1. Preventing Post-ERCP Pancreatitis
Michael Chang, MD

2. Overview Risk of Post-ERCP pancreatitis (PEP)
Basics – Patient, Procedural
Pancreatic duct stenting
Rectal Indomethacin
Hydration

3. Overall Risk of PEP Systematic review in GIE 2015. -108 RCTs
-13,296 patients in the placebo or no-stent arms.
Incidence of PEP:
-Overall 9.7% (CI, 8.6%-10.7%)
-13% in North America, 8.4% in Europe, 9.9% in Asia RCTs.
ERCPs conducted before and after 2000 had a PEP incidence of 7.7% and 10%, respectively.
Overall Mortality rate was 0.7%.
Severity of Pancreatitis: 8857 patients where severity was recorded
-65% (5.7%) mild, 30% (2.6%) moderate, and 5% (0.5%) severe
“High-risk”: 2345 patients
-Overall 14.7%
-8.6% mild, 3.9% moderate, and 0.8% severe
-0.2% mortality rate.
Kochar B. at al. GIE 2015

4. High risk: 1 or more of the following
Risk of PEP
High risk: 1 or more of the following
Suspicion of SOD
Pancreatic sphincterotomy
History of PEP
Precut sphincterotomy
Age <50
Pneumatic dilation
Female sex
Ampullectomy
>2 episodes of pancreatitis
Multiple contrast injections to PD
Multiple cannulation attempts
Excessive injection into PD
Kochar B. at al. GIE 2015

5. Basics of Prevention Patient selection and proper indication!
Avoid ERCP if an alternative, less invasive modality is available (EUS or MRCP)
Endoscopic proficiency / Good endoscopic technique:
-Selective biliary cannulation
-Avoid excessive contrast injection
-Less attempts at cannulation
-Wire guided cannulation(?)
-Experienced team/technician

6. Wire Guided Cannulation
Multiple RTC analyzing risk of PEP using wire guided cannulation (GWC) vs. dye injection
First and large RTC published in GIE, 2004
-400 patients randomized to GWC vs contrast dye injection with sphincterotome
-Similar baseline characteristics
-PEP occurred in 0/200 cases in GWC arm vs 8/200 cases in contrast arm. P<0.01
*Single center, single endoscopist
Lella F. et al. GIE 2004

7. Wire Guided Cannulation
Prospective, RTC comparing GWC vs dye injection.
-Cross over if cannulation was unsuccessful in 10 minutes (Fellow 5 minutes, Attending 5 minutes)
Cannulation was successful without crossover in 323/413 patients (78.2 %): 167/202 (81.4 %) in the guide-wire arm and 156/211 (73.9 %) in the contrast arm (P = 0.03).
413 patients
PEP occurred in 29/413 (7.0 %)
16/202 (7.9%) in GWC arm
13/211 (6.2%) in contrast arm
P = 0.48
Bailey A. et al. Endoscopy 2008

8. Wire Guided Cannulation
Meta-analysis from Endoscopy, 2013
12 RCTs, 3450 patients
GWC significantly reduced PEP vs contrast-assisted cannulation. Risk ratio [RR] 0.51, CI 0.32 – 0.82
Guide Wire Cannulation:
-Greater primary cannulation success. RR 1.07
-Fewer precut sphincterotomies. RR 0.75
-Risk reduction in PEP with GWC existed only in “non-crossover” trials (RR 0.22, 95 %CI 0.12 – 0.42)
Tse F. et al. Endoscopy 2013

9. Pancreatic Duct Stenting
Prospective, RTC, 80 patients
All patients with suspected pancreatic sphincter hypertension (SOD)
41 patients randomized to pancreatic duct stent
39 patients to no stent
Tarnasky PR et al. Gastroenterol 1998

10. Pancreatic Duct Stenting
Post ERCP Pancreatitis:
10/39 (26%) in the no stent group
3/41 (7.3%) in the PD stent group
P = 0.03
Relative risk, 10.5 (95% CI, )
*Only 1 patient in the stent group developed pancreatitis after sphincterotomy, and 2 others developed pancreatitis at the time of stent extraction.
Tarnasky PR et al. Gastroenterol 1998

11. Pancreatic Duct Stenting
Prospective, RTC, 74 patients included in analysis
High-risk patients;
Young, women, SOD ~ 70%
36 patients to standard of care
38 patients to stenting;
-5F nasopancreatic catheter
-5F, 2-cm long pancreatic stent
Fazel A, et al. Gastrointest Endosc. 2003

