This chapter will review the pharmacotherapy for management of severe acute pancreatitis and liver failure according to the American College of Gastroenterology and American Association for the Study of Liver Diseases guidelines.
Severe acute pancreatitis
Definition
Pancreatitis associated with hypovolemia, organ failure, or local complications including necrosis, abscess, or pseudocyst.
Management
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Fluid resuscitation
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Isotonic crystalloid 250–500 mL/h
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Caution in cardiovascular and/or renal disease
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Aggressive intravenous hydration most beneficial first 12–24 h
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Pain control
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Intravenous (IV) hydromorphone 0.1–0.4 mg q10min as needed (PRN)
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IV fentanyl 20–50 mcg q10min PRN
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Endoscopic retrograde cholangiopancreatography (ERCP)
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Indicated in selected acute pancreatitis with concomitant acute cholangitis
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Postprocedure rectal nonsteroidal anti-inflammatory (NSAID) suppositories: indomethacin 100 mg ×1 immediately after ERCP
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Antibiotics
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Indicated in extrapancreatic infection (e.g., cholangitis, bloodstream infections, pneumonia, urinary tract infections) and infected necrosis
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Empiric antibiotic therapy for extrapancreatic infection: see Chapter 11
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Empiric antibiotic therapy for infected necrosis ( Table 9.1 )
Table 9.1
Empiric Antibiotic Therapy for Infected Necrosis
Data from Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol . 2013;108(9):1400–1415.
ANTIBIOTICS
STANDARD DOSING (IV)
RENAL DOSING
COMMENTS
Carbapenems
Doripenem (Doribax)
250 mg, 500 mg
500 mg q8h
CrCl 30–50: 250 mg q8h
CrCl 11–29: 250 mg q12h
HD: 250 mg q24h a ; if PSA, 500 mg q12h ×1 day then 500 mg q24h a
Similar spectrum of activity as meropenem except more potent in vitro activity against PSA than meropenem
Ertapenem (Invanz)
1 g
1 g q24h
CrCl ≤30 and HD: 500 mg daily
Compared to imipenem/meropenem, less active against PSA, acinetobacter, enterococci, and Pcn-resistant pneumococci
Imipenem-cilastatin (Primaxin)
250 mg, 500 mg
500 mg to 1 g q6h
CrCl 60–89: 500–750 mg q8h
CrCl 30–59: 500 mg q6–8h
CrCl 15–29 and HD: 500 mg q12h a
CrCl <15 without HD: avoid use
Imipenem: consider decreasing dose in patients <70 kg to prevent seizures
Meropenem (Merrem)
500 mg, 1 g
1 g q8h
CrCl 26–50: same dose q12h
CrCl 10–25: half dose q12h
CrCl <10: half dose q24h
HD: 500 mg q24h a
Similar spectrum of activity as imipenem; slightly lower risk of seizures than imipenem
Antipseudomonal Cephalosporins
Cefepime (Maxipime)
1 g, 2 g
2 g q8–12h
CrCl 30–60: 2 g q12–24h
CrCl <30: 1–2 g q24h
HD: 0.5–1 g q24h a
Must be combined with metronidazole for anaerobic coverage
10% cross sensitivity with Pcn allergy
Ceftazidime (Fortaz)
500 mg, 1 g, 2 g
2 g q8h
CrCl 31–50: 2 g q12h
CrCl 16–30: 2 g q24h
CrCl ≤15 & HD: 1 g q24h a
Fluoroquinolones
Ciprofloxacin (Cipro)
200 mg, 400 mg
400 mg q12h
CrCl 5–29 and HD: 400 mg q24h a
Must be combined with metronidazole for anaerobic coverage
ADR: tendonitis/tendon rupture, CNS effects, peripheral neuropathy, hepatotoxicity, crystalluria, photosensitivity, QT prolongation
CI: myasthenia gravis, children due to musculoskeletal toxicity
Levofloxacin (Levaquin)
250 mg, 500 mg, 750 mg
750 mg q24h
CrCl 20–49: 750 mg q48h
CrCl 10–19: 750 mg ×1, then 500 mg q48h
HD: 750 mg ×1, then 500 mg q48h a
Moxifloxacin (Avelox)
400 mg
400 mg q24h
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Nitroimidazole
Metronidazole
500 mg q8h
Give post HD on HD days
250mg, 500mg
Notes:
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Common pathogens in infected necrosis: Escherichia coli, Klebsiella, Enterococcus, Pseudomonas
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Routine use of prophylactic antibiotics in severe acute pancreatitis or sterile necrosis is not recommended
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Carbapenems, quinolones, high-dose cephalosporins, and metronidazole penetrate pancreatic necrosis
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Discontinue empiric antibiotics if pancreatic culture negative
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Treatment duration for confirmed infection up to 14 days
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