What are the next steps for a patient who remains restless despite receiving midazolam (Benzodiazepine) and fentanyl (Opioid analgesic)?

Management of Restlessness Despite Midazolam and Fentanyl

For a patient who remains restless despite receiving midazolam and fentanyl, increase the dose of midazolam by giving a bolus dose equal to or double the hourly infusion rate, followed by doubling the infusion rate if two bolus doses are required within an hour. 1

Assessment of Potential Causes

Before escalating sedation, assess for reversible causes of restlessness:

• Evaluate for pain that may be inadequately controlled
• Check for hypoxia, which can occur in up to 92% of patients receiving midazolam and fentanyl combination 2
• Rule out urinary retention and constipation 1
• Consider delirium as a potential cause of agitation

Medication Management Algorithm

1. Optimize Current Regimen

• For midazolam:

  • Administer a bolus dose equal to or double the hourly infusion rate
  • Give bolus doses every 5 minutes as required 1
  • If patient receives two bolus doses within an hour, double the infusion rate 1
  • Maximum dose: No specified dose limit during symptom management 1

• For fentanyl:

  • Ensure pain is adequately controlled
  • If receiving continuous infusion, give a bolus dose of twice the hourly infusion dose 1
  • Administer IV bolus doses every 15 minutes as required 1
  • If patient receives two bolus doses within an hour, double the infusion rate 1

2. If Restlessness Persists After Optimization

For delirium or persistent agitation despite optimized midazolam and fentanyl:

• Add haloperidol:

  • 0.5-1 mg orally at night and every 2 hours as required
  • Increase dose in 0.5-1 mg increments as needed (maximum 10 mg daily, or 5 mg daily in elderly patients)
  • For severe distress: consider higher starting dose (1.5-3 mg) 1

• Alternative for patients unable to swallow:

  • Levomepromazine: 12.5-25 mg subcutaneously as starting dose, then hourly as required
  • Maintain with subcutaneous infusion of 50-200 mg over 24 hours 1

3. Consider Alternative Sedatives

• Propofol is an alternative sedative for patients who:
  • Are already comfortable on a stable propofol infusion
  • Have physicians familiar with using propofol for sedation 1
  • May benefit from reduced mortality risk compared to midazolam (28-day mortality: 25.5% vs 30.8%) 3

Monitoring and Safety Considerations

• Monitor oxygen saturation continuously with pulse oximetry due to high risk of hypoxemia (92% incidence) when combining midazolam and fentanyl 2
• Provide supplemental oxygen if needed for comfort 1
• Ensure availability of personnel skilled in airway management 2
• Have naloxone readily available to reverse opioid effects if respiratory depression occurs 1
• Have flumazenil available to reverse benzodiazepine effects if needed 1

Important Caveats

• The combination of midazolam and fentanyl produces a potent drug interaction with high risk for hypoxemia and apnea 2
• Respiratory depression is more likely in patients with underlying respiratory disease 1
• Rapid withdrawal of midazolam and fentanyl after prolonged use can lead to withdrawal syndrome, including seizures 4
• Paradoxical excitement can occur with midazolam, which may worsen agitation 1
• Chest wall rigidity can occur with fentanyl, especially at higher doses or with rapid administration 1

By following this structured approach, you can effectively manage restlessness in patients receiving midazolam and fentanyl while minimizing adverse effects and optimizing patient comfort.