Remifentanil (Ultiva) is a short-acting potent opioid analgesic medication that is used for pain and sedation during anesthesia and short procedures.

Remifentanil Uses:

• Anesthesia:

  • When general anaesthesia is being induced and maintained, it can be utilised as an analgesic. Adults who need ongoing analgesia during the first several days after surgery can receive it. This should be administered to patients who will be closely watched.

• Off Label Use of Remifentanil in Adults:

  • It is used in the management of mechanically ventilated patients as on off-label use.

Remifentanil (Ultiva) Dose in Adults

Remifentanil (Ultiva) Dose in the treatment of Anesthesia: IV continuous infusion:

• Induction of anesthesia:

  • The dosage ranges from 0.5 to 1 mcg/kg/minute.
    Moreover, if endotracheal intubation needs to be performed in less than 8 minutes, a 1 mcg/kg first dose can be given over 30 to 60 seconds.
  • The dose for coronary bypass surgery is 1 mcg/kg/minute.

• Maintenance of anesthesia:

  • Every 2 to 5 minutes, an additional bolus dosage of 1 mcg/kg can be given.
  • Concomitant anaesthetics should be increased if the infusion rate is greater than 1 mcg/kg/minute.
  • The infusion rate may be titrated up to 100% in increments or down to 25% in decrements.
  • With nitrous oxide (66%):
    • 0.4 mcg/kg/minute with range of 0.1 to 2 mcg/kg/minute.
  • With isoflurane:
    • 0.25 mcg/kg/minute with range of 0.05 to 2 mcg/kg/minute.
  • With propofol:
    • 0.25 mcg/kg/minute with range of 0.05 to 2 mcg/kg/minute.
  • Coronary bypass surgery:
    • 1 mcg/kg/minute with range of 0.125 to 4 mcg/kg/minute.
    • The supplemental dose is 0.5 to 1 mcg/kg.

• Continuation as an analgesic in the immediate postoperative period:

  • With a range of 0.025 to 0.2 mcg/kg/minute, it is specified as 1 mcg/kg/minute.
  • Every 5 minutes, the infusion rate can be changed by 0.025 mcg/kg/minute.
  • Bolus dosages should not be used. Respiratory depression is linked to infusion rates higher than 0.2 mcg/kg/min.
  • Coronary bypass surgery, continuation as an analgesic into the ICU:
    • It is given as 1 mcg/kg/minute with a range of 0.05 to 1 mcg/kg/minute.

Remifentanil (Ultiva) Dose as an Analgesic component of monitored anesthesia care:

Supplemental oxygen is recommended during its administration.

• Single IV dose administered 90 seconds prior to local anesthetic:

  • Remifentanil alone:
    • 1 mcg/kg over 30 to 60 seconds.
  • With midazolam:
    • 0.5 mcg/kg over 30 to 60 seconds

• Continuous infusion beginning 5 minutes prior to local anesthetic:

  • Remifentanil alone:
    • the dose is 0.1 mcg/kg minute
  • With midazolam:
    • the dose is 0.05 mcg/kg/minute

• Continuous infusion administered after local anesthetic:

  • Remifentanil alone:
    • it is administered as 0.05 mcg/kg/minute with range of 0.025 to 0.2 mcg/kg/minute.
  • With midazolam:
    • it is given concurrently as 0.025 mcg/kg/minute (range: 0.025 to 0.2 mcg/kg/minute)

It is important to remember that the infusion rate should be decreased to 0.05 mcg/kg/minute following local or anaesthetic block. At intervals of 5 minutes, the rate modifications of 0.025 mcg/kg/minute can be made. Respiratory depression is linked to infusion rates higher than 0.2 mcg/kg/min.

Remifentanil (Ultiva) Dose in the treatment of pain in mechanically ventilated patients (management) (off-label dose):

• The loading dose in this indication is 1.5 mcg/kg. 0.008 to 0.25 mcg/kg/minute (or 0.5 to 15 mcg/kg/hour) is the maintenance dose.

