Remifentanil

Remifentanil is used for: Analgesia, during induction of anaesthesia, Analgesia during maintenance of anaesthesia in ventilated patients, Continuation of analgesia into immediate postoperative period, Analgesia and sedation in ventilated patients under intensive care, Analgesia in cardiac anaesthesia

Intravenous Analgesia during induction of anaesthesia Adult: To be used in conjunction an hypnotic agent (e.g. propofol, thiopentone, isoflurane): Infuse at 0.5-1 mcg/kg/minute. If the patient is to be intubated <8 minutes after the start of the infusion, an additional initial IV bolus of 1 mcg/kg may be given over 30-60 seconds. Analgesia during maintenance of anaesthesia in ventilated patients Adult: Usual infusion doses range: 0.05-2 mcg/kg/minute depending on the anaesthetic drug used and titrated according to patient response. In response to light anaesthesia or intense surgical stress, supplemental IV boluses of 0.5-1 mcg/kg may be admin every 2-5 minutes. In spontaneous respiration, infuse at 0.04 mcg/kg/minute, then titrated according to response. Usual range of 0.025- 0.1 mcg/kg/minute. Bolus doses not recommended during spontaneous ventilation. Continuation of analgesia into immediate postoperative period Adult: Usual range: 100-200 nanograms/kg per minute, given via IV infusion. Infusion rates >0.2 mcg/kg/minute may be associated with respiratory depression. Not recommended to give supplemental bolus doses during the postoperative period. Analgesia and sedation in ventilated patients under intensive care Adult: Initially, IV infusion 0.1-0.15 mcg/kg/minute, titrated in increments of 0.025 mcg/kg/minute according to response, allowing at least 5 minutes between dose adjustments. Add additional sedative drugs if desired response not obtained after an infusion rate of 0.2 mcg/kg/minute reached. If patient undergoing stimulating or painful procedures (e.g. endotracheal suctioning, wound dressing), maintain an infusion rate of at least 0.1 mcg/kg/minute 5 minutes before procedure, adjust rate every 2-5 minutes according to response, max: 0.75 mcg/kg/min; bolus doses not recommended. For extubation and discontinuation of remifentanil, titrate infusion rate downwards in stages to 0.1 mcg/kg/minute up to 1 hr before extubation. After extubation, infusion rate to be further reduced in 25% decrements in at least 10 minute intervals until infusion is discontinued. Do not increase infusion rate during weaning from ventilator. Analgesia in cardiac anaesthesia Adult: Induction of anaesthesia: By continuous infusion at a rate of 1 mcg/kg/minute, endotracheal intubation to start at least 5 minutes after start of infusion. Maintenance of anaesthesia (in conjunction with hypnotic agent): After intubation, titrate infusion upwards or downwards by 25-50% every 2-5 minutes, depending on patient response. Supplemental IV bolus of 0.5-1 mcg/kg, admin over at least 30 seconds, may be given every 2-5 minutes as needed. Max bolus dose in high risk cardiac patients (e.g. undergoing valve surgery) and hypothermic cardiopulmonary bypass: 0.5 mcg/kg. Infusion of remifentanil to be maintained at final intra-operative rate post-operatively, titrated according to patient's needs. Prior to discontinuation of remifentanil, alternative analgesic and sedative agents to be admin and allowed to reach therapeutic effects. Reduce infusion rate by 25% decrements at least every 10 minutes until infusion is discontinued.

Intravenous Analgesia during maintenance of anaesthesia in ventilated patients Child: Neonates: IV infusion 0.4-1.0 mcg/kg/minute depending on the anaesthetic method and adjust according to patient response, supplemental IV inj of 1 mcg/kg dose may be given. 1-12 yr: initially 0.1-1 mcg/kg by IV inj over at least 30 seconds (excluded if not needed), followed by IV infusion 0.05-1.3 mcg/kg/minute depending on the anaesthetic method and adjust according to patient response, supplemental IV bolus inj may be admin during infusion. 12-18 yr: 0.1-1 mcg/kg IV inj over at least 30 seconds (excluded if not needed), followed by IV infusion of 0.05-2 mcg/kg/minute depending on anaesthetic method and adjust according to patient response, supplemental IV bolus inj may be admin during infusion.

IV Preparation Add 1 ml of diluent per mg of remifentanil and shake well. The reconstituted solution should be further diluted to 20, 25, 50 or 250 mcg/ml before admin. Suitable diluents include sterile water for inj, 5% dextrose, 5% dextrose and 0.9% sodium chloride, 0.9% sodium chloride, 0.45% sodium chloride. IV Administration IV injection over 30-60 sec May also do IV infusion

Not for epidural or intrathecal admin due to glycine present in the formulation. Hypersensivity to fentanyl analogs. Not to be used as sole agent for anaesthesia induction.

Addiction, abuse, and misuse Therapy exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death Assess each patient’s risk prior to prescribing therapy, and monitor all patients regularly for the development of these behaviors and conditions. Not recommended in patients with poor ventricular function (LVEF <0.35). Severe hepatic impairment. Not for long term use as analgesia in intensive care patients. Avoid inadvertent admin by administering remifentanil into fast flowing IV line or dedicated IV line and removing the IV tubing once the drug is discontinued. Monitor vital signs and oxygenation continually during admin. Pregnancy, lactation.

Pregnancy Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage Labor or delivery Opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression Lactation The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped

Increased CNS depression with inhaled and IV anaesthetics, benzodiazepines; decrease dose if used concomitantly. Increased hypotension and bradycardia with cardiac depressants (e.g. β-blockers, calcium channel blockers). Potentially Fatal: Increased CNS depressant with sodium oxybate.

Side effects of Remifentanil : >10% Nausea Vomiting 1-10% Respiratory depression Bradycardia (dose dependent) Hypertension Hypotension (dose dependent) Tachycardia Skeletal muscle rigidity (dose dependent) Postoperative pain Shivering Apnea Hypoxia Respiratory depression Biliary tract disease

Remifentanil, an anilidopiperidine derivative, is a short-acting mu-receptor opioid, related to fentanyl.