Fentanyl

Brand Names Reversal Agents Warnings
Description Special Circumstances Alternative Medications
Dosing Side effects and risks Contraindications
Over sedation Common Issues  

Brand Names

Sublimaze 

Description
  • Fentanyl is a short-acting synthetic opioid narcotic. It is highly lipid soluble and rapidly relieves pain by stimulating opioid receptors in the CNS.  A dose of 100 mcg (0.1 mg) (2 mL) is approximately equivalent in analgesic activity to 10 mg of morphine or 75 mg of meperidine.
  • Alterations in respiratory rate and alveolar ventilation, associated with narcotic analgesics, may last longer than the analgesic effect. As the dose of narcotic is increased, respiratory depression becomes greater. Even small doses of fentanyl may produce apnea because of the pharmacokinetic and pharmacodynamic variability in patients.
  • Fentanyl appears to have less emetic activity than either morphine or meperidine. 
  • Histamine assays and skin wheal testing in normal human volunteers indicate that clinically significant histamine release rarely occurs with fentanyl. Recent assays in man show no clinically significant histamine release in dosages up to 50 mcg/kg (0.05 mg/kg) (1 mL/kg).

How supplied

  • Fentanyl Citrate Injection, USP, equivalent to 50 mcg (0.05 mg) fentanyl base per mL, is available as:
    • Infusion, as citrate [premixed in NS]: 0.05 mg (10 mL); 1 mg (100 mL); 1.25 mg (250 mL); 2 mg (100 mL); 2.5 mg (250 mL)
    • Injection, solution, as citrate [preservative free]: 0.05 mg/mL (2 mL, 5 mL, 10 mL, 20 mL, 30 mL, 50 mL)   Sublimaze®: 0.05 mg/mL (2 mL, 5 mL, 10 mL, 20 mL)
Dosing

The onset of action of fentanyl is almost immediate when the drug is given intravenously; however, the maximal analgesic and respiratory depressant effect may not be noted for several minutes. The usual duration of action of the analgesic effect is 30 to 60 minutes after a single intravenous dose of up to 100 mcg (0.1 mg) (2 mL). In clinical practice, opioids are usually combined with a benzodiazepine for endoscopic sedation.

Fentanyl Dosing for Endoscopic Sedation

Adult*  

  • Initial dose:  50-100 mcg
  • Additional doses: doses of 25 mcg can be administered every 2-5 minutes until adequate sedation is achieved
  • Onset of action: 1-2 minutes
  • Peak effect: 3-5 minutes
  • Duration of effect: 30-60 minutes
*A dose reduction of 50% or more is indicted for the elderly.

Pediatric* (Children over age 12)

  • Initial dose: 0.5-1 mcg/kg (maximum dose 50 mcg)
  • Maximum dose: 5 mcg/kg or 250 mcg (whichever is less)

*The safety and efficacy of fentanyl citrate in pediatric patients under two years of age has not been established. Dosing recommendations are based on institutional experience described in peer reviewed literature.

Over sedation

Symptoms

The manifestations of fentanyl overdosage are an extension of its pharmacologic actions as with other opioid analgesics.

Treatment

  • In the presence of hypoventilation or apnea, oxygen should be administered and respiration should be assisted or controlled as indicated. A patent airway must be maintained; an oropharyngeal airway or endotracheal tube might be indicated.
  • A specific narcotic antagonist such as naloxone should be available for use as indicated to manage respiratory depression. This does not preclude the use of more immediate countermeasures.
  • If hypotension occurs and is severe or persists, the possibility of hypovolemia should be considered and managed with appropriate parenteral fluid therapy.
  • The duration of respiratory depression following overdosage of fentanyl may be longer than the duration of narcotic antagonist action.
Reversal Agents

