Severe acute  pancreatitis S_c7 ©  Academy for Infection Management 2006 (All Rights Reserved)
History <ul><li>33-year-old male </li></ul><ul><li>Alcohol binge: vodka </li></ul><ul><li>Awake and conversant </li></ul><...
Physical and laboratory examinations <ul><li>Temperature 38.1 ° C </li></ul><ul><li>Pulse 96 bpm, respirations 20/min </li...
Which evaluations would you perform to determine if the patient has severe pancreatitis? <ul><li>C-reactive protein </li><...
Initial tests and treatment <ul><li>Fluid resuscitation  </li></ul><ul><li>Chest radiography </li></ul><ul><li>CT </li></u...
The patient has severe pancreatitis by CT criteria <ul><li>Central necrosis of the pancreas >30% </li></ul><ul><li>Peripan...
Ranson score: a pancreatitis-specific severity of illness score <ul><li>Age >55 years  </li></ul><ul><li>WBC >16 000/mm 3 ...
The patient has eight positive Ranson criteria <ul><li>SGOT >250 IU/L </li></ul><ul><li>LDH >350 IU/L  </li></ul><ul><li>W...
Would you start prophylactic antibiotics? <ul><li>No </li></ul><ul><li>Yes, with … </li></ul><ul><ul><li>Ceftriaxone? </li...
Penetration of pancreatic tissue and pancreatic juice by antimicrobial agents <ul><li>Poor </li></ul><ul><ul><li>Aminoglyc...
What is this patient’s risk of developing infection? <ul><li><10% </li></ul><ul><li>10%–30% </li></ul><ul><li>30%–50% </li...
Incidence of peripancreatic infection after acute pancreatitis <ul><li>All episodes   3%–7% </li></ul><ul><li>Any pancreat...
Pancreatic infections almost never occur before Day 7   The peak incidence is at Day 14 Day 14 Day 7 Day 21 Should prophyl...
How long would you administer  antibiotic prophylaxis? <ul><li>Would not administer prophylaxis </li></ul><ul><li>1 week <...
Prophylactic antibiotics for severe acute pancreatitis First double-blind, placebo-controlled trial <ul><li>114 patients e...
Results: intention-to-treat analysis (n=114) 11 17 Need for operation (%) 7 5 Mortality (%) 23 22 Extra-pancreatic infecti...
Prophylactic antibiotics for severe acute pancreatitis: double-blind, placebo-controlled trial <ul><li>100 patients with s...
Prophylactic antibiotics for severe acute pancreatitis: trial results <ul><ul><li>Dellinger et al.  Ann Surg (in press) </...
The downside of prolonged antibiotic prophylaxis <ul><li>Allergy </li></ul><ul><li>Expense </li></ul><ul><li>Resistance </...
Prophylactic antibiotics for severe acute pancreatitis <ul><li>Recovery of resistant bacteria </li></ul>p<0.0001 Isenmann ...
What antibiotic regimen was prescribed initially? <ul><li>This patient was NOT started on antibiotic prophylaxis </li></ul>
The patient’s condition improves <ul><li>Resolution of leukocytosis </li></ul><ul><li>Resolution of pain </li></ul><ul><li...
The patient develops multiple organ dysfunction syndrome <ul><li>Day 16 </li></ul><ul><li>New fever and leukocytosis </li>...
Repeat CT scan shows a large peripancreatic fluid collection Small amount of still-perfused pancreas
What action(s) should be taken now? <ul><li>Continue to observe </li></ul><ul><li>Microbiological sampling  </li></ul><ul>...
What specimen(s)  would you collect? <ul><li>None </li></ul><ul><li>Blood </li></ul><ul><li>Sputum </li></ul><ul><li>Perip...
Incidence of infected pancreatitis when sought by fine-needle aspiration 98 89 Accuracy (%) 98 93 Neg. pred. value (%) 100...
Results of culture and susceptibility testing <ul><li>Patient underwent CT-guided fine-needle aspiration </li></ul><ul><ul...
