Severe necrotizing pancreatitis

ICU Fellowship Training Radboudumc

Acute pancreatitisPatients with acute pancreatitis

van Dijk SM. Gut 2017;66:2024-2032

Diagnosis

• Abdominal pain consistent with pancreatitis

• Serum amylase and/or lipase at least 3 times upper limit

• Findings consistent with acute pancreatitis on CECT, MRI or ultrasound

Revised Atlanta classification

At least two out of three criteria

Banks PA. Gut 2013;62:102-111

Severity classification

• Mild - no local or systemic complications

• Moderate - local (e.g. peripancreatic fluid collections or systemic complications or transient organ failure < 48 hrs

• Severe - persistent organ failure > 48 hrs

Banks PA. Gut 2013;62:102-111

Aetiology

15%

15%

20%

50%

Gallstones/sludge Alcohol Unknown Rest

• Medication • ERCP • Hypercalcaemia • Hypertriglyceridemia • Surgery • Trauma

Perform EUS later on

Sludge

Severity prediction• APACHE II score

• Ranson score

• Modified Glasgow/Imrie score

• SIRS criteria > 48 hrs

• Bedside Index for the Severity in Acute Pancreatitis

• Harmless in Acute Pancreatitis Score

• CRP

Mainly used to exclude the possibility of severe pancreatitis

Vasudevan S. Pancreas 2018;47:65-71

Treatment acute phase• Fluid resuscitation

• Pain management (no evidence for specific pain protocol)

• Antibiotics and probiotics

• Nutrition

• Endoscopic retrograde cholangiography in biliary pancreatictis

Fluid resuscitation• IAP/APA guidelines suggest using cristalloids in the form

of Ringer’s lactate or other balanced fluids (not confirmed in general ICU setting)

• End-points for early goal-directed therapy unknown - use SvO2, lactate, diuresis, capillary refill etc

% (S

IRS)

or m

g/dl

(CRP

)

-90-60-30

0306090

120

SIRS after 24 hrs CRP after 24 hrs

104

051,5

-84

RL NaCl 0.9%

p = 0.035

p = 0.02

N = 40

Wu BU. Clin Gastroenterol Hepatol 2011;9:710-717

Antibiotics and probiotics prophylaxis

• Aim is to prevent secondary infection of pancreatic or peripancreatic necrosis - result of bacterial translocation

• Antibiotic prophylaxis (several RCT’s) does not prevent secondary infection

• Probiotics increased mortality in a multicentre RCT

Infected pancreatic necrosis

Mortality

Lim CLL. J Gastrointest Surg 2015;19:480-491

Randomized controlled trials

Surgical intervention

Extra-pancreatic infection

Probiotics in predicted severe acute pancreatitis

• Multicentre randomized DB placebo-controlled trial (N = 298)

• Predicted severe acute pancreatitis (AP II ≥ 8, Imrie ≥ 3, CRP > 150 mg/L)

• < 72 hrs of onset of symptoms probiotics vs placebo 2 td for 28 days

• Primary outcome composite of infectious complications during admission and 90-D follow-up

Besselink MGH. Lancet 2008;371:651-659

Probiotics in predicted severe acute pancreatitis

0

7,5

15

22,5

30

Infectious complications Mortality Bowel ischemia

6

16

30

06

28

Placebo ProbioticsP = 0.80 P = 0.01 P = 0.004

Besselink MGH. Lancet 2008;371:651-659

Nutrition

• Enteral nutrition reduces rates of infection, organ failure and mortality compared to parenteral nutrition

• In patients with predicted severe pancreatitis, enteral can be limited to those who have an insufficient oral intake after 3 - 5 days

• Nasogastric feeding is non-inferior to nasojejunal feeding (3 RCT’s)

Mortality

Enteral versus parenteral nutrition in acute pancreatitis

Operative intervention

Al-Omran M. Cochrane Database Syst Rev 2010;1:CD002837

Early enteral feeding in predicted severe acute pancreatitis

• Multicentre randomized trial (N = 208)

• Predicted severe acute pancreatitis (AP II ≥ 8, Imrie ≥ 3, CRP > 150 mg/L)

• Nasoenteric tube feeding < 24 hrs after randomization vs oral diet after 72 hrs with tube feeding if not tolerated

• Primary outcome composite of major infection or death during 6 months follow-up

Bakker OJ. New Engl J Med 2014;371:1983-1993

PYTHON trial

Caloric intake

Bakker OJ. New Engl J Med 2014;371:1983-1993

Early enteral feeding in predicted severe acute pancreatitis

0

7,5

15

22,5

30

Major infection / Death Major infection Mortality

7

2627

11

2530

Early EN On demandP = 0.76 P = 0.87 P = 0.33

Bakker OJ. New Engl J Med 2014;371:1983-1993In the on-demand group 69% tolerated an oral diet