12. Pancreatic Duct Stenting
Post ERCP Pancreatitis:
10/36 in no stent group
2/38 in stent group
*both cases mild
P = 0.05
Fazel A, et al. Gastrointest Endosc. 2003

13. Pancreatic Duct Stenting
Meta-analysis; 4 RTCs and 1 prospective trial included
481 patients
Singh, P. et al. Gastrointest Endosc 2004

14. Pancreatic Duct Stenting
Singh, P. et al. Gastrointest Endosc 2004

15. Pancreatic Duct Stenting
Updated meta-analysis; 14 RTCs
1541 patients
-760 Stent placement
781 Control group
201/1541 had PEP
-53 (7 %) Stent group
-148 (19 %) Control group
Overall RR = 0.39, CI 0.29– RR = 0.45, mild to moderate PEP RR = 0.26, severe PEP
P < 0.001
Mazaki T. et al. J Gastroenterol. 2014

16. Rectal Indomethacin RTC, multicenter All high-risk patients
602 patients enrolled
-295 pts 100mg indomethacin
-307 pts in placebo group
Elmunzer BJ et al. NEJM. 2012

17. Post-ERCP pancreatitis: Indomethacin group - 27/295 patients (9.2%)
Placebo group – 52/307 patients (16.9%) P=0.005
NNT 13, Relative risk reduction of 46%
Indomethacin appeared to be protective regardless of whether patients had undergone pancreatic stenting
Elmunzer BJ et al. NEJM. 2012

18. Rectal Indomethacin Single blinded, RTC, multicenter 2600 patients;
1297 Pre-procedure indomethacin
1303 “risk-stratified”, post-procedural indomethacin
Luo, H. et al. Lancet. 2016

19. Rectal Indomethacin
Luo, H. et al. Lancet. 2016

20. Aggressive Hydration Pilot study from 2014
62 patients, assigned to groups (2:1) to receive aggressive hydration with Lactated Ringer's solution or standard hydration with the same solution
Aggressive group: n=39
- 3 mL/kg/h during the procedure (~200mL/hr for 70kg male)
-20mL/kg bolus after (~1.5L for 70k male)
- 3 mL/kg/h for 8 hours after the procedure (~1.5L for 70kg male)
Standard of care group: n=23
1.5 mL/kg/h (~100mL/hr for 70kg male) during and for 8 hours after procedure
Buxbaum J et al. Clin Gastroenterol Hepatol. 2014

21. Aggressive Hydration
Buxbaum J et al. Clin Gastroenterol Hepatol. 2014

22. Aggressive Hydration
Pancreatic duct stents only used in “high risk cases”; pre-cut, only 5% of pts
No rectal indomethacin used
Buxbaum J et al. Clin Gastroenterol Hepatol. 2014

23. Aggressive Hydration RTC - 510 patients Vigorous IVF with LR:
10 mL/kg bolus prior and after
3 mL/kg/h during and for 8 hours after
Standard IVF:
LR 1.5 mL/kg/h during and 8 hours after
Choi. et al. CGH 2017

24. Aggressive Hydration Post ERCP Pancreatitis:
11/255 patients w/vigorous IVFR
25/255 patients w/standard IVFR
RR 0.41
(P = .016)
Moderate or severe PEP:
0.4% in the vigorous IVFR group
2% in the standard IVFR
(P = .040)
Choi. et al. CGH 2017

25. Rectal Indomethacin +IV Hydration
Randomized, Double Blind, Clinical Trial
Total of 192 patients
All patients had at least 1 high-risk criterion for PEP and 56% had >1
IVF was 1L bolus prior to procedure in all groups
100mg Indomethacin PR
Patients randomized 1:1:1:1
NS + Placebo
NS + Retcal Indomethacin
LR + Placebo
LR + Rectal Indomethacin
Mok. et al. GIE 2016

26. Rectal Indomethacin +IV Hydration
PEP
3 patients (6%) in the LR + IND
10 (21%) in the NS + placebo group (P = .04)
Readmission rates:
1 patient (2%) LR + IND
6 patients (13%) NS + placebo group (P = .03)
Mok. et al. GIE 2016

27. Conclusion Overall Risk of Post-ERCP pancreatitis (PEP) ~ 10%
Most efficient method to reduce Post-ERCP pancreatitis is not to perform ERCP if not indicated
Pancreatic duct stenting
Rectal Indomethacin
Hydration

28. Questions/Comments
Thank you