Microbiology of infected  pancreatic necrosis (%) Fernandez-del Castillo et al. Ann Surg 1998;228:676–684 Buchler et al. A...
Therapy <ul><li>Formal operative debridement and drainage </li></ul><ul><li>Only one operation required </li></ul><ul><li>...
Outcome <ul><li>Fever and leukocytosis resolve </li></ul><ul><li>Organ dysfunction resolves </li></ul><ul><li>Renal functi...
Key learning points <ul><li>Most patients (~85%) with acute pancreatitis do not develop severe disease </li></ul><ul><li>D...
AIM core principles <ul><li>Select the most appropriate antibiotic depending on the patient, risk factors, suspected infec...
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8 Severe Acute Pancreatitis

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8 Severe Acute Pancreatitis

  1. 1. Severe acute pancreatitis S_c7 © Academy for Infection Management 2006 (All Rights Reserved)
  2. 2. History <ul><li>33-year-old male </li></ul><ul><li>Alcohol binge: vodka </li></ul><ul><li>Awake and conversant </li></ul><ul><li>Severe abdominal pain, vomiting, dyspnoea </li></ul>
  3. 3. Physical and laboratory examinations <ul><li>Temperature 38.1 ° C </li></ul><ul><li>Pulse 96 bpm, respirations 20/min </li></ul><ul><li>Blood pressure 110/70 mmHg </li></ul><ul><li>Abdomen tender, distended, quiet </li></ul><ul><li>Amylase 3500 IU/L </li></ul><ul><li>Lipase 1100 IU/L </li></ul><ul><li>AST >250 IU/L </li></ul><ul><li>LDH >350 IU/L </li></ul><ul><li>WBC count 16 000/mm 3 </li></ul><ul><li>Arterial blood gases: </li></ul><ul><ul><li>pH 7.30, PaCO 2 32, PaO 2 58, BE -5 </li></ul></ul>
  4. 4. Which evaluations would you perform to determine if the patient has severe pancreatitis? <ul><li>C-reactive protein </li></ul><ul><li>Computed tomography (CT) scan </li></ul><ul><li>Severity scores </li></ul><ul><ul><li>Ranson score </li></ul></ul><ul><ul><li>Glasgow (Imrie) score </li></ul></ul><ul><ul><li>APACHE II or III score </li></ul></ul><ul><ul><li>Balthazar score </li></ul></ul>
  5. 5. Initial tests and treatment <ul><li>Fluid resuscitation </li></ul><ul><li>Chest radiography </li></ul><ul><li>CT </li></ul><ul><li>Calculation of Ranson score (at 48 hours) </li></ul>
  6. 6. The patient has severe pancreatitis by CT criteria <ul><li>Central necrosis of the pancreas >30% </li></ul><ul><li>Peripancreatic oedema and inflammation </li></ul>
  7. 7. Ranson score: a pancreatitis-specific severity of illness score <ul><li>Age >55 years </li></ul><ul><li>WBC >16 000/mm 3 </li></ul><ul><li>Glucose >200 mg/dL </li></ul><ul><li>LDH >350 IU/L </li></ul><ul><li>AST >250 IU/L </li></ul><ul><li>Haematocrit decrease >10% points </li></ul><ul><li>BUN increase >5 mg/dL </li></ul><ul><li>Serum calcium <8 mg/dL </li></ul><ul><li>PaO 2 <60 mm Hg </li></ul><ul><li>Base deficit <-4 mEq/L </li></ul><ul><li>Fluid sequestration >6 L </li></ul>Present on admission During the first 48 hours
  8. 8. The patient has eight positive Ranson criteria <ul><li>SGOT >250 IU/L </li></ul><ul><li>LDH >350 IU/L </li></ul><ul><li>WBC count >16 000/mm 3 </li></ul><ul><li>PaO 2 <60 mm Hg </li></ul><ul><li>Base deficit <-4 mEq/L </li></ul><ul><li>Net fluid sequestration >6 L </li></ul><ul><li>Calcium concentration </li></ul><ul><li><8 mg/dL </li></ul><ul><li>Haematocrit decrease </li></ul><ul><li>>0 percentage points </li></ul>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. 9. Would you start prophylactic antibiotics? <ul><li>No </li></ul><ul><li>Yes, with … </li></ul><ul><ul><li>Ceftriaxone? </li></ul></ul><ul><ul><li>Gentamicin plus metronidazole? </li></ul></ul><ul><ul><li>Imipenem/cilastatin or meropenem? </li></ul></ul><ul><ul><li>Ciprofloxacin plus metronidazole? </li></ul></ul><ul><ul><li>Other? </li></ul></ul><ul><li>Yes, plus fluconazole </li></ul>