Remifentanil (Ultiva) Dose in Children

The dose should be determined on the ideal body weight (IBW) in obese individuals (>30% over IBW) if it is used for continuous IV infusion.

Remifentanil (Ultiva) Dose for postoperative analgesia (mechanically ventilated patient): Limited data available:

• Children and Adolescents 3-16 years:

  • Continuous IV infusion:
    • It is administered at 0.1 mcg/kg/minute, either with or without an additional drug.
    • The infusion can be increased till the desired effect.

Remifentanil (Ultiva) Dose in Analgesia and sedation in mechanically ventilated patients: Limited data available:

• Infants ≤2 months:

  • Continuous IV infusion:
    • It is administered first at 0.15 mcg/kg/minute and then titrated up to effect.

Remifentanil (Ultiva) Dose in the maintenance of anesthesia: Continuous IV infusion:

• Infants 1-2 months:

  • Nitrous oxide (70%) anaesthesia maintenance: 0.4 mcg/kg/minute, with a range of 0.4-1 mcg/kg/minute.
  • With potent inhalation medications, potent neuraxial anaesthesia, major comorbidities, considerable fluid changes, or in the
  • absence of atropine preparation, a lower additional bolus dose may be necessary.

• Infants ≥3 months, Children, and Adolescents: Limited data available:

  • Maintenance of anesthesia with halothane, sevoflurane, or isoflurane:
    • Its dose ranges from 0.05 to 1.3 mcg/kg/minute and is 0.25 mcg/kg/minute.
    • Every 2 to 5 minutes, a 1 mcg/kg supplementary bolus dosage may be given.
    • When using concurrent anaesthetics with an infusion rate more than 1 mcg/kg/minute, the dose should be raised.
    • The infusion rate may be adjusted in increments of up to 50% for an increase or 25% to 50% for a decrease. It can be adjusted every two to five minutes.

Remifentanil (Ultiva) Dose in the treatment of Anesthesia, total intravenous (TIVA); with or without propofol induction: Limited data available:

• Infants, Children, and Adolescents:

  • IV:Dosage of loading (may omit if propofol induction used):
    • It is administered in three minutes at a rate of 0.5 mcg/kg each minute, giving a total dose of 1.5 mcg/kg, or 1 mcg/kg over one minute.
  • A 0.05–0.1 mcg/kg/minute initial maintenance dose is given after that.
  • To get the desired effect, it can be increased by 0.05 mcg/kg/minute every three minutes.
  • 0.2 to 0.5 mcg/kg/minute is the typical effective range. It has been combined with either a bolus or an infusion of propofol.

Remifentanil (Ultiva) Dose in Endotracheal intubation for elective procedures: Limited data available:

• IV: Infants, Children, and Adolescents:

  • Its typical dosing range is 1-3 mcg/kg, while higher doses of 4 mcg/kg have been employed.
  • Dosage based on numerous trials in patients undergoing elective procedures requiring intubation who weren't receiving neuromuscular blockers and remifentanil given in conjunction with other induction drugs like propofol, ketamine, or sevoflurane.

• Intranasal (using parenteral 100 mcg/mL formulation): Children ≤7 years:

  • 4 mcg/kg/dose is the suggested dosage.
  • Half of the whole dose should be given into each nostril, followed by a two to three minute pause before trying intubation.

Remifentanil (Ultiva) Dose in the Procedural sedation:

• Infants, Children, and Adolescents:

  • IV:
    • Prior to esophagogastroduodenoscopy and brief hemato-oncologic invasive procedures, it has been administered at a dose of 0.5 mcg/kg with propofol to induce analgesia and adjunct sedation.
    • Infants and young children who had already been sedated (with sevoflurane) and needed apnea for CT or MRI imaging received a larger dose of 3 mcg/kg.
    • Remifentanil was continuously infused intravenously at a rate of 0.2 mcg/kg/minute in a dose-finding experiment on
    • 60 children aged 2 to 12 who were undergoing diagnostic cardiac catheterization.
    • Both a local groyne anaesthetic and an oral midazolam pre-treatment were employed.