Naloxone

Special Circumstances
  • Use in elderly and disabled patients: The initial dose of fentanyl citrate should be appropriately reduced in elderly and debilitated patients. The effect of the initial dose should be considered in determining incremental doses.
  • Use with nitrous oxide: Nitrous oxide has been reported to produce cardiovascular depression when given with higher doses of fentanyl.
  • Use with droperidol: (see droperidol). Elevated blood pressure, with and without pre-existing hypertension, has been reported following administration of fentanyl citrate combined with droperidol.
  • Respiratory depression: Respiratory depression caused by opioid analgesics can be reversed by opioid antagonists such as naloxone. Because the duration of respiratory depression produced by fentanyl may last longer than the duration of the opioid antagonist action, appropriate surveillance should be maintained. As with all potent opioids, profound analgesia is accompanied by respiratory depression and diminished sensitivity to CO2 stimulation which may persist into or recur in the recovery period. Intraoperative hyperventilation may further alter postoperative response to CO2. Appropriate postoperative monitoring should be employed to ensure that adequate spontaneous breathing is established and maintained in the absence of stimulation prior to discharging the patient from the recovery area. (see Recovery and Discharge)
  • Impaired Respiration: Fentanyl should be used with caution in patients with chronic obstructive pulmonary disease, patients with decreased respiratory reserve, and others with potentially compromised respiration.
  • Impaired Hepatic or Renal Function: Fentanyl citrate should be administered with caution to patients with liver and kidney dysfunction because of the importance of these organs in the metabolism and excretion of drugs.
  • Cardiovascular Effects: Fentanyl may produce bradycardia, which may be treated with atropine. Fentanyl should be used with caution in patients with cardiac bradyarrhythmias.
  • Drug Interactions: Other CNS depressant drugs (e.g., barbiturates, tranquilizers, narcotics and general anesthetics) will have additive or potentiating effects with fentanyl. When patients have received such drugs, the dose of fentanyl required will be less than usual. Following the administration of fentanyl citrate, the dose of other CNS depressant drugs should be reduced.
  • Carcinogenesis, Mutagenesis, Impairment of Fertility: No carcinogenicity or mutagenicity studies have been conducted with fentanyl citrate. Reproduction studies in rats revealed a significant decrease in the pregnancy rate of all experimental groups. This decrease was most pronounced in the high dosed group (1.25 mg/kg—12.5X human dose) in which one of twenty animals became pregnant.
  • Teratogenic Effects: Pregnancy Category C. Fentanyl citrate has been shown to impair fertility and to have an embryocidal effect in rats when given in doses 0.3 times the upper human dose for a period of 12 days. No evidence of teratogenic effects have been observed after administration of fentanyl citrate to rats. There are no adequate and well-controlled studies in pregnant women. Fentanyl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Pediatric Use: The safety and efficacy of fentanyl citrate in pediatric patients under two years of age has not been established. Rare cases of unexplained clinically significant methemoglobinemia have been reported in premature neonates undergoing emergency anesthesia and surgery which included combined use of fentanyl, pancuronium and atropine.  A direct cause and effect relationship between the combined use of these drugs and the reported cases of methemoglobinemia has not been established.
Side Effects and Risks

As with other narcotic analgesics, the most common serious adverse reactions reported to occur with fentanyl are respiratory depression, apnea, rigidity and bradycardia; if these remain untreated, respiratory arrest, circulatory depression or cardiac arrest could occur. Other adverse reactions that have been reported are hypertension, hypotension, dizziness, blurred vision, nausea, emesis, laryngospasm and diaphoresis. Additional adverse reactions may include:

  • Secondary rebound respiratory depression following procedure. Patients should be monitored for this possibility and appropriate countermeasures taken as necessary.
  • Fentanyl citrate injection is a Schedule II controlled drug substance that can produce drug dependence of the morphine type and, therefore, has the potential for being abused.
Common Issues

As with other narcotic analgesics, the most common serious adverse reactions reported to occur with fentanyl are respiratory depression, apnea, rigidity and bradycardia; if these remain untreated, respiratory arrest, circulatory depression or cardiac arrest could occur. 

Warnings
  • If fentanyl is administered with a tranquilizer such as droperidol, the user should become familiar with the special properties of each drug, particularly the widely differing durations of action. In addition, when such a combination is used, fluids and other countermeasures to manage hypotension should be available.
  • As with other potent narcotics, the respiratory depressant effect of fentanyl may persist longer than the measured analgesic effect. The total dose of all narcotic analgesics administered should be considered by the practitioner before ordering narcotic analgesics during recovery from sedation. It is recommended that narcotics, when required, should be used in reduced doses initially, as low as 1/4 to 1/3 those usually recommended.
  • Adequate facilities should be available for postoperative monitoring and ventilation of patients administered anesthetic doses of fentanyl. Where moderate or high doses are used there must be adequate facilities for postoperative observation, and ventilation if necessary, of patients who have received fentanyl. It is essential that these facilities be fully equipped to handle all degrees of respiratory depression.
  • Fentanyl may also produce other signs and symptoms characteristic of narcotic analgesics including euphoria, miosis, bradycardia and bronchoconstriction.
  • Severe and unpredictable potentiation by MAO inhibitors has been reported for other narcotic analgesics. Although this has not been reported for fentanyl, there are insufficient data to establish that this does not occur with fentanyl. Therefore, when fentanyl is administered to patients who have received MAO inhibitors within 14 days, appropriate monitoring and ready availability of vasodilators and beta-blockers for the treatment of hypertension is indicated.
Alternative Medications
Contraindications

Fentanyl is contraindicated in people with hypersensitivity to opiates and individuals with myasthenia gravis.


Sources

Cohen LB, DeLegge MH, Aisenberg J, Brill JV, Inadomi JM, et al. AGA Institute review of endoscopic sedation. Gastroenterology. 2007 Aug;133(2):675-701.

Fentanyl Citrate Injection, solution  [package insert], Baxter Healthcare Corporation. September 2006. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=1618  Accessed April 20, 2008.

Skidmore-Roth L, McKenry L, Mosby’s Drug Guide for Nurses, 3rd ed.St. Louis, MO: Mosby; 1999:526-8.

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