  10. 10. Penetration of pancreatic tissue and pancreatic juice by antimicrobial agents <ul><li>Poor </li></ul><ul><ul><li>Aminoglycosides </li></ul></ul><ul><ul><li>Vancomycin </li></ul></ul><ul><li>Variable </li></ul><ul><ul><li>Penicillins </li></ul></ul><ul><ul><li>Cephalosporins </li></ul></ul><ul><li>Good </li></ul><ul><ul><li>Carbapenems </li></ul></ul><ul><ul><li>Metronidazole </li></ul></ul><ul><ul><li>Quinolones </li></ul></ul><ul><ul><li>Fluconazole </li></ul></ul>Bassi et al. Antimicrob Agents Chemother 1994;38:830–836
  11. 11. What is this patient’s risk of developing infection? <ul><li><10% </li></ul><ul><li>10%–30% </li></ul><ul><li>30%–50% </li></ul><ul><li>>50% </li></ul>
  12. 12. Incidence of peripancreatic infection after acute pancreatitis <ul><li>All episodes 3%–7% </li></ul><ul><li>Any pancreatic necrosis 20%–70% </li></ul><ul><li>Pancreatic necrosis >30% 15%–30% </li></ul><ul><li>Pancreatic necrosis >50% 40%–70% </li></ul>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. 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. 14. How long would you administer antibiotic prophylaxis? <ul><li>Would not administer prophylaxis </li></ul><ul><li>1 week </li></ul><ul><li>2 weeks </li></ul><ul><li>3 weeks </li></ul><ul><li>Until ICU discharge </li></ul>Should prophylaxis be administered for the entire risk period?
  15. 15. Prophylactic antibiotics for severe acute pancreatitis First double-blind, placebo-controlled trial <ul><li>114 patients enrolled, 76 with necrosis </li></ul><ul><li>Entry criteria </li></ul><ul><ul><li>C-reactive protein >150, or </li></ul></ul><ul><ul><li>Necrosis on contrast-enhanced CT, and </li></ul></ul><ul><ul><li><72 hours from onset of pain </li></ul></ul><ul><li>Ciprofloxacin plus metronidazole vs placebo </li></ul><ul><li>All patients treated 14–21 days unless converted to open-label (therapeutic) use </li></ul>Isenmann et al. Gastroenterology 2004;126:997
  16. 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. 17. Prophylactic antibiotics for severe acute pancreatitis: double-blind, placebo-controlled trial <ul><li>100 patients with severe acute pancreatitis </li></ul><ul><ul><li>Contrast-enhanced CT </li></ul></ul><ul><ul><ul><li>multiple peripancreatic fluid collections by non-contrast CT, plus </li></ul></ul></ul><ul><ul><ul><li>C-reactive protein >120 mg/dL, or </li></ul></ul></ul><ul><li>Multiple organ dysfunction score >2 points </li></ul><ul><li>Meropenem 1 g q8h vs placebo </li></ul><ul><li>Primary end-point </li></ul><ul><ul><li>Pancreatic/peripancreatic infection within 42 days </li></ul></ul><ul><ul><li>Dellinger et al. Ann Surg (in press) </li></ul></ul>
  18. 18. Prophylactic antibiotics for severe acute pancreatitis: trial results <ul><ul><li>Dellinger et al. Ann Surg (in press) </li></ul></ul>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. 19. The downside of prolonged antibiotic prophylaxis <ul><li>Allergy </li></ul><ul><li>Expense </li></ul><ul><li>Resistance </li></ul><ul><li>Superinfection </li></ul>
