Pancreatitis - It’s all about the timing

Jan J. De

Waele

Jan.DeWaele@UGent.be

@CriticCareDoc

Faculty/Presenter Disclosure

• Faculty: Jan DE WAELE

• Relationships with commercial interests: – Grants/Research Support: Sr. Clinical Researcher Fund Scientific

Research

– Speakers Bureau/Honoraria*: Accelerate, Bayer Healthcare, Grifols, MSD

– Consulting Fees*: AtoxBio, Bayer Healthcare, Cubist, MSD, Pfizer

– Other: none

* Fees and honoraria paid to institution

Background

• Acute pancreatitis management has changed

• Better understanding of pathophysiology

• Many paradigms no longer valid

Less is more

Early

• Inflammation

• MODS

• Often fulminant

Late

• (Peri)pancreatic infection

• Severity of disease variable

Intra-abdominal hypertension

Intra-abdominal hypertension?

Disease

• Pancreatic edema

• Peripancreatic fluid collections

• Ascites

• Ileus

Therapy

• Resuscitation induced edema

• Pancreatic tissue

• Intra-abdominal

• Abdominal wall

Epidemiology

De Waele JJ et al., World J Surg 2009, 33: 1128-33.

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Pupelis, 2002 De Waele, 2005 Keskinen, 2007 Chen, 2008 Al-Bahrani, 2008

IAH ACS

Consequences of increased IAP

IAH

Systemic

Shock

AKI

Respiratory insufficiency

Local

Intestinal hypoperfusion

Pancreatic necrosis

Intestinal ischemia

Bacterial translocation

Pancreatic infection

Intra-abdominal hypertension

Prevention

• Fluid management

• Nasogastric decompression

Target for intervention

• Percutaneous drainage of ascites

• Surgical intervention when necessary

Percutaneous drainage

• Prospective study in

acute pancreatitis

• ‘Routine therapy’ vs.

PCD

• n=110

• Improved APACHE II

scores at day 2 and 5

• Improved mortality

Sun ZX, World J Gastroenterol 2006 12: 5068-

70.

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35

D1 D2 D3

IAP

1800mL

Surgical decompression

Decompressive midline

laparotomy

• Effective in reducing

IAP

• Open abdomen and

risk for infection

• No debridement!

• Leave the peritoneum

intact when possible

Antibiotics in pancreatitis

Timing of infection

Besselink MG et al., Br J Surg 2009, 96: 267-273.

Mechanisms of infection

Bacterial translocation from the gut

• Ileus

• Intra-abdominal hypertension, low abdominal perfusion pressure

Direct contamination, e.g. GI perforation

Hematogenous Reflux from the

duodenum

AB prophylaxis studies

First author n Treatment in intervention group

Blinded Setting

Sainio 1995 60 Cefuroxime No Single center

Pederzoli 1993 74 Imipenem No Single center

Delcenserie 1996 23 Ceftazidime, amikacin + metronidazole

No Single center

Nordback 2001 58 Imipenem No Single center

Isenmann 2004 114 Ciprofloxacin + metronidazole

Double blind Multicenter

Dellinger 2007 100 Meropenem Double blind Multicenter

Rokke 2007 73 Imipenem No Multicenter

Xue 2009 56 Imipenem No Single center

Yang 2009 54 Imipenem No Single center

Barreda 2009 58 Imipenem No Single center

Garcia Barrassa 2009 41 Ciprofloxacin Double blind Single center

Antibiotic prophylaxis meta analysis

Jiang K, World J Gastroenterol 2012 18: 279-84.

Study quality and treatment effect

RCTs of antibiotic prophylaxis

de Vries AC, Pancreatology 2007 7: 531-

538.

Probiotics in SAP?

Probiotics

Reduction of bacterial overgrowth

Restoration of GI barrier function

Modulation of the immune system

Reduction of infectious complications

GI surgery

Pancreatitis

Besselink, MG. Lancet 2008 9613:651-659

Probiotics in SAP: PROPATRIA trial

Besselink, MG. Lancet 2008 9613:651-

659

Bowel rest and nutrition

Nutritional support in severe AP

EN in SAP

Tolerance of EN may be problematic

Abdominal pain

Nausea and vomiting

Ileus

Compression of duodenum by inflamed pancreas

Nasogastric feeding often possible – nasojejunal

when failure

Nutritional support in severe AP

EN preferred over PN

Well tolerated

• Pain scores similar

• Caloric targets reached

• Nitrogen balance comparable

Lower complication rate

• Infections

• MODS

Lower mortality (in some

studies)

Lower cost

The Python study

Bakker, OJ. N Engl J Med 2014 21:1983-

1993

The Python study

Bakker, OJ. N Engl J Med 2014 21:1983-

1993

The Python study

Bakker, OJ. N Engl J Med 2014 21:1983-

1993

Nutritional support in pancreatitis summary

• EN better than PN – optimal timing unclear

• Avoid early PN

• NG feeding can be attempted

NJ in case of symptoms or extensive necrosis

• Think of intra-abdominal hypertension

• If PN is used, consider glutamine

• Potential benefit of special EN formulations

Surgery for infection

Conservative vs interventional management

van Santvoort, HC. Gastroenterology 2011 4:1254-1263

Conservative patients (62%)

• Most had peripancreatic or <30% pancreatic necrosis

• 1/6 had organ failure

• 3% documented infection

• Mortality 7%

Intervention patients (38%)

• 75% pancreatitis necrosis

• 73% organ failure

• 78% infected necrosis

• Mortality 27%

Timing of intervention and outcome

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0-14d 14-29d >29d

Mortality Complications

van Santvoort, HC. Gastroenterology 2011 4:1254-1263

Source control in pancreatitis

van Santvoort HC et al., N Engl J Med

2010, 362: 1491-502.

PANTER study results

Outcome

van Santvoort HC et al., N Engl J Med

2010, 362: 1491-502.

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Major complicationsor death

Mortality New onset MODS

Open

Step-up

Predicting the need for surgery

Hollemans, RA. Ann Surg 2015

Predicting the need for surgery

Hollemans, RA. Ann Surg 2015

In conclusion – at the bedside

• IAP monitoring – targeted therapy – surgery if

persistent

• No antibiotics without infection – no probiotics

• Enteral nutrition – early – nasogastric if

tolerated

• Step-up approach in case of infection – though

failure of percutaneous drainage may be

predicted

Jan.DeWaele@UGent.be

@CriticCareDoc