Remifentanil (Ultiva)

Remifentanil (Ultiva) is a potent, short-acting, selective μ opioid receptor agonist. In critical care, it has been used for sedation and analgesia in mechanically ventilated adult patients.The concept of analgesia-based sedation represents a move away from traditional analgesic/hypnoticbased sedation, and with appropriate training this may be an easier regimen to manage. Remifentanil is also licensed for use in general anaesthesia. It has an onset of action of approximately 1 min and quickly achieves steady state. It is metabolised rapidly by non-specific blood and tissue esterases into clinically inactive metabolites.Thus the terminal half-life of 10–20 min is independent of infusion duration and renal and hepatic dysfunction.Though more expensive than traditional nanalgesic/hypnotic-based regimens, some units use remifentanil particularly in patients with renal or hepatic dysfunction, to avoid accumulation and prolonged sedation. Other possible indications for remifentanil include overnight ventilation, tracheostomy and ready to wean, difficult weans (e.g. COPD cardiovascular disease, obesity, problems of withdrawal following long-term sedation), head injuries or patients with low GCS requiring regular assessment, raised intracranial pressure (resistant to medical management) and to assess neurological function in mechanically ventilated patients.

Concerns around use of remifentanil include side-effects of hypotension and bradycardia, possible development of tolerance (common to all opioids) and the onset of pain on discontinuation of remifentanil.

Uses
Analgesia and sedation in mechanically ventilated adults. Trials have been conducted for up to 3 days of use.

Contraindications
Epidural and intrathecal use, as formulated with glycine
Hypersensitivity to fentanyl analogues

Administration
• IV: initially 0.1 μg/kg/min, evaluate after 5 min, if pain, anxiety or agitation or difficult to wake, then titrate infusion up or down with steps of 0.025 μg/kg/min (range 0.007–0.75 μg/kg/min).At a dose of 0.2 μg/kg/min, if the patient is in pain or ventilator intolerant, increase the infusion by additional steps of 0.025 μg/kg/min until adequate pain relief. At a dose of 0.2 μg/kg/min, if the patient is anxious or agitated then add a hypnotic agent, e.g. midazolam (bolus up to 0.03 mg/kg or initial infusion 0.03 mg/kg/h) or propofol (bolus up to 0.5 mg/kg or initial infusion 0.5 mg/kg/h)

• Additional analgesia will be required for ventilated patients undergoing stimulating procedures such as suctioning,wound dressing and physiotherapy. An infusion of 0.1 μg/kg/min should be maintained for at least 5 min prior to intervention. Further adjustments every 2–5 minutes in increments of 25–50% may be needed

• To extubate and discontinue remifentanil, titrate in stages to 0.1 μg/kg/min over 1 hour prior to extubation. After extubation, reduce infusion rate by 25% at least every 10 min till discontinuation. If residual pain is expected use alternative opioid

Reconstitute vial to 100 μg/ml, i.e. 5-mg vial with 50 ml, 2 mg with 20 ml, and 1 mg with 10 ml of diluent. Suitable diluents are WFI, glucose 5% or sodium chloride 0.9% In obesity, use ideal body weight rather than actual weight In the elderly, reduce initial dose by 50% Due to the short half-life, a new syringe should be ready for use at the end of each infusion.

How not to use remifentanil
Bolus doses are not recommended in the critical care setting. Not to be used as a sole induction agent

Adverse effects:
• hypomagnesaemia
• bradycardia
• hypotension
• respiratory depression
• muscle rigidity
• dependency

Cautions
Upon discontinuation, the IV line should be cleared or removed to prevent subsequent inadvertent administration

Organ failure
Renal: no dose adjustment necessary
Hepatic: no dose adjustment, but in severe disease respiratory depression more common

Organ replacement therapy
Not removed by dialysis, so no dose adjustment required in renal replacement therapy