Spontaneous Bacterial Peritonitis (SBP) & Hepatic EncephalopathyKimberly Treier

PharmD Candidate 2016

2 May 2016

SBP- Definition

Ascitic fluid infection without evident intra-abdominal surgicically treatable source

Usually occurs in patients with cirrhosis and ascites

SBP - Pathogenesis

Overgrowth of intestinal flora (usually E. coli) and spread outside into mesentery and lymph nodes (translocation) Cirrhosis decreases intestinal motility Increased permeability

OR from other infections (e.g. UTI, cellulitis) Lymphatic rupture of contaminated lymph d/t portal

hypertension (bacteriascites) Microbes overwhelm host defenses

Cirrhosis = acquired immune deficiency (decreased compliment capability)

Spontaneous Bacterial Peritonitis

Spontaneous Bacterial Peritonitis

SBP – Risk Factors

Advanced cirrhosis Ascitic fluid total protein <1g/dL Prior SBP Serum total bilirubin >2.5 mg/dL Variceal hemorrhage Malnutrition PPI use Ascitic fluid total protein <1.5 g/dL +

Child-Pugh score ≥9 points + serum bilirubin ≥3 gm/dL OR Plasma creatinine ≥1.2 mg/dL, BUN ≥25 mg/dL or plasma Na ≤130

mEq/L

SBP – Signs and Symptoms

Fever (most common) Abdominal pain/tenderness

Altered mental status

Diarrhea Paralytic ileus* Hypotension* Hypothermia* Abnormal laboratory values (e.g. leukocytosis, metabolic acidosis,

azotemia)

*Advanced infection

SBP - Diagnosis

Clinical presentation Ascitic fluid positive for bacteria Ascitic fluid absolute polymorphonuclear leukocyte

(PMN) count ≥250 cells/mm3

Exclusion of secondary causes

SBP - Treatment

Ascitic PMN <250 cells/mm3 + Signs/symptoms of infection:

Empiric antibiotic therapy, e.g. ceftotaxime 2 g IV q8h, while awaiting cultures

American Association for the Study of Liver Disease (2012)

SBP - Treatment

Ascitic PMN ≥250 cells/mm3 + Community-acquired setting + absence of β-lactam antibiotic

exposure: Empiric antibiotic therapy, e.g. IV third generation cephalosporin,

preferably cefotaxime 2 g IV q8h

Nosocomial setting ± in the presence of recent β-lactam antibiotic exposure: Empiric antibiotic therapy based on local susceptibility testing of bacteria

in patients with cirrhosis

Can substitute with ofloxacin 400 mg PO BID in inpatients without prior exposure to quinolones, vomiting, shock, grade ≥II hepatic encephalopathy, or SCr >3 mg/dL

American Association for the Study of Liver Disease (2012)

SBP - Treatment

Ascitic PMN ≥250 cells/mm3 + High suspicion of secondary peritonitis

Test for protein, LDH, glucose, gram stain, carcinoembryonic antigen and alkaline phosphatase (distinguish between SBP and secondary peritonitis)

Computed tomographic scanning

Nosocomial setting ± recent β-lactam antibiotic exposure ± atypical organism or atypical clinical response to treatment Follow-up paracentesis after 48 hours of treatment

Clinical suspicion of SBP, SCr >1 mg/dL, BUN >30 mg/dL or tBili >4 mg/dL Albumin 1.5 g/kg within 6 hours and 1 g/kg on day 3

American Association for the Study of Liver Disease (2012)

SBP - Prophylaxis

Cirrhosis and GI bleeding IV ceftriaxone or norfloxacin BID x 7 days

Survived an episode of SBP Long-term norfloxacin 400 mg QD (or SMX/TMP)

Cirrhosis and ascites but no GI bleeding + ascitic fluid protein <1.5 g/dL + renal insufficiency (SCr ≥1.2 mg/dL, BUN ≥25 mg/dL or serum Na+ ≤130 mE/L) or hepatic failure (Child-Pugh ≥9 points + bilirubin ≥3 mg/dL) Long-term norfloxacin (or SMX/TMP)

Daily (vs. intermittent) antibiotic dosing recommendedAmerican Association for the Study of Liver Disease (2012)

Hepatic Encephalopathy - definition

Hepatic Encephalopathy - pathogenesis

Drugs Benzodiazepines Narcotics Alcohol

Increased ammonia production, absorption or Brain entry Excess dietary protein intake GI bleeding Infection Electrolyte disturbances Constipation Metabolic alkalosis

Hepatic Encephalopathy - pathogenesis

Dehydration Vomiting/diarrhea Hemorrhage Diuretics Large volume paracentesis

Portosystemic shunting Radiographic or surgically placed shunts Spontaneous shunts

Vascular occlusion Hepatic vein thrombosis Portal vein thrombosis

Primary hepatocellular carcinoma

Hepatic Encephalopathy – ClassificationUnderlying Disease

Hepatic encephalopathy occurring in the setting of…Type A Acute liver failureType B Portal-systemic bypass with no intrinsic hepatocellular

diseaseType C Cirrhosis with portal hypertension or systemic shunting

Severity of ManifestationsMinimal Abnormal results on psychometric or neurophysiologic testing

without clinical manifestationsGrade I Changes in behavior, mild confusion, slurred speech,

disordered sleepGrade III Marked confusion (stupor), incoherent speech, sleeping but

arousableGrade IV Coma, unresponsive to pain

Hepatic Encephalopathy - Diagnosis

History and physical exam Cognitive and neuromuscular impairments

Laboratory tests Ammonia, glucose, urea, electrolytes

Psychometric tests Changes in mental function Number connection test (NCT; Reitan Test), Psychometric Hepatic

Encephalopathy Score (PHES)

Electrophysiology tests E.g. electroencephalogram (EEG)

Imaging MRI, CT

Hepatic Encephalopathy – Differential Diagnosis

Reye syndrome GI bleeding Renal disease UTI with urease-producing microbe (e.g. P. mirabilis) Shock Severe muscle exertion Metabolic abnormalities Salicylate intoxication

Hepatic Encephalopathy - Treatment

Hepatic Encephalopathy - Treatment

Hepatic Encephalopathy - Treatment

References

Runyon BA. Pathogenesis of spontaneous bacterial peritonitis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed 27 April 2016.

Runyon BA. Spontaneous bacterial peritonitis in adults: Clinical manifestations. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed 27 April 2016.

Runyon BA. Spontaneous bacterial peritonitis in adults: Diagnosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed 27 April 2016.

Runyon BA. Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed 27 April 2016.

Runyon BA. Practice Guideline: Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012. American Association for the Study of Liver Diseases. (2012). p. 1-96.

Ferenci P. Hepatic encephalopathy: Pathogenesis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed 27 April 2016.

Ferenci P. Hepatic encephalopathy in adults: Clinical manifestations and diagnosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed 28 April 2016.

Leise MD, Poterucha JJ, Kamath PS, et al. Management of Hepatic Encephalopathy in the Hospital. Mayo Clin Proc. 2014; 89(2): 241-253. PMC4128786