Severe acute pancreatitis

S_c7

© Academy for Infection Management 2006 (All Rights Reserved)

History

• 33-year-old male• Alcohol binge: vodka• Awake and conversant• Severe abdominal pain, vomiting, dyspnoea

Physical and laboratory examinations

• Temperature 38.1°C• Pulse 96 bpm, respirations 20/min• Blood pressure 110/70 mmHg• Abdomen tender, distended, quiet• Amylase 3500 IU/L• Lipase 1100 IU/L• AST >250 IU/L• LDH >350 IU/L • WBC count 16 000/mm3 • Arterial blood gases:

– pH 7.30, PaCO2 32, PaO2 58, BE -5

Which evaluations would you perform to determine if the patient has severe pancreatitis?

1. C-reactive protein

2. Computed tomography (CT) scan

3. Severity scoresa. Ranson score

b. Glasgow (Imrie) score

c. APACHE II or III score

d. Balthazar score

Initial tests and treatment

• Fluid resuscitation • Chest radiography• CT• Calculation of Ranson score (at 48 hours)

The patient has severe pancreatitisby CT criteria

Central necrosis of the pancreas >30%Peripancreatic oedema and inflammation

Ranson score: a pancreatitis-specific severity of illness score

• Age >55 years • WBC >16 000/mm3 • Glucose >200 mg/dL • LDH >350 IU/L • AST >250 IU/L

• Haematocrit decrease >10% points

• BUN increase >5 mg/dL • Serum calcium <8 mg/dL

• PaO2 <60 mm Hg

• Base deficit <-4 mEq/L • Fluid sequestration >6 L

Present on admission During the first 48 hours

The patient has eight positive Ranson criteria

• SGOT >250 IU/L• LDH >350 IU/L • WBC count >16 000/mm3

• PaO2 <60 mm Hg

• Base deficit <-4 mEq/L• Net fluid sequestration >6 L• Calcium concentration • <8 mg/dL• Haematocrit decrease • >0 percentage points

The predicted mortality rate for a Ranson score of 8 is 60%Eachempati et al. Arch Surg 2002

0

10

20

30

40

50

60

70

80

90

100

1–2 3–4 5–6 7–8 > 8

Ranson score

Mo

rta

lity

(%

)

Figure reproduced with permission from Arch Surg

Would you start prophylactic antibiotics?

1. No

2. Yes, with …a. Ceftriaxone?

b. Gentamicin plus metronidazole?

c. Imipenem/cilastatin or meropenem?

d. Ciprofloxacin plus metronidazole?

e. Other?

3. Yes, plus fluconazole

Penetration of pancreatic tissue and pancreatic juice by antimicrobial agents

• Poor– Aminoglycosides– Vancomycin

• Variable– Penicillins– Cephalosporins

• Good– Carbapenems– Metronidazole– Quinolones – Fluconazole

Bassi et al. Antimicrob Agents Chemother 1994;38:830–836

What is this patient’s risk of developing infection?

1. <10%

2. 10%–30%

3. 30%–50%

4. >50%

Incidence of peripancreatic infection after acute pancreatitis

All episodes 3%–7%

Any pancreatic necrosis 20%–70%

Pancreatic necrosis >30% 15%–30%

Pancreatic necrosis >50% 40%–70%

Beger et al. Gastroenterology 1986;91:433–438Beger et al. Pancreatology 2003;3:93–101Buchler et al. Ann Surg 2000;232:619–625

Day 14Day 7 Day 21

Should prophylaxis be given? for the entire at-risk period?

Pancreatic infections almost never occur before Day 7

The peak incidence is at Day 14

Beger et al. Gastroenterology 1986;91:433–438

99% of data

95% of data

68% of data

How long would you administer antibiotic prophylaxis?

1. Would not administer prophylaxis

2. 1 week

3. 2 weeks

4. 3 weeks

5. Until ICU discharge

Should prophylaxis be administered for the entire risk period?