  20. 20. Prophylactic antibiotics for severe acute pancreatitis <ul><li>Recovery of resistant bacteria </li></ul>p<0.0001 Isenmann et al. Gastroenterology 2004;126:997
  21. 21. What antibiotic regimen was prescribed initially? <ul><li>This patient was NOT started on antibiotic prophylaxis </li></ul>
  22. 22. The patient’s condition improves <ul><li>Resolution of leukocytosis </li></ul><ul><li>Resolution of pain </li></ul><ul><li>Oral intake resumed </li></ul>
  23. 23. The patient develops multiple organ dysfunction syndrome <ul><li>Day 16 </li></ul><ul><li>New fever and leukocytosis </li></ul><ul><li>Increased abdominal distention </li></ul><ul><li>ARDS </li></ul><ul><ul><li>Low V T ventilation </li></ul></ul><ul><ul><li>PEEP </li></ul></ul><ul><li>Renal dysfunction </li></ul><ul><li>What do you do now? </li></ul>
  24. 24. Repeat CT scan shows a large peripancreatic fluid collection Small amount of still-perfused pancreas
  25. 25. What action(s) should be taken now? <ul><li>Continue to observe </li></ul><ul><li>Microbiological sampling </li></ul><ul><li>Repeat CT scan with fine-needle aspiration </li></ul><ul><li>Operate </li></ul>
  26. 26. What specimen(s) would you collect? <ul><li>None </li></ul><ul><li>Blood </li></ul><ul><li>Sputum </li></ul><ul><li>Peripancreatic fluid (fine-needle aspiration) </li></ul>
  27. 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. 28. Results of culture and susceptibility testing <ul><li>Patient underwent CT-guided fine-needle aspiration </li></ul><ul><ul><li>Peripancreatic fluid </li></ul></ul><ul><ul><ul><li>Proteus mirabilis (pan-sensitive) </li></ul></ul></ul><ul><li>Blood </li></ul><ul><ul><li>No growth </li></ul></ul><ul><li>Urine </li></ul><ul><ul><li>No growth </li></ul></ul><ul><li>Sputum </li></ul><ul><ul><li>No growth </li></ul></ul>
  29. 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. 30. Therapy <ul><li>Formal operative debridement and drainage </li></ul><ul><li>Only one operation required </li></ul><ul><li>Meropenem x 14 days </li></ul><ul><li>Choice based on tissue penetration </li></ul><ul><li>Dosage reduction for creatinine clearance 35 mL/min </li></ul>
  31. 31. Outcome <ul><li>Fever and leukocytosis resolve </li></ul><ul><li>Organ dysfunction resolves </li></ul><ul><li>Renal function improves </li></ul><ul><ul><li>Creatinine stabilises at ~2.0 mg/dL </li></ul></ul><ul><li>Patient recovers </li></ul>
  32. 32. Key learning points <ul><li>Most patients (~85%) with acute pancreatitis do not develop severe disease </li></ul><ul><li>Determination of severity of illness provides prognostic information and can guide therapy </li></ul><ul><li>Antimicrobial prophylaxis does not prevent secondary infection in severe acute pancreatitis, but does increase risk of resistant pathogens if infection does occur </li></ul><ul><li>Antibiotics may be withheld until needed for therapy </li></ul>
  33. 33. AIM core principles <ul><li>Select the most appropriate antibiotic depending on the patient, risk factors, suspected infection and resistance </li></ul><ul><li>Recognise that prior antimicrobial administration is a risk factor for the presence of resistant pathogens </li></ul><ul><li>Ensure adequate containment of the infection source by removing contaminated devices and draining/debriding infectious tissue </li></ul>
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