Endoscopic retrograde cholangiopancreatography (ERCP) , a key tool that is used in diagnosis
and treatment of pancreato-biliary diseases. Post-ERCP pancreatitis (PEP) is the most common
and serious complication that can occur following this procedure and can lead to significant
morbidity and mortality. A variety of patient-related and procedure-related factors have been
associated with higher rates of PEP.
Two definitions were used for diagnosis of PEP. In both definitions, PEP is diagnosed if two
of the three criteria are found in the patient .The consensus criteria that was developed by
Cotton and Colleagues in 1991 defined PEP as the presence of a new pancreatic-type abdominal
pain associated with at least a threefold elevation in pancreatic enzyme concentration
occurring 24 hours following the ERCP procedure, with the necessity for a new or extended
hospitalization for at least two nights. Severity of pancreatitis is defined based on the
number of hospitalized days following ERCP as mild (< 4 days), moderate (4 to 10 days), or
severe (>10 days). The revised Atlanta Classification in 2012 lists abdominal pain consistent
with acute pancreatitis, amylase or lipase elevation to more than 3 times the upper limit of
normal, and abdominal imaging that reveals pancreatic inflammation.
Several potential triggers can contribute to PEP. Mechanical trauma caused by ERCP
instrumentation can harm the papilla and pancreatic duct, affecting pancreatic drainage.
Thermal injury can occur during biliary or pancreatic sphincterotomy electrosurgical current.
Chemical damage can occur when contrast medium is introduced into the pancreatic duct.
Hydrostatic damage can occur when injecting contrast media into the pancreatic duct or
infusing fluids such as water or saline solution during sphincter manometry. Regardless of
the cause, the initial injury sets in motion a chain of events that include premature
activation of proteolytic enzymes, autodigestion of pancreatic tissue, and impaired secretion
from acinar cells. These events result in pancreatitis clinical symptoms, which have an
influence both locally and systemically. Most PEP prevention techniques try to disrupt one or
more steps in this cascade.
While the precise mechanism of PEP remains unknown, it is most likely induced by a
proinflammatory cascade initiated by pancreatic acinar cell damage, which results in systemic
cytokine release. Cytokines play a major role in the pathogenesis of acute pancreatitis as
part of the underlying systemic inflammatory response, tissue damage, and organ dysfunction.
Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that promotes the
inflammatory response, whereas Interleukin-10 (IL-10) is an immunosuppressive cytokine that
inhibits inflammation. These markers can be used in measurement of the degree of systemic
inflammation as predictors of the development of PEP.
Phospholipase A2 is essential in this signaling cascade. Diclofenac is a nonsteroidal
anti-inflammatory drug (NSAID) that effectively inhibits phospholipase A2 activity. According
to this notion, anti-inflammatory drugs such as diclofenac can stop or attenuate the first
cascade that leads to clinical PEP.
Previous meta-analyses have suggested that NSAIDs are effective in preventing PEP. The
European Society of Gastrointestinal Endoscopy guidelines recommend routine rectal
administration of 100 mg of diclofenac or indomethacin immediately before ERCP procedure in
all patients without contraindications to NSAIDs administration. Rectal administration route
of diclofenac is the most effective in the prevention of PEP. Rectal diclofenac is a cheap,
widely available agent with easy administration method and favorable side effect profile.
Oxidative stress and active oxygen species can activate inflammatory cascade and immune
responses. N-acetyl cysteine (NAC), an antioxidant drug with anti-inflammatory properties can
inhibit oxidative stress as well as inflammatory intermediates, suggesting that it could aid
in the prevention of PEP. Despite the failure of intravenous N-acetyl cysteine studies, 2013
pilot research revealed that oral NAC may be useful in reducing PEP. This would be due to the
different pharmacokinetics of NAC followed in different studies. In a multicenter global
randomized controlled trial investigation, It is reported that oral NAC is more effective
than indomethacin in the prevention of PEP.
Although both oral NAC and rectal diclofenac are widely used pharmacological agents, till now
no study has evaluated their comparative safety and efficacy in preventing PEP. Hence this
study is planned to evaluate and compare their efficacy and safety in preventing PEP.