Anaes · Anaesthetic adjuncts

Fentanyl

Also known as Synthetic phenylpiperidine opioid · Workhorse intraoperative opioid · Cardiac-anaesthesia opioid · Rising context-sensitive half-time opioid

Fentanyl is a synthetic phenylpiperidine opioid and a full agonist at the mu-opioid receptor, typically 50 to 100 times more potent than morphine, and the workhorse intraoperative analgesic (Ramos-Matos 2023, Patocka 2024). Two pharmacological features make it exam-critical. First, it is a histamine NON-RELEASER, so it avoids morphine-type histamine-mediated haemodynamic and cutaneous effects, is the opioid of choice for cardiac anaesthesia and the haemodynamically unstable, and is the safer choice in asthma where morphine is used cautiously (Bowdle 1998, Baldo 2023). Second, it is highly lipid-soluble with a faster onset than morphine and a rapid apparent offset after a single bolus, but this early offset is due to REDISTRIBUTION from brain to muscle and fat, NOT elimination; with repeated boluses or a prolonged infusion the peripheral compartments saturate, the CONTEXT-SENSITIVE HALF-TIME LENGTHENS, and the drug ACCUMULATES, producing delayed and prolonged respiratory depression and slow emergence (Hughes 1992, Egan 1995). It is metabolised by hepatic CYP3A4 to norfentanyl with no active metabolite accumulating, so it is preferred over morphine in renal failure. At high doses or with rapid intravenous bolus it can cause chest-wall rigidity (the wooden chest) impairing ventilation, and its respiratory depression is reversed by naloxone (Lewis 2026, Voronkov 2026). Built on the fentanyl overview (Ramos-Matos 2023), the fentanyl-derivatives review (Patocka 2024), the opioid-adverse-effects-in-anaesthesia review (Bowdle 1998), the opioid-histamine-MRGPRX2 review (Baldo 2023), the human-liver-microsome metabolism study (Feierman 1996), the context-sensitive half-time paper (Hughes 1992), the remifentanil pharmacokinetic appraisal (Egan 1995), the acute-toxicity O2-delivery review (Lewis 2026), the opioid-sparing PONV trial (Sung 2026), and the rat tranq-dope reversal study (Voronkov 2026).