Remifentanil is a potent, short-acting synthetic opioidanalgesicdrug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. 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.
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 /min. Children may require higher infusion rates. The clinically useful infusion rates are 0.025-0.1 /min for sedation. 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. Remifentanil can be administered as part of an anesthesia technique called TIVA using computer controlled infusion pumps in a process called 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. 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. In combination with propofol, remifentanil is used for anesthesia of patients undergoing electroconvulsive therapy.
Metabolism
Remifentanil is considered a 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. Remifentanil is metabolized to a compound which has 1/4600th the potency of the parent compound. Due to its quick metabolism and short effects, remifentanil has opened up new possibilities in anesthesia. When remifentanil is used together with a hypnotic it can be used in relative high doses. This is because remifentanil will be rapidly eliminated from the blood plasma on termination of the remifentanil infusion, hence the effects of the drug will quickly dissipate even after very long infusions. Owing to synergism between remifentanil and hypnotic drugs 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.
Side-effects
Remifentanil is a specific μ-receptoragonist. Hence, it causes a reduction in sympathetic nervous system tone, respiratory depression and analgesia. The drug's effects include a dose-dependent decrease in heart rate and arterial pressure and respiratory rate and tidal volume. Muscle rigidity is sometimes noted. The most common side effects reported by patients receiving this medication are a sense of extreme "dizziness" and intense itching, often around the face. These side effects are often controlled by either altering the administered dose or by administering other sedatives that allow the patient to tolerate or lose awareness of the side effect. Because pruritus is due to excessive serum histamine levels, antihistamines such as diphenhydramine are often co-administered. This is done with care, however, as excessive sedation may occur. Nausea can occur as a side effect of remifentanil, however, it is usually transient in nature due to the drug's short half-life which rapidly removes it from the patient's circulation once the infusion is terminated.
Potency
Remifentanil is approximately twice as potent as fentanyl, and 100-200 times as potent as morphine.
Remifentanil has been used with some success to circumvent naltrexone in patients who are in need of pain management.
Abuse potential
Remifentanil, being a μ-receptor agonist, functions like other μ-receptor agonists, such as morphine and codeine, and can cause euphoria and has the potential for abuse. However, due to its rapid metabolism and short-acting half-life the likelihood of becoming abused is quite low. Nevertheless, there have been some documentations of remifentanil abuse.
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. Remifentanil is patented by Glaxo Wellcome Inc. and was FDA approved on July 12, 1996.
Pricing for Ultiva
1 mg vial - US$30.19
3 mg vial - US$57.20
5 mg vial - US$118.15
Regulation
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 $10000. The penalty for trafficking or manufacturing the substance is a $5,000,000 fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 fine and/or 7 years of jail time. 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 3750 grams, unchanged from the prior year.
