Usual Adult Dose for Anesthesia

INDUCTION of Anesthesia (through intubation): 0.5 to 1 mcg/kg/min via continuous IV infusion; an initial dose of 1 mcg/kg over 30 to 60 seconds may be administered

• If endotracheal intubation is to occur less than 8 minutes after start of the induction infusion, an initial IV dose should be given

MAINTENANCE of Anesthesia:

• With Nitrous Oxide at 66%: Continuous IV infusion at 0.4 mcg/kg/min (range 0.1 to 2 mcg/kg/min)
• With Isoflurane at 0.4 to 1.5 MAC or Propofol at 100 to 200 mcg/kg/min: Continuous IV infusion at 0.25 mcg/kg/min (range 0.05 to 2 mcg/kg/min)
• An IV bolus of 1 mcg/kg over 30 to 60 seconds may be used every 2 to 5 minutes as needed in response to light anesthesia or transient episodes of intense surgical stress

POSTOPERATIVE: Bolus IV injections are not recommended

• Use continuous IV infusion at 0.1 mcg/kg/min; adjust infusion rate every 5 minutes in 0.025 mcg/kg/min increments to balance level of analgesia and respiratory rate

Maximum rate: 0.2 mcg/kg/min

MONITORED ANESTHESIA CARE (MAC): Supplemental oxygen should be supplied
IV BOLUS Doses: Give 90 seconds before local anesthetic

• With midazolam 2 mg: Administer 0.5 mcg/kg IV over 30 to 60 seconds
• Without midazolam: Administer 1 mcg/kg IV over 30 to 60 seconds

CONTINUOUS IV Infusion: Start infusion 5 minutes before local anesthetic

• With midazolam 2 mg: Initiate at 0.05 mcg/kg/min, then after local anesthetic decrease to 0.025 mcg/kg/min (range 0.025 to 0.2 mcg/kg/min)
• Without midazolam: Initiate IV infusion at 0.1 mcg/kg/min, then after local anesthetic decrease to 0.05 mcg/kg/min (range 0.025 to 0.2 mcg/kg/min)

Comments:

• Dosing should be individualized based on response.
• Monitor patients closely for respiratory depression, especially with initiation and following all dose increases; adjust dose accordingly
• Continuous IV infusions should be administered by a calibrated infusion device.
• Due to rapid offset of action, no residual analgesic activity will be present 5 to 10 minutes after discontinuation; if pain is expected, alternative analgesics should be administered prior to discontinuing.

Uses: As an analgesic during induction and maintenance of general anesthesia; for continuation of analgesia into the immediate postoperative period; and as an analgesic component of monitored anesthesia.

Usual Adult Dose for Pain

INDUCTION of Anesthesia (through intubation): 0.5 to 1 mcg/kg/min via continuous IV infusion; an initial dose of 1 mcg/kg over 30 to 60 seconds may be administered

• If endotracheal intubation is to occur less than 8 minutes after start of the induction infusion, an initial IV dose should be given

MAINTENANCE of Anesthesia:

• With Nitrous Oxide at 66%: Continuous IV infusion at 0.4 mcg/kg/min (range 0.1 to 2 mcg/kg/min)
• With Isoflurane at 0.4 to 1.5 MAC or Propofol at 100 to 200 mcg/kg/min: Continuous IV infusion at 0.25 mcg/kg/min (range 0.05 to 2 mcg/kg/min)
• An IV bolus of 1 mcg/kg over 30 to 60 seconds may be used every 2 to 5 minutes as needed in response to light anesthesia or transient episodes of intense surgical stress

POSTOPERATIVE: Bolus IV injections are not recommended

• Use continuous IV infusion at 0.1 mcg/kg/min; adjust infusion rate every 5 minutes in 0.025 mcg/kg/min increments to balance level of analgesia and respiratory rate

Maximum rate: 0.2 mcg/kg/min

MONITORED ANESTHESIA CARE (MAC): Supplemental oxygen should be supplied
IV BOLUS Doses: Give 90 seconds before local anesthetic

