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8 Severe Acute Pancreatitis

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  • 1. Severe acute pancreatitis S_c7 © Academy for Infection Management 2006 (All Rights Reserved)
  • 2. History
    • 33-year-old male
    • Alcohol binge: vodka
    • Awake and conversant
    • Severe abdominal pain, vomiting, dyspnoea
  • 3. 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/mm 3
    • Arterial blood gases:
      • pH 7.30, PaCO 2 32, PaO 2 58, BE -5
  • 4. Which evaluations would you perform to determine if the patient has severe pancreatitis?
    • C-reactive protein
    • Computed tomography (CT) scan
    • Severity scores
      • Ranson score
      • Glasgow (Imrie) score
      • APACHE II or III score
      • Balthazar score
  • 5. Initial tests and treatment
    • Fluid resuscitation
    • Chest radiography
    • CT
    • Calculation of Ranson score (at 48 hours)
  • 6. The patient has severe pancreatitis by CT criteria
    • Central necrosis of the pancreas >30%
    • Peripancreatic oedema and inflammation
  • 7. Ranson score: a pancreatitis-specific severity of illness score
    • Age >55 years
    • WBC >16 000/mm 3
    • 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
    • PaO 2 <60 mm Hg
    • Base deficit <-4 mEq/L
    • Fluid sequestration >6 L
    Present on admission During the first 48 hours
  • 8. The patient has eight positive Ranson criteria
    • SGOT >250 IU/L
    • LDH >350 IU/L
    • WBC count >16 000/mm 3
    • PaO 2 <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 Figure reproduced with permission from Arch Surg
  • 9. Would you start prophylactic antibiotics?
    • No
    • Yes, with …
      • Ceftriaxone?
      • Gentamicin plus metronidazole?
      • Imipenem/cilastatin or meropenem?
      • Ciprofloxacin plus metronidazole?
      • Other?
    • Yes, plus fluconazole
  • 10. 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
  • 11. What is this patient’s risk of developing infection?
    • <10%
    • 10%–30%
    • 30%–50%
    • >50%
  • 12. 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;91:433–438 Beger et al. Pancreatology 2003;3:93–101 Buchler et al. Ann Surg 2000;232:619–625
  • 13. Pancreatic infections almost never occur before Day 7 The peak incidence is at Day 14 Day 14 Day 7 Day 21 Should prophylaxis be given? for the entire at-risk period? Beger et al. Gastroenterology 1986;91:433 –43 8 99% of data 95% of data 68% of data
  • 14. How long would you administer antibiotic prophylaxis?
    • Would not administer prophylaxis
    • 1 week
    • 2 weeks
    • 3 weeks
    • Until ICU discharge
    Should prophylaxis be administered for the entire risk period?
  • 15. 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) use
    Isenmann et al. Gastroenterology 2004;126:997
  • 16. Results: intention-to-treat analysis (n=114) 11 17 Need for operation (%) 7 5 Mortality (%) 23 22 Extra-pancreatic infection (%) 9 12 Infected necrosis (%) Placebo Ciprofloxacin/ metronidazole
  • 17. 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 days
      • Dellinger et al. Ann Surg (in press)
  • 18. Prophylactic antibiotics for severe acute pancreatitis: trial results
      • Dellinger et al. Ann Surg (in press)
    0.80 18 20 Mortality 0.48 20 26 Surgical intervention 0.41 12 18 Pancreatic/peri pancreatic infection p-value Placebo % Meropenem % Outcome
  • 19. The downside of prolonged antibiotic prophylaxis
    • Allergy
    • Expense
    • Resistance
    • Superinfection
  • 20. Prophylactic antibiotics for severe acute pancreatitis
    • Recovery of resistant bacteria
    p<0.0001 Isenmann et al. Gastroenterology 2004;126:997
  • 21. What antibiotic regimen was prescribed initially?
    • This patient was NOT started on antibiotic prophylaxis
  • 22. The patient’s condition improves
    • Resolution of leukocytosis
    • Resolution of pain
    • Oral intake resumed
  • 23. The patient develops multiple organ dysfunction syndrome
    • Day 16
    • New fever and leukocytosis
    • Increased abdominal distention
    • ARDS
      • Low V T ventilation
      • PEEP
    • Renal dysfunction
    • What do you do now?
  • 24. Repeat CT scan shows a large peripancreatic fluid collection Small amount of still-perfused pancreas
  • 25. What action(s) should be taken now?
    • Continue to observe
    • Microbiological sampling
    • Repeat CT scan with fine-needle aspiration
    • Operate
  • 26. What specimen(s) would you collect?
    • None
    • Blood
    • Sputum
    • Peripancreatic fluid (fine-needle aspiration)
  • 27. Incidence of infected pancreatitis when sought by fine-needle aspiration 98 89 Accuracy (%) 98 93 Neg. pred. value (%) 100 83 Pos. pred. value (%) 100 90 Specificity (%) 97 88 Sensitivity (%) > Week 1 All
  • 28. 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
  • 29. Microbiology of infected pancreatic necrosis (%) Fernandez-del Castillo et al. Ann Surg 1998;228:676–684 Buchler et al. Ann Surg 2000;232:619–626 10 Not reported Mixed 6 17 Candida spp. 4 2 Anaerobes 36 26 Gram-negative 46 55 Gram-positive Buchler 2000 Fernandez-del Castillo 1998
  • 30. 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
  • 31. Outcome
    • Fever and leukocytosis resolve
    • Organ dysfunction resolves
    • Renal function improves
      • Creatinine stabilises at ~2.0 mg/dL
    • Patient recovers
  • 32. Key learning points
    • Most patients (~85%) with acute pancreatitis do not develop severe disease
    • Determination of severity of illness provides prognostic information and can guide therapy
    • Antimicrobial prophylaxis does not prevent secondary infection in severe acute pancreatitis, but does increase risk of resistant pathogens if infection does occur
    • Antibiotics may be withheld until needed for therapy
  • 33. 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