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.