Remifentanil pregnancy Category: C

• No adverse outcomes have been found in animal reproduction studies.
• Remifentanil crosses the placenta. It was found that the maternal and fetal concentrations of Remifentanil are equal.
• It is not recommended to be used during labor.

Remifentanil use during breastfeeding:

• It is unknown if breast milk contains it.
• Remifentanil's use during lactation is a matter of clinical judgment.
• Remifentanil's action is short-lived. Remifentanil is safe for breastfeeding women who are undergoing short procedures.

Dose in Kidney Disease:

No particular dose reductions are necessary. Remifentanil pharmacokinetics in patients with end-stage renal disease, however, are unaltered.

Dose in Liver disease:

In cases of hepatic impairment, no particular dose adjustment is necessary.

The frequency of adverse events may vary based on surgical procedures and the rate of infusion.

Common Side Effects of Remifentanil (Ultiva):

• Cardiovascular:

  • Hypotension

• Central Nervous System:

  • Headache

• Dermatologic:

  • Pruritus

• Gastrointestinal:

  • Nausea
  • Vomiting

• Neuromuscular & Skeletal:

  • Muscle Rigidity

Less Common Side Effects Of Remifentanil (Ultiva):

• Cardiovascular:

  • Bradycardia
  • Shivering
  • Hypertension
  • Flushing
  • Flushing Sensation
  • Tachycardia

• Central Nervous System:

  • Dizziness
  • Chills
  • Agitation

• Dermatologic:

  • Diaphoresis

• Local:

  • Pain At Injection Site

• Respiratory:

  • Respiratory Depression
  • Apnea
  • Hypoxia

• Miscellaneous:

  • Fever
  • Postoperative Pain

Contraindications to Remifentanil (Ultiva):

• Hypersensitivity to remifentanil (eg, anaphylaxis), is a severe contraindication.

Canadian labeling

• Any type of bowel transit disease (eg: ileus) that may be present or suspected.
• Suspected surgical abdomen
• Status asthmaticus, acute or severe bronchial asthma, chronic obstruction of the airway, status asthmaticus
• Acute respiratory depression.
• Hypercapnia.
• Cor pulmonale.
• Acute alcoholism, convulsive disorders, and delirium tremens.
• Grave CNS depression can lead to increased cerebrospinal and intracranial pressures, as well as head injury.
• Concurrent use of MAO inhibitors or within 14 days

There is not much evidence of cross-reactivity between opioids and allergenic opioids. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Hypotension

  • It can cause hypotension. Patients with hypovolemia, heart disease, acute MI and drugs that can exaggerate hypotensive effects, such as phenothiazines, general anesthetics, should not use it.
  • After dose titration or initiation, monitor for hypotension symptoms.

• Intraoperative awareness:

  • Patients aged 55 years have reported intraoperative awareness when propofol infusion rates are less than 75 mg/kg/minute.

• Respiratory depression

  • Even though it is recommended, serious, life-threatening or fatal respiratory depression should be reported.
  • Pay attention to respiratory depression during dose escalation or initiation.
  • The sedating effects of opioids can be exacerbated by carbon dioxide retention due to opioid-induced respiratory depression.

• Serotonin syndrome:

  • A potentially life-threatening serotonin disorder (SS) has been linked to concurrent use of remifentanil, SNRIs and serotonergic drugs (eg, SSRIs and SNRIs), mirtazapine and trazodone as well as agents that impair serotonin metabolism (eg MAO inhibitors).
  • Observe patients carefully for signs of SS, such as mental state changes (eg, agitation and hallucinations), delirium, coma, and other symptoms. 
  • Also, autonomic instability (eg tachycardia and labile blood pressure, diaphoresis), has been observed. 
  • In addition, there have been reports of seizures, Gastrointestinal symptoms (such as nausea, vomiting, and diarrhoea), and neuromuscular alterations such as tremors, rigidity, and myoclonus.
  • Withhold remifentanil if serotonin syndrome is thought to be present.

