Prevention of post endoscopic retrograde cholangiopancreatography pancreatitis

Abstract:

Pancreatitis is the most common and important complication of ERCP. Several risk factors exist that help to formation and progress pancreatitis. These risk factors may be factors that are related to patient, and factors that related to Procedure, or factors related to operator. All of the risk factors should be considered and as far as possible may be lowered with attention to pathogenesis of the development of post-ERCP pancreatitis. These pathogenesis are include: sphincter spasm, infection, contrast toxicity and pancreatic secretion that induce activation of proteolytic enzymes and inflammatory process. Some of methods and pharmacologic agent assessed for prevention pathogenesis pathway to decrease post-ERCP pancreatitis.

Introduction:

In about 75 percent of patients after endoscopic retrogradecholangiopancreato-graphy (ERCP) may have elevation in serum amylase ; but acute clinical pancreatitis (defined as a clinical syndrome of abdominal pain and hyperamylasemia) is less common. However, acute pancreatitis is the important complication of ERCP and need to pay attention it to prevent from its morbidity and mortality [1].

Mechanism for post ERCP pancreatitis:

The exact mechanism for PEP is unknown. It needs to be a trigger event that turn on the inflammatory process, that can be the fallowing: thermal injury from sphincterotomy, mechanical obstruction to outflow of the pancreatic secretions , papillary edema from attempted multiple cannulations, sphincterotomy etc., injury from guide wire, chemical injury of the contrast, microbiological injury due to introduction of duodenal flora into the pancreas etc [2].

Risk Factors for Post-ERCP Pancreatitis:

It is important to identify cases in which there are high risks for pancreatitis that we can prevent the complications of the prophylactic method such as pancreatic stenting or pharmacological prophylaxis. Assessment of both patient- and procedure-related factors is necessary to detect the high-risk cases (Table 1) [3].

Table 1: Risk Factors for Post-ERCP Pancreatitis [3].

Definition of post ERCP pancreatitis:

To diagnose PEP need to be at least two of the following criteria:

1. Epigastric pain with radiation to the back,
2. Elevation of amylase and / or lipase at least 3 times higher than normal.
3. Radiological imaging that suggests pancreatitis.

Amylase and lipase may have an elevation despite the patients does not has any symptom. Radiological imaging is helpful when the diagnosis is difficult [4].

Methods and pharmacologic prevention of post-ERCP pancreatitis

A. the Following techniques should be adhered to in order to decrease the risk of post-ERCP pancreatitis:

1. Endoscopic techniques

2. Cannulation

3. Electrocautery

4. Pancreatic stenting

B. Pharnacologic prophylams:

1. Nonsteroidal anti-inflammatory drugs
2. Steroidal anti-inflammatory agents
3. Other anti-inflammatory agents – Allopurinol semapimod- interleukin 10- pentoxifylline- Platelet-activating factor-Epinephrine
4. Inhibitors of pancreatic secretion: Somatostatin- Somatostatin combined with diclofenac- octerotide- calcitonin
5. Agents that stimulate pancreatic secretion and reduce sphincter tone: Secretin
6. Agents that reduce of sphincter tone: Nifedipine-Nitrates-Glyceryl trinitrate botulinum toxin-topical lidocaine
7. Inhibitors of protease activation: Gabexate mesilate- Nafamostat- Ulinastatin- C₁-inhibitor- Heparin
8. Antioxidants: N-acetylcysteine- Sodium selenite- Beta- Carotene
9. Antimicrobial agents
10. Antimetabolites : 5-FU (5 Fluoro Uracil)[5].

Some of the drugs that tested in different trials are described below:

Pharmacological Prevention for Post-ERCP Pancreatitis:

Since the introduction of ERCP, numerous pharmacologic drugs have been assessed to prevent post-ERCP pancreatitis based on their pharmacologic mechanism and their effect on one or more of the factors associated with pancreatic damage (Figure 1) [6].

1- NSAIDs:

NSAIDs (diclofenac or indomethacin) are the most drugs that are using for prevention of post-ERCP pancreatitis [7].

The European Society of Gastrointestinal Endoscopy recommends routine rectal administration of 100 mg diclofenac or indomethacin for prevention of post-ERCP pancreatitis [8].

