Remifentanil: Biological Mechanisms, Surgical Applications and Side Effects

Remifentanil is an ultrashort-acting opioid drug that is a derivative of fentanyl.¹ It was first introduced into medical practice in 1996,² and it serves as an analgesic and adjunct to anesthetics.³ Remifentanil is marketed as Ultiva by the U.S. pharmaceutical company Abbott.³ Because of its uses in anesthesiology, anesthesia providers must understand its biological mechanisms, surgical applications and side effects.

Remifentanil, also known as remifentanil hydrochloride, has a molecular formula of C₂₀H₂₈N₂O₅.³ Remifentanil is chemically derived from fentanyl and possesses similar pharmacodynamic properties, but it is slightly more potent.⁴ Like other opioid drugs, remifentanil’s primary mechanism of action is agonism of the µ-opioid receptor, which inhibits neuronal activity.⁵ Unlike other drugs, however, remifentanil is metabolized independent of liver function.⁶ Instead, remifentanil metabolism involves hydrolysis by enzymes in muscles and blood plasma.⁷ The primary metabolite is an inactive carboxylic acid derivative that is eventually excreted in the urine.⁴ Because of its unique metabolism, remifentanil can be administered as a single dose or as an infusion,⁷ and it has a rapid onset and short duration of action.⁵ While remifentanil’s pharmacodynamics are similar to those of other opioids, its pharmacokinetics make it distinct from other anesthetic drugs.

Remifentanil can be used for general anesthesia, during local or regional anesthesia as part of monitored anesthesia care, for postoperative analgesia or potentially for spinal anesthesia.⁸ Its effects include decreased blood pressure and heart rate and increased intracranial pressure and cerebral blood flow.^8,9 In adults, it is used for induction and maintenance of general anesthesia, conscious analgesia and postoperative analgesia; in children, it is used only for maintenance of general anesthesia.¹⁰ Due to its metabolism in nonspecific tissues and plasma, any dose of remifentanil may be used during general anesthesia without significant lengthening of emergence times.⁸ Also, clinicians can use remifentanil in patients who have renal or hepatic dysfunction because it can be metabolized regardless.⁸ Remifentanil is highly effective as an adjunct to other anesthetic drugs, such as propofol, in its ability to reduce movement, provide analgesia and cause sedation.¹¹ It also adds “smoothing” even in patients who require sedation only.¹¹ Remifentanil is too potent to be administered by bolus injection, and should be administered as a titrated infusion.¹² Thanks to remifentanil’s distinct metabolic profile, it has a variety of purposes in surgery.

Like other opioids, remifentanil has several dose-dependent adverse effects.³ For one, its rapid offset of analgesia can result in greater postoperative pain.¹³ Common side effects of remifentanil include apnea, muscle rigidity, nausea, vomiting and itchiness.⁴ Due to its potency and fast-acting nature, remifentanil is accompanied by a higher risk than other opioids of life-threatening respiratory depression at subtherapeutic levels.¹⁴ Thus, remifentanil is not preferred for conscious sedation without other anesthetics.¹⁴

Remifentanil is an ultrashort-acting synthetic opioid with a fast onset and offset. It acts on opioid receptors in the central nervous system, and it is metabolized throughout the body’s muscle tissues and blood plasma. Remifentanil can be used for induction and maintenance of general anesthesia, conscious sedation and postoperative analgesia. Side effects of remifentanil are similar to those of other opioids, though the risk for respiratory depression is high. Remifentanil is a strong opioid that should be used with caution in controlled settings.

1.         Artime CA, Sanchez A. Chapter 11—Preparation of the Patient for Awake Intubation. In: Hagberg CA, ed. Benumof and Hagberg’s Airway Management (Third Edition). Philadelphia: W.B. Saunders; 2013:243–264.e243.

2.         Vardanyan RS, Hruby VJ. Fentanyl-related compounds and derivatives: Current status and future prospects for pharmaceutical applications. Future Medicinal Chemistry. 2014;6(4):385–412.

3.         Remifentanil. PubChem Database. Web: National Center for Biotechnology Information; 2020.

4.         Simmons B, Kuo A. 40—Analgesics, Tranquilizers, and Sedatives. In: Brown DL, ed. Cardiac Intensive Care (Third Edition). Philadelphia: Elsevier; 2019:421–431.e425.

5.         Lee MK, Gerstein NS, Schulman PM, Jessel PM. Chapter 15—Anesthesia for Cardioversion and Electrophysiologic Procedures. In: Kaplan JA, Cronin B, Maus TM, eds. Essentials of Cardiac Anesthesia for Noncardiac Surgery. New York: Elsevier; 2019:379–403.

6.         Hammond R, Christie M, Nicholson A. Chapter 14—Opioid analgesics. In: Maddison JE, Page SW, Church DB, eds. Small Animal Clinical Pharmacology (Second Edition). Edinburgh: W.B. Saunders; 2008:309–329.

7.         Lobo EP, Pellegrini F, Pusceddu E. Chapter 1: Anesthesia Complications in Head and Neck Surgery. In: Eisele DW, Smith RV, eds. Complications in Head and Neck Surgery (Second Edition). Philadelphia: Mosby; 2009:3–27.

8.         Servin F. Remifentanil: When and how to use it. European Journal of Anaesthesiology (EJA). 1997;14:41–44.

9.         Komatsu R, Turan AM, Orhan-Sungur M, McGuire J, Radke OC, Apfel CC. Remifentanil for general anaesthesia: A systematic review. Anaesthesia. 2007;62(12):1266–1280.

10.       Medscape. remifentanil (Rx). Drugs & Diseases 2020; https://reference.medscape.com/drug/ultiva-remifentanil-343316.

11.       Anderson BJ, Houghton J. 8—Total Intravenous Anesthesia and Target-Controlled Infusion. In: Coté CJ, Lerman J, Anderson BJ, eds. A Practice of Anesthesia for Infants and Children (Sixth Edition). Philadelphia: Content Repository Only!; 2019:177–198.e173.

12.       Mallick A, Elliot S. Remifentanil is too potent to be given by bolus. BJA: British Journal of Anaesthesia. 2004;93(2):305–306.

13.       Muellejans B, López A, Cross MH, Bonome C, Morrison L, Kirkham AJT. Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713]. Critical Care. 2003;8(1):R1.

14.       Litman RS. Conscious Sedation with Remifentanil During Painful Medical Procedures. Journal of Pain and Symptom Management. 2000;19(6):468–471.