As the analgesic component in the maintenance of balanced anesthesia (e.g., IV hypnotic and/or inhalation anesthetic, analgesic, skeletal muscle relaxant).
Particularly useful when postoperative ventilation is anticipated and in providing favorable myocardial and cerebral oxygen balance.
Cardiovascular parameters generally are more stable intraoperatively with use of sufentanil compared with inhalation agents. Incidence of postoperative hypertension and requirements for vasoactive agents or postoperative analgesics generally are decreased following use of moderate or high doses of sufentanil as compared with use of inhalation agents.
Pain
Obstetric analgesia during labor and vaginal delivery.
Dosage and Administration
General
Premedication
Selection of preanesthetic medication(s) should be based on the individual needs of the patient.
Administration
Administer by IV injection, intermittent or continuous IV infusion, or epidural injection.
IV Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administration of small volumes may require use of a tuberculin syringe or equivalent.
Rate of Administration
Administer by slow injection or intermittent or continuous infusion; individualize rate based on patient’s needs.
Concomitant Administration of a Neuromuscular Blocking Agent
Risk of muscular rigidity (particularly of the truncal muscles) is related to the dose and rate of the infusion; however, administration of a neuromuscular blocking agent prior to sufentanil therapy can reduce the risk.
The neuromuscular blocking agent used should be compatible with the patient’s condition, taking into account the hemodynamic effects of the drug, the cardiovascular status of the patient, existing drug therapy (e.g., preoperative use of β-adrenergic blocking agents), and the degree of skeletal muscle relaxation required.
Administration of a Neuromuscular Blocking Agent with Sufentanil
Sufentanil Dosage
Neuromuscular Blocking Agent Dosage
<8 mcg/kg
Administer up to 25% of the full paralyzing dose just prior to sufentanil
>8 mcg/kg (titrated by slow IV infusion)
Administer a full paralyzing dose following loss of consciousness (e.g., loss of eyelash reflex, loss of response to voice command)
>8 mcg/kg (rapidly administered anesthetic doses)
Administer a full paralyzing dose simultaneously with sufentanil or immediately after loss of consciousness
Epidural Administration
For drug compatibility information, see Compatibility under Stability.
Specialized techniques are required for epidural administration; administration should be performed only by qualified individuals familiar with the techniques of administration, dosages, and special patient management problems associated with epidural administration.
Dosage
Available as sufentanil citrate; dosage expressed in terms of sufentanil.
Adjust dosage carefully according to body weight, individual requirements and response, physical status and underlying pathologic condition, premedication or concomitant medication(s), the anesthetic(s) being used, and the nature and duration of the surgery.
Administer additional doses when patient movement and/or changes in vital signs indicate surgical stress or lightening of analgesia, and adjust according to individual requirements, response, and the anticipated remaining duration of the surgical procedure.
Pediatric Patients
Anesthesia
General Anesthesia (as sole anesthetic agent) for Cardiovascular Surgery
IV
Children <12 years of age: Initially, 10–25 mcg/kg in conjunction with 100% oxygen and a skeletal muscle relaxant. Additional doses of up to 25–50 mcg each (or, alternatively, 1–2 mcg/kg each) may be given as needed based on response to the initial dose and as determined by changes in vital signs that indicate surgical stress or lightening of anesthesia.
Neonates: Reduce dosage, especially in those with cardiovascular disease, according to the decrease in clearance. (See Pediatric Use under Cautions.)
Adults
Anesthesia
Analgesic Component of General Anesthesia
IV
Minor surgical procedures (expected duration of anesthesia is 1–2 hours): Total dosage of 1–2 mcg/kg in conjunction with nitrous oxide and oxygen; ≥75% of the total dosage may be given by slow injection or infusion prior to intubation. May administer supplemental doses of 10–25 mcg or administer intermittent or continuous maintenance infusions as necessary when movement and/or changes in vital signs indicate surgical stress or lightening of anesthesia; adjust maintenance infusion rate so that total dosage does not exceed 1 mcg/kg per hour of expected surgical time.
Major surgical procedures (expected duration of anesthesia is 2–8 hours): Total dosage of 2–8 mcg/kg in conjunction with nitrous oxide and oxygen; ≤75% of the total dosage may be given by slow injection or infusion prior to intubation. May administer supplemental doses of 10–50 mcg or administer intermittent or continuous maintenance infusions as necessary when movement and/or changes in vital signs indicate surgical stress or lightening of anesthesia; adjust maintenance infusion rate so that total dosage does not exceed 1 mcg/kg per hour of expected surgical time.