Endoscopic retrograde cholangiography

• Early ERC not effective in patients with predicted mild pancreatitis

• Emergency ERC with sphincterotomy < 24 hrs is indicated in case of concomitant cholangitis

• Routine early ERC with sphincterotomy in predicted severe biliary pancreatitis is controversial

Beyond the early phase

• Imaging

• Infected necrotising pancreatitis

CECT-scan

• In the first 3 - 4 days unreliable for detection of extent of necrosis or presence of collections

• Urgent CECT only in case of suspected abdominal catastrophe including perforation, bleeding and ischemia

• If a patient does not improve after 5 - 7 days CECT is indicated to determine the presence and extent of necrosis

Revised Atlanta criteria

• Interstitial oedematous pancreatitis

• Necrotising pancreatitis

✓ parenchymal

✓ peripancreatic

✓ both

Banks. PA. Gut 2013;62:102-111

“Acute pancreatic fluid collections”

Complications of interstitial oedematous pancreatitis

• Rare

• Usually after > 4 weeks

• Well circumscribed (round/oval)

• Homogenous fluid density

• Well defined wallPancreatic pseudocyst

Necrotizing pancreatitisOnly peripancreatic Both

Only pancreatic

“Acute necrotic collections”Heterogenous with varying density

No definable wall

Walled-off necrosis

• Encapsulation of necrotic tissue

• Usually around 4 - 6 weeks

• Intervention only in case of infection!

• Consider intervention after 6-8 weeks in case of mechanical obstruction or failure to thrive

Heterogenous with liquid/non-liquid density - well defined complete wall

Walled-off necrosis

Outcome acute collections

Acute pancreatitis N = 189

Acute interstitial pancreatitis (36)

Acute necrotic pancreatitis (153)

Acute peripancreatic fluid collection

(N = 8)Pseudocyst

(N = 1)

Acute necrotic collection (143)

23 died 21 resolved collection

WON (N = 84)

8 died 53 intervention 23 conservative

Manrai M. Ann Surg 2018;267:357-363

CECT-scan infected necrosis

• Extraluminal gas in pancreas and peripancreatic tissues

• Positive gram stain/culture after FNA

Infected necrotizing pancreatitis

• Acute necrotic collections or walled-off necrosis become infected in one third of patients

• With proven infection or high clinical suspicion antibiotics are indicated

• Although antibiotics only may be successful, further intervention (catheter drainage / necrosectomy) is usually necessary

Intervention

• Delay intervention until stage of WON

• Catheter drainage followed by necrosectomy if clinically indicated

• Endosonography-guided transgastric necrosectomy may be the preferred technique

Step-up approach

• Multicentre randomized trial (N = 88)

• Necrotizing pancreatitis with confirmed or suspected infection

• Primary open necrosectomy vs step-up approach (percutaneous drainage, minimally invasive retroperitoneal necrosectomy)

• Primary outcome composite of major complications or death

van Santvoort HC. N Engl J Med 2010;362:1491-1502

Step-up approach

0

17,5

35

52,5

70

Major complicateon / Death New MOF Mortality New onset diabetes

161912

40 38

16

40

69

Open necrosectomy Step-up approachP = 0.006 P = 0.002 P = 0.70 P = 0.03

van Santvoort HC. N Engl J Med 2010;362:1491-1502

644 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 84 • NUMBER 8 AUGUST 2017

NECROTIZING PANCREATITIS

Antibiotic therapy may provide a bridge to intervention

atic necrosis. Antibiotics with gram-negative coverage and appropriate penetration such as carbapenems, metronidazole, fl uoroquino-lones, and selected cephalosporins are most commonly used. Meropenem is the antibiotic of choice at our institution. CT-guided fi ne-needle aspiration is often done if suspected infected pancreatic ne-crosis fails to respond to empiric antibiotic therapy. Debridement or drainage. Generally, the diagnosis or suspicion of infected pancreatic necrosis (suggestive signs are high fever, el-evated white blood cell count, and sepsis) warrants an intervention to debride or drain infected pancreatic tissue and control sepsis.21 While source control is integral to the suc-cessful treatment of infected pancreatic ne-crosis, antibiotic therapy may provide a bridge to intervention for critically ill patients by suppressing bacteremia and subsequent sep-sis. A 2013 meta-analysis found that 324 of 409 patients with suspected infected pancre-atic necrosis were successfully stabilized with antibiotic treatment.21,22 The trend toward conservative management and promising out-comes with antibiotic therapy alone or with minimally invasive techniques has lessened the need for diagnostic CT-guided fi ne-needle aspiration.

