ALFENTANIL SHOULD BE ADMINISTERED ONLY BY PERSONS SPECIFICALLY TRAINED IN THE USE OF INTRAVENOUS AND GENERAL ANESTHETIC AGENTS AND IN THE MANAGEMENT OF RESPIRATORY EFFECTS OF POTENT OPIOIDS.
AN OPIOID ANTAGONIST, RESUSCITATIVE AND INTUBATION EQUIPMENT AND OXYGEN SHOULD BE READILY AVAILABLE.
BECAUSE OF THE POSSIBILITY OF DELAYED RESPIRATORY DEPRESSION, MONITORING OF THE PATIENT MUST CONTINUE WELL AFTER SURGERY.
Alfentanil administered in initial dosages up to 20 mcg/kg may cause skeletal muscle rigidity, particularly of the truncal muscles. The incidence and severity of muscle rigidity is usually dose-related. Administration of alfentanil at anesthetic induction dosages (above 130 mcg/kg) will consistently produce muscular rigidity with an immediate onset. The onset of muscular rigidity occurs earlier than with other opioids. Alfentanil may produce muscular rigidity that involves all skeletal muscles, including those of the neck and extremities. The incidence may be reduced by: 1) routine methods of administration of neuromuscular blocking agents for balanced opioid anesthesia; 2) administration of up to 1/4 of the full paralyzing dose of a neuromuscular blocking agent just prior to administration of alfentanil at dosages up to 130 mcg/kg; following loss of consciousness, a full paralyzing dose of a neuromuscular blocking agent should be administered; or 3) simultaneous administration of alfentanil and a full paralyzing dose of a neuromuscular blocking agent when alfentanil is used in rapidly administered anesthetic dosages (above 130 mcg/kg).
The neuromuscular blocking agent used should be appropriate for the patient’s cardiovascular status. Adequate facilities should be available for postoperative monitoring and ventilation of patients administered alfentanil. It is essential that these facilities be fully equipped to handle all degrees of respiratory depression.
PATIENTS RECEIVING MONITORED ANESTHESIA CARE (MAC) SHOULD BE CONTINUOUSLY MONITORED BY PERSONS NOT INVOLVED IN THE CONDUCT OF THE SURGICAL OR DIAGNOSTIC PROCEDURE; OXYGEN SUPPLEMENTATION SHOULD BE IMMEDIATELY AVAILABLE AND PROVIDED WHERE CLINICALLY INDICATED; OXYGEN SATURATION SHOULD BE CONTINUOUSLY MONITORED; THE PATIENT SHOULD BE OBSERVED FOR EARLY SIGNS OF HYPOTENSION, APNEA, UPPER AIRWAY OBSTRUCTION AND/OR OXYGEN DESATURATION.
Severe and unpredictable potentiation of monoamine oxidase (MAO) inhibitors has been reported for other opioid analgesics, and rarely with alfentanil. Thereforewhen alfentanil 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 recommended.
DELAYED RESPIRATORY DEPRESSION, RESPIRATORY ARREST, BRADYCARDIA, ASYSTOLE, ARRHYTHMIAS AND HYPOTENSION HAVE ALSO BEEN REPORTED. THEREFORE, VITAL SIGNS MUST BE MONITORED CONTINUOUSLY.
The initial dose of alfentanil should be appropriately reduced in elderly and debilitated patients. The effect of the initial dose should be considered in determining supplemental doses. In obese patients (more than 20% above ideal total body weight), the dosage of alfentanil should be determined on the basis of lean body weight.
In one clinical trial, the dose of alfentanil required to produce anesthesia, as determined by appearance of delta waves in EEG, was 40% lower in geriatric patients than that needed in healthy young patients.
In patients with compromised liver function and in geriatric patients, the plasma clearance of alfentanil may be reduced and postoperative recovery may be prolonged.
Induction doses of alfentanil should be administered slowly (over three minutes). Administration may produce loss of vascular tone and hypotension. Consideration should be given to fluid replacement prior to induction.
Diazepam administered immediately prior to or in conjunction with high doses of alfentanil may produce vasodilation, hypotension and result in delayed recovery.
Bradycardia produced by alfentanil may be treated with atropine. Severe bradycardia and asystole have been successfully treated with atropine and conventional resuscitative methods.
