2025 PACUPrep BCCCP Preparatory Course Ascites & Spontaneous Bacterial Peritonitis Advanced Pharmacotherapy of Ascites & SBP in the Critically Ill
Advanced Pharmacotherapy of Ascites & SBP in the Critically Ill

Advanced Pharmacotherapy of Ascites & SBP in the Critically Ill

Objective Icon A target symbol, representing the primary goal of the chapter.

Lesson Objective

Design an evidence-based, escalating pharmacotherapy plan for a critically ill patient with ascites and spontaneous bacterial peritonitis (SBP).

1. Principles of Pharmacotherapy Design

Effective management of ascites and SBP in critically ill patients requires a dynamic, stepwise approach. This involves integrating evidence-based guidelines with patient-specific factors, hemodynamic data, and overarching supportive care goals. Treatment algorithms must be adaptable, allowing for escalation or de-escalation based on clinical response and evolving organ function.

Key Principles

  • Evidence Hierarchy: Base initial therapy on major societal guidelines (AASLD, EASL), followed by evidence from landmark trials, cohort studies, and expert consensus.
  • Escalation Algorithms: Start with first-line agents and titrate or broaden therapy based on predefined endpoints (e.g., weight loss for ascites, PMN count reduction for SBP).
  • Holistic Alignment: Ensure drug choices are compatible with hemodynamic targets and organ support strategies. Avoid nephrotoxins and optimize therapies to maintain perfusion.
  • Multidisciplinary Collaboration: Regularly engage hepatology, nephrology, infectious disease, and critical care teams to review regimens, plan de-escalation, and ensure comprehensive care.
Pearl IconA shield with an exclamation mark. Clinical Pearl: Data-Driven Titration

Use real-time hemodynamic data (e.g., from advanced monitoring or POCUS) when titrating albumin or vasoconstrictors. This allows for a precise balance between improving organ perfusion and avoiding iatrogenic fluid overload, a critical consideration in these fragile patients.

2. Ascites Management

First-line pharmacotherapy combines an aldosterone antagonist with a loop diuretic, titrated to achieve effective natriuresis while closely monitoring renal function and electrolytes. The goal is a weight loss of approximately 0.5 kg/day in patients without peripheral edema and up to 1 kg/day in those with edema.

First-Line Diuretics for Ascites in Cirrhosis
Parameter Spironolactone Furosemide
Mechanism Aldosterone antagonist; counters hyperaldosteronism in the distal nephron. Inhibits Na⁺-K⁺-2Cl⁻ cotransporter in the thick ascending limb of Henle.
Role Initial and cornerstone diuretic therapy. Adjunct to spironolactone for enhanced natriuresis.
Dosing Start 100 mg PO daily. Titrate q3-5 days to max 400 mg/day. Start 40 mg PO daily. Titrate q2-3 days to max 160 mg/day.
Ratio Maintain a 100:40 mg ratio (Spironolactone:Furosemide) to promote K⁺ balance.
Key Monitoring Serum K⁺, creatinine. Watch for hyperkalemia and gynecomastia. Serum Na⁺, K⁺, Mg²⁺, renal function. Watch for hypokalemia and volume depletion.
Pitfall IconA warning triangle with an exclamation mark. Pitfall: Overdiuresis

Aggressive diuresis can precipitate intravascular volume depletion, leading to acute kidney injury (AKI), hyponatremia, and hepatic encephalopathy. If orthostasis or a rapid rise in creatinine occurs, reduce the diuretic dose or switch to alternate-day dosing rather than abrupt cessation. If ascites is refractory, consider large-volume paracentesis or TIPS referral instead of escalating diuretics beyond maximal doses.

3. SBP Antibiotic Therapy

Prompt initiation of empiric antibiotics is critical upon diagnosis of SBP (ascitic fluid polymorphonuclear [PMN] count ≥ 250 cells/mm³). The initial choice is tailored to the likely setting of acquisition, with subsequent adjustment at 48 hours based on clinical response and culture data.