HemorrhageSpontaneous hemorrhage into pancreatic ne-crosis is a rare but life-threatening complica-tion. Because CT is almost always performed with contrast enhancement, this complica-tion is rarely identifi ed with imaging. The di-agnosis is made by noting a drop in hemoglo-bin and hematocrit. Hemorrhage into the retroperitoneum or the peritoneal cavity, or both, can occur when an infl ammatory process erodes into a nearby artery. Luminal gastrointestinal bleeding can occur from gastric varices arising from splenic vein thrombosis and resulting left-sided por-tal hypertension, or from pseudoaneurysms. These can also bleed into the pancreatic duct (hemosuccus pancreaticus). Pseudoaneurysm is a later complication that occurs when an arterial wall (most commonly the splenic or gastroduodenal artery) is weakened by pan-creatic enzymes.23

FIGURE 4. Treatment of infected walled-off necrosis in the patient shown in Figure 3. Under computed tomographic guidance, 3 large-bore catheters were placed in the left fl ank (arrows).

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 84 • NUMBER 8 AUGUST 2017 645

CHUA AND COLLEAGUES

Prompt recognition of hemorrhagic events and consultation with an interventional ra-diologist or surgeon are required to prevent death.

Infl ammation and abdominal compartment syndromeInfl ammation from necrotizing pancreatitis can cause further complications by blocking nearby structures. Reported complications in-clude jaundice from biliary compression, hy-dronephrosis from ureteral compression, bowel obstruction, and gastric outlet obstruction. Abdominal compartment syndrome is an increasingly recognized complication of acute pancreatitis. Abdominal pressure can rise due to a number of factors, including fl uid collec-tions, ascites, ileus, and overly aggressive fl uid resuscitation.24 Elevated abdominal pressure is associated with complications such as de-creased respiratory compliance, increased peak airway pressure, decreased cardiac preload, hy-potension, mesenteric and intestinal ischemia, feeding intolerance, and lower-extremity isch-emia and thrombosis. Patients with necrotizing pancreatitis who have abdominal compartment syndrome have a mortality rate 5 times higher than patients without abdominal compartment syndrome.25 Abdominal pressures should be monitored using a bladder pressure sensor in critically ill or ventilated patients with acute pancreatitis. If the abdominal pressure rises above 20 mm Hg, medical and surgical interventions should be offered in a stepwise fashion to decrease it. Interventions include decompression by naso-gastric and rectal tube, sedation or paralysis to relax abdominal wall tension, minimization of intravenous fl uids, percutaneous drainage of ascites, and (rarely) surgical midline or subcos-tal laparotomy.

■ ROLE OF INTERVENTIONThe treatment of necrotizing pancreatitis has changed rapidly, thanks to a growing experi-ence with minimally invasive techniques.

Indications for interventionInfected pancreatic necrosis is the primary indication for surgical, percutaneous, or endo-scopic intervention. In sterile necrosis, the threshold for inter-

Infl ammation from necrotizing pancreatitis can cause further complications by blocking nearby structures

FIGURE 5. Further treatment of infected walled-off necrosis in the patient shown in Figures 3 and 4. At 10 weeks after symptom onset and 6 weeks after catheter placement, laparoscopic-assisted debride-ment was done via the catheter sites. Computed tomography without contrast enhancement shows the results of debride-ment. Large drains (arrows) were placed after debridement.

VARDCatheter drainage

Endoscopic necrosectomy

• Multicentre randomized trial (N = 98)

• Necrotizing pancreatitis with confirmed or suspected infection and indication for invasive intervention

• Endoscopic (transluminal drainage, necrosectomy) versus surgical (percutaneous catheter drainage, VARD)

• Primary outcome composite of major complications or death (6 M)

van Brunschot S. Lancet 2018

Endoscopic necrosectomy

0

12,5

25

37,5

50

Major complicateon / Death Mortality

13

45

18

43

Endoscopic SurgicalP = 0.88 P = 0.50

van Brunschot S. Lancet 2018

Decreased incidence of pancreatic fistula and decreased hospital LOS

Candida infection

Hall AM. Crit Care 2013;17:R49

Candida infection

Hall AM. Crit Care 2013;17:R49

Local complications• Acute peripancreatic fluid collection

• Pancreatic pseudocyst

• Acute necrotic collection

• Walled-off necrosis

• Gastric outlet dysfunction

• Splenic and portal vein thrombosis

• Colonic necrosis

Aftercare• Prevention of recurrence

• Exocrine and endocrine insufficiency (19 - 80%)

Prevention of recurrence• In total 17 - 22% recurrence of pancreatitis and 8 - 16%

chronic pancreatitis

• Refrain from alcohol and cigarettes

• Cholecystectomy (severe pancreatitis - wait until recovery or 6 weeks after discharge, mild pancreatitis - during same hospital admission)

%

0

5

10

15

20

Gallstone related complications Recurrent pancreatitis

Same hospital admission Interval after 4 weeks

Mild pancreatitis

0.002 0.03

Conclusion