2025 PACUPrep BCCCP Preparatory Course Ascites & Spontaneous Bacterial Peritonitis Foundational Principles of Ascites & SBP: Epidemiology, Pathophysiology, and Risk Factors
Ascites & Spontaneous Bacterial Peritonitis: Principles

Foundational Principles of Ascites & Spontaneous Bacterial Peritonitis

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Lesson Objective

Describe foundational principles of ascites and spontaneous bacterial peritonitis (SBP), focusing on epidemiology, pathophysiology, and risk factors relevant to critical care pharmacists.

1. Epidemiology and Impact

The development of ascites marks the critical transition from compensated to decompensated cirrhosis, a turning point that dramatically worsens prognosis. Spontaneous bacterial peritonitis (SBP) is a frequent and life-threatening complication in this population, contributing significantly to both short- and long-term mortality.

Key Data Points

  • The annual incidence of new-onset ascites in patients with compensated cirrhosis is 5–10%. Its appearance causes the 5-year survival rate to plummet from approximately 80% to just 30%.
  • SBP complicates 10–30% of hospital admissions for patients with cirrhosis and ascites, with a one-year mortality rate approaching 40%.
  • In the outpatient setting, the incidence of SBP is lower but still significant, at around 3.5% per year for decompensated cohorts.
  • Multidrug-resistant (MDR) pathogens are a growing concern, accounting for 20–25% of community-acquired SBP cases and rising to 35–40% in nosocomial SBP.
  • Timeliness of diagnosis is critical: delaying diagnostic paracentesis by more than 12 hours after admission increases in-hospital mortality by approximately 3.3% for every hour of delay.
Table 1. Incidence and Outcomes in Cirrhosis by Patient Setting
Patient Setting Ascites Incidence SBP Incidence One-Year Mortality
Compensated Outpatient 5–10% per year N/A ~20%
Decompensated Outpatient N/A ~3.5% per year ~40%
Hospitalized with Cirrhosis N/A 10–30% per admission ~40%
Clinical Pearl: Early Paracentesis is Key Expand/Collapse Icon

Prompt diagnostic paracentesis (ideally within 12 hours of admission) is a proven mortality-reducing intervention. The presence of coagulopathy (elevated INR) or thrombocytopenia is common in cirrhosis and should not be considered a contraindication to this vital procedure, as the risk of clinically significant bleeding is very low.

2. Pathophysiology of Ascites Formation

Ascites formation is a complex process driven by severe portal hypertension and profound splanchnic vasodilation. This combination creates a state of effective arterial underfilling, which activates powerful neurohormonal systems that command the kidneys to retain sodium and water, eventually leading to the accumulation of fluid in the peritoneal cavity.

Pathophysiology of Ascites Formation Flowchart A flowchart showing the cascade from portal hypertension to ascites. Portal hypertension causes splanchnic vasodilation, leading to decreased effective arterial blood volume. This activates RAAS, SNS, and ADH, causing sodium and water retention, which results in ascites. The Cascade to Ascites Formation Portal Hypertension Splanchnic Arteriolar Vasodilation (NO-mediated) ↓ Effective Arterial Blood Volume Neurohormonal Activation RAAS Activation SNS Activation ADH Release
Figure 1. Pathophysiology of Ascites. Portal hypertension initiates a cascade of splanchnic vasodilation, perceived by the body as systemic hypotension. This triggers the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), and antidiuretic hormone (ADH) release, all of which promote intense sodium and water retention by the kidneys, ultimately overwhelming the capacity of the lymphatic system and causing fluid to accumulate in the peritoneum.
Clinical Pearl: Diuretic Dosing & Albumin Support Expand/Collapse Icon

Diuretics: The cornerstone of medical management is combination therapy with spironolactone and furosemide, typically started at a 100:40 mg ratio. The goal is a weight loss of about 0.5 kg/day in patients without peripheral edema. Titrate every 3–5 days to a maximum of 400 mg spironolactone and 160 mg furosemide.

Albumin: For large-volume paracentesis (LVP), where >5 liters of fluid are removed, post-paracentesis circulatory dysfunction (PPCD) is a major risk. Administering intravenous albumin (6–8 grams per liter of fluid removed) significantly reduces the incidence of PPCD, hepatorenal syndrome, and mortality.

3. Pathogenesis of Spontaneous Bacterial Peritonitis

SBP is an infection of the ascitic fluid that occurs without an evident intra-abdominal source. It arises from gut-derived bacteria that translocate across a compromised intestinal barrier into ascitic fluid, which has severely impaired local immune defenses.

Key Pathways

  • Bacterial Translocation: Portal hypertension leads to intestinal bacterial overgrowth, gut dysbiosis, and increased mucosal permeability. This allows bacteria and their byproducts (e.g., endotoxin) to escape the gut lumen and seed the mesenteric lymph nodes and, ultimately, the peritoneal cavity.
  • Impaired Ascitic Fluid Defenses: The ascitic fluid in cirrhosis is a prime culture medium. A low total protein concentration (<1.5 g/dL) is a major risk factor because it correlates with low levels of complement and other opsonins, which are crucial for phagocytosis and bacterial clearance.
  • Common Pathogens: The most frequent culprits are enteric Gram-negative bacteria, such as Escherichia coli and Klebsiella species. However, Gram-positive cocci (e.g., Staphylococcus, Enterococcus) are increasingly identified, especially in nosocomial cases.
Key Point: The PMN Threshold Expand/Collapse Icon

The diagnostic criterion for SBP is an ascitic fluid absolute polymorphonuclear (PMN) leukocyte count of ≥250 cells/mm³. Treatment should be initiated immediately upon reaching this threshold, without waiting for culture results. A significant number of cases are “culture-negative neutrocytic ascites,” which have the same prognosis and are treated identically to culture-positive SBP.

