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.

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.

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.

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.

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.

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.

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.