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
- Fentanyl (Sublimaze)EMS Field Drugs: Analgesia: synthetic opioid for moderate to severe pain
- Opioid equianalgesic dosesEquivalents and Conversions: Equal to morphine 10 mg IV
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
- Airway and RSIInduction and paralysis: pharmacology in depth: Fentanyl 1–3 mcg/kg, pretreatment: Blunts the laryngoscopy surge: ICH, dissection, ischemia; skip in shock
- 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.
- Toxins, Stings and Anaphylaxis in the FieldOpioids and sedatives: Fentanyl patch: Heat (heating pad, fever) raises absorption: Remove patch and heat; naloxone to breathing; levels fall only 50% in 20-27 h and naloxone may end within 1 h: transport
- Abdominal, GI Bleeding, GU and Dialysis EmergenciesEvery abdomen: first steps: Treat pain: analgesia does not hide the diagnosis (Merck). Fentanyl and ondansetron doses: ems-pharmacology. Ketorolac 15 mg IV or 30 mg IM, not with hypotension, kidney disease, peptic ulcer or pregnancy (NASEMSO).
- Asthma and COPD ExacerbationsSedation, paralysis and rescue therapies: Deep sedation early suppresses the air hunger that drives a fast rate and dyssynchrony. Propofol (bronchodilating, but hypotensive) with fentanyl is common; ketamine adds bronchodilation with less hypotension but more secretions; avoid morphine, which releases histamine. Lighten sedation as obstruction resolves.
- Common EMS MedicationsPain, sedation, nausea and bleeding: Fentanyl, opioid: Moderate to severe pain: 1 mcg/kg, first dose ≤100 mcg; IV/IO/IN/IM: Hypotension, hypoventilation, MAOI in 14 days
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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 your local protocols and medical direction.