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:

  • It can be used as an analgesic for use during the induction and maintenance of general anesthesia. It can be given for continued analgesia into the immediate postoperative period in adults. The patients receiving this should be monitored closely.

• 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:

  • It is administered as 0.5 to 1 mcg/kg/minute.
  • And if endotracheal intubation is to occur in less than 8 minutes, an initial dose of 1 mcg/kg can be administered over 30 to 60 seconds
  • Coronary bypass surgery: the dose is 1 mcg/kg/minute

• Maintenance of anesthesia:

  • A supplemental bolus dose of 1 mcg/kg can be administered every 2 to 5 minutes.
  • Consider increasing concomitant anesthetics with infusion rate >1 mcg/kg/minute.
  • The infusion rate can be titrated upward in increments of 25% to 100% or downward in decrements of 25% to 50% every 2 to 5 minutes.
  • 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:

  • it is given as 1 mcg/kg/minute with range of 0.025 to 0.2 mcg/kg/minute.
  • The infusion rate can be adjusted every 5 minutes in increments of 0.025 mcg/kg/minute.
  • Bolus doses are not preferred. Infusion rates of more than 0.2 mcg/kg/minute are associated with respiratory depression.
  • 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 noteworthy that after local or anesthetic block, the infusion rate should be reduced to 0.05 mcg/kg/minute. The rate adjustments of 0.025 mcg/kg/minute can be done at 5-minute intervals. Infusion rates of more than 0.2 mcg/kg/minute are associated with respiratory depression.

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

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

Remifentanil (Ultiva) Dose in Childrens

If it is used for continuous IV infusion in obese patients, the dose should be based on ideal body weight (IBW) in obese patients (>30% over IBW).

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

• Children and Adolescents 3-16 years:

  • Continuous IV infusion:
    • it is given as 0.1 mcg/kg/minute with or without adjunctive medication.
    • The infusion can be titrated up to the effect.

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

• Infants ≤2 months:

  • Continuous IV infusion:
    • Initially, it is given as 0.15 mcg/kg/minute and titrate it up to effect.

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

• Infants 1-2 months:

  • For maintenance of anesthesia with nitrous oxide (70%): 0.4 mcg/kg/minute with range of 0.4-1 mcg/kg/minute.
  • The supplemental bolus dose of 1 mcg/kg can be administered, smaller bolus dose can be required with potent inhalation agents, potent neuraxial anesthesia, significant comorbidities, significant fluid shifts, or without atropine pretreatment

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

  • Maintenance of anesthesia with halothane, sevoflurane, or isoflurane:
    • its dose is 0.25 mcg/kg/minute with a range of 0.05 - 1.3 mcg/kg/minute.
    • The supplemental bolus dose of 1 mcg/kg may be administered every 2-5 minutes.
    • The dose should be increased with concomitant anesthetics with an infusion rate of more than 1 mcg/kg/minute.
    • The infusion rate can be titrated upward in increments up to 50% or titrated downward in decrements of 25% to 50%. It can be titrated every 2-5 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: Loading dose (may omit if propofol induction used):
    • its given as 0.5 mcg/kg/minute for 3 minutes with total dose of 1.5 mcg/kg or 1 mcg/kg over 1 minute.
  • Its followed by an initial maintenance dose of 0.05-0.1 mcg/kg/minute.
  • It can be titrated in 0.05 mcg/kg/minute increments every 3 minutes to effect.
  • The usual effective range is 0.2-0.5 mcg/kg/minute. It has been used in combination with propofol either bolus or infusion).

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

• IV: Infants, Children, and Adolescents:

  • Its usual range is 1-3 mcg/kg/dose and doses as high as 4 mcg/kg have been used.
  • Dosing based on multiple trials in patients undergoing elective procedures requiring intubation who were not receiving neuromuscular blockers and remifentanil administered in combination with other induction agents such as propofol, ketamine, or sevoflurane.

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

  • Its recommended dose is 4 mcg/kg/dose.
  • Administer half of the total dose in each nostril then wait 2-3 minutes before attempting intubation.

Remifentanil (Ultiva) Dose in the Procedural sedation:

• Infants, Children, and Adolescents:

  • IV:
    • Its dose is 0.5 mcg/kg with propofol has been used to induce analgesia and adjunct sedation prior to esophagogastroduodenoscopy and short hemato-oncologic invasive procedures.
    • A higher dose of 3 mcg/kg was used in already sedated (sevoflurane) infants and young children who required apnea for CT or MRI imaging.
    • In a dose-finding trial, continuous IV infusion of remifentanil at 0.2 mcg/kg/minute has been shown more effective than a lower 0.1 mcg/kg/minute in 60 children 2-12 years undergoing diagnostic cardiac catheterization.
    • The pre-treatment with oral midazolam and local groin anesthetic were also used.

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 specific dose reductions are required. However, remifentanil pharmacokinetics are unchanged in patients with end-stage renal disease.

Dose in Liver disease:

No specific dose adjustment is required in hepatic impairment.

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 such as acute appendicitis, pancreatitis or pancreatitis.
• Mild pain can be controlled with pain medication.
• 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. 
  • Also, neuromuscular changes such as tremors, rigidity, myoclonus, GI symptoms (eg nausea, vomiting, diarrhea) and seizures have been observed.
  • If serotonin syndrome is suspected, withhold remifentanil.

• Conditions abdominales:

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

• Insufficiency of the biliary tract:

  • It should not be used in patients suffering from biliary dysfunction or acute pancreatitis. Opioid can cause constriction in the sphincter Oddi.

• 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:

• The Numeric Rating Scale should be used in patients who are able to self-report pain.
• In patients who are unable to self-report pain, the Behavioral Pain Scale and the Critical Care Pain Observational Tool can be used in intubated or non-intubated patients.

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. 
• To prevent any residual effects from other fluids being administered through the same IV line, it is important to clear the tubing.

Mechanism of action of Remifentanil (Ultiva):

• It binds to stereospecific mu-opioid receptors in many locations within the CNS.
• This increases pain threshold, alters perception, and inhibits 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 rapidly metabolized via blood and tissue esterases. It is not metabolized by plasma cholinesterase (pseudocholinesterase) and is not appreciably metabolized by the liver

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.