• Conditions abdominales:

  • It can make it difficult to diagnose or follow the clinical course of acute abdominal conditions.

• Insufficiency of the biliary tract:

  • Those with acute pancreatitis or biliary dysfunction shouldn't use it.
  • The sphincter Oddi may contract as a result of an opioid.

• Bradycardia

  • Patients with bradycardia should exercise caution.

• Delirium tremens:

  • Patients with delirium are advised to exercise caution

• Head trauma

  • Patients with intracranial injuries, intracranial lesions or elevated intracranial pressure (ICP) should be used with caution. You can raise the ICP.

• Obesity:

  Remifentanil should not be administered to obese patients.

• Prostatic hyperplasia/urinary restriction:

  • Patients with prostatic hyperplasia or urinary stricture should be cautious.

• Psychosis:

  • Toxic psychosis should not be treated with opioids.

• Respiratory disease

  • Patients with severe chronic obstructive lung disease (cor pulmonale) or significant chronic obstructive breathing problems, as well as those who have a significantly decreased respiratory reserve, hypoxia or hypercapnia or who are predisposed to developing or titrating respiratory depression should exercise caution. Even at therapeutic doses, severe respiratory depression can still occur.

• Seizures:

  • Remifentanil should not be given to patients with seizure disorder. It can worsen or increase the risk of preexisting seizure conditions.

• Thyroid dysfunction:

  • Thyroid dysfunction is a serious problem that requires caution.

Remifentanil: Drug Interaction

Monitoring parameters:

• Respiratory and cardiovascular status.
• Blood pressure and heart rate

Critically ill:

• Patients who can self-report their pain should use the Numeric Rating Scale.
• The Critical Care Pain Observational Tool and the Behavioral Pain Scale can be utilised in intubated or non-intubated patients who are unable to self-report their pain.

How to administer Remifentanil (Ultiva)?

IV: Continuous infusions should be administered intravenously using an infusion device.

• IV boluses can be administered for up to 30-60 seconds during general anesthesia maintenance.
• Injections should only be administered through IV tubing that is close to the venous catheter. 
• It's crucial to clean the tubing before administering any fluids through the same IV line to avoid any lingering effects.

Mechanism of action of Remifentanil (Ultiva):

• It binds to stereospecific mu-opioid receptors throughout the central nervous system (CNS).
• This affects perception, raises pain thresholds, and blocks ascending pain pathways.

The onset of action:

• IV: 1 to 3 minutes.
• Its Peak effect is seen in 3 to 5 minutes

Duration:

• 3 to 10 minutes.

Protein binding:

• ~70% (primarily alpha-1 acid glycoprotein)

Metabolism:

• It is quickly digested by tissue and blood esterases. It is not significantly processed by the liver or plasma cholinesterase (pseudocholinesterase).

Half-life elimination (dose dependent):

• Pediatric patients: Effective:
  • Neonates ≤2 months: 5.4 minutes (range: 3 to 8 minutes)
  • Infants and Children >2 months to <2 years: 3.4 minutes (range: 2 to 6 minutes)
  • Children 2 to 6 years: 3.6 minutes (range: 1 to 6 minutes)
  • Children 7 to 12 years: 5.3 minutes (range: 3 to 7 minutes)
  • Adolescents: 13 to <16 years: 3.7 minutes (range: 2 to 5 minutes)
  • Adolescents 16 to 18 years: 5.7 minutes (range: 5 to 6 minutes)
• Adults:
  • Terminal: 10 to 20 minutes;
  • Effective: 3 to 10 minutes
• Time to peak, serum: Intranasal:
  • Children ≤7 years: ~3.5 minutes

Excretion: Urine

International Brands of Remifentanil:

• Ultiva
• Remiva
• Remwareed
• Restinil
• Rui Jei
• Sagal
• Ulremif

Remifentanil Brand Names in Pakistan:

No Brands Available in Pakistan.