|Effectiveness and tolerability of NSAIDs in the prophylaxis of pancreatitis after endoscopic retrograde cholangiopancreatography: a systematic review and meta-analysis
|Zheng MH, Meng MB, Gu DN, Zhang L, Wu AM, Jiang Q, Chen YP
This review reported that non-steroidal anti-inflammatory drugs were effective and well tolerated in the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography, especially in low-risk patients. These findings might not be reliable as there were statistical and clinical differences between trials and a small amount of data was analysed.
To determine the effectiveness and tolerability of non-steroidal anti-inflammatory drugs (NSAIDs) as prophylaxis against pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP).
MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to January 2009; search terms were reported. The reference lists of retrieved articles and reviews were screened for further studies. Poster presentations were eligible for inclusion and several topic experts were contacted for further data.
Randomised controlled trials (RCTs) comparing NSAIDs with placebo, in patients undergoing ERCP, endoscopic sphincterotomy, or both, were eligible for inclusion. The NSAIDs were not limited by type, dose, initial time of treatment, treatment duration, and administration route. Trials of patients with active acute pancreatitis were excluded.
Two included trials assessed diclofenac 100mg per rectum, administered immediately after ERCP. One study assessed oral diclofenac 100mg, given 30 to 60 minutes before and four to six hours after ERCP. The remaining study assessed rectal indomethacin 100mg, given immediately before ERCP. The reported outcomes were the prevalence of pancreatitis, the case-to-fatality ratio with pancreatitis, and the incidence of adverse events. All of the trials defined pancreatitis according to the criteria of Cotton et al. and the risk factors according to Freeman and Guda. Two of the trials were carried out in Iran and the other two trials were carried out in Scotland and the USA.
Two reviewers independently assessed the eligibility of the trials for inclusion and discrepancies were resolved through discussion.
Assessment of study quality
The quality of the included trials was assessed using the Jadad scale, with criteria for randomisation, blinding, and withdrawals. Each trial was awarded a score ranging from zero to five points. Trials that scored three or more points were considered to be of good quality and those that scored zero to two points were considered to be of poor quality. The authors did not state how many reviewers assessed the validity.
Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each trial. Where two-by-two tables contained cells with no events, a correction factor of 0.5 was added to each cell. It seems that two reviewers extracted the necessary data.
Methods of synthesis
The trials were grouped by outcome and intervention to calculate pooled odds ratios with 95% confidence intervals, using a fixed-effect model. Statistical heterogeneity was assessed using the Cochran Q statistic. Where significant heterogeneity was detected a random-effects model was used. Further analyses were carried out to assess the effect sizes dependent on the risk and severity of pancreatitis. Publication bias was assessed in a funnel plot, the Begg-Mazumdar test, and the Egger test.
Results of the review
Four RCTs, with 969 patients, were included in the review. Adequate randomisation methods were reported in all trials and all of them scored five on the Jadad scale. The sample sizes ranged from 100 to 442 patients.
A significant reduction in pancreatitis prevalence was reported with NSAIDs compared with placebo (OR 0.44, 95% CI 0.21 to 0.93; four RCTs), but significant heterogeneity was detected (p=0.08). No significant differences between NSAIDs and placebo were detected when the trials were analysed by severity of pancreatitis; mild (three RCTs) and moderate-to-severe (three RCTs).
There was no significant difference in pancreatitis prevalence for NSAIDs compared with placebo in high-risk patients (OR 0.49, 95% CI 0.17 to 1.39; four RCTs); but there was a significant reduction in pancreatitis, with NSAIDs in low-risk patients (OR 0.29, 95% CI 0.12 to 0.71; three RCTs). Significant heterogeneity was reported for the analysis of low-risk patients (p=0.04).
No deaths were reported in any trial and all reported that patients were discharged in good health and enjoyed a good quality of life during the follow-up period. No treatment-related adverse events were reported with NSAIDs.
The authors found no evidence of publication bias.
NSAIDs were effective and well tolerated for the prevention of pancreatitis after ERCP, especially in low-risk patients.
This review assessed a clearly defined research question. A number of literature sources were searched to identify both published and unpublished data. The authors assessments suggested that there was no risk of publication bias, but given the number of included trials, these assessments might not be reliable. Two reviewers independently selected the trials for inclusion and extracted the data, thereby reducing the risk of reviewer error and bias. An assessment of trial validity was carried out using appropriate criteria, but it was unclear whether there was a risk of reviewer error and bias in this process. The pooled analyses showed evidence of significant statistical heterogeneity in some instances and it was difficult to assess the level of clinical heterogeneity, given the limited description of the trials and their patient populations.
The findings of this review might not be reliable, given the statistical and clinical differences between trials, and the small amount of data analysed.
Implications of the review for practice and research
Practice: The authors stated that physicians should make a judgement when selecting patients with appropriate indications for ERCP.
Research: The authors stated that large, multicentre, double-blind RCTs were required to assess the efficacy of NSAIDs in preventing pancreatitis after ERCP in low- and high-risk patients. Similar trials were required to assess the efficacy of other anti-inflammatory drugs and combinations of drugs.
Zheng MH, Meng MB, Gu DN, Zhang L, Wu AM, Jiang Q, Chen YP. Effectiveness and tolerability of NSAIDs in the prophylaxis of pancreatitis after endoscopic retrograde cholangiopancreatography: a systematic review and meta-analysis. Current Therapeutic Research 2009; 70(4): 323-334
Subject indexing assigned by CRD
Acute Disease; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde /adverse effects; Humans; Pancreatitis /prevention & control
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.