Remifentanil

A. Approved Indications

1.        Adjunct to General Anesthesia

o    For induction and maintenance of general anesthesia in adults and pediatric patients (≥2 months old)

o    Used in combination with hypnotics, muscle relaxants, and inhalational agents or total intravenous anesthesia (TIVA)

2.        Analgesic in Mechanically Ventilated Intensive Care Unit (ICU) Patients

o    For the provision of analgesia and sedation in mechanically ventilated adult patients in ICU settings (short-term use only)

B. Clinically Accepted Off-label Uses

• Sedation in procedural anesthesia for short diagnostic or therapeutic procedures (e.g., endoscopy, bronchoscopy)
• Supplemental analgesia during monitored anesthesia care (MAC)
• Use in rapid sequence intubation in high-risk surgical settings

A. Adults

General Anesthesia (Induction):

• 1.0 μg/kg to 2.5 μg/kg IV bolus over 30 to 60 seconds
• Administer just before induction with hypnotic agent

General Anesthesia (Maintenance):

• Continuous IV infusion: 0.1–2.0 μg/kg/min, titrated based on response
• Use lower doses (0.05–1 μg/kg/min) when combined with other sedatives or inhalational agents

B. ICU Analgesia in Mechanically Ventilated Adults:

• Initial infusion: 0.1 μg/kg/min, titrated up to 0.2 μg/kg/min
• Use for short-term duration only (≤3 days recommended)
• Not recommended for prolonged sedation due to risk of tolerance and withdrawal

C. Pediatric Dosing (≥2 months old)

• Induction bolus: 1–3 μg/kg IV
• Maintenance infusion: 0.05–1.3 μg/kg/min
• Titrate individually during surgical anesthesia

D. Special Populations

• Elderly:
• Increased sensitivity; initiate at lower end of dosage range
• Maintenance infusion usually requires 50% dose reduction
• Renal Impairment:
• No adjustment necessary (organ-independent metabolism)
• Hepatic Impairment:
• No dose adjustment required

Administration:

• Administer via IV infusion using a controlled infusion device
• Infusion must be prepared and diluted appropriately (see storage section)
• Do not administer as intramuscular injection or undiluted IV push

Remifentanil is a potent, ultra-short-acting μ-opioid receptor agonist. It binds selectively to μ-opioid receptors in the central nervous system (CNS), inhibiting ascending pain pathways, altering the perception of and response to pain. It also produces analgesia and sedation by suppressing neuronal excitability in pain-transmitting circuits. Unlike other opioids, Remifentanil is unique in being rapidly metabolized by nonspecific plasma and tissue esterases, allowing for precise and predictable offset even after prolonged infusions.

• Absorption: Not orally bioavailable; administered via intravenous route only
• Onset of Action: 1–3 minutes after IV administration
• Peak Effect: Within 3–5 minutes
• Duration: 5–10 minutes (rapid offset)
• Distribution: Volume of distribution ~0.3–0.4 L/kg
• Protein Binding: ~70% (primarily to albumin)
• Metabolism:
• Rapidly hydrolyzed by nonspecific blood and tissue esterases to inactive carboxylic acid metabolite (remifentanil acid)
• Elimination Half-life:
• Terminal half-life: 3 to 10 minutes
• Context-sensitive half-time remains short, even with prolonged infusion
• Excretion:
• Primarily renal excretion of inactive metabolite (~95%)

Pregnancy:

• FDA Pregnancy Category C
• Use only if potential benefit justifies potential fetal risk
• May cause respiratory depression in the neonate if used during labor and delivery
• Not recommended for use during labor (outside controlled settings)

Lactation:

• Unknown if remifentanil is excreted in human breast milk
• Due to its short half-life and rapid metabolism, systemic exposure to infants via milk is expected to be low
• Caution advised during breastfeeding; consider withholding breastfeeding for several hours after dosing

• Primary Class: Opioid Analgesic
• Subclass: Ultra-short-acting μ-opioid receptor agonist (Anilidopiperidine class)
• Use: Procedural and surgical anesthesia adjunct, ICU sedation

• Known hypersensitivity to remifentanil or other fentanyl analogs
• Known or suspected opioid intolerance or allergy
• Epidural or intrathecal administration (not approved for these routes)
• Absence of resuscitative equipment and personnel trained in airway management
• Use in neonates and infants <2 months old (safety not established)

• Respiratory Depression:
• Dose-dependent and can be profound; requires continuous respiratory monitoring and emergency airway support readiness
• Bradycardia & Hypotension:
• Significant risk, especially with co-administration of other CNS depressants or in elderly
• Muscle Rigidity:
• May occur with high-dose or rapid bolus; may interfere with ventilation
• Preventable by co-administration of neuromuscular blockers
• Withdrawal Syndrome:
• Rapid offset may lead to opioid withdrawal and acute pain if not transitioned to longer-acting agents
• Tolerance Development:
• Particularly in ICU use with prolonged infusion
• Monitoring:
• Requires continuous cardiovascular and respiratory monitoring
• Adjust dosage to response; titration essential

Common Adverse Effects:

• Central Nervous System: Sedation, dizziness
• Respiratory: Respiratory depression, apnea
• Cardiovascular: Bradycardia, hypotension
• Musculoskeletal: Muscle rigidity (including chest wall)
• GI: Nausea, vomiting
• Injection Site: Pain or phlebitis at infusion site

Serious Adverse Effects:

• Severe respiratory depression or apnea
• Cardiac arrest in rare cases (due to bradycardia)
• Anaphylaxis or hypersensitivity reactions (rare)
• Withdrawal symptoms with abrupt discontinuation
• Tolerance or opioid-induced hyperalgesia in prolonged ICU settings

Onset & Severity:

• Adverse effects typically occur rapidly after administration due to fast onset
• Severity is dose-dependent and more likely with higher or bolus doses

• Other CNS Depressants (e.g., benzodiazepines, propofol, barbiturates):
• Additive or synergistic effects → increased risk of sedation, hypotension, and respiratory depression
• Inhaled Anesthetics (e.g., sevoflurane, isoflurane):
• Potentiate remifentanil effects → dosage reduction advised
• Neuromuscular Blocking Agents:
• No direct pharmacodynamic interaction but commonly co-administered for muscle rigidity prevention
• No CYP450 interaction:
• Remifentanil is not metabolized by CYP enzymes, avoiding common CYP3A4-based interactions
• Alcohol:
• Not applicable due to inpatient use; however, avoid additional CNS depressants

• Guidelines:
• Endorsed in multiple anesthesia protocols as a preferred opioid for short procedures and rapid recovery cases
• ERAS (Enhanced Recovery After Surgery) programs recommend remifentanil for fast-track anesthesia strategies
• COVID-19 ICU Protocols:
• Temporarily used in some ICUs for ventilated COVID-19 patients, due to rapid onset and offset, though caution advised with prolonged infusion
• Safety Communications:
• Emphasis from regulatory bodies (e.g., FDA, MHRA) on avoiding off-label epidural/intrathecal use

• Powder for Reconstitution (Vial):
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from light and moisture
• Reconstitution Instructions:
• Reconstitute with sterile water or 0.9% NaCl
• Must be diluted to final concentration (typically 20–50 mcg/mL) before infusion
• After Reconstitution:
• Stable for up to 24 hours at room temperature (depending on dilution fluid)
• Do not freeze
• Handling Instructions:
• Use aseptic technique
• Single-use vial; discard unused portion