Enter drug's generic or brand name below. Results will appear here. Note: all drug related information obtained on this page is provided by RX List.
Using the RX LIST database:
(1) Enter the drug name in the search box below and hit ENTER
(2) The rx list web site will open here with the drug search completed. Next, scroll down the page to locate the link to the drug you are searching for and then click on the link.
SUPRANE
(desflurane) Volatile Liquid for Inhalation
SUPRANE (desflurane, USP), a nonflammable liquid administered via vaporizer, is a general inhalation anesthetic. It is (±)1,2,2,2-tetrafluoroethyl difluoromethyl ether:
 |
Some physical constants are:
| Molecular weight | 168.04 |
| Specific gravity (at 20°C/4°C) | 1.465 |
| Vapor pressure in mm Hg | 669 mm Hg @ 20°C |
| 731 mm Hg @ 22°C | |
| 757 mm Hg @ 22.8°C (boiling point;1atm) | |
| 764 mm Hg @ 23°C | |
| 798 mm Hg @ 24°C | |
| 869 mm Hg @ 26°C |
Partition coefficients at 37°C:
| Blood/Gas | 0.424 |
| Olive Oil/Gas | 18.7 |
| Brain/Gas | 0.54 |
Mean Component/Gas Partition Coefficients:
| Polypropylene (Y piece) | 6.7 |
| Polyethylene (circuit tube) | 16.2 |
| Latex rubber (bag) | 19.3 |
| Latex rubber (bellows) | 10.4 |
| Polyvinylchloride (endotracheal tube) | 34.7 |
SUPRANE is nonflammable as defined by the requirements of International Electrotechnical Commission 601-2-13.
SUPRANE is a colorless, volatile liquid below 22.8°C. Data indicate that SUPRANE is stable when stored under normal room lighting conditions according to instructions.
SUPRANE is chemically stable. The only known degradation reaction is through prolonged direct contact with soda lime producing low levels of fluoroform (CHF3). The amount of CHF3 obtained is similar to that produced with MAC-equivalent doses of isoflurane. No discernible degradation occurs in the presence of strong acids.
SUPRANE does not corrode stainless steel, brass, aluminum, anodized aluminum, nickel plated brass, copper, or beryllium.
SUPRANE is indicated as an inhalation agent for induction of anesthesia for inpatient and outpatient surgery in adults.
SUPRANE is contraindicated as an inhalation agent for the induction of anesthesia in pediatric patients because of a high incidence of moderate to severe upper airway adverse events.
SUPRANE is indicated as an inhalation agent for maintenance of anesthesia for inpatient and outpatient surgery in adults and in pediatric patients.
After induction of anesthesia with agents other than SUPRANE, and tracheal intubation, SUPRANE is indicated for maintenance of anesthesia in infants and children.
SUPRANE is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm, and secretions [see WARNINGS AND PRECAUTIONS and Clinical Studies].
Only persons trained in the administration of general anesthesia should administer SUPRANE. Only a vaporizer specifically designed and designated for use with desflurane should be utilized for its administration. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, and circulatory resuscitation must be immediately available.
SUPRANE is administered by inhalation. The administration of general anesthesia must be individualized based on the patient’s response. Hypotension and respiratory depression increase as anesthesia with SUPRANE is deepened. The minimum alveolar concentration (MAC) of SUPRANE decreases with increasing patient age. The MAC for SUPRANE is also reduced by concomitant N2O administration (see Table 1). The dose should be adjusted accordingly. The following table provides mean relative potency based upon age and effect of N2O in predominately ASA physical status I or II patients.
Benzodiazepines and opioids decrease the MAC of SUPRANE [see DRUG INTERACTIONS]. SUPRANE also decreases the doses of neuromuscular blocking agents required [see DRUG INTERACTIONS]. The dose should be adjusted accordingly.
Table 1 Effect of Age on Minimum Alveolar Concentration of Desflurane
Mean ± SD (percent atmospheres)
| Age | N | O2 100% | N | N2O 60%/40% O2 |
| 2 weeks | 6 | 9.2 ± 0.0 | - | - |
| 10 weeks | 5 | 9.4 ± 0.4 | - | - |
| 9 months | 4 | 10.0 ± 0.7 | 5 | 7.5 ± 0.8 |
| 2 years | 3 | 9.1 ± 0.6 | - | - |
| 3 years | - | - | 5 | 6.4 ± 0.4 |
| 4 years | 4 | 8.6 ± 0.6 | - | - |
| 7 years | 5 | 8.1 ± 0.6 | - | - |
| 25 years | 4 | 7.3 ± 0.0 | 4 | 4.0 ± 0.3 |
| 45 years | 4 | 6.0 ± 0.3 | 6 | 2.8 ± 0.6 |
| 70 years | 6 | 5.2 ± 0.6 | 6 | 1.7 ± 0.4 |
| N = number of crossover pairs (using up-and-down method of quantal response) | ||||
Issues such as whether or not to premedicate and the choice of premedication(s) must be individualized. In clinical studies, patients scheduled to be anesthetized with SUPRANE frequently received IV preanesthetic medication, such as opioid and/or benzodiazepine.
