Drug Update

Remifentanil hydrochloride : an Opioid for the 21st

Century
Lt Col DK Sreevastava*, Col AK Bhargava+

MJAFI 2004; 60 : 177-178

Introduction remifentanil or by administering a neuromuscular

Remifentanil hydrochloride is a recent addition to the blocking agent. Unlike morphine, it does not cause
group of narcotic analgesics [1]. It is structurally unique elevation in plasma histamine levels after administration
as it has an ester linkage that renders it susceptible to of higher doses.
hydrolysis by nonspecific plasma and tissue esterases Clinical uses, dosages and administration
to inactive metabolites. This pathway of metabolism is
During general anaesthesia, as the analgesic
responsible for its uniquely evanescent effect. Thus,
component, remifentanil is initially administered as a
the side effects for which opioids are much maligned
bolus of 1 µg/kg intravenous (IV) over 60 to 90 seconds,
are extremely transient when remifentanil is used.
followed by an infusion rate of 0.25-1 µg/kg/min along
Pharmacokinetics with a hypnotic or volatile agent for the induction of
Remifentanil has certain remarkable pharmacokinetic anaesthesia [3]. Maintenance infusion doses are in the
features [2] such as an extraordinary clearance of nearly range of 0.05-2µg/kg/min. Additional boluses of 1µg/kg
3 litres/minute, very short half-life of 3-10 minutes, can be given on as required basis. The rate of
exceptionally short time to peak effect of about 1.6 administration during anaesthesia can be titrated upward
minutes (as effect-site concentration of remifentanil in 25-100% increments or downward in 25-50%
reaches a peak within 1.1 minutes only). Clinically, these decrements every 2-5 minutes to attain the desired level
properties translate into prompt achievement of steady- of effect.
state concentration in the plasma and its effect site In similar dosages, it is useful in selected, at-risk
leading to rapid onset of effect and less accumulation patients for suppression of the transient sympathetic
than other opioids irrespective of the duration of the nervous system response to direct laryngoscopy and
infusion. It also implies predictable termination of effects, tracheal intubation.
hence allowing precise titration of its dose and action. During general anaesthesia with a laryngeal mask,
The pharmacokinetics are unchanged in renal or hepatic remifentanil infusion @ 0.05 µg/kg/min or less, provides
failure. In addition, esterase metabolism appears to be supplemental analgesia while allowing spontaneous
a very well preserved system with little variability ventilation with propofol or isoflurane. In these situations,
between individuals, which contributes further to the bolus doses of remifentanil are not recommended
predictability of drug effect and enhances its safety because of high incidence of side effects.
profile.
Remifentanil has been evaluated in a clinical trial in
Clinical effects children 2-12 years of age undergoing strabismus surgery
The effects are similar to all other opioids in equipotent with satisfactory results [4, 5]. While in paediatric
doses. However, because of rapidity of onset, the patients, the doses remain unchanged, in elderly patients
effects may seem to be exaggerated. It causes dose- (> 65 years) the pharmacodynamic activity of
dependent hypotension, bradycardia and depression of remifentanil increases with advancing age and therefore
respiration. Peak effects occur within 3-5 minutes of a the starting doses should be decreased by 50%.
single dose of remifentanil, however recovery is equally It has been used safely in coronary artery bypass
rapid. Remifentanil may cause chest wall rigidity after graft (CABG) and neurosurgery with good results.
single doses of >1µg/kg administered over 30-60 Particularly, it is useful for long operations, when a quick
seconds. Excessive muscle rigidity can be treated by recovery is desired (neurological assessment, wake-up
decreasing the rate or discontinuing the infusion of test).

*
Associate Professor, +Professor and Head, Department of Anaesthesia and Critical Care, Armed Forces Medical College, Pune.
178 Sreevastava and Bhargava

For postoperative analgesia, remifentanil should be tubing at or close to the venous cannula and should
initially administered by continuous infusion at a rate of immediately be cleared to prevent the inadvertent
0.1 µg/kg/min. The infusion rate may be adjusted every administration of remifentanil at a later point in time.
5 minutes in 0.025 µg/kg/min increments to balance the Failure to do so has been associated with the appearance
patient’s level of analgesia and respiratory rate. Rates of respiratory depression, apnea and muscle rigidity upon
greater than 0.2 µg/kg/min are generally associated with the administration of additional fluids or medications
respiratory depression (respiratory rates less than 8 through the same IV tubing.
breaths/min). In addition, bolus doses also should be Remifentanil should not be administered into the same
avoided because of a high incidence of apnea, muscle IV tubing with blood due to potential inactivation by
rigidity and tachycardia. nonspecific esterases in blood products.
As a part of sedation technique, remifentanil, in the Due to the presence of glycine in the formulation,
dosages of 0.05 to 0.10 µg/kg/min in combination with remifentanil is contraindicated for epidural or intrathecal
midazolam, 2 mg IV, provides effective sedation and administration. Remifentanil is also contraindicated in
analgesia during monitored anaesthesia care or when a patients with known hypersensitivity to fentanyl analogs.
profound analgesic effect is desired transiently (eg.
performance of a block). Conclusion
Its use in obstetric practice cannot be recommended The utility of remifentanil stems from rapidity of onset
at present since it is associated with high incidence of of its effect, ability to titrate its desired effect and to
maternal desaturation and other side effects and is not maintain a sufficient plasma opioid concentration to
shown to be superior to any of the existing methods. suppress the stress response and finally rapidity of
recovery from its effects. It has proven to be of immense
Precautions value in anaesthetic practice. It is because of these
Remifentanil produces adverse events that are features, remifentanil has been called a “designer drug”
characteristic of opioids, such as respiratory depression, and rightly so, since it allows the user to practically “dial”
bradycardia, hypotension and skeletal muscle rigidity. its effect making it truly the opioid for the 21st century.
These events fortunately dissipate within minutes of References
discontinuing or decreasing the infusion rate of
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remifentanil. Notwithstanding this, precautions as acting µ-opioid. Anesth Analg 1996;83:646-51.
mentioned below should be taken to avoid accidents.
2. Egan TD, Lemmens JHM, Fiset P et al. The pharmacokinetics
Remifentanil should be administered only by persons of the new short acting opioid remifentanil (G187084B) in
specifically trained in the use of potent opioids. Such healthy adult male volunteers. Anesthesiology 1993;79:881-
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of a patent airway and assisted ventilation. 3. Hogue CW, Bowdle TA, O’Leary C et al. A multicenter
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should be preceded by the establishment of adequate intravenous anaesthesia with propofol and remifentanil in
postoperative analgesia. paediatric patients : a comparison with a desflurane-nitrous
oxide inhalation anaesthesia. Acta Anaes Scand 1998;42:845-
Continuous infusions of remifentanil should be 50.
administered only by an infusion device. IV bolus
5. Sreevastava DK, Madan R, Mahendru A, Rewari V, Kaul HL.
administration of remifentanil should be used only during Total intravenous anaesthesia with propofol and remifentanil
the maintenance of general anaesthesia. versus inhalational anaesthesia using halothane, nitrous oxide
Injections of remifentanil should be made into IV and pethidine in children undergoing strabismus surgery. (In
press).

MJAFI, Vol. 60, No. 2, 2004