The hemodynamic effects of a particular muscle relaxant and the degree of skeletal muscle relaxation required should be considered in the selection of a neuromuscular blocking agent.
Following an anesthetic induction dose of alfentanil, requirements for volatile inhalation anesthetics or alfentanil infusion are reduced by 30 to 50% for the first hour of maintenance.
Alfentanil infusions should be discontinued at least 10-15 minutes prior to the end of surgery during general anesthesia. During administration of alfentanil for Monitored Anesthesia Care (MAC), infusions may be continued to the end of the procedure.
Respiratory depression caused by opioid analgesics can be reversed by opioid antagonists such as naloxone. Because the duration of respiratory depression produced by alfentanil 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 postoperative period. Intraoperative hyperventilation may further alter postoperative response to CO2. Appropriate postoperative monitoring should be employed, particularly after infusions and large doses of alfentanil, to ensure that adequate spontaneous breathing is established and maintained in the absence of stimulation prior to discharging the patient from the recovery area.
Head Injuries: Alfentanil should be used with caution in patients with head injury or increased intracranial pressure, due to the increased risk of respiratory depression. As with all opioids, alfentanil may obscure the clinical course of patients with head injuries and should be used only if clinically indicated.
Impaired Respiration: Alfentanil should be used with caution in patients with pulmonary disease, decreased respiratory reserve or potentially compromised respiration. In such patients, opioids may additionally decrease respiratory drive and increase airway resistance. During anesthesia, this can be managed by assisted or controlled respiration.
Impaired Hepatic or Renal Function: In patients with liver or kidney dysfunction, alfentanil should be administered with caution due to the importance of these organs in the metabolism and excretion of alfentanil.
Both the magnitude and duration of central nervous system and cardiovascular effects may be enhanced when alfentanil is administered in combination with other CNS depressants such as barbiturates, tranquilizers, opioids, or inhalation general anesthetics. Postoperative respiratory depression may be enhanced or prolonged by these agents. In such cases of combined treatment, the dose of one or both agents should be reduced. Limited clinical experience indicates that requirements for volatile inhalation anesthetics are reduced by 30 to 50% for the first sixty (60) minutes following alfentanil induction.
The concomitant use of erythromycin with alfentanil can significantly inhibit alfentanil clearance and may increase the risk of prolonged or delayed respiratory depression.
Cimetidine reduces the clearance of alfentanil. Therefore smaller alfentanil doses will be required with prolonged administration and the duration of action of alfentanil may be extended.
Perioperative administration of drugs affecting hepatic blood flow or enzyme function may reduce plasma clearance and prolong recovery.
Carcinogenesis, Mutagenesis and Impairment of Fertility:
No long-term animal studies of alfentanil have been performed to evaluate carcinogenic potential. No structural chromosome mutations were produced in the in vivo micronucleus test in female rats at single intravenous doses of alfentanil as high as 20 mg/kg body weight (approximately 40 times the upper human dose), equivalent to a dose of 103 mg/m2 body surface area. No dominant lethal mutations were produced in the in vivo dominant lethal test in male and female mice at the maximum intravenous dose of 20 mg/kg (60 mg/m2). No mutagenic activity was revealed in the in vitro Ames Salmonella typhimurium test, with and without metabolic activation.
Pregnancy Category C:
Alfentanil has been shown to have an embryocidal effect in rats and rabbits when given in doses 2.5 times the upper human dose for a period of 10 days to over 30 days. These effects could have been due to maternal toxicity (decreased food consumption with increased mortality) following prolonged administration of the drug.
No evidence of teratogenic effects has been observed after administration of alfentanil in rats or rabbits.
There are no adequate and well-controlled studies in pregnant women. Alfentanil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery:
There are insufficient data to support the use of alfentanil in labor and delivery. Placental transfer of the drug has been reported; therefore, use in labor and delivery is not recommended.
In one study of nine women undergoing postpartum tubal ligation, significant levels of alfentanil were detected in colostrum four hours after administration of 60 mcg/kg of alfentanil, with no detectable levels present after 28 hours. Caution should be exercised when alfentanil is administered to a nursing woman.
Adequate data to support the use of alfentanil in children under 12 years of age are not presently available.