10.1055/a-1190-3777Pancreatitis remains the most frequent and lethal adverse event (AE) that may follow
endoscopic retrograde cholangiopancreatography (ERCP). Fortunately, it is also the
only AE for which significant advances have been made. Since 2010, four scientific
societies have issued guidelines about the prophylaxis of post-ERCP pancreatitis (PEP).
All of them have recommended rectal nonsteroidal anti-inflammatory drugs (NSAIDs)
as the cornerstone of pharmacological prophylaxis of PEP ([Table 1]).
Table 1
Recommendations from Scientific Societies about pharmacological prophylaxis of post-ERCP
pancreatitis.
|
Society, date
|
First-line prophylaxis
|
Target population
|
Timing
|
|
European Society of Gastrointestinal Endoscopy, 2010 [18]
|
Rectal NSAIDs
|
All patients
|
Pre-ERCP [5]
|
|
American Society of Gastrointestinal Endoscopy, 2017 [9]
|
Rectal NSAIDs
|
High-risk patients
|
Pre- or post-ERCP
|
|
Japanese Society of Gastroenterology, 2017 [10]
|
Rectal NSAIDs
|
NR
|
Pre- or post-ERCP
|
|
Chinese Societies Consortium[1], 2019 [11]
|
Rectal NSAIDs/somatostatin (minimum 11 hours)
|
High-risk patients
|
Pre-ERCP if patient-related risk factors are present; post-ERCP if only procedure-related
risk factors are present
|
ERCP, endoscopic retrograde cholangiopancreatography; NR, not reported; NSAIDs, non-steroidal
anti-inflammatory drugs
1 Chinese Digestive Endoscopist Committee, Chinese Endoscopist Association, Chinese
Physicians’ Association, Pancreatic Disease Committee, Chinese Physicians’ Association
This has led to slow adoption in the community: In 10 years, the proportion of endoscopists
who use rectal NSAIDs for PEP prophylaxis has increased from 15 % to 54 % to 98 %
[1]
[2]
[3]
[4]. The latest survey reported use of rectal NSAIDs by 98 % of pancreaticobiliary endoscopists
but by only 40 % of them in average-risk patients [4]. This is despite the demonstration of NSAID efficacy in this risk category of patients
by 11 of 14 meta-analyses published to date [5]. Reasons accounting for this slow and incomplete adoption include disbelief and
confusion because scientific societies recommend NSAIDs in different risk categories
of patients ([Table 1]). Surprisingly, cost could become another reason: a single NSAID suppository costs
$ 347 in the United States, and it is billed between $ 50 and $ 5000 to ambulatory
patients by Californian hospitals [6]. Therefore, exploration for alternatives that might be even more widely available,
easy to use, innocuous, and cheap than NSAIDs is welcome.
In the current issue of Endoscopy International Open, a meta-analysis suggests that
spraying epinephrine onto the papilla is effective to prevent PEP [7]. Overall, the meta-analysis found no significant difference between PEP rates in
patients who received topical epinephrine or not (relative risk [RR], 0.63; 95 % confidence
interval [CI], 0.32–1.24). Because some of the studies included in the meta-analysis
also used rectal indomethacin for PEP prophylaxis, the authors performed a subgroup
analysis that excluded such studies. In this subgroup, topical epinephrine was associated
with a lower risk of PEP compared with no topical epinephrine or placebo (RR,0.32;
95 % CI, 0.18–0.57). Hence, the authors suggest considering topical epinephrine for
PEP prophylaxis in the case of rectal NSAIDs unavailability or if there is any contraindication
to their use.
In 2013, a network meta-analysis identified topical epinephrine as the most efficacious
prophylaxis for PEP [8]. However, epinephrine was not retained in any of the four subsequent guidelines
from large Endoscopy Societies on this topic [5]
[9]
[10]
[11]. That is because the network meta-analysis included only two randomized controlled
trials (RCTs); furthermore, these excluded (!) therapeutic ERCP and used a non-standard
definition of PEP [12]
[13]. The only new data since 2013 consist of a RCT published in abstract form with no
information about the type of ERCP (diagnostic or therapeutic) and the definition
of PEP [14]. Two low-quality case-control studies published in 2001 and 2009 have been included
in the current meta-analysis. One, again, excluded therapeutic ERCP and the other
one was restricted to patients who had balloon sphincteroplasty [15]
[16].
The authors suggest using topical epinephrine as a replacement for rectal NSAIDs in
patients with “absolute contraindications to NSAIDs such as allergies to NSAIDs, end-stage
kidney disease, or patients who have had proctocolectomy”. End-stage renal disease
is an important concern as it may be a risk factor for PEP [17]. Patients undergoing chronic dialysis can receive a single dose of NSAIDs without
concerns. Other patients should not receive topical epinephrine of dubious efficacy
and be deprived from effective alternatives such as high-volume hydration with lactated
Ringer’s solution, sublingual glyceryl trinitrate, infusion of somatostatin for 11
hours or prophylactic pancreatic stenting [5]. We also think that rather than using topical epinephrine if rectal indomethacin
is unavailable, solutions should be found to make rectal indomethacin or diclofenac
available or alternatives with proven efficacy should be used.
In conclusion, the current meta-analysis could stimulate further research on topical
epinephrine in placebo-controlled RCTs of therapeutic ERCP, in combination with effective
regimens different from rectal NSAIDs. However, it does not support a change in current
recommendations from the ESGE. If rectal NSAIDs are contraindicated, which is truly
exceptional, several alternatives are effective. Until now, that has not been demonstrated
for topical epinephrine.
