Remifentanil

Overview

Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics. WP

Uses, dosage and effects

Medical uses

Remifentanil is used as an opioid analgesic that has a rapid onset and rapid recovery time. It has been used effectively during craniotomies, spinal surgery, cardiac surgery, and gastric bypass surgery. While opioids function similarly, with respect to analgesia, the pharmacokinetics of remifentanil allows for quicker post-operative recovery.[1–7] WP

Remifentanil can be administered as part of an anesthesia technique called TIVA (total intravenous anesthesia) using computer controlled infusion pumps in a process called TCI (target controlled infusion). A target plasma concentration is entered as ng/mL into the pump, which calculates its infusion rate according to patient factors like age and weight. Induction levels of 40 ng/mL are commonly used, but it generally varies between 3–8 ng/mL. For certain surgical procedures that produce particularly strong stimuli a level of up to 15 ng/mL might be needed. The relatively short context-sensitive half-life of remifentanil allows the desired blood plasma level to be achieved quickly, and also for the same reason, recovery occurs quickly. This allows remifentanil to be used in unique circumstances such as cesarean section.[8] WP

Remifentanil's short context-sensitive half-life makes it ideal for intense pain of short duration. As such, it has been used for analgesia in labor successfully; however, it is not as effective as epidural analgesia.[9] WP

In combination with propofol, remifentanil is used for anesthesia of patients undergoing electroconvulsive therapy.[10] WP

Available forms

It is administered in the form remifentanil hydrochloride and in adults is given as an intravenous infusion in doses ranging from 0.1 microgram per kilogram per minute to 0.5 (μg/kg)/min. Children may require higher infusion rates (up to 1.0 (μg/kg)/min). The clinically useful infusion rates are 0.025–0.1 (μg/kg)/min for sedation (rates adjusted to age of patient, severity of their illness and invasiveness of surgical procedure). Small amounts of other sedative medications are usually co-administered with remifentanil to produce sedation. Clinically useful infusion rates in general anesthesia vary but are usually 0.1–1 (μg/kg)/min.[11][12] WP

Veterinary use

Remifentanil has a very short half-life and quick onset with recovery occurring in a few minutes regardless of length and dosage provided. Remifentanil is more effective in dogs than cats, although an increase in the dosage in cats can achieve equivalent analgesia and anti-nociception. The half-life is 6 minutes in the dog. This half-life does not increase with increased dosage or prolonged usage and thus remifentanil recovery is very quick. Hyperalgesia and tolerance has been demonstrated in rodents and rabbits but not dogs and cats. In equines remifentanil can provide long-lasting sedation when combined with xylazine and used as constant rate infusion.[13] WP

Pharmacology

Pharmacokinetics

Remifentanil is considered a metabolic soft drug, one that is rapidly metabolized to an inactive form. Unlike other synthetic opioids which are hepatically metabolized, remifentanil has an ester linkage which undergoes rapid hydrolysis by non-specific tissue and plasma esterases. This means that accumulation does not occur with remifentanil and its context-sensitive half-life remains at 4 minutes after a 4-hour infusion.[13][14] WP

Remifentanil is metabolized to remifentanil acid, which has 1/4600th the potency of the parent compound.[15] WP

Due to its quick metabolism and short effects, remifentanil has opened up new possibilities in anesthesia. When remifentanil is used together with a hypnotic (i.e. one that produces sleep) it can be used in relative high doses. This is because remifentanil is rapidly eliminated from the blood plasma on termination of the remifentanil infusion; hence the effects of the drug quickly dissipate even after very long infusions. Owing to synergism between remifentanil and hypnotic drugs (such as propofol) the dose of the hypnotic can be substantially reduced. This leads often to more hemodynamic stability during surgery and a quicker post-operative recovery time.[16] WP

Pharmacodynamics

Comparing its analgesia-sedation effect in ventilated patients, remifentanil may be superior to morphine but not to fentanyl.[17][18] WP

Legal status

Development and marketing

Prior to the development of remifentanil, most short-acting hypnotics and amnestics faced issues with prolonged use, where accumulation would result in unfavorable lingering effects during post-operative recovery. Remifentanil was designed to serve as a strong anesthetic with an ultra-short and predictable duration that would not have accumulation issues.[19] WP

Remifentanil was patented by Glaxo Wellcome Inc. and was FDA approved on July 12, 1996. Its patent ended on the 10th of September 2017.[20][21] WP

Legal status

In Hong Kong, remifentanil is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined. The penalty for trafficking or manufacturing the substance is a fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a fine and/or 7 years of jail time. WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

