FENTANYL 

 1. Introduction

  • Synthetic μ-opioid receptor agonist
  • Highly lipophilic → rapid CNS penetration
  • ~100 times more potent than morphine
  • Preferred ICU opioid due to:
    • Hemodynamic stability
    • Minimal histamine release
    • Rapid onset

 2. Pharmacology

 Mechanism of Action

  • Acts on μ-opioid receptors (G-protein coupled)

Result:

  • Analgesia
  • Sedation (mild)
  • Respiratory depression

Pharmacokinetics

Parameter

Details

Onset

1–2 min IV

Peak

3–5 min

Duration (bolus)

30–60 min

Context-sensitive half-time

Prolonged with infusion
  • Accumulates in fat tissues → prolonged sedation in long infusions

 3. Pharmacodynamics

System

Effects

CNS

Analgesia, mild sedation

Respiratory

Dose-dependent respiratory depression

CVS

Minimal effect (stable BP/HR)

GIT

↓ motility → ileus

Pupils

Miosis

4. ICU Indications 

Analgesia (Primary use)

  • Post-operative ICU patients
  • Trauma
  • Burns
  • Cancer pain

 Sedation adjunct

  • Used with:
    • Propofol
    • Midazolam

 Mechanical ventilation

  • Improves:
    • Ventilator synchrony
    • Tolerance to ETT

 Hemodynamically unstable patients

  • Preferred over morphine (no histamine release)

 Procedural analgesia

  • Intubation
  • Central line insertion

 5. Dosing in ICU 

 Bolus Dose in Adult

  • 25–100 mcg IV (repeat as needed)

 Infusion Dose

  • 1–3 mcg/kg/hr (typical)
  • Severe pain → up to 5 mcg/kg/hr

 SCCM PADIS recommendation:

  • Opioid-first analgesia strategy preferred

 6. Adverse Effects 

 Respiratory

  • Respiratory depression
  • Apnea

 Chest Wall Rigidity (“Wooden Chest Syndrome”)

  • Seen with:
    • High doses
    • Rapid IV push
  • Causes:
    • Difficult ventilation

 Management:

  • Naloxone
  • Neuromuscular blockade

 CNS

  • Sedation
  • Delirium (ICU)

GIT

  • Ileus
  • Constipation

 CVS

  • Bradycardia

 Tolerance & Dependence

  • Common in prolonged ICU stay

 7. Comparison with Other Opioids

Feature

Fentanyl

Morphine

Onset

Rapid

Slow

Histamine release

NO

✔

Hemodynamics

Stable

Hypotension

Active metabolites

No

✔ (M6G)

Renal safety

✔

NO

 8. Reversal

  • Drug: Naloxone
  • Dose:
    • 0.04–0.4 mg IV (titrate)

 Risk:

  • Acute withdrawal
  • Re-sedation (short duration vs fentanyl)

 9. Guidelines & Evidence 

 SCCM PADIS Guidelines

  • Opioids preferred over sedatives for pain control
  • Avoid deep sedation
  • Use analgesia-first sedation strategy

 ERAS Protocols

  • Fentanyl widely used but:
    • Preference shifting toward shorter-acting opioids (remifentanil)
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