Fentanyl (Sublimaze, Duragesic)

Anesthesia Implications

Classification: opioid, μ receptor agonist
Therapeutic Effects: Analgesia, Sedation, CNS depression
Time to Onset: IV: 3-4 min; Intrathecal bolus: 5 min; Epidural bolus: 5 min;
Time to Peak: IV: 6 minutes
Duration: 30 minutes. Higher doses or subsequent doses produce longer duration.

Contraindications

Relative:
Patient taking any agent that blocks CYP3A4 (such as Ritonavir). This will reduce the metabolizing capabilities of the liver and raise the risk of overdose.

Primary Considerations

The most prominent and primary opioid used during the perisurgical period

Fentanyl is important in the surgical world because of its short time to peak effects, short duration of effects, cardiovascular safety, and its additive/synergistic effects with volatile agents which allow for a lower MAC – which is otherwise termed as “MAC-sparing” effects.

An important note to take about fentanyl is that it while the patient may lose respiratory capabilities, consciousness may still be preserved.  Therefore, when using fentanyl as the primary agent in a general anesthetic, midazolam or another drug should be used in conjunction to induce unconsciousness and amnesia.

Time to optimum effects is 6 minutes.  If attempts are being made to blunt the sympathetic response to intubation, there should be enough time to allow onset/peak effects.

Subsequent doses or infusion of fentanyl will result in prolonged effects (this is especially problematic with sedation and respiratory depression).

High doses bolus’s of opioids in general can result in chest wall and masseter rigidity.

Side effects that are particularly of note are: nausea, vomiting, itching

Pruritus / urticaria / itching is far less common in fentanyl than in other opioids such as morphine.  When itching/pruritus occurs, it is due to mast cell degranulation (same mechanism as morphine).

Fentanyl does not result in release of histamine.  Modest hemodynamic effects (reduction in blood pressure) are due to vagal activation.  Minimal direct myocardial depression.

Muscle rigidity is possible after high doses.  This is most common following induction.

Roughly 100x the potency of morphine and 1/10th the potency of sufentanil.

Opioids, in general, may promote hyperglycemia

Concomitant administration of Fentanyl is known to increase the half-life and potency of Etomidate

OB: 1 µg/kg provides good analgesia with no appreciable hemodynamic effect, no adverse effects on Apgar scores, no adverse effects on neurobehavioral scores at 2 and 24 hours.  Crosses the placenta, but average umbilical-to-maternal concentration remains low

IV push dose

Intubation: 1-3 mcg/kg
Obese – use TOTAL body weight

IV infusion dose

Obese – use LEAN body weight

Epidural bolus dose

25-100 mcg

Epidural maintenance rate

25-100 mcg/hour; Epidural PCA: 10-30 mcg every 10 minutes;

Spinal bolus dose

5-25 mcg

Method of Action

μ opioid agonist.

highly lipid soluble. Effects seen are a result of rapid entry into the brain and the apparent rapid return to baseline is actually a result of redistribution.

μ receptor agonism is primarily utilized for analgesia (spinal and supraspinal) and sedation.  Other effects include: reduced respiratory rate, reduced GI kinetics, increased release of prolactin and growth hormone, inhibition of acetylcholine and dopamine.

Metabolism

Liver and intestinal mucosa (CYP-450 34A). Active metabolite (Norfentanyl). 84% protein bound.

Elimination

Renal. Elimination half-life: 3-4 hours

Additional Notes
Fentanyl is also available for the oral/transmucosal and nasal route, but these are reserved for the treatment of cancer pain.

Fentanyl comes also as a patch for patients that have sustained moderate-severe pain. Increasing the temperature of the skin/patch will increase the absorption and potentially lead to overdose.

Schedule II controlled substance