Comparative Clinical Study to Evaluate the Possible Efficacy and Safety of Oral N-Acetyl Cysteine Versus Rectal Diclofenac in the Prevention of Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis

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.