emDOCs Podcast – Episode 110: Primary Spontaneous Bacterial Peritonitis

Background:

• End-stage liver disease with cirrhosis and ascites is a major cause of death worldwide.
• Primary spontaneous bacterial peritonitis (SBP) is one of the most common infections in those with cirrhosis and ascites.
• Definition: SBP is an infection of the peritoneal ascitic fluid without an intra-abdominal focus of infection.
• SBP accounts for over 30% of all infections in those with cirrhosis; present in 5-30% of cirrhotic patients admitted with ascites.
• Mortality rates per episode of SBP are 15-40%.
• Older age, recurrent episodes of SBP, hepatorenal syndrome, hepatic encephalopathy, acute kidney injury (AKI), concurrent GI bleeding, and higher MELD scores are predictors of worse outcomes.
• Commonly a monomicrobial infection with gram-negative bacteria like E. coli (50-90% of cases). Infection with gram-positive bacteria and multidrug resistant (MDR) bacteria are becoming more common. One study found that half of infections were community acquired, 25% were nosocomial, and another 25% were healthcare associated.

Risk factors:

• Upper GI bleeding: SBP can occur in up to 25-65% of patients with ascites and GI bleeding.
• Prior episode of SBP: recurrence rate of SBP after the first episode if the patient is not on prophylaxis is close to 70%.
• Others: ascitic protein concentration less than 1.5 g/dL, serum total bilirubin > 2.5 mg/dL, renal disease, serum sodium less than 130, malnutrition, refractory ascites, older age, and endoscopic management of esophageal varices.
• Literature concerning risk with PPIs is controversial.

Presentation:

• Classic presentation is abdominal pain or tenderness, fever, and altered mental status.
• Literature suggests 10-33% of patients are asymptomatic or only have mild symptoms. Clinician sensitivity for SBP based on bedside assessment is between 40-75%.
• Abdominal pain or tenderness is the most common and sensitive finding for SBP (90%), but no specific. Pain/tenderness is typically diffuse but may be subtle
• Fever is less than 40% sensitive, but specificity is over 90%.
  • Mild hypothermia is normal in patients with advanced cirrhosis; consider lowering threshold for fever to 37.8 degrees C.
• Marked hypothermia is specific for SBP (> 90%), and it’s a poor prognostic finding.
• Approximately 50% have altered mental status, but it may be subtle.
• Nausea, vomiting, diarrhea occur in 30-70% of patients.
• Patients can also present with GI bleeding, AKI.
• Critically ill: hypotensive, tachycardic, may be hypothermic, may have paralytic ileus.
• Major takeaway: Consider SBP in any patient who comes into the ED with ascites. Also consider in those with cirrhosis and ascites plus fever, abdominal pain, worsening ascites, fever with no other source, AMS with no other source, GI bleeding.

Diagnostic testing:

• Diagnostic modality of choice is paracentesis to obtain ascitic fluid for cell count and culture.
• Ascites absolute neutrophil count (ANC) of > 250 cells/mm³ is diagnostic.
• Guidelines recommend performing paracentesis in patients with clinical suspicion for SBP or in a patient with cirrhosis and ascites who is being admitted for a complication of cirrhosis.
• One study suggested that each hour of delay in obtaining ascitic fluid was associated with a 3.3% increase in mortality. Paracentesis performed within 12 hours was associated with lower in-hospital mortality and shorter length of stay when compared to paracentesis performed within 12-72 hours (13% compared to 27%).
• Paracentesis is a safe procedure with a low complication rate (< 1%).
• Ultrasound can assist: confirm ascites, evaluate for best site, abdominal wall thickness, blood vessels along needle track.
• Send fluid for cell count and culture. If possible, inoculate the fluid into blood culture bottles (at least 10 mL per bottle). Increases sensitivity to > 90%. Make sure to use a different needle to inoculate the blood culture bottles.
• For the remaining fluid inject 1 mL into a purple top EDTA blood tube for cell count; send 2-3 mL for Gram stain in a red-top tube or sterile urine container.
• May consider sending fluid for total protein and albumin, glucose, and LDH.
• Reagent strips are available.
• Obtain blood cultures.
• May find anemia (GI bleeding, malnutrition, hypersplenism, alcohol use), thrombocytopenia (portal hypertension, hypersplenism), elevated total bilirubin and prothrombin time, hyponatremia (excess water intake), elevated AST and ALT, and elevated creatinine and BUN.
• CRP and procalcitonin have also been studied but should not be used to exclude SBP.
• Imaging with CT is not necessary in all patients, but consider in those with localized tenderness, severe pain, or critical illness.

