Indomethacin – a new usage as prevention of post-Endoscopic Retrograde Choleangiopancreatography pancreatitis (post-ERCP pancreatitis)

There is a lot of reasons of acute pancreatitis, There are mechanic causes like bile ducts obstruction because of gallstones or Vater pupile stenosis (55%), toxic – alcohol abuse (35%) the other 10% are as well genetic predisposition (PRSS1 tripsinogen mutation) as iatrogenic factors associated with medicaments (diuretics, betablocers, NSAR) or medical procedures, like endoscopic retrograde cholangiopancreatography (ERCP). (3) The pancreatography is the most common, dangerous and expensive complication of ERCP. According to preliminary studies a single doses of rectal indomethacin could prevent post-ERCP acute pancreatitis by the risk group patients.(4)

Nonsteroidal anti-inflammatory drugs work through phospholipase A2 inhibition, cyklooxigenase inhibition, what seems to have a big role in formation of pancreatitis. According to sources a single dose of rectal indomethacin or diclofenac may successfully prevent these complications.

In four academical centers in the USA were conducted the double blind studies. The patients were risk group patients with suspicious of Oddi sphincter stenosis, after recent post-ERCP pancreatitis, after sphincterectomy of Oddi sphincter, after more than eight cannulation attempts, after pneumatic dilatation of intact biliary sphincter or ampullectomy. There were also patients with two minor risk factors, like age less than 50, female, with history of the recurrent pancreatitis, after at least three injection with contrast agent into biliary tracts or the acquisition of a cytologic specimen from the pancreatic duct with the use of a brush. The patients with contraindication to NSAID-therapy or NSAID-treated patients (without antithrombotic ASS) were excluded. There were also control group treated. (1)

Immediately after ERCP the endoscopist had applicated the corresponding patients 2×50 mg rectal suppositories with indomethacin or placebo. Only this application way can be useful by prevent of pancreatitis owing to better and rapid bioavailability. The patients were observed at least 90 minutes after the procedure, in a case of pancreatitis they were hospitalisated The post-ERCP pancreatitis diagnose were based of severe new pain in the upper abdomen, at least three times elevated blood plasma enzymes in 24 hours after the procedure. Then they were contacted 5 days after ERCP to recognize the post-ERCP pancreatitis (it occurs up to 48h after the procedure) and 30 days after ERCP, to estimate the patient’s condition, or to know how long the patients were hospitalized, significant was hospitalization time more than 2 days.

The results were satisfactory, rectal indomethacin has decreased the outcome of post-ERCP pancreatitis of 50%, by 10% placebo group, according to 5% indomethacin group. The time of hospitalization was also reduced about of 0.5 of the day, according to placebo patients. By 11 from 612 patients is a significant clinical bleeding occurred. The complication like heart infarct, stroke or death have not occurred.

Perhaps the indomethacin can be included as a part of ERCP protocol, to decrease the incidence of the most harmful ERCP complication. The usage of NSAID to pancreatitis prevention is interesting, because NSAID-therapy may lead to pancreatitis. A similar situations occur in pharmacology, e.g. antiarrhythmic drugs, which may cause an arrhythmy. One drug and a lot of application options leading to various effects. We need to order the drugs carefully, but we can also find a lot of functions of common drugs. (2)

Written by: Magdalena Chorążka

Source:
1.A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis B. Joseph Elmunzer MD N Engl J Med 2012; 366:1414-1422April 12, 2012
2.Pharmakologie und Toxicologie, T. Karow, R. Lang-Roth, Köln 2012
3.Innere Medizin, Gerd Herold und Mitarbeiter, Köln 2011 462-464
4.Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Lankisch PG.Am J Gastroenterol. 2008 Jan;103(1):244.

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