SBP Treatment Algorithm A flowchart showing the decision-making process for treating SBP. It starts with suspected SBP, moves to empiric therapy based on acquisition setting (community vs. healthcare-associated), and then to reassessment at 48 hours for escalation or de-escalation of antibiotics. Suspected SBP (PMN ≥ 250/mm³) Determine Acquisition Setting Community Nosocomial / MDRO Risk Cefotaxime / Ceftriaxone First-line empiric therapy Pip-Tazobactam or Carbapenem Consider Vancomycin/Dapto Reassess at 48 Hours Clinical status & PMN count Culture results
Figure 1: Empiric Antibiotic Selection Algorithm for SBP. Initial antibiotic choice is guided by the setting of acquisition. All patients require reassessment at 48 hours to guide therapy de-escalation (e.g., to oral agents) or escalation for non-responders or resistant pathogens.
Pearl IconA shield with an exclamation mark. Clinical Pearl: Oral Step-Down Therapy

In clinically stable patients with community-acquired SBP who demonstrate a good response to initial IV therapy, consider an early switch to an oral fluoroquinolone (e.g., ofloxacin 400 mg BID) to complete the treatment course. This can facilitate earlier hospital discharge and reduce costs associated with IV therapy.

4. Adjunctive Therapies

In addition to antibiotics, certain adjunctive therapies are crucial for preventing complications like hepatorenal syndrome (HRS) and improving survival, particularly in patients with more severe SBP or established renal dysfunction.

Key Adjunctive Therapies in SBP and HRS
Therapy Indication Dosing Mechanism & Goal
Intravenous Albumin SBP with renal dysfunction (SCr ≥1 mg/dL), hyperbilirubinemia (≥4 mg/dL), or significant azotemia (BUN ≥30 mg/dL). 1.5 g/kg on Day 1,
1.0 g/kg on Day 3.		 Oncotic expansion to prevent intravascular volume depletion and subsequent HRS-AKI.
Terlipressin Established HRS-AKI. 0.5–1 mg IV q4-6h. Titrate to MAP and urine output. Splanchnic vasoconstrictor; reverses arterial vasodilation to improve renal perfusion.
Norepinephrine Alternative to terlipressin for HRS-AKI, especially in an ICU setting. Continuous infusion (0.5–3 mcg/kg/min) to target MAP increase of 10-15 mmHg. Systemic vasoconstrictor; improves effective arterial blood volume and renal perfusion.

5. PK/PD and Organ Dysfunction Adjustments

Critically ill patients with cirrhosis exhibit profound pharmacokinetic (PK) and pharmacodynamic (PD) alterations that necessitate careful dose adjustments.

  • Increased Volume of Distribution (Vd): Ascites and peripheral edema increase the Vd for hydrophilic drugs (e.g., β-lactams). This may require higher loading doses to achieve therapeutic concentrations quickly.
  • Hypoalbuminemia: Low serum albumin increases the free (active) fraction of highly protein-bound drugs (e.g., ceftriaxone, phenytoin), raising the risk of toxicity even at standard total drug concentrations.
  • Renal and Hepatic Dysfunction: Dose adjustments are essential for drugs cleared by the kidneys or liver. Renal replacement therapy (RRT) further complicates dosing, often requiring supplemental doses of antibiotics post-dialysis.
Pearl IconA shield with an exclamation mark. Clinical Pearl: Optimize Time-Dependent Antibiotics

For time-dependent antibiotics like β-lactams (e.g., piperacillin-tazobactam), use extended or continuous infusions. This strategy maximizes the time the drug concentration remains above the minimum inhibitory concentration (T>MIC), which is particularly beneficial for treating infections in high-Vd states like severe ascites and can improve clinical outcomes.

6. Routes of Administration & Delivery Devices

The choice of administration route and delivery device is critical for ensuring drug efficacy and safety in the ICU.

  • Intravenous (IV) Infusions: Vasoactive drugs (norepinephrine, terlipressin) require a dedicated central line lumen and volumetric infusion pump to ensure precise, uninterrupted delivery. Standardized concentrations should be used to minimize errors.
  • Enteral Conversion: Transition from IV to enteral administration as soon as GI function allows. This is common for diuretics (spironolactone, furosemide) and for SBP step-down therapy (oral ofloxacin).
  • Enteral Access Devices: When using nasogastric or other feeding tubes, ensure medications are crushable and compatible. Avoid administering cephalosporin suspensions enterally, as their bioavailability is poor. Consult a pharmacist for appropriate formulations.