2- Glyceryl trinitrate:

Glyceryl trinitrate reduces sphincter of Oddi pressure and may uses to prevent post-ERCP pancreatitis. ManuelMoretó in his study assessed that could transdermal glyceryl trinitrate be effective in the prevention of post-ERCP pancreatitis? The results of his study show that transdermal glyceryl trinitrate patch significantly reduces post-ERCP pancreatitis [7].

3- Nifedipine:

Calcium channel inhibitors can prevent the development of experimental pancreatitis.

Nifedipine is from the calcium channel blocker drugs and its effect is reducing sphincter spasm.

Part done randomized, placebo-controlled trial to determine whether the calcium channel blocker nifedipine prevents post-ERCP pancreatitis. Nifedipine or placebo was administered before and within 6 hours after ERCP.

This study failed to show significant effect of nifedipine in the prevention of post-ERCP pancreatitis [8].

4-Antibiotics:

Infections that occur when ERCP is done can activation proteolytic enzymes and lead to pancreatitis. Now there is this question that antibiotics can use in the prevention of post-ERCP pancreatitis. One prospective randomized controlled trial showed that the ceftazidime administration before ERCP significantly decreased the incidence of post-ERCP pancreatitis in the control group that did not receive antibiotic [9].

The quality of the study is questionable because the control group did not received no antibiotic [10].

5- Risperidone:

Ulinastatin inhibited systemic inflammatory responses and may benefit for prevention post-ERCP pancreatitis.

Tsujino assessed the effect of risperidone (a selective serotonin 2A antagonist) combined with ulinastatin for the prevention of PEP in high-risk patients.

In a multicenter, randomized, controlled trial, patients were randomly compared to administration ulinastatin with or without risperidone.

The incidence of PEP was not significantly different between two groups, but pancreatic enzymes level were significantly lower in the risperidone+ulinastatin group as compared with ulinastatin alone [11].

6- Indomethacin

Indometacin is from nonstroidal antiinflamatory drugs that are used for prevention of post-ERCP pancreatitis.

Joseph Elmunzer in a multicenter, randomized, placebo-controlled, double-blind clinical trial assigned patients that were high risk for post-ERCP pancreatitis to receive a single dose of indomethacin or placebo immediately after ERCP. Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the post-ERCP pancreatitis [12].

Yaghoobi also assigned one meta-analysis to assessed rectal indomethacin for the prevention of post-ERCP pancreatitis. This meta-analysis showed that the rate of pancreatitis was significantly lower when using indomethacin as compared with placebo. [13].

7- Corticosteroid:

Corticosteroids are anti-inflammatory drugs and may be able to decrease the risk of post-ERCP pancreatitis.

In a prospective randomized controlled multicentre study, administration of prednisone did not reduce the incidence of pancreatitis rather than placebo [14].

8- N-acetyl Cysteine:

N-acetyl Cysteine can reduce inflammation and may be useful in post-ERCP pancreatitis.

Pezhman Alavi Nejad wants to evaluate efficacy of N-acetyl Cysteine for the Prevention of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis. He assigned a prospective double blind randomized study.

There were significant reduce in the prevalence of acute pancreatitis between the groups. This study shows that NAC could be used for the prevention of post-ERCP pancreatitis [15].

9- Aprepitant

Aprepitant is one drug from the classification of neurokinin-1 receptor antagonists. Upendra Shah wants to assess the efficacy of aprepitant at preventing post-ERCP pancreatitis in high risk patients. A randomized, double-blind, placebo controlled trial assigned. Patients received either placebo or oral aprepitant. Aprepitant could not decrease the incidence of post-ERCP pancreatitis against placebo [16].

pancreatic stents:

Abhishek Choudhary assessed a meta-analysis and to determined effect of pancreatic stents for prevention of post-ERCP pancreatitis.

This meta-analysis of the RCTs showed that pancreatic stent placement reduces the incidence pancreatitis and hyperamylasemia [17].

Conclusion:

Considering the fact that pancreatitis is the most important of the ERCP complications we should pay attention the methods for prevention of post-ERCP pancreatitis. Pancreatic stents are useful for this aim. From the pharmacologic agents, Glyceryl trinitrate, Indometacin and N-acetyl Cysteine could significantly decrease the incidence of post-ERCP pancreatitis. Other drug that assessed in this review article such as Nifedipine, Risperidone, Corticosteroids, and Aprepitant did not show significant effect for prevention of post-ERCP pancreatitis.