Prophylactic antibiotics for severe acute pancreatitis

First double-blind, placebo-controlled trial

• 114 patients enrolled, 76 with necrosis• Entry criteria

– C-reactive protein >150, or– Necrosis on contrast-enhanced CT, and– <72 hours from onset of pain

• Ciprofloxacin plus metronidazole vs placebo• All patients treated 14–21 days unless

converted to open-label (therapeutic) useIsenmann et al. Gastroenterology 2004;126:997

Results: intention-to-treat analysis (n=114)

Ciprofloxacin/metronidazole

Placebo

Infected necrosis (%) 12 9

Extra-pancreaticinfection (%)

22 23

Mortality (%) 5 7

Need for operation (%) 17 11

Prophylactic antibiotics for severe acute pancreatitis: double-blind, placebo-controlled trial

• 100 patients with severe acute pancreatitis– Contrast-enhanced CT

• multiple peripancreatic fluid collections by non-contrast CT, plus

• C-reactive protein >120 mg/dL, or

• Multiple organ dysfunction score >2 points• Meropenem 1 g q8h vs placebo• Primary end-point

– Pancreatic/peripancreatic infection within 42 daysDellinger et al. Ann Surg (in press)

Prophylactic antibiotics for severe acute pancreatitis: trial results

OutcomeMeropenem

%Placebo

%p-

value

Pancreatic/peripancreatic infection

18 12 0.41

Surgical intervention 26 20 0.48

Mortality 20 18 0.80

Dellinger et al. Ann Surg (in press)

The downside of prolonged antibiotic prophylaxis

• Allergy• Expense• Resistance• Superinfection

Prophylactic antibiotics for severe acute pancreatitis

• Recovery of resistant bacteria

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Antibiotic group Placebo group

p<0.0001

Isenmann et al. Gastroenterology 2004;126:997

What antibiotic regimen was prescribed initially?

This patient was NOT started on antibiotic prophylaxis

The patient’s condition improves

• Resolution of leukocytosis• Resolution of pain• Oral intake resumed

The patient develops multiple organ dysfunction syndrome

• Day 16• New fever and

leukocytosis• Increased abdominal

distention• ARDS

– Low VT ventilation– PEEP

• Renal dysfunction• What do you do now?

Repeat CT scan shows a large peripancreatic fluid collection

Small amount ofstill-perfused pancreas

What action(s) should be taken now?

1. Continue to observe

2. Microbiological sampling

3. Repeat CT scan with fine-needle aspiration

4. Operate

What specimen(s) would you collect?

1. None

2. Blood

3. Sputum

4. Peripancreatic fluid (fine-needle aspiration)

Incidence of infected pancreatitis when sought by fine-needle aspiration

All > Week 1

Sensitivity (%) 88 97

Specificity (%) 90 100

Pos. pred. value (%) 83 100

Neg. pred. value (%) 93 98

Accuracy (%) 89 98

Results of culture and susceptibility testing

• Patient underwent CT-guided fine-needle aspiration– Peripancreatic fluid

• Proteus mirabilis (pan-sensitive)

• Blood– No growth

• Urine– No growth

• Sputum– No growth

Microbiology of infected pancreatic necrosis (%)

Fernandez-del Castillo

1998

Buchler

2000

Gram-positive 55 46

Gram-negative 26 36

Anaerobes 2 4

Candida spp. 17 6

Mixed Not reported 10

Fernandez-del Castillo et al. Ann Surg 1998;228:676–684Buchler et al. Ann Surg 2000;232:619–626

Therapy

• Formal operative debridement and drainage• Only one operation required• Meropenem x 14 days• Choice based on tissue penetration • Dosage reduction for creatinine clearance

35 mL/min

Outcome

• Fever and leukocytosis resolve• Organ dysfunction resolves• Renal function improves

– Creatinine stabilises at ~2.0 mg/dL

• Patient recovers

Key learning points

1. Most patients (~85%) with acute pancreatitis do not develop severe disease

2. Determination of severity of illness provides prognostic information and can guide therapy

3. Antimicrobial prophylaxis does not prevent secondary infection in severe acute pancreatitis, but does increase risk of resistant pathogens if infection does occur

4. Antibiotics may be withheld until needed for therapy

AIM core principles

• Select the most appropriate antibiotic depending on the patient, risk factors, suspected infection and resistance

• Recognise that prior antimicrobial administration is a risk factor for the presence of resistant pathogens

• Ensure adequate containment of the infection source by removing contaminated devices and draining/debriding infectious tissue