7. Monitoring Plan

A systematic monitoring plan is essential to guide therapy, assess response, and detect adverse effects early.

Comprehensive Monitoring Plan
Efficacy Monitoring Safety Monitoring
Ascites:
  • Daily weight (target ~0.5 kg loss/day)
  • Strict intake and output (net fluid balance)
  • Abdominal girth measurement
 Electrolytes & Renal:
  • Daily serum Na⁺, K⁺, Mg²⁺
  • Daily serum creatinine and BUN
  • Urine output (target >0.5 mL/kg/hr)
SBP:
  • Repeat paracentesis at 48 hours (target ≥25% PMN reduction)
  • Clinical signs (fever, abdominal pain)
  • Procalcitonin trends (adjunctive)
 Hemodynamics & Side Effects:
  • Blood pressure (orthostatics with diuretics)
  • Signs of fluid overload (edema, rales)
  • Signs of ischemia with vasoconstrictors

8. Pharmacoeconomic Considerations

Balancing drug acquisition costs with clinical impact is a key aspect of pharmacotherapy. While some first-line agents are inexpensive, high-cost adjunctive therapies can provide significant downstream savings by preventing costly complications.

  • Acquisition Costs: Generic diuretics (spironolactone, furosemide) and antibiotics (cefotaxime) have low acquisition costs. In contrast, albumin and terlipressin represent a high upfront expense.
  • Monitoring Resources: Frequent laboratory monitoring and the potential need for therapeutic drug monitoring (TDM) add to the overall cost and workload.
  • Cost-Effectiveness: The high unit price of albumin is often offset by its proven ability to reduce the incidence of AKI, shorten ICU and hospital length of stay, and decrease mortality. This highlights the importance of considering total episode-of-care costs rather than just initial drug prices.

References

  1. Biggins SW, Angeli P, Garcia-Tsao G, et al. AASLD practice guidance: ascites, SBP, hepatorenal syndrome. Hepatology. 2021;74(2):1014–1048.
  2. Runyon BA. Management of adult patients with ascites due to cirrhosis: update. Hepatology. 2009;49(6):2087–2107.
  3. Sort P, Navasa M, Arroyo V, et al. Albumin reduces renal impairment and mortality in SBP. N Engl J Med. 1999;341(6):403–409.
  4. Navasa M, Follo A, Llovet JM, et al. Oral ofloxacin vs IV cefotaxime in SBP. Gastroenterology. 1996;111(4):1011–1017.
  5. Marciano S, Díaz JM, Dirchwolf M, Gadano A. SBP in cirrhosis: incidence, outcomes, treatment. Hepat Med Evid Res. 2019;11:13–22.
  6. Popoiag RE, Fierbințeanu-Braticevici C. SBP: update on diagnosis and treatment. Rom J Intern Med. 2021;59(4):345–350.
  7. European Association for the Study of the Liver. EASL guidelines: decompensated cirrhosis. J Hepatol. 2018;69(2):406–460.
  8. Angeli P, Ginès P, Wong F, et al. AKI in cirrhosis: ICA consensus. J Hepatol. 2015;62(4):968–974.
  9. Garcia-Martinez R, Caraceni P, Bernardi M, et al. Albumin in cirrhosis: pathophysiology and treatment. Hepatology. 2013;58(4):1836–1846.
  10. Schrier RW, Arroyo V, Bernardi M, et al. Peripheral arterial vasodilation hypothesis. Hepatology. 1988;8(5):1151–1157.
  11. Yang Y, Li L, Qu C, et al. Procalcitonin for SBP diagnosis: meta-analysis. Medicine (Baltimore). 2015;94(49):e2077.
  12. Piano S, Singh V, Caraceni P, et al. Global study: MDR infections in cirrhosis. Dig Liver Dis. 2018;50(1):2–3.
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