Diclofenac is associated with a reduced incidence of post-ERCP pancreatitis: results from a Danish cohort study Digestive Disease Center, Bispebjerg Hospital Bonna Leerhøy, Andreas Nordholm-Carstensen, Srdan Novovic, Mark Berner Hansen og Lars Nannestad Jørgensen Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Baggrund Hvad er den mest almindelige, frygtede komplikation efter ERCP? Hvornår har man post-ERCP pancreatitis? Serum amylase på 3 gange øvre normal niveau (>195 U/L) og nye eller forværrede, øvre abdominalsmerter 18-24 timer efter ERCP¹. Hvad er incidensen af post-ERCP pancreatits? - 8-20% (enkelte studier har vist op til 40%) ¹ Cotton consensus criteria 1991. Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Prognose Svær pancreatitis: 11% Død: 3% Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Case 3.3.2010 54-årig kvinde indlægges til ERCP grundet UL- og MRCP verificeret choledochus-sten. 4.3.2010 ERCP – svær kanylation 5.3.2010 ”Ondt i maven” + amylase 1020U/L (CRP 36) 7.3.2010 Amylase 1320, CRP 423, svært meteoristisk abdomen, smerter 10.3.2010 Cerebralt påvirket, takypnø, ingen mave-tarm funktion, vægtøgning på 13kg Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Case fortsat Ultralydsscanninger: 8 CT-scanninger: 10 Bedøvet: 8 Opereret: 4 Røntgen: 11 Ul-vejledt punktur/drænage: 9 Blødprøver: 256 Stomi, dialyse, organisk delir. Udskrives 21.6.2010 (110 dage) Herefter set ambulant 34 gange, genindlagt 2 gange Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Økonomiske konsekvenser Store udgifter under indlæggelse Store udgifter efter indlæggelse Creon/medicin Diabetes Tabt arbejdsfortjeneste Psykolog Andre følger/risici efter langvarig indlæggelse og mange røntgen undersøgelser Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Tal fra patientforsikringen Post-ERCP pancreatitis, 2006-2010: 30 anmeldelser, 27 afgjorte sager, 19 anerkendte sager (70%) Samlede anerkendelsesprocent for alle afgørelser af behandlingsskader var 36%   2006 2007 2008 2009 2010 I alt Antal anmeldelser 8 6 3 7 30 Anerkendte sager 4 2 19 Afviste sager 1 Afgørelser i alt 9 27 Erstatninger udbetalt i alt, kr. 635.273 2.542.870 627.280 2.003.985 5.809.408 Død som følge af skaden Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Background Inflammation, not infection! - NSAIDs?1 - Evidence supporting effect in high-risk patients1 - Not used in Denmark - Implemented 2011: 100mg diclofenac rectally adm. to all ERCP patients 1. Elmunzer BJ, Waljee AK, Elta GH, et al. A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis. Gut. 2008;57:1262-1267. Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Aim To assess the clinical effect of diclofenac administered as a single dose for the prevention of post-procedure pancreatitis in a consecutive series of patients undergoing ERCP. Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Materials Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Methods Primary outcome: post-ERCP pancreatitis, defined as a serum amylase level three times above the upper level of normal and new or worsened upper abdominal pain 24 hours following ERCP. Secondary outcome: moderate to severe post-ERCP pancreatitis Assessed retrospectively by reviewing patients’ charts and blood tests. Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

TABLE 1. Patient Characteristics Control Group Diclofenac Group P   Control Group Diclofenac Group P n = 218 n = 182 Female - n (%) 131 (60) 104 (57) 0.610 Age - mean, years (SD) 65 (18.2) 64 (17.2) 0.556 BMIa (SD) 26.5 (5.7) 26.1 (5.2) 0.519 ASA (%) 1 2 3 4 25 (11.5) 118 (54.1) 72 (33.0) 3 (1.4) 39 (21.4) 68 (37.4) 72 (39.6) 3 (1.6) 0.004 Cholelithiasis - n (%) 141 (65) 108 (59) 0.301 Cancer - n (%) 50 (23) 46 (25) 0.639 Cholangitis - n (%) 9 (4) 5 (3) 0.588 a BMI, Body Mass Index (kg/m2) Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Biliary sphincterotomy - n (%) 122 (56.0) 96 (52.7) 0.546 Therapy Control Group Diclofenac Group P Biliary stent - n (%) 124 (56.9) 114 (62.6) 0.261 Biliary sphincterotomy - n (%) 122 (56.0) 96 (52.7) 0.546 Precut sphincterotomy 4 (1.8) 5 (2.7) 0.737 Biliary ballon sphincter dilation 6 (2.8) 4 (2.2) 0.761 Moderate to difficult cannulation 91 (41.7) 54 (29.7) 0.016 Unintended pancreatic duct injection 7 (3.2) 8 (4.4) 0.603 Failure to clear bile duct stone 60 (27.5) 62 (34.1) 0.191 Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Results Ret 17 til 17.0

Adjustment for potential confounders Included in univariable analyses: Age Sex BMI Diclofenac Papillotomy Stent Stone Malignancy ASA group ASA group Endoscopist Difficult cannulation Precut Pancreatic duct injection Success of procedure Normal bilirubin Failure to clear bile duct stone. Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Adjustment for potential confounders Factors Associated with Post-ERCP Pancreatitis   Multivariable OR (95% CI) P BMI 1.05 (0.99-1.12) 0.082 Diclofenac 0.012 No 1.00 Yes 0.35 (0.15-0.77) Papillotomy 0.234 1.71 (0.72-4.35) Stent 0.757 0.88 (0.41-1.94) Difficult cannulation <0.001 No 1.00 Yes 6.49 (2.96-15.47) Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Considerations Costs Adverse events Limitations Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Perspectives Prospective cohort study, using blood tests to determine the therapeutic interval of diclofenac needed to prevent post-ERCP pancreatitis. Is there a need for a weight adjusted dose? Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Perspektivering Skal alle have ERCP patienter have NSAID? Ulcus Nyresyg Hjertesyg Cave Retningslinje – konsekvenser hvis patienterne ikke modtager post-ERCP pancreatitis profylakse Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Conclusion The implementation of a single dose of 100 mg diclofenac rectally administered is associated with a reduced incidence of post-ERCP pancreatitis in an unselected material of patients with native papilla. Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen

Lassendagen 2013, Bonna Leerhøy Runov Bispebjerg Hospital, University of Copenhagen

Spørgsmål? Kommentarer? Bonna Leerhøy E-mail: bonna.leerhoey@regionh.dk Bonna Leerhøy Bispebjerg Hospital, University of Copenhagen