Remifentanil is a Schedule II narcotic controlled substance in the United States with a DEA ACSCN of 9739 and a 2013 annual aggregate manufacturing quota of 3,750 grams, unchanged from the prior year. WP

Chemistry

Formula

C20H28N2O5 PC

CAS number

132875-61-7 PC

Molar mass (g/mol)

376.4 PC

IUPAC name (computed by PubChem)

methyl 1-(3-methoxy-3-oxopropyl)-4-(N-propanoylanilino)piperidine-4-carboxylate PC

SMILES

CCC(=O)N(C1=CC=CC=C1)C2(CCN(CC2)CCC(=O)OC)C(=O)OC PC

InChIKey

ZTVQQQVZCWLTDF-UHFFFAOYSA-N PC

PubChem CID

60815

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Remifentanil, IV opioid analgesic, Remi | Ultiva
2. Journal / agency Gesztesi Z, Mootz BL, White PF. The use of a remifentanil infusion for hemodynamic control during intracranial surgery. Anesthesia and Analgesia. November 1999. doi:10.1213/00000539-199911000-00038 · PMID 10553851
3. Journal / agency Grottke O, Dietrich PJ, Wiegels S, Wappler F. Intraoperative wake-up test and postoperative emergence in patients undergoing spinal surgery: a comparison of intravenous and inhaled anesthetic techniques using short-acting anesthetics. Anesthesia and Analgesia. November 2004. doi:10.1213/01.ANE.0000134684.25322.26 · PMID 15502058
4. Journal / agency Knapik M, Knapik P, Nadziakiewicz P, Misiołek H, Saucha W, Walaszczyk M, Dyaczyńska-Herman A. Comparison of remifentanil or fentanyl administration during isoflurane anesthesia for coronary artery bypass surgery. Medical Science Monitor. August 2006. PMID 16865075
5. Journal / agency De Baerdemaeker LE, Jacobs S, Pattyn P, Mortier EP, Struys MM. Influence of intraoperative opioid on postoperative pain and pulmonary function after laparoscopic gastric banding: remifentanil TCI vs sufentanil TCI in morbid obesity. British Journal of Anaesthesia. September 2007. doi:10.1093/bja/aem164 · PMID 17606479
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7. Journal / agency Guy J, Hindman BJ, Baker KZ, Borel CO, Maktabi M, Ostapkovich N, Kirchner J, Todd MM, Fogarty-Mack P, Yancy V, Sokoll MD, McAllister A, Roland C, Young WL, Warner DS. Comparison of remifentanil and fentanyl in patients undergoing craniotomy for supratentorial space-occupying lesions. Anesthesiology. March 1997. doi:10.1097/00000542-199703000-00002 · PMID 9066316
8. Journal / agency White LD, Hodsdon A, An GH, Thang C, Melhuish TM, Vlok R. Induction opioids for caesarean section under general anaesthesia: a systematic review and meta-analysis of randomised controlled trials. International Journal of Obstetric Anesthesia. November 2019. doi:10.1016/j.ijoa.2019.04.007 · PMID 31230994
9. Journal / agency Stocki D, Matot I, Einav S, Eventov-Friedman S, Ginosar Y, Weiniger CF. A randomized controlled trial of the efficacy and respiratory effects of patient-controlled intravenous remifentanil analgesia and patient-controlled epidural analgesia in laboring women. Anesthesia and Analgesia. March 2014. doi:10.1213/ANE.0b013e3182a7cd1b · PMID 24149580
10. Journal / agency Ulusoy H, Cekic B, Besir A, Geze S, Hocaoglu C, Akdogan A. Sevoflurane/remifentanil versus propofol/remifentanil for electroconvulsive therapy: comparison of seizure duration and haemodynamic responses. The Journal of International Medical Research. February 2014. doi:10.1177/0300060513509036 · PMID 24398757
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12. Other Remifentanil Actavis
13. Other Simon BT, Lizarraga I. Veterinary Anesthesia and Analgesia, The 6th Edition of Lumb and Jones. 11 September 2024
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15. Journal / agency Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE. Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. The Journal of Pharmacology and Experimental Therapeutics. April 1997. doi:10.1016/S0022-3565(24)36558-9 · PMID 9103501
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18. Journal / agency Spies C, Macguill M, Heymann A, Ganea C, Krahne D, Assman A, Kosiek HR, Scholtz K, Wernecke KD, Martin J. A prospective, randomized, double-blind, multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients. Intensive Care Medicine. March 2011. doi:10.1007/s00134-010-2100-5 · PMID 21165734
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20. Other Stable formulations of remifentanil
21. Other Orange book: approved drug products with therapeutic equivalence evaluations. 2010

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