prise en charge des pancréatites aiguës -...

Myriam DelhayeDépartement de Gastro-entérologieHôpital Erasme, Bruxelles

DES en Médecine Interne, 15/02/2014

Prise en charge des pancréatites aiguës

2

Acute pancreatitis

Diagnosis

Severity stratification

Predicted Predicted

mild disease severe disease

Etiological Early management

assessment

Hydratation Antibioprophylaxy Nutrition      EBS

FIRST

WEEK

FROM

ONSET

3

Acute pancreatitis

Definition Acute inflammatory process of the pancreas Variable involvement of regional tissues

of remote organ systems

Diagnosis Abdominal pain characteristic of AP Serum lipase 3 N (lipase better than amylase)

CE-CT scan / MRI characteristic of AP 2/3

4

1997 2003

Europe 12.4 15.9/100,000/y (+30%)

Mean mortality 1.9% 1.4% p<0.001

Median LOS 6.4 d 5.8 d p=0.002

Acute pancreatitis

5

1st clinically based classification Atlanta 1992Mild AP vs. Severe AP(80-90%) (10-20%)

Bradley, Arch Surg 1993; 128: 586‐590

Acute pancreatitis

6

1st clinically based classification Atlanta 1992Mild AP vs. Severe AP(80-90%) (10-20%)

Local complications (necrosis > 30%, abscess, pseudocyst)

and/or Organ failure: shock syst BP < 90 mmHg pulmonary insufficiency PaO2 60 mmHg renal failure creat > 2 mg/dl after rehydratation GI bleeding > 500 ml/24h

or Ranson score 3 (at 48h)

or APACHE II score 8 (at any time)

Bradley, Arch Surg 1993; 128: 586‐590

Acute pancreatitis

7

Ranson scoreAt admission At 48 h

Age > 55 y Hct > 10%

WBC > 16000/mm3 BUN > 5 mg/dl

Glucose > 200 mg/dl Calcium < 8 mg/dl

LDH > 1,5 N PO2 < 60 mmHg

AST > 6 N Base deficit > 4 mEq/l

Fluid sequestration > 6 l

Ranson score Mortality0 – 2 0 – 3%3 – 5 11 – 15% 6 40%

moderately accurate to predict SAPrequires 48hmissing data

8

A. Variables +4 +3 +2 +1 0 +1 +2 +3 +4

Temperature (°C) ≥41 39/40,9 38,5/38,9 36/38,4 34/35,9 32/33,9 30/31,9 <30

MAP (mmHg) ≥160 130/159 110/129 70/109 50/69 <50

HR (bpm) ≥180 140/179 110/139 70/109 55/69 40/54 <40

RR (cpm) ≥50 35/49 25/34 12/24 11/10 6/9 <6

PO2 (mmHg)

If FiO2 : (A-a) DO2* ≥500 350/499 200/349 <200

If FiO2 < 0,5: PaO >70 61/70 55/60 <55

pH ≥7,7 7,6/7,69 7,5/7,59 7,33/7,49 7,25/7,32 7,15/7,24 <7,15

Na+ (mmol/l) ≥180 161/179 156/160 151/155 130/150 120/129 110/119 <110

K+ (mmol/l) ≥7,0 6/6,9 5,5/5,9 3,5/5,4 3/3,4 2,5/2,9 <2,5

Creatinine (µmol/l) ≥318 180/317 136/179 54/135 <0,6 <54

Hct (%) ≥60 50/59,9 46/49,9 30/45,9 20/29,9 <20

WBC (x1000/mm3) ≥40 20/39,9 15/19,9 3/14,9 1/2,9 <1

GCS Points = 15 – Actual GCS

Apache II score

9

B. Age 44 y 0

45 - 54 2

55 – 64 3

65 – 74 5

75 6

C. Comorbidity: add 2 points (elective surgery) or add 5 points (emergency surgery) for each associated disease:

Cardiac failure

Cirrhosis Child C

Severe BPCO

Dialysis

Immunosuppression

APACHE II score: points for A + points for B + points for C

Apache II score

Severe AP if score  8originally designed to predict ICU survivallarge number of parameters

10

Acute pancreatitis Need for revised classification

Heterogeneity in SAP pancreatic necrosis pseudocyst or abscess no OF SOF MOF transient OF persistent OF