4. Risk Factors for SBP

The risk of developing SBP is not uniform among patients with ascites. It can be stratified based on the characteristics of the ascitic fluid itself, a history of prior infections, comorbid conditions, and certain medications.

1. Clinical and Laboratory Factors

  • Low Ascitic Fluid Protein: A concentration <1.5 g/dL is the single strongest predictor, increasing SBP risk by at least five-fold.
  • Prior SBP: Patients who have survived one episode of SBP have a 70% chance of recurrence within one year if they do not receive antibiotic prophylaxis.
  • Recent Upper GI Bleeding: Variceal hemorrhage increases SBP risk due to mucosal ischemia and enhanced bacterial translocation.

2. Comorbidities

  • Renal Dysfunction: A baseline serum creatinine ≥1 mg/dL is a significant risk factor.
  • Advanced Liver Disease: Indicated by severe hyponatremia (serum Na⁺ ≤130 mmol/L) or high bilirubin.
  • Other Conditions: Diabetes mellitus and congestive heart failure also increase risk.

3. Medications

  • Proton Pump Inhibitors (PPIs): Data are conflicting, but some studies suggest that by reducing gastric acid, PPIs may promote bacterial overgrowth and increase SBP risk. Their use should be regularly re-evaluated.
  • Nonselective β-blockers: While essential for variceal prophylaxis, they may worsen circulatory dysfunction and increase mortality risk in patients with refractory ascites.
Clinical Pearl: Secondary Prophylaxis Expand/Collapse Icon

After an initial episode of SBP, long-term secondary prophylaxis is mandatory. Daily norfloxacin 400 mg (or ciprofloxacin/trimethoprim-sulfamethoxazole) dramatically reduces the one-year recurrence rate from ~70% to ~20%. Prophylaxis should be continued indefinitely unless the patient undergoes liver transplantation or the ascites resolves completely.

5. Clinical Presentation

The signs and symptoms of ascites can be subtle initially but become more obvious as fluid accumulates. SBP often presents with classic signs of peritonitis, but its presentation can be occult, especially in critically ill or elderly patients, where it may manifest only as a change in mental status or hemodynamic stability.

Ascites Findings

  • Physical Exam: Shifting dullness on percussion is the most sensitive physical sign. A fluid wave and flank dullness are more specific but appear later. Ultrasound can detect as little as 100 mL of fluid.
  • Tense Ascites: Large volumes can cause significant abdominal distention, leading to dyspnea from diaphragmatic elevation, early satiety, and umbilical hernias.

SBP Presentation

  • Classic Triad: Fever, diffuse abdominal pain, and rebound tenderness. However, all three are present in less than half of patients.
  • Occult Presentation: In the ICU or in elderly patients, SBP may present without localizing signs. The only clues may be worsening hepatic encephalopathy, acute kidney injury, hypotension, or unexplained acidosis.
  • Laboratory Clues: Peripheral leukocytosis, rising serum creatinine, and an elevated procalcitonin (>0.5 ng/mL) can suggest an underlying infection.
Clinical Pearl: Low Threshold for Tapping Expand/Collapse Icon

Maintain a very low threshold for performing a diagnostic paracentesis. Any cirrhotic patient with ascites who presents with a fever, abdominal pain, altered mental status, renal dysfunction, or any other sign of clinical deterioration should be tapped. Up to 30% of patients diagnosed with SBP do not report any abdominal pain.

References

  1. Biggins SW et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 AASLD guidance. Hepatology. 2021;74(2):1014–1048.
  2. Runyon BA. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49(6):2087–2107.
  3. Marciano S et al. Spontaneous bacterial peritonitis in cirrhosis: incidence, outcomes, and treatment strategies. Hepat Med Evid Res. 2019;11:13–22.
  4. Popoiag RE, Fierbințeanu-Braticevici C. Spontaneous bacterial peritonitis: update on diagnosis and treatment. Rom J Intern Med. 2021;59(4):345–350.
  5. Sort P et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and SBP. N Engl J Med. 1999;341(6):403–409.
  6. Kim JJ et al. Delayed paracentesis is associated with increased in-hospital mortality in patients with SBP. Am J Gastroenterol. 2014;109(9):1436–1442.
  7. Tandon P, Garcia-Tsao G. Renal dysfunction is the most important predictor of mortality in cirrhotic SBP. Clin Gastroenterol Hepatol. 2011;9(3):260–265.
  8. Bernardi M et al. Albumin in decompensated cirrhosis: new concepts and perspectives. Gut. 2020;69(6):1127–1138.
  9. Miura K et al. Proton pump inhibitor use is associated with SBP in liver cirrhosis. Intern Med. 2014;53(10):1037–1042.
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