1. Assessing Appropriateness of Life-Sustaining Therapies

Continuously reevaluating invasive or supportive therapies against evolving patient goals is a cornerstone of ethical critical care. When curative measures conflict with advance directives or patient and family wishes, the focus must shift from life prolongation to symptom control and comfort.

A. Curative vs. Comfort-Focused Goals

The primary intent of care dictates the aggressiveness of pharmacotherapy. This table contrasts the two primary approaches.

B. Vasopressors

The use of vasopressors must directly reflect patient goals. They may be used to support organ function for a trial period, provide temporary support for symptom relief, or extend life if consistent with advance directives. Their use should be re-evaluated daily.

C. Antimicrobials

Empiric and definitive antimicrobial use should balance infection control against the discomfort or burden of therapy when comfort is the primary goal. Initiate broad-spectrum therapy for suspected sepsis if curative intent or symptom relief (e.g., fever reduction) is desired. De-escalation should be assessed at 48–72 hours based on hemodynamic stability, pathogen data, and biomarker trends.

D. Mechanical Ventilation

Decisions to initiate, continue, or withdraw mechanical ventilation must align with patient directives. If the prolongation of life via mechanical support offers no curative or comfort benefit, its use may be limited or withdrawn in a structured, symptom-managed process.

2. Sedation and Analgesia for Comfort-Focused Care

In comfort-focused care, analgosedation prioritizes opioid-driven relief of pain and dyspnea before adding sedatives. Agent selection and titration must account for organ dysfunction to maximize comfort and minimize adverse effects.

A. Opioids for Pain and Dyspnea

Opioids like morphine and fentanyl are first-line agents for managing pain and the sensation of dyspnea in critically ill patients. They act as mu-receptor agonists, modulating the central perception of these distressing symptoms.

• Initiation: Start with low, as-needed doses (e.g., morphine 2–5 mg IV q2h PRN; fentanyl 25–50 mcg IV q1h PRN). Continuous infusions may be used for persistent symptoms.
• Titration: Increase doses by 25–50% based on validated symptom scales (e.g., Behavioral Pain Scale for pain, numeric rating for dyspnea).
• PK Adjustments: In renal impairment, the active metabolite of morphine accumulates; fentanyl is preferred. In hepatic dysfunction, reduce doses of both agents and monitor closely.

B. Sedative Agents

When opioids alone are insufficient to manage anxiety or agitation, sedative agents are added. Non-benzodiazepine sedatives are generally preferred to minimize delirium.

3. Pharmacokinetic and Pharmacodynamic Adjustments

Critical illness and organ support therapies profoundly alter drug clearance and distribution. Individualizing dosing is essential to avoid toxicity while ensuring comfort.

A. Renal Impairment

Renal dysfunction necessitates dose reduction for many drugs. Decrease doses for renally excreted opioids (e.g., morphine metabolites) and hydrophilic antibiotics (e.g., beta-lactams, vancomycin). Remember to account for drug removal by continuous renal replacement therapies (CRRT), which can clear low-molecular-weight, unbound drugs.

B. Hepatic Dysfunction

For patients with liver failure, prefer agents with organ-independent metabolism (e.g., remifentanil, cisatracurium) or those with predictable clearance (e.g., hydromorphone). Standard agents like propofol and dexmedetomidine should be used with caution, often requiring dose reduction and careful monitoring.

4. De-escalation and Withdrawal Protocols

Structured tapering of life-sustaining or symptom-modifying drugs is critical to prevent withdrawal symptoms and rebound distress. All de-escalation plans must be tailored to comfort-oriented goals and communicated clearly among the care team.

A. Antimicrobial De-escalation Pathways

A systematic approach to antimicrobial de-escalation is a key component of antibiotic stewardship and goal-concordant care.

5. Fluid and Nutritional Management

In comfort-focused care, hydration and nutrition should be provided to relieve the sensations of thirst and hunger without exacerbating symptoms like edema or dyspnea.

A. Goals of Hydration in Comfort Care

The primary goal is patient comfort, not physiologic correction. This often means providing minimal effective fluids (e.g., 500–1,000 mL/day) to alleviate thirst while avoiding the negative consequences of fluid overload. Whenever possible, meticulous mouth care, ice chips, or small sips of water are preferred over large-volume IV infusions, as they directly address the sensation of a dry mouth with less systemic impact.

6. Interprofessional Collaboration and Decision Support

Ensuring goal-concordant pharmacotherapy is a team effort. Clinical pharmacists play a key role in medication reviews, protocol development, and providing real-time decision support. Regular case conferences involving physicians, nurses, pharmacists, and palliative care specialists are essential for aligning the care plan with the patient’s evolving goals.