Scoring system for organ failure added

GI bleeding deleted

Organized necrosis

Banks, Am JGE 2006; 101: 2379‐2400

11

Marshall Scoring System

Score

Organ system 0 1 2 3 4

Respiratory (PO2 /FiO2 ) > 400 301 - 400 201 - 300 101 - 200 101

Renal (serum creatinine, mg/dl)

1.5 > 1.5 - 1.9 > 1.9 - 3.5 > 3.5 - 5.0 > 5.0

Cardiovascular (systolic blood pressure, mmHg)

> 90 < 90Fluid

responsive

< 90Not fluid

responsive

< 90pH < 7.3

< 90pH < 7.2

OF = score  2 for each organ systemMOF =  2 OF the same dayPersistent OF = OF > 48 h

12

Acute pancreatitis Severity stratification Sequential Organ Failure Assessment score (SOFA score)

Vincent et al, Int Care Med 1996; 22: 707‐710

severity / number of OF transient vs. persistent OF

most significant predictor of death

13

Acute pancreatitis Transient OF vs. persistent OF

NOF Transient OF Persistent OFn = 116 n = 60

at entry

n = 11

new (7 d)

n = 88

at entry

n = 15

new (7 d)

Mortality 2.6% 1.4% 35%

duration of OF: marker of subsequent poor outcome in AP

persistent early OF high risk of local complications (77%)of death (35%)

aggressive supportive therapy

NOF / transient OF low risk of local complications (17%)of death (2%)Johnson et al, Gut 2004; 53: 1340-1344

14

Acute pancreatitis Factors associated with development of OF

OR

extent of necrosis < 30% vs. 30 – 50% 5.8 p=0.03

< 30% vs. > 50% 18.9 p=0.0004

infected necrosis vs. sterile necrosis(later)

3.3 p=0.02

Garg et al, Clin GE Hepatol 2005; 3: 159-166

15

Acute pancreatitis Predicted severity Multifactor scoring systems

Ranson score 3 (1974) Apache II score 8 (1985) Apache – 0 score = Apache II score + 1 pt BMI 26 – 30

+ 2 pts BMI > 30 SIRS / persistent SIRS

CRP > 15 mg/dl (at 48h after onset)

Serum hematocrit 44 – 47%

Creat > 2 mg/dl + glu > 250 mg/dl

at admissionat 24hat 48h

16

Acute pancreatitis Severity stratification

SIRS when 2 of the following

T° > 38° or < 36° HR > 90 b/min RR > 20 b/min or PaCO2 < 32 mmHg WBC > 12000 or < 4000/mm3

17

Acute pancreatitis: Severity stratification

Number of SIRS criteria within 24h of admission

Singh et al, Clin GE Hepatol 2009; 7: 1247‐1251

n = 252 patients with AP  SIRS n = 155 (62%) on Day 1

18

Acute pancreatitis Severity stratification: Duration of SIRS

0

5

10

15

20

25

30

35

No SIRS Transient SIRS Persistent SIRS

Persistent OFPancreatic necrosisNeed for ICUDeath

Singh et al, Clin GE Hepatol 2009; 7: 1247‐1251

%

n=65 n=116 n=71

19

HAPs = Harmless AP score on admission (2009) No rebound tenderness and/or guarding Hematocrit 43% (♂) 39.6% (♀) Serum creat < 2 mg/dlHarmless course no necrosis

no need for dialysis or artificial ventilation

no death identification of patients with mild AP with PPV = 98%

Lankisch et al, Clin GE Hepatol 2009; 7: 702‐705

Acute pancreatitis

20

Management of acute pancreatitis

CT scan at admission? yes, in all cases IF unclear diagnosis yes, to assess severity if 48h after onset no :

• if clear diagnosis• if clinically mild AP• if < 48h after onset

21

Acute pancreatitis Severity stratification – Radiological criteria

Balthazar, Radiology 1985; 156: 767‐772   Balthazar, Radiology 1990; 174: 331‐336

CT severity index points

Morbidity (%)

Mortality (%)

Grade A Normal 0 0 B Pancreatic enlargement 1 0 C Peripancreatic changes 2 7 D Single fluid collection 3 42 E 2 or more fluid collections 4 60 Necrosis None 0 12 Mild (0-30%) 2 40 Moderate (30-50%) 4 75 Extensive (> 50%) 6 100 Total CT 0-3 8 3 severity index points 4-6

