients with difficult biliary cannulation, early precut is an effective technique and can significantly reduce the incidence of PEP. Repeated biliary cannulation attempts are a real risk factor for this complication.