FRCA Notes

Remifentanil

Resources

  • Remifentanil is a synthetic phenylpiperidine derivative
  • It is differentiated from other similar drugs by the presence of an ester linkage
  • A white, crystalline, lyophilized powder which requires reconstitution prior to use
  • Stored in glass vials at room temperature, containing 1mg, 2mg or 5mg of remifentanil hydrochloride
  • Contains glycine as a buffer and therefore not licensed for spinal/epidural use
  • Reconstitutes to a clear, colourless solution

  • As a TCI infusion using the Minto or Eleveld models:
    • Alongside propofol as part of a TIVA anaesthetic
    • To facilitate intubation and ETT tolerance in patients in whom NMBA are contraindicated or otherwise not desired e.g. ENT surgery with nerve monitoring
    • To facilitate awake tracheal intubation

  • As a 'bog-standard' infusion:
    • To provide sedation and analgesia on intensive care

  • As a PCA to provide analgesia for labour pain

Respiratory

  • Potent respiratory depressant; reduces both RR & VT and can cause apnoea
  • Reduces central response to hypoxia or hypercapnoea
  • Chest wall rigidity (wooden chest phenomenon) due to μ-opioid receptor interaction with dopaminergic and GABAergic pathways in the substantia nigra and striatum

Cardiac

  • Bradycardia - a reported 20% drop in HR
  • Reduced MAP
  • Variably decrease myocardial contractility
  • Doesn't cause histamine release

Neurological

  • Analgesia via pure MOP agonism, with similar potency to fentanyl (i.e. 100x that of morphine)
  • Minimal hypnotic/sedative activity
  • Mioisis due to stimulation of the Edinger-Westphal nucleus as with other opioids
  • Centrally mediated vagal activity (hence bradycardia)

Gastrointestinal

  • Nausea and vomiting à la all opioids, though lower rates when compared to other opioids
  • Reduced gastric motility

Other

  • Potential antanalgesia or hyperalgesia - often requires use of other opioids as the infusion ends in order to provide suitable post-operative analgesia
  • Crosses the placenta and can potentially cause neonatal respiratory depression
  • Higher rates of post-operative shivering compared to other opioids

  • TCI uses the three-compartment Minto model, requiring age, gender, height and weight (LBW)

Absorption

  • pKa 7.1 - therefore 68% unionised at physiological Ph
  • Relative lipid solubility vs. morphine: 20x

Distribution

  • Low volume of distribution: 0.1 - 0.3L/kg
  • 70% plasma protein bound (approximately 2/3rds to ɑ1-acid glycoprotein)
  • Use lean body weight for infusion models

Metabolism

  • Rapidly broken down by non-specific muscle (tissue) and plasma esterases to an inactive carboxylic acid derivative
    • 1/4,600 potency of remifentanil
    • Metabolism isn't prolonged by hepatic or renal impairment
    • Unaffected by psuedo-cholinesterase deficiency and anti-cholinesterases

  • It uniquely has a context insensitive half-time of 3 - 5mins due to the abundance of these esterases

Excretion

  • Clearance 40ml/kg/min
  • Elimination half-life of remifentanil is 3-10mins, and is unaffected by hepatic or renal dysfunction
  • Carboxylic acid metabolite is excreted in the urine (95%) with an elimination half-life of ~2hrs
    • This metabolite can accumulate in renal failure, though owing to its low potency doesn't cause opioid effects