• With midazolam 2 mg: Administer 0.5 mcg/kg IV over 30 to 60 seconds
• Without midazolam: Administer 1 mcg/kg IV over 30 to 60 seconds

CONTINUOUS IV Infusion: Start infusion 5 minutes before local anesthetic

• With midazolam 2 mg: Initiate at 0.05 mcg/kg/min, then after local anesthetic decrease to 0.025 mcg/kg/min (range 0.025 to 0.2 mcg/kg/min)
• Without midazolam: Initiate IV infusion at 0.1 mcg/kg/min, then after local anesthetic decrease to 0.05 mcg/kg/min (range 0.025 to 0.2 mcg/kg/min)

Comments:

• Dosing should be individualized based on response.
• Monitor patients closely for respiratory depression, especially with initiation and following all dose increases; adjust dose accordingly
• Continuous IV infusions should be administered by a calibrated infusion device.
• Due to rapid offset of action, no residual analgesic activity will be present 5 to 10 minutes after discontinuation; if pain is expected, alternative analgesics should be administered prior to discontinuing.

Uses: As an analgesic during induction and maintenance of general anesthesia; for continuation of analgesia into the immediate postoperative period; and as an analgesic component of monitored anesthesia.

Usual Geriatric Dose for Anesthesia

Reduce initial adult dose by 50%

• Titrate dose cautiously to effect

Usual Geriatric Dose for Pain

Reduce initial adult dose by 50%

• Titrate dose cautiously to effect

Usual Pediatric Dose for Anesthesia

Birth to 2 months old:

• Continuous IV Infusion (with 70% nitrous oxide): 0.4 mcg/kg/min (range 0.4 to 1 mcg/kg/min)
• Supplemental IV bolus of 1 mcg/kg every 2 to 5 minutes may be given in response to light anesthesia or transient episodes of intense surgical stress

1 to 12 years:
MAINTENANCE of Anesthesia:

• IV Bolus: Initial dose of 1 mcg/kg may be administered over 30 to 60 seconds
• Continuous IV Infusion (concomitant administration with Halothane [0.3 to 1.5 MAC], Sevoflurane [0.3 to 1.5 MAC], or Isoflurane [0.4 to 1.5 MAC]): 0.25 mcg/kg/min (range 0.05 to 1.3 mcg/kg/min)
• Supplemental IV bolus of 1 mcg/kg every 2 to 5 minutes may be given in response to light anesthesia or transient episodes of intense surgical stress

Comments:

• Drug clearance in neonates is highly variable (on average 2 times higher than young, healthy adults, therefore, increased infusion rates or supplemental IV bolus doses may be needed in these patients.
• In neonates with significant co-morbidities, those undoing significant fluid shifts, those who have not been pretreated with atropine, or those receiving potent inhalation agents or neuraxial anesthesia, smaller IV bolus doses should be considered to avoid hypotension and/or bradycardia.
• Due to rapid offset of action, no residual analgesic activity will be present 5 to 10 minutes after discontinuation; if pain is expected, alternative analgesics should be administered prior to discontinuation.
• This drug has not been studied in patients under 12 years of age for use in the immediate postoperative period or for use as a component of monitored anesthesia care.

Use: As an analgesic agent during maintenance of general anesthesia.

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

For ASA III/IV patients (American Society of Anesthesiology Classification corresponding to patients with severe systemic disease with definite functional impairment and severe systemic impairment that is a constant threat to life): Consider initial dose reductions and slower titration to effect as the hemodynamic effect may be more pronounced

Concomitant use with Mixed Agonist/Antagonist or Partial Agonist Opioid Analgesic:
Observe closely for reduced analgesic effect or potential withdrawal symptoms; if patient is not responding appropriately, may need to discontinue this drug

Obese Patients:
For patients greater than 30% over ideal body weight (IBW): Use IBW for initial doses

