1. Supportive Measures in Severe Infections

Severe infections frequently lead to respiratory and circulatory failure. Timely mechanical ventilation and hemodynamic support are critical interventions that preserve organ perfusion and improve survival.

A. Mechanical Ventilation: Indications, Modes, and Weaning

Indications

• Refractory hypoxemia (PaO₂/FiO₂ < 150)
• Respiratory muscle fatigue or elevated work of breathing
• Impaired airway protection (e.g., encephalopathy)

Lung-Protective Strategy

• Tidal volume set to 6 mL/kg of predicted body weight
• Maintain plateau pressure < 30 cm H₂O
• Optimize PEEP to recruit alveoli while avoiding overdistension

Weaning

• Conduct daily spontaneous breathing trials (SBTs) with sedation interruption.
• Assess for extubation criteria: PaO₂/FiO₂ > 200, Rapid Shallow Breathing Index (RSBI) < 105 breaths/min/L, hemodynamic stability, and adequate mental status.

B. Hemodynamic Support: Fluid Resuscitation and Vasopressors

Initial Fluid Resuscitation

• Administer 30 mL/kg of a balanced crystalloid solution within the first 3 hours.
• Prefer lactated Ringer’s or Plasma-Lyte over 0.9% saline to reduce the risk of hyperchloremic metabolic acidosis and acute kidney injury (AKI).

Dynamic Fluid Responsiveness Assessment

• Use methods like passive leg raise, pulse pressure variation, or bedside ultrasound to guide fluid administration.
• Continuously monitor for signs of fluid overload, such as pulmonary edema or rising central venous pressure, to avoid iatrogenic harm.

Vasopressor Therapy

• Norepinephrine is the first-line agent; titrate to a mean arterial pressure (MAP) of 65–70 mm Hg.
• Add vasopressin (up to 0.03 U/min) as a catecholamine-sparing agent if needed.
• Consider epinephrine or phenylephrine in refractory shock states.

2. Prevention of ICU-Related Complications

ICU patients receiving antimicrobial therapy are at high risk for thrombosis, stress ulcers, and secondary nosocomial infections. Implementing evidence-based prophylaxis bundles is essential to reduce morbidity.

A. VTE Prophylaxis: Risk Assessment and Pharmacologic Strategies

Key risk factors for venous thromboembolism (VTE) in the ICU include immobility, sepsis, mechanical ventilation, and the presence of central venous catheters.

Monitor anti-Xa levels in patients with obesity or significant renal dysfunction. Routinely check platelet counts to screen for heparin-induced thrombocytopenia (HIT).

B. Stress Ulcer Prophylaxis (SUP)

Indications

• Mechanical ventilation for > 48 hours
• Coagulopathy (platelets < 50,000/mm³ or INR > 1.5)
• History of GI ulcer or bleeding within the past year

Agents

• Proton Pump Inhibitors: Pantoprazole 40 mg IV once daily
• H2-Receptor Antagonists: Famotidine 20 mg IV twice daily

Monitor for potential side effects such as nosocomial pneumonia and Clostridioides difficile infection. Reassess the need for SUP daily and discontinue it as soon as risk factors resolve.

C. Secondary Infection Prevention: Infection Control Bundles

• Ventilator-Associated Pneumonia (VAP) Bundle: Maintain head-of-bed elevation at 30–45°, perform daily sedation interruptions, provide regular oral care with chlorhexidine, and ensure appropriate SUP and DVT prophylaxis.
• Central Line–Associated Bloodstream Infection (CLABSI) Bundle: Use maximal barrier precautions during insertion, apply chlorhexidine for skin antisepsis, and conduct a daily review of line necessity to facilitate prompt removal.

3. Management of Pharmacotherapy-Related Toxicities

Early detection of adverse drug effects and proactive dose optimization are crucial to preventing iatrogenic complications from high-risk antimicrobials in the ICU.

A. Nephrotoxicity: Detection and Dose Adjustment

• Vancomycin: Target an Area Under the Curve (AUC) to MIC ratio of 400–600 mg·h/L, preferably guided by Bayesian software. Monitor serum creatinine (SCr) and vancomycin levels, adjusting the dose if the AUC exceeds 600 or SCr rises significantly.
• Aminoglycosides: Utilize extended-interval dosing to leverage concentration-dependent killing (target Cₘₐₓ/MIC > 8–10) while minimizing toxicity. Aim for trough levels < 2 mg/L.

B. Ototoxicity: Monitoring and Mitigation

Aminoglycosides (e.g., gentamicin, tobramycin) pose the highest risk. For prolonged courses, obtain baseline and weekly audiometry. Clinically assess for vestibular symptoms like vertigo and ataxia. Once-daily dosing and maintaining adequate hydration can help mitigate risk.

C. Additional Common Toxicities

• Cefepime Neurotoxicity: Risk increases when trough concentrations exceed 20 µg/mL, especially in patients with renal impairment. Manifests as encephalopathy, myoclonus, or seizures. Management involves dose reduction or drug discontinuation.
• Linezolid Hematologic Toxicity: Thrombocytopenia is a known risk, particularly with therapy lasting over two weeks. Monitor complete blood counts twice weekly during prolonged courses.

4. Interdisciplinary Goals-of-Care Conversations

Structured, patient-centered communication is essential to ensure that invasive interventions and ongoing critical care align with individual patient goals, values, and overall prognosis.

A. Ethical Frameworks for Invasive Treatments

Decisions should be guided by the core principles of medical ethics: beneficence, nonmaleficence, and patient autonomy. A key consideration is the proportionality of any intervention—whether the potential benefit outweighs the associated burdens for that specific patient.

B. Structured Communication Models

Using a structured model can facilitate difficult conversations. The SPIKES protocol is a widely recognized framework for delivering serious news.

C. Documentation and Continuity

• Early inclusion of palliative care teams can facilitate shared decision-making.
• Clearly document patient values, advance directives, and family meeting outcomes in the electronic health record.
• Use standardized handoff tools to ensure that established goals of care are preserved across shifts and among different clinical disciplines.