7-10 35 92

6 17

Interobserver agreement 0.48 – 0.70no reflection of SIRS

Mild Moderate Severe

CE-CT scan CTSI (1994) 0 – 3 4 – 6 7 – 10

22

CT CE - CT

23

Acute pancreatitis Severity stratification – CTSI vs. MRSI

Arvanitakis et al, Gastroenterology 2004; 126: 715-723; Stimac et al, Am JGE 2007; 102: 997-1004

CE-CT

MRI

4h 48h

72h 72h

T1 -w T2 -w

24

Acute pancreatitis: New classification

Mild AP Moderate AP Severe AP

Structural changes

Interstitial edema Interstitial edema + local complications (necrosis and/or FC)

Interstitial edema + local complications (necrosis and/or FC)

Functional changes

No OF Transient OF – persistent OFMarshall score 2> 48h

No MOF No MOF – MOF (transient or persistent)

Morbidity Low High High

Mortality No Low High

Talukdar et al, Clin GE Hepatol 2009; 7: S3‐S9; Vege et al, Am JGE 2009; 104: 710‐715; de Madaria et al, Pancreatology 2010; 10: 613‐619

25

Mild AP(n=91)

Moderate AP (n=42)

Severe AP (n=11)

LOS 10 d 20 d* 27 d*

ICU 0 2.4% 54.5%*

Nutritional support 2.2% 33.3%* 63.6%*

Invasive treatment 0 2.4% 45.5%*

Mortality 0 0 45.5%*

de Madaria et al, Pancreatology 2010; 10: 613-619

Acute pancreatitis: New classification

26

Acute pancreatitis: How to early stage?

Mild AP Moderate AP Severe AP Harmless AP score Apache II 6 Apache II 8

Ranson score 3

CTSI < 3 CTSI 3 CTSI 3

No OF Transient OF Persistent OF

No MOF No MOF MOF

No SIRS Transient SIRS Persistent SIRS

CRP 15 mg/dl CRP 15 mg/dl CRP > 15 mg/dl

at admissionat 24hat 48h

27

Acute pancreatitis

Diagnosis

Severity stratification

Predicted Predictedmild disease severe disease

Etiological Early managementassessment

Hydratation Antibioprophylaxy Nutrition EBS

FIRST

WEEK

FROM

ONSET

Predictedmoderate disease

28

Acute pancreatitis Etiology Clinical history:

alcohol intake u/w, previous gallstones, family history, viral illness, drugs intake, trauma,…

Laboratory data: liver function tests, TG, Ca++ (viral studies, autoimmune markers,

genetic testing,…)

Radiological findings: US early and repeated (CE-CT scan, MRI)

29

Acute pancreatitis

Early identification of patients with acute biliary pancreatitis ALT 3 N PPV 95% gallstones and/or sludge on US CBD dilated on US / CT ( 75 y: > 8 mm; > 75 y: > 10 mm) stones in the CBD (EUS / MRCP)

Sens (%) Spec (%) ACC (%)Liver function tests 85 69 76US 72 98 86US + LFT 95 100 98EUS 87 100 97MRCP 83 97 94

30

Acute pancreatitis

Diagnosis

Severity stratification

Predicted Predictedmild disease severe disease

Etiological Early managementassessment

Hydratation Antibioprophylaxy Nutrition EBS

FIRST

WEEK

FROM

ONSET

Predictedmoderate disease

31

AP: Rationale for aggressive hydratation in SAP

SAP

acute renal failure

intravascular volume

pancreatic infection

intestinal permeabilityto bacteria

intestinal ischemia perfusion in microcirculation of pancreasimpaired pancreatic microcirculation

pancreatic ischemia

NECROSIS

vascular permeability of capillaries

arterial vasospasmvasoactive mediators

NECROSIS

pancreatic ischemia

Microthrombi

Hypercoagulability

extravasation of intravascular fluid into 3d space

ischemia / reperfusioninjury

free radicals

32

Severe acute pancreatitis Early management

Fluid resuscitation recommendations

Gardner et al, Clin GE Hepatol 2008; 6: 1070‐1076

– Crystalloids preferred in most instance– Packed RBC when Hct < 25%– Albumin when serum alb < 2 g/dl

