1. Respiratory and Hemodynamic Support

DRESS-related pulmonary and vascular injury can precipitate hypoxemic respiratory failure and hemodynamic instability. Early recognition and a protocolized approach to ventilation, sedation, fluids, and vasopressors are essential.

A. Indications for Intubation

• PaO₂/FiO₂ < 200 on high-flow nasal cannula support
• Rising PaCO₂ with arterial pH < 7.30, indicating respiratory muscle fatigue
• Altered mental status jeopardizing airway protection

B. Lung-Protective Ventilation Strategy

• Set tidal volume to 6 mL/kg of predicted body weight.
• Maintain plateau pressure below 30 cm H₂O.
• Individualize Positive End-Expiratory Pressure (PEEP) to optimize alveolar recruitment and oxygenation.
• Consider prone positioning for patients with refractory hypoxemia.

C. Sedation and Analgesia

• Employ an analgesia-first strategy (e.g., fentanyl infusion).
• Use propofol or dexmedetomidine to achieve light sedation (target Richmond Agitation-Sedation Scale [RASS] of –1 to +1).
• Perform daily spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs).
• Reserve benzodiazepines for managing seizures or refractory agitation.

D. Hemodynamic Support

A stepwise approach is crucial, balancing fluid resuscitation against the risk of worsening capillary leak and edema.

2. ICU-Related Prophylaxis

Critically ill DRESS patients carry elevated risks for venous thromboembolism (VTE), stress ulcers, and opportunistic infections. Prophylactic strategies must be tailored to renal function, bleeding risk, and the degree of immunosuppression.

A. Venous Thromboembolism (VTE) Prophylaxis

B. Stress Ulcer Prophylaxis (SUP)

• Indications: Mechanical ventilation for >48 hours, coagulopathy, or shock requiring vasopressors.
• Options: Proton-pump inhibitors (PPIs) like pantoprazole 40 mg IV daily are generally more effective at preventing clinically significant GI bleeding than histamine-2 receptor antagonists (H₂RAs).
• Considerations: H₂RAs may be considered in patients at very high risk for nosocomial pneumonia or C. difficile, though evidence is conflicting.

C. Pneumocystis jirovecii Pneumonia (PJP) Prophylaxis

• Indication: Use of corticosteroids at a dose of ≥20 mg of prednisone-equivalent daily for ≥4 weeks.
• First-line: Trimethoprim-sulfamethoxazole (TMP/SMX), one double-strength tablet orally three times weekly or one single-strength tablet daily.
• Alternatives (for sulfa allergy/intolerance): Atovaquone 1,500 mg PO daily or Dapsone 100 mg PO daily (requires G6PD screening).
• Monitoring: Complete blood count (CBC) for cytopenias and renal function.

3. Management of Iatrogenic Complications

The high-dose and prolonged corticosteroid therapy required for DRESS can drive significant complications, including hyperglycemia, bone loss, and adrenal suppression. Proactive monitoring and management protocols are essential to mitigate these risks.

A. Steroid-Induced Hyperglycemia

• Target: Maintain blood glucose levels between 140–180 mg/dL in critically ill patients.
• Insulin Infusion Protocol:
  • Initiate at a rate of 0.05 units/kg/hour.
  • Perform hourly glucose checks and adjust the infusion rate by 1–2 units/hour according to a validated algorithm.
  • Transition to a subcutaneous basal–bolus insulin regimen once the steroid dose is tapering and the patient resumes consistent enteral intake.

B. Osteoporosis Prevention

• Supplementation: Provide all patients on long-term steroids with calcium 1,000–1,200 mg and vitamin D 800–1,000 IU daily.
• Bisphosphonates: Indicated for patients receiving a prednisone-equivalent of >7.5 mg daily for over 3 months.
  • Oral alendronate 70 mg weekly is a common first choice.
  • IV zoledronic acid 5 mg once yearly is an alternative for patients with malabsorption, oral intolerance, or mucositis.
• Monitoring: Obtain a baseline DEXA scan within 6 months of initiating long-term steroid therapy.

C. Adrenal Suppression Screening

4. Multidisciplinary Goals-of-Care Conversations

The severity and potential for prolonged illness in DRESS necessitate early, structured discussions to align invasive support and immunosuppression with patient values and expected outcomes.

• Identify Candidates Early: Patients with severe multi-organ involvement, an anticipated prolonged ICU stay, or a high and extended steroid burden are candidates for early goals-of-care discussions.
• Use a Communication Framework: Models like SPIKES (Setting, Perception, Invitation, Knowledge, Empathy, Summary) provide a structured approach to these sensitive conversations.
• Pharmacist’s Role: The clinical pharmacist is key to clarifying medication risks and benefits, explaining dosing intensity, and outlining necessary monitoring milestones to the patient and family.
• Document Clearly: All decisions regarding code status, thresholds for escalating or de-escalating immunosuppression, and other care plans must be clearly documented and accessible to the entire care team.
• Involve Ethics: If there is conflict or uncertainty in balancing life-prolonging therapy with quality of life, an ethics consultation should be considered.