General Anesthesia (as sole anesthetic agent)
IV
Total dosage of 8–30 mcg/kg (by slow injection, infusion, or injection followed by infusion) in conjunction with oxygen and a skeletal muscle relaxant. Depending on the initial dose, may administer additional incremental doses of 0.5–10 mcg/kg by slow injection in anticipation of surgical stress (e.g., incision, sternotomy, cardiopulmonary bypass). Alternatively, may administer intermittent or continuous maintenance infusions as necessary as determined by changes in vital signs that indicate surgical stress and lightening of anesthesia; adjust maintenance infusion rate so that total dosage for the procedure does not exceed 30 mcg/kg.
Pain
Obstetric Analgesia
Epidural
10–15 mcg (in combination with 10 mL of bupivacaine 0.125% with or without epinephrine). Doses may be repeated twice (for a total of 3 doses) at ≥1-hour intervals until delivery.
Prescribing Limits
Adults
Anesthesia
Analgesic Component of General Anesthesia
IV
Minor or major surgical procedures: Total dose of ≤1 mcg/kg per hour of expected surgical time.
General Anesthesia (as sole anesthetic agent)
IV
Total dose for procedure: ≤ 30 mcg/kg.
Special Populations
Hepatic Impairment
Adjust dosage carefully; elimination of the drug may be decreased.
Renal Impairment
Adjust dosage carefully; elimination of the drug may be decreased.
Geriatric and Debilitated Patients
Reduce initial dosage; adjust additional doses according to the initial response and desired effect.
Obese Patients
Base dosage on an estimate of ideal (lean) body weight if body weight exceeds ideal weight by >20%.
Shares the toxic potentials of the opiate agonists; observe the usual precautions of opiate agonist therapy.
Respiratory Depression
Respiratory function can be severely compromised.
Consider the possibility of a recurrence of respiratory depression during recovery. A secondary rise in plasma concentrations may occur during the recovery period as blood perfusion to peripheral tissues increases and drug redistribution occurs.
Administration of an opiate antagonist (e.g., naloxone) can reverse respiratory depression. The duration of respiratory depression produced by sufentanil may be longer than the duration of the opiate antagonist; therefore, continue appropriate patient monitoring following apparent initial reversal.
Supervised Administration
Should be administered only by individuals experienced in the use of parenteral anesthetics and in the maintenance of an adequate airway and respiratory support.
Opiate antagonist (e.g., naloxone) and facilities for intubation, administration of oxygen, and assisted or controlled respiration should be immediately available.
Monitor vital signs routinely during administration; facilities for postoperative monitoring and assisted or controlled respiration should be available following administration of anesthetic doses of the drug (i.e., ≥8 mcg/kg).
Major Toxicities
Musculoskeletal Effects
Possible skeletal muscle rigidity (e.g., of the truncal muscles); onset may be more rapid than with fentanyl. Administration of a neuromuscular blocking agent may be necessary. (See Concomitant Administration of a Neuromuscular Blocking Agent under Dosage and Administration.)
General Precautions
CNS Effects
Caution in patients with head injuries; sufentanil may obscure the clinical course.
Impaired Respiration
Caution in patients with pulmonary disease, decreased respiratory reserve, or potentially compromised respiratory function. Further decreases in respiratory function and increases in airway resistance may occur.
Cardiovascular Effects
Generally produces few cardiovascular effects. Possible hypotension or hypertension. Bradycardia occurs infrequently during anesthesia and may be corrected by administration of atropine.
Specific Populations
Pregnancy
Category C.
Used epidurally for analgesia during labor and delivery. Not recommended for IV use during labor and delivery; avoid epidural dosages in excess of the recommended dosage.
Lactation
Not known whether sufentanil is distributed into milk. Caution if used in nursing women.
Pediatric Use
Safety and efficacy documented in a limited number of children ≥1 day of age undergoing cardiovascular surgery.
Use with caution in neonates because decreased clearance may result in increased blood concentrations of the drug. Clearance in healthy neonates is approximately one-half that reported in adults and children; may be further reduced by up to one-third in neonates with cardiovascular disease.
Geriatric Use
Consider dosage reduction. (See Geriatric and Debilitated Patients under Dosage and Administration.)
Hepatic Impairment
Use with caution, since the drug undergoes metabolism in the liver.
Renal Impairment
Use with caution, since the drug and its metabolites are eliminated mainly by the kidneys.