33

Acute pancreatitis

Diagnosis

Severity stratification

Predicted Predictedmild disease severe disease

Etiological Early managementassessment

Hydratation Antibioprophylaxy Nutrition EBS

FIRST

WEEK

FROM

ONSET

Predictedmoderate disease

34

Severe acute pancreatitis Prophylactic antibiotics

Cochrane review of 7 RCT: 404 patients

Antibiotic s

Placebo p RR

Mortality (n=7) 8.4% 14.4% 0.07 0.60

Infected pancreatic necrosis (n=7)

19.7% 24.4% 0.42 0.85

Non-pancreatic infection (n=5) 23.7% 36% 0.08 0.62

Overall infections (n=5) 37.5% 51.9% 0.12 0.69

Surgery (n=6) 22.6% 24% 0.58 0.90

Fungal infections (n=7) 3.9% 5% 0.91 1.06

Villatoro E, Cochrane Database of Systematic Reviews 2010; 5: 1‐49

No major problems with antibiotic resistance

vs

35

Infected pancreatic necrosis

Antibiotics versus  placebo

Imipenem versus  placebo

36

Severe acute pancreatitis Antibiotic prophylaxis

7 – 10 d imipenem in patients with pancreatic necrosis + OFin septic-appearing patients

Stop AB if blood culture, FNA culture,… ⊝

Talukdar and Vege, Clin GE Hepatol 2009; 7: S3‐S9

prophylactic antibiotics NOT recommended for patients with necrotizing pancreatitis

AB for patients – with evidence of sepsis– with proven pancreatic / extrapancreatic

infection

37

Acute pancreatitis

Diagnosis

Severity stratification

Predicted Predictedmild disease severe disease

Etiological Early managementassessment

Hydratation Antibioprophylaxy Nutrition EBS

FIRST

WEEK

FROM

ONSET

Predictedmoderate disease

38

Severe acute pancreatitis Early nutritional support

Lack of enteral feeding atrophy of the GI mucosa bacterial overgrowth intestinal permeability

bacterial translocation

39

Severe acute pancreatitis Early nutritional support

Metaanalysis of 5 RCT: TEN vs. TPN in predicted SAP (202 patients)

Infectious complications Mortality

TEN infectious complications in patients with predicted SAP mortality Petrov et al, Arch Surg 2008; 143: 1111‐1117

RR = 0.47 (p<0.001) RR = 0.32 (p<0.03)

40

Enteral nutrition which route?

41

Severe acute pancreatitis Early nutritional support

2 RCT on NG feeding vs NJ feeding comparable safety, morbidity, mortality

Eatcock, Am JGE 2005; 100: 432‐439

49 patients with SAP (Glasgow  3 or APACHE II  6 or CRP > 15 mg/dl)27 NG / 22 NJ

42

Acute pancreatitis Early management of nutrition Mild AP

refeeding within 24 – 72h of onset low fat solid diet > clear liquid diet

Severe AP enteral nutrition jejunal route if gastric feeding not tolerated start with standard formulae peptide-based formulae if standard formulae not tolerated

Espen guidelines, Meier et al, Clin Nutr 2006; 25: 275‐284

43

Acute pancreatitis

Diagnosis

Severity stratification

Predicted Predictedmild disease severe disease

Etiological Early managementassessment

Hydratation Antibioprophylaxy Nutrition EBS

FIRST

WEEK

FROM

ONSET

Predictedmoderate disease

44

Biliary APMild

Severe

ImprovementNo cholangitisNo jaundiceNo CBD stone

Cholecystectomy+OC

If stone in CBD

Early EBS

EBS

CholangitisJaundice

Biliary symptomssuggestive of CBD stone

Elective EBS

No improvementafter 48 h

cholecystectomy CIor prior cholecystectomy

Delayed cholecystectomy

45

Acute biliary pancreatitis

3rd metaanalysis: 702 patients      early ERCP vs. conservative management(1st 1999: 3 RCT + 1 abstract           2nd 2004: 3 RCT           3rd 2008: 5 RCT)

