Remifentanil
Encyclopedia
Remifentanil is a potent ultra short-acting synthetic opioid
analgesic
drug
. 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.
Remifentanil can be administered as part of an anaesthesia technique called TIVA (Total Intravenous Anaesthesia) using computer controlled infusion pumps in a process called target controlled infusion or TCI
. 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 4 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.
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 (remifentanil acid) which has 1/4600th the potency of the parent compound.
Owing 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 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 (such as propofol
) the dose of the hypnotic can be substantially reduced. This leads often to more haemodynamic stability during surgery and a quicker post-operative recovery time.
agonist. 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" (often short lived, a common side effect of other fast-acting synthetic phenylpiperidine narcotics such as fentanyl and alfentanil
) and intense itching (pruritus), often around the face. These side effects are often controlled by either altering the administered dose (decreasing or in some cases, increasing the dose) or by administering other sedative
s 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 (Benadryl) 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.
in patients who are in need of pain management.
, 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 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD
) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.
Regulation in the US is as a schedule II narcotic.
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
drug
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation
Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
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.
Administration
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). Doses listed in the package insert from its manufacturer are much higher than those used in actual clinical practice. 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/minhttp://www.fass.se/LIF/produktfakta/artikel_produkt.jsp?NplID=19980206000098&DocTypeID=3&UserTypeID=0.Remifentanil can be administered as part of an anaesthesia technique called TIVA (Total Intravenous Anaesthesia) using computer controlled infusion pumps in a process called target controlled infusion or TCI
TCI
-Medicine:*Transient Cerebral Ischaemic attack, see Transient ischemic attack*Tricyclic antidepressant medication*Target Controlled Infusion, a method for controlling intravenous infusions.-Psychology:*Theme-Centered Interaction, a method of psychotherapy by Dr...
. 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 4 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
Context-sensitive half-life
Context-sensitive half-life or context sensitive half-time is defined as the time taken for blood plasma concentration of a drug to decline by one half after an infusion designed to maintain a steady state has been stopped...
of Remifentanil allows the desired blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
level to be achieved quickly and also for the same reason recovery occurs quickly.
Metabolism
Unlike other synthetic opioids which are hepatically metabolised, remifentanil has an esterEster
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
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
Context-sensitive half-life
Context-sensitive half-life or context sensitive half-time is defined as the time taken for blood plasma concentration of a drug to decline by one half after an infusion designed to maintain a steady state has been stopped...
remains at 4 minutes after a 4 hour infusion.
Remifentanil is metabolized to a compound (remifentanil acid) which has 1/4600th the potency of the parent compound.
Owing 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 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 (such as propofol
Propofol
Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
) the dose of the hypnotic can be substantially reduced. This leads often to more haemodynamic stability during surgery and a quicker post-operative recovery time.
Side-effects
Remifentanil is a specific μ-receptorOpioid receptor
Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...
agonist. Hence, it causes a reduction in sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
tone, respiratory depression and analgesia. The drug's effects include a dose-dependent decrease in heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
and arterial pressure and respiratory rate
Respiratory rate
Respiratory rate is also known by respiration rate, pulmonary ventilation rate, ventilation rate, or breathing frequency is the number of breaths taken within a set amount of time, typically 60 seconds....
and tidal volume
Tidal volume
Tidal volume is the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied.Typical values are around 500ml or 7ml/kg bodyweight.-Mechanical Ventilation:...
. Muscle rigidity is sometimes noted.
The most common side effects reported by patients receiving this medication are a sense of extreme "dizziness" (often short lived, a common side effect of other fast-acting synthetic phenylpiperidine narcotics such as fentanyl and alfentanil
Alfentanil
Alfentanil is a potent but short-acting synthetic opioid analgesic drug, used for anaesthesia in surgery. It is an analogue of fentanyl with around 1/4 the potency of fentanyl and around 1/3 of the duration of action, but with an onset of effects 4x faster than fentanyl...
) and intense itching (pruritus), often around the face. These side effects are often controlled by either altering the administered dose (decreasing or in some cases, increasing the dose) or by administering other sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
s 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 (Benadryl) 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
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
once the infusion is terminated.
Potency
Remifentanil is approximately twice as potent as fentanyl, and 2000 times as potent as morphine.Circumventing Naltrexone
Remifentanil has been used with some success to circumvent naltrexoneNaltrexone
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade...
in patients who are in need of pain management.
Regulation
In Hong KongHong Kong
Hong Kong is one of two Special Administrative Regions of the People's Republic of China , the other being Macau. A city-state situated on China's south coast and enclosed by the Pearl River Delta and South China Sea, it is renowned for its expansive skyline and deep natural harbour...
, Remifentanil is regulated under Schedule 1 of Hong Kong's
Hong Kong
Hong Kong is one of two Special Administrative Regions of the People's Republic of China , the other being Macau. A city-state situated on China's south coast and enclosed by the Pearl River Delta and South China Sea, it is renowned for its expansive skyline and deep natural harbour...
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 (HKD). The penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD
Hong Kong dollar
The Hong Kong dollar is the currency of the jurisdiction. It is the eighth most traded currency in the world. In English, it is normally abbreviated with the dollar sign $, or alternatively HK$ to distinguish it from other dollar-denominated currencies...
) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time.
Regulation in the US is as a schedule II narcotic.