Possible increased incidence and degree of bradycardia and hypotension during sufentanil induction in patients receiving chronic β-blocker therapy
Patients with CAD receiving chronic preoperative β-blocker therapy appear to require lower initial and fewer supplemental doses of sufentanil during CABG surgery than do patients who have not received preoperative β-blocker therapy
Increased incidence and degree of bradycardia and hypotension during sufentanil induction in patients receiving chronic calcium-channel blocker therapy
Use with caution; reduce dosage of at least one of the drugs when used concomitantly
Nitrous oxide
Possible cardiovascular depression, manifested by bradycardia and decreases in mean arterial pressure and cardiac output, following concomitant administration of nitrous oxide with high doses of sufentanil
Possible tachycardia following administration of high doses of pancuronium during anesthesia with sufentanil and oxygen; hypertension and an increase in cardiac index may occur
Bradycardia and hypotension reported during anesthesia during concomitant administration of neuromuscular blocking agents with sufentanil and oxygen; effects may be increased in patients also receiving calcium-channel blockers or β-blockers; bradycardia reported rarely following concomitant administration of sufentanil with succinylcholine
To maintain a stable, lower HR and BP during anesthesia, use moderate doses of pancuronium or use a neuromuscular blocking agent with a lesser inhibitory effect on the vagus nerve
Pharmacokinetics
Absorption
Onset
Following IV administration, the onset of action as determined by time to unconsciousness (i.e., loss of response to voice command) is 1.2–3 minutes.
Following epidural administration of 10–15 mcg and 0.125% bupivacaine with epinephrine 1:200,000 during the first stage of labor, the onset of action occurs within 10 minutes.
Duration
The mean duration of anesthesia is 40 minutes following initial IV dose of 0.4 mcg/kg and 41–44 minutes following additional doses of 0.1 mcg/kg. Following administration of anesthetic doses (about 13–19 mcg/kg total), patient response to verbal command and adequate ventilation occurs at 0.6–1.8 and 5.6 hours, respectively.
Following IM administration of single doses of 0.15, 0.3, or 0.5 mcg/kg in patients with pain, the approximate duration of detectable analgesia was 2.3, 3.7, and 3.8 hours, respectively.
Following epidural administration of 10–15 mcg and 0.125% bupivacaine with epinephrine 1:200,000 during the first stage of labor, the duration of action was 1–2 hours.
Distribution
Extent
Distribution into human body tissues and fluids has not been fully characterized; however, the drug is highly lipophilic and is rapidly and extensively distributed in animals.
Not known whether sufentanil crosses the placenta or distributes into milk.
Plasma Protein Binding
Approximately 93% bound at plasma pH 7.4 (mainly to albumin; α-, α1-, β-, and γ-globulins; and α1-acid glycoprotein).
Because a large portion of the drug appears to be bound to α1-acid glycoprotein, binding may be affected by disease states in which this protein is altered.
Binding in plasma is independent of plasma drug concentration within the therapeutic range (i.e., 0.1–10 ng/mL); however, binding is affected by changes in plasma pH. Increases in plasma pH from 7.4 to 7.8 increase sufentanil binding by about 30%; decreases in plasma pH from 7.4 to 7 decrease binding by about 30%.
Elimination
Metabolism
Appears to be metabolized mainly in the liver and small intestine via N-dealkylation and O-demethylation.
The O-demethylated metabolite appears to have about 10% of the analgesic activity of the unchanged drug.
Elimination Route
Excreted principally in urine and also in feces via biliary elimination; only 2% of a dose is excreted unchanged in urine and feces.
Half-life
Triphasic; plasma concentrations decline rapidly secondary to redistribution.
In adults with normal renal and hepatic function, the plasma half-life averages 0.72–1.2 minutes in the initial (distribution) phase, 13.7–17 minutes in the second (redistribution) phase, and 140–158 minutes in the terminal (elimination) phase.
Elimination half-life is longer (434 minutes) in neonates but shorter in infants and children (97 minutes), compared with adults and adolescents.
Stability
Storage
Parenteral
Injection
15–25°C; protect from light.
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Sufentanil citrate is hydrolyzed in acidic solutions.
Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.
Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).
Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.
Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.
High affinity and selectivity for the μ-opiate receptor in the CNS; reportedly is more selective and binds more tightly to this receptor than does fentanyl.
Produces dose-related analgesia; at doses up to 8 mcg/kg, the drug has a potent analgesic effect, but higher doses usually produce substantial CNS depression resulting in hypnosis and anesthesia.
Analgesic potency appears to be 5–12 times that of fentanyl on a weight basis.
Appears to have little effect on histamine release.
May have a centrally mediated vagal effect.
Advice to Patients
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