Author (year) Patients % SAP Timing ERCP

MorbidityERCP / contr

MortalityERCP / contr

Neoptolemos (1988) 121 44 72h adm 17 34 2 8

Fan (1993) 195 42 24h adm 18 30 5 9

Folsch (1997) 238 19 72h onset 46 51 11 6

Zhou (2002) 45 31 24h adm 5 20 0 0

Oria (2007) 103 37 72h adm 22 17 6 2

Total 702 33 27 36 6 6

Moretti et al, Dig Liv Dis 2008; 40: 379‐385

46

Acute biliary pancreatitis

Complications Mortality Complications

Moretti et al, Dig Liv Dis 2008; 40: 379‐385

p=0.01NNT = 12

p=0.6

p=0. 9

p<0.0001NNT = 3

47

Acute biliary pancreatitis

Meta-analysis of early ES in acute biliary pancreatitis

cholangitis excluded

Talukdar and Vege, Clin GE Hepatol 2009; 7: S3‐S9

48

Management of acute pancreatitis: 1st week

Conclusions

Aggressive hydratation (cristalloids) aim: Hct of 10% if initial value 47% minimum : 3l / 24h no complaint of thirst!

Painkillers : Morphine IV (titration)

No systematic antibioprophylaxyNB : * infection of necrosis after 2 – 3 w from onset

* T° and CRP < SIRS at onset of AP* if antibioprophylaxy (immunocompromised, MOF,…) : Meronem

ICU admission if suspected severe AP for monitored hyperhydratation

49

Oedémateuse (75%) Nécrosante (25%)

Histoire naturellePancréatite aiguë

Collection liquidienne aiguë Collection post-nécrotique

Résolution Pseudokyste

Stérile Infecté

Nécrose organisée

Stérile Infectée

< 4 sem :

> 4 sem :

5050

Acute pancreatitis complications

Pancreatic fluid collectionsRevised Atlanta Classification

Early PFC ( 4 w of onset) Late PFC (> 4 w of onset)

– acute fluid collection Acute Pseudocyst (10-25% of AP)

> 50% of AP

most resolve spontaneously

– acute necrotic collection WON (80% of NP)

> 90% of NP

Banks PA et al, Gut 2013; 62: 102-111Resolution

5151

Acute fluid collection

Early ( 4 w), no wall, retroperitoneal space

Most resolve spontaneously within a few weeks

Banks PA et al, Gut 2013; 62: 102-111

5252

Acute necrotic collectionEarly ( 4 w), necrosis of pancreatic and/or peripancreatic tissues

Banks PA et al, Gut 2013; 62: 102-111

5353

Acute pseudocyst

Late (> 4 w), well-defined wall, liquid content

Banks PA et al, Gut 2013; 62: 102-111

5454

Walled-off necrosis (WON)

Late (> 4 w), liquefied necrosis, encapsulated in a wall variable amount of solid debris

54

5555

Acute pancreatitis complications

Imaging techniques: CT or MRI? Both show PFC localisation and extension Contrast injection can determine the presence of

pseudoaneurysms Solid material better demonstrated by MRI or EUS than CT

CTCT

Morgan, Radiology 1997; 203: 773-778; Morgan, Clin GE Hepatol 2008; 6: 1077-1085

MRIMRI

5656

Acute pancreatitis complications: WON

Indications for endoscopic intervention: for who?

Common indications: Suspected or confirmed infected necrosis clinical deterioration

In absence of infection: Ongoing OF (> 4 w) Ongoing gastric outlet, intestinal or biliary obstruction (> 4-8 w) Persistent symptoms (pain, unwellness > 8 w)

5757

Acute pancreatitis complications: WON

Optimal timing of intervention for suspected or confirmed infected WON: when?

conservative treatment n = 397N = 639 patients & NP(21 Dutch hospitals) intervention n = 242 (38%)

Time from admission to intervention

0 – 14 d(n = 45)

14 – 29 d(n = 98)

> 29 d(n = 99)

Mortality 56% 26% 15% P<0.001

The longer the time between admission and intervention the lower the risk of mortality

Van Santvoort HC et al, GE 2011; 141: 1254-1263

5858

Acute pancreatitis complications: WON Conservative treatment?

