remifentanil (Rx)

>10%

Nausea

Vomiting

1-10%

Respiratory depression

Bradycardia (dose dependent)

Hypertension

Hypotension (dose dependent)

Tachycardia

Skeletal muscle rigidity (dose dependent)

Postoperative pain

Shivering

Apnea

Hypoxia

Respiratory depression

Biliary tract disease

Postmarketing Reports

Serotonin syndrome

Contraindications

Epidural or intrathecal administration

Known hypersensitivity to fentanyl analogs

Cautions

In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma

Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate

Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected

Muscle rigidity occurring during induction of can be treated by decreasing rate or discontinuing infusion of drug or by administering a neuromuscular blocking agent; neuromuscular blocking agents used should be compatible with patient's cardiovascular status

Bradycardia may occur; monitor heart rate during dosage initiation and titration; responsive to ephedrine or anticholinergic drugs

Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

Not to be administered into same IV tubing with blood due to potential inactivation by nonspecific esterases in blood products

Therapy may increase frequency of seizures in patients with seizure disorders and in other clinical settings associated with seizures; monitor patients for worsened seizure control during therapy

May cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients; monitor closely

Continuous infusions should be administered only by an infusion device

Clear IV tubing after discontinuation of remifentanil

May be associated with apnea and respiratory depression, skeletal muscle rigidity

Should not be administered in same IV tubing as blood

Intraoperative awareness in some pts under 55 yo when admin. with propofol infusion < 75 mcg/kg/min

Pregnancy

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage

Labor or delivery

• Opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression

Lactation

The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Opioid agonist; inhibits ascending pain pathways, which causes alteration in response to pain; produces analgesia, respiratory depression, and sedation, increases pain threshold

Pharmacokinetics

Half-Life: 3-10 min

Onset: 1-3 min (IV)

Protein Bound: 70%

Vd: 100 mL/kg

Clearance: 40 mL/min/kg

Excretion: Urine

IV Incompatibilities

Y-site: amphotericin B(?), ampho B cholesteryl SO4, cefoperazone(?), chlorpromazine(?), diazepam(?)

IV Compatibilities

Solution: D5/LR, D5/NS, D5W, NS, ½NS, SWI

Y-site: (partial list) acyclovir, aminophylline, ampicillin, ampicillin/sulbactam, Ca gluconate, ceftazidime, ceftriaxone, cimetidine, cistracurium, clindamycin, dexamethasone, digoxin, diphenhydramine, dobutamine, dopamine, epinephrine, famotidine, fentanyl, furosemide, heparin, hydrocortisone, hydromorphone, imepenem/cilastatin, inamrinone, lidocaine, linezolid, lorazepam, magnesium sulphate, meperidine, methylprednisolone, metoclopramide, metronidazole, midazolam, morphine, nitroglycerin, norepinephrine, ondansetron, KCl, procainamide, prochlorperazine, promethazine, propofol (do not administer in same tubing with blood), sodium bicarbonate, thiopental, sufentanil, trimethoprim/sulfamethoxazole, vancomycin, zidovudine

IV Preparation

Reconstitute solution with 1 mL of diluent per mg of remifentanil; shake well to dissolve; should be diluted to final concentration of 25, 50 or 250 mcg/mL prior to administration

IV Administration

IV injection over 30-60 sec

May also do IV infusion

Storage

Store intact vials at 2-25°C