Opioid · Analgesic
Fentanyl
Indications
- Analgesia and analgosedation in ventilated ICU patients (off-label as a prolonged infusion)
- Analgesic supplement for general or regional anesthesia and procedural sedation
- Blunting the pressor response to laryngoscopy
- ED and prehospital pain (intranasal use is off-label)
Dosing
Fentanyl drip card and mL/h converterStart: 25–50 mcg/h (range 0.7–10 mcg/kg/h)
| Where | Dose |
|---|---|
| Airway and RSI | Fentanyl bolus: 25–100 mcg IV |
| Other common pushes | Fentanyl: 25–50 mcg IV every 5 min; fast, short, no histamine |
| Opioid equianalgesic doses | Fentanyl: 100 mcg IV (patch: 25 mcg/h ≈ morphine 60–90 mg PO/day) |
| Other ICU drugs | Fentanyl: Preferred opioid in kidney failure (no active metabolites) |
On the quick cards
Mechanism of action
Fentanyl is a full agonist at the μ-opioid receptor, which couples to Gi/o proteins. Gαi inhibits adenylyl cyclase and lowers cAMP; Gβγ opens GIRK potassium channels, hyperpolarizing the neuron, and closes presynaptic N-type calcium channels, so pain fibers release less glutamate and substance P. This blocks pain transmission in the dorsal horn and brainstem; in the brainstem respiratory network it slows breathing.
Pharmacology
- CNS: analgesia, sedation, miosis; blunts the response to intubation; amnesia is unreliable
- Respiratory: slower rate and blunted CO₂ response, which can outlast the analgesia; fast large boluses stiffen the chest wall and close the vocal cords
- Cardiovascular: no histamine release, little myocardial depression; vagal bradycardia; BP falls when sympathetic tone was holding it up
- GI: constipation, slowed gastric emptying (delays oral ticagrelor, PACIFY), biliary spasm
Pharmacokinetics
| Onset | Almost immediate IV; 7–8 min IM (label) |
|---|---|
| Peak | Analgesia 3–5 min; respiratory depression 5–15 min after IV (label) |
| Duration | 30–60 min after IV doses up to 100 mcg, ended by redistribution (label) |
| Context-sensitive half-time | Rises with infusion length: about 4 h after a 4-h infusion and 5 h after 8 h (Hughes 1992) |
| Half-life | About 3.7 h (label); longer in older adults and liver disease |
| Distribution | Vd about 4 L/kg (3–8); lungs take up 75% of the first pass (Roerig 1987); stored in fat and muscle |
| Protein binding | About 80–85%, to α₁-acid glycoprotein, albumin and lipoproteins |
| Metabolism | CYP3A4 in liver and gut wall to inactive norfentanyl; high hepatic extraction |
| Elimination | Urine, mostly as metabolites; under 10% unchanged (label) |
| Organ failure and ECMO | No active metabolites, so preferred in kidney failure; ECMO circuits bind it (3% left at 24 h ex vivo) |
Chemistry
- Synthetic phenylpiperidine (4-anilidopiperidine), parent of sufentanil, alfentanil and remifentanil; achiral
- pKa about 8.4 (PubChem 8.4–9.0), so under 10% is un-ionized at pH 7.4, yet it is so lipophilic (log P about 4) that it enters the brain within minutes
- Citrate 50 mcg/mL in water, preservative-free, pH 4.0–7.5; protect from light (label)
Adverse effects and cautions
In the one-pagers
- Sedation, Pain and Delirium ScalesPharmacology and ICU pitfalls: Fentanyl: 0.7–10 mcg/kg/h: Accumulates after long infusions
- Airway and RSIInduction and paralysis: pharmacology in depth: Fentanyl 1–3 mcg/kg, pretreatment: Blunts the laryngoscopy surge: ICH, dissection, ischemia; skip in shock
- Mental Health: Meds and CommunicationAntidepressants in the ICU and serotonin toxicity: In the ICU the second drug is often not an antidepressant: linezolid and methylene blue inhibit MAO, and fentanyl, methadone, tramadol, meperidine, dextromethorphan and ondansetron are implicated. The ZYVOX label (June 2026) now asks for monitoring rather than avoidance with serotonergic drugs; in an older-adult cohort (n = 1,134) serotonin syndro
- Toxidromes and AntidotesThe first hour: approach to the poisoned patient: Urine immunoassays show exposure, not cause; standard opiate screens miss fentanyl, methadone, buprenorphine and often oxycodone.
- End of Life, Brain Death and Organ DonationWithdrawing life support: Fentanyl: 0.5–2 mcg/kg: 0.5–10 mcg/kg/h
- Acute Abdomen and GI Surgical EmergenciesReading the acute abdomen: High-risk groups are the very old, the very young and anyone on corticosteroids or other immunosuppressants. These drugs blunt the inflammatory response, so a perforation can cause less pain, less tenderness and a smaller WBC rise than expected; a new tachycardia may be the main clue. Merck states that moderate IV analgesia (fentanyl 50-100 mcg or morphine 4-6 mg) does n
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Sources
- FDA label: Fentanyl Citrate Injection, Hospira (2026)
- PubChem: fentanyl
- Hughes 1992 (context-sensitive half-time)
- Shekar 2012 (ECMO)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.