Coagulopathy and Thrombocytopenia:

• Over 70% of patients with liver dysfunction have thrombocytopenia and/or abnormal coagulation panel testing.
• Literature suggests that patients with cirrhosis have a balanced coagulopathy due to reduced production of procoagulant and anticoagulant factors.
• The overall risk of bleeding with paracentesis is less than 1%, even with platelet counts less than 20,000 to 50,000 and elevated INR (> 8).
• Thrombocytopenia and elevated INR are not contraindications to paracentesis.
• Current guidelines recommend against routine assessment of prothrombin time and platelet count before paracentesis.
• Guidelines also recommend against routinely transfusing blood products to correct coagulation panel abnormalities; transfusion is associated with adverse events and does not reduce the risk of bleeding.

Management:

• Patients can rapidly progress to septic shock and multiorgan failure.
• Administer antibiotics after paracentesis if the patient has abdominal pain/tenderness, altered mental status, temperature > 37.8° C (100° F), or if the ascitic fluid ANC is > 250 cells/mm³
• Mortality increases by 8-10% for every hour delay in antibiotics for patients with cirrhosis and septic shock.
• For antibiotics, utilize local antibiogram.
• Most common first line antibiotic is a third-generation cephalosporin like ceftriaxone 2g IV daily or cefotaxime 2g IV every 8 hours.
  • However, cephalosporins have become less effective; 20-50% of cases are due to MDR organisms.
• More recent data suggest that carbapenems are associated with reduced end organ injury and mortality in patients with nosocomial infections and those who are critically ill.
• In patients with shock, critical illness, end-organ injury, recurrent SBP, or recent hospitalization, administer a broader spectrum agent like a carbapenem (ertapenem, imipenem, meropenem). Piperacillin-tazobactam may also be used in place of the carbapenem.
• There is increasing prevalence of Staphylococcus aureus in patients with nosocomial SBP. If there are risk factors for MRSA or the patient has recent healthcare exposure, add vancomycin or linezolid.
• IV albumin is essential. Renal injury occurs in 30-50% of patients with SBP, and AKI is a major predictor of mortality. The mortality rate increases by 30 to over 50% if AKI is present.
  • A 2013 meta-analysis found IV albumin was associated with 22.3% absolute reduction in risk of developing renal impairment (NNT 5) and a 19.4% absolute reduction in risk of mortality (NNT 6).
  • Dosing is 1.5 g/kg of 20% albumin IV at the time of diagnosis and 1 g/kg IV 48 hours later.

Summary:

• SBP is an infection of the peritoneal ascitic fluid without an intra-abdominal focus of infection.
• Variety of causative organisms, including Gram-negative bacteria, Gram-positive bacteria, and MDR bacteria.
• Consider in any patient with liver disease and abdominal pain, worsening ascites, fever, altered mental status, upper GI bleeding, or if they’re being admitted with ascites.
• Diagnosis requires paracentesis; look for an ascites ANC > 250 cells/mm³.
• US can help determine the best site for paracentesis.
• Patients do not require routine transfusion to correct coagulation panel or platelet abnormalities prior to paracentesis.
• Treatment includes IV antibiotics and albumin.

References