Conservative treatment vs Intervention

Van Santvoort HC et al, GE 2011; 141: 1254-1263

n = 397(62%)

n = 242(38%)

CTSI 4 (4 – 6) 8 (6 – 10) p<0.001Pancreatic necrosis 35% 76% p<0.001Peripancreatic necrosis alone 65% 24% p<0.001Extent of necrosis

30%30 – 50%> 50%

83% 6%11%

49%24%27%

p<0.001

51%

5959

Acute pancreatitis complications: WON Conservative treatment?

Primary conservative treatment for IPNSystematic review 8 studies (n = 324 patients)

Mouli et al, GE 2013; 144: 333-340

Success 64% (51 – 78)

Need for percutaneous drainage, necrosectomy or surgery

26% (15 – 37)

Mortality 12% (6 – 18)

Conservative management without necrosectomy is a successful approach for 64% of patients with IPN

6060

Acute pancreatitis complications: WON

Endoscopic intervention: How?

Step-up approach1st step:EUS-guided transmural drainage (ETD)

– initial access to the necrotic cavity– catheter/stents drainage of the collection

with infected fluid & necrosis– trans-gastric access >> transduodenal access

Baron TH, Clin GE Hepatol 2012; 10: 1202-1207

6161

Acute pancreatitis complications: WON

Endoscopic intervention: How?

Step-up approach2nd step: endoscopic transmural necrosectomy (ETN)

when no improvement or deterioration after ETD to remove infected necrotic debris

Baron TH, Clin GE Hepatol 2012 Seewald et al, GIE 2005

6262

A 25 y.o. man with acute alcoholic NP

1st step: ETD1 DP stent + NGC catheter

Infected WON

6363

2nd step: ETN2 DP stents + 1 UF SEMS + NGC catheter

6464

Acute pancreatitis complications: WON

Step-up approach (PANTER trial)Primary open necrosectomy vs Step-up-approach

n = 45 n = 43

1) percutaneous or endoscopic drainage

2) no clinical improvement after 72h VARD

3) failure open necrosectomy

Van Santvoort HC et al, NEJM 2010; 362: 1491-1502

Bakker OJ et al, JAMA 2012

6565

Acute pancreatitis complications: WON

Step-up approach (PANTER trial)Primary open necrosectomy vs Step-up-approach

n = 45 n = 43

Van Santvoort HC et al, NEJM 2010; 362: 1491-1502

outcomes significantly better in the step-up group compared to the open surgery group

Time since onset 29 d 30 d NS

New onset MOF or systemic complications

42% 12% p=0.001

Major complications or death 69% 40% p=0.006

Death 16% 19% NS

6666

Acute pancreatitis complications: WON

Results of endoscopic necrosectomyRetrospective series > 20 patients

N Median delay to drainage (d)

Success (%)

Complications (%)

Overall mortality

(%)

Gardner (2011)* 104 63 91 14 5.8

Seifert (2009) 93 41 68 26 19

Coelho (2008) 56 35 87 20 3.5

Lopes (2007) 26 – 94 8 0

Voermans (2007) 25 84 95 40 0

Papachristou (2007) 53 49 77 49 6

Baron (2002) 43 – 72 37 –

TOTAL 400 35 – 84 81.5% 26% 6.7%

Median procedures / patient: 3.2 *BMI > 32 = risk factor for failed ETN

6767

Acute pancreatitis complications: WON

Endoscopicnecrosectomy

New onset OF 0% 50% p=0.03

Pancreatic fistula 10% 70% p=0.002

Major compl. or death 20% 80% p=0.03

Mortality 10% 40% NS

suggests superiority of endoscopic necrosectomy over surgical necrosectomy for infected necrosis

Bakker OJ et al, JAMA 2012; 307: 1053-1061

vs VARD or opensurgical necrosectomy

n = 10 n = 10

6868

Acute pancreatitis complications: WON

Multigate way approach

Baron HT et al, Clin GE Hepatol 2012; 10: 1202-1207

Combined TM and percutaneous drainage

6969

What’s new for both pancreatic pseudocysts and WON?

Forward-view scope Can be used for “difficult” localizations…

Combination access devices One-step drainage

Stents Fully covered SEMS with wide flanges

69Yamamoto N et al, GIE 2013; 77: 809-814

7070

New stents

7171From M. Giovannini

7272

Treatment algorithm for SAP

van Brunschot S et al, Clin GE Hepatol 2012

7373

Treatment algorithm for SAP

van Brunschot S et al, Clin GE Hepatol 2012

74