Coronary Artery Bypass Surgery: Dose modifications are recommended to avoid hypotension during the induction phase; it is important to consider concomitant medication regimens:
INDUCTION of Anesthesia (through intubation): 1 mcg/kg/min via continuous IV infusion
MAINTENANCE of Anesthesia: 1 mcg/kg/min (range 0.125 to 4 mcg/kg/min) via IV infusion

• Supplemental IV bolus of 1 mcg/kg every 2 to 5 minutes may be given in response to light anesthesia or transient episodes of intense surgical stress

POSTOPERATIVE: Continuation as Analgesic into ICU: 0.05 to 1 mcg/kg/min via continuous IV infusion

Dose Modifications of Preanesthetic Medications:

• Individualize the need for, and the choice of, preanesthetic medications.

Dose Modification of Concomitant Medications:

• Anesthetic protocols should be followed; this drug decreases the amounts/doses of inhaled anesthetics, hypnotics, and benzodiazepines necessary for anesthesia.

Precautions

US BOXED WARNING: ADDICTION, ABUSE, AND MISUSE

• This drug exposes patients and others users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing.

Safety and efficacy for use in the induction of anesthesia have not been established in patients younger than 12 years.
Safety and efficacy for use as a postoperatve analgesic or as analgesic agent of monitored anesthesia care have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II

Dialysis

Data not available

Other Comments

Administration advice:

• For IV use
• Bolus IV injections should be administered slowly over 30 to 60 seconds
• Continuous IV infusions should be administered via a calibrated infusion device; reconstituted solutions should be diluted prior to IV infusion
• For IV infusions, the injection sites should be close to the venous cannula; all IV tubing should be cleared when drug is discontinued to prevent inadvertent administration

Storage requirements: Store lyophilized powder between 2C and 25C (36F to 77F)

Reconstitution/preparation techniques:

• Add 1 mL of diluent per mg of lyophilized drug; shake well to dissolve; concentration of reconstituted solution should be 1 mg/mL
• Prior to administration, this drug should be diluted to a final concentration of 20, 25, 50 or 250 mcg/mL
• When used as the analgesic component of monitored analgesia care: final concentration should be 25 mcg/mL
• When used for pediatric patients (1 year or older): final concentration should be 20 or 25 mcg/mL
• Manufacturer product labeling may be consulted for tables that detail infusion rates by body weight and drug delivery rates based on infusion delivery rates.

IV compatibility:

• Following reconstitution and further dilution with sterile water, 5% dextrose, 5% dextrose/0.9% sodium chloride, 0.9% sodium chloride, 0.45% sodium chloride, or Lactated Ringer's/5% dextrose: Stable for 24 hours at room temperature
• Following reconstitution and further dilution to concentrations of 20 to 250 mcg/mL with Lactated Ringer's: Stable for 4 hours at room temperature

Compatible with propofol when coadministered into a running IV line

Incompatible with blood products

General:

• Administration of this drug is restricted to healthcare professionals specifically trained in the use of IV anesthetics and the management of the respiratory effects of potent opioids.
• This drug should be administered in facilities that have qualified personnel that are adequately equipped to handle any degree of respiratory depression; the following should be readily available during drug administration: opioid antagonists, resuscitative and intubation equipment, and oxygen.
• This drug should not be the sole agent in general anesthesia as loss of consciousness is not assured and a high incidence of apnea, muscle rigidity, and tachycardia are possible.
• This drug should be used synergistically with other agents and when used, doses of other anesthetics should be reduced.
• The need for premedication and choice of anesthetic agents should be individualized.

Monitoring:

• Vital signs should be continuously monitored during and following use
• Monitor oxygen saturation and watch for early signs of hypotension, apnea, upper airway obstruction and/or oxygen desaturation
• Elderly, debilitated, and patients with brain tumors or head injuries, those on concomitant medications including CNS depressants, serotonergic medications, or neuromuscular blocking agents should be observed very closely

Patient advice:

• Patients should be advised not to drive or operate machinery for a sufficient time after having received this drug.