In adults, some premedicated with opioid, a frequent starting concentration was 3% SUPRANE, increased in 0.5-1.0% increments every 2 to 3 breaths. End-tidal concentrations of 4-11%, SUPRANE with and without N2O, produced anesthesia within 2 to 4 minutes. When SUPRANE was tested as the primary anesthetic induction agent, the incidence of upper airway irritation (apnea, breathholding, laryngospasm, coughing and secretions) was high. During induction in adults, the overall incidence of oxyhemoglobin desaturation (SpO2 < 90%) was 6% [see ADVERSE REACTIONS].
After induction in adults with an intravenous drug such as thiopental or propofol, SUPRANE can be started at approximately 0.5-1 MAC, whether the carrier gas is O2 or N2O/O2.
Inspired concentrations of SUPRANE greater than 12% have been safely administered to patients, particularly during induction of anesthesia. Such concentrations will proportionately dilute the concentration of oxygen; therefore, maintenance of an adequate concentration of oxygen may require a reduction of nitrous oxide or air if these gases are used concurrently.
Surgical levels of anesthesia in adults may be maintained with concentrations of 2.5-8.5% SUPRANE with or without the concomitant use of nitrous oxide. In children, surgical levels of anesthesia may be maintained with concentrations of 5.2-10% SUPRANE with or without the concomitant use of nitrous oxide.
During the maintenance of anesthesia with inflow rates of 2 L/min or more, the alveolar concentration of SUPRANE will usually be within 10% of the inspired concentration [FA/FI , see Figure 2 in CLINICAL PHARMACOLOGY].
During the maintenance of anesthesia, increasing concentrations of SUPRANE produce dose-dependent decreases in blood pressure. Excessive decreases in blood pressure may be due to depth of anesthesia and in such instances may be corrected by decreasing the inspired concentration of SUPRANE.
Concentrations of SUPRANE exceeding 1 MAC may increase heart rate. Thus with this drug, an increased heart rate may not serve reliably as a sign of inadequate anesthesia.
SUPRANE is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than SUPRANE, and tracheal intubation.
SUPRANE, with or without N2O, and halothane, with or without N2O were studied in three clinical trials of pediatric patients aged 2 weeks to 12 years (median 2 years) and ASA physical status I or II. The concentration of SUPRANE required for maintenance of general anesthesia is age-dependent [see Clinical Studies].
Changes in blood pressure during maintenance of and recovery from anesthesia with SUPRANE /N2O/O2 are similar to those observed with halothane/N2O/O2. Heart rate during maintenance of anesthesia is approximately 10 beats per minute faster with SUPRANE than with halothane. Patients were judged fit for discharge from post-anesthesia care units within one hour with both SUPRANE and halothane. There were no differences in the incidence of nausea and vomiting between patients receiving SUPRANE or halothane.
The recovery from general anesthesia should be assessed carefully before patients are discharged from the post anesthesia care unit (PACU).
In patients with coronary artery disease, maintenance of normal hemodynamics is important to prevent myocardial ischemia. A rapid increase in desflurane concentration is associated with marked increase in pulse rate, mean arterial pressure and levels of epinephrine and norepinephrine. SUPRANE should not be used as the sole agent for anesthetic induction in patients with coronary artery disease or patients where increases in heart rate or blood pressure are undesirable. It should be used with other medications, preferably intravenous opioids and hypnotics [see Clinical Studies].
SUPRANE may produce a dose-dependent increase in cerebrospinal fluid pressure (CSFP) when administered to patients with intracranial space occupying lesions. SUPRANE should be administered at 0.8 MAC or less, and in conjunction with a barbiturate induction and hyperventilation (hypocapnia) until cerebral decompression in patients with known or suspected increases in CSFP. Appropriate attention must be paid to maintain cerebral perfusion pressure [see Clinical Studies].
SUPRANE (desflurane, USP) is a colorless, non-flammable, volatile liquid (below 22.8°C) for inhalation, 100% desflurane.
SUPRANE (desflurane, USP) is available in an amber-colored glass bottle or an aluminum bottle containing 240 mL of desflurane as follows:
| NDC | Container | Unit(s) |
| 10019-641-60 | Amber-colored Glass | 1 |
| 10019-641-24 | 6 | |
| 10019-641-64 | Aluminum Bottle | 1 |
| 10019-641-34 | 6 |
There is no specific work exposure limit established for SUPRANE. However, the National Institute for Occupational Safety and Health Administration (NIOSH) recommends that no worker should be exposed at ceiling concentrations greater than 2 ppm of any halogenated anesthetic agent over a sampling period not to exceed one hour.
Principle routes of exposure include:
Skin contact
May cause skin irritation. In case of contact, immediately flush skin with plenty of water. Remove contaminated clothing and shoes. Seek medical attention if irritation develops.
Eye contact
May cause eye irritation. In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Seek medical attention if irritation develops.
Ingestion
No specific hazards other than therapeutic effects. Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. If large quantities of this material are swallowed, seek medical attention immediately.
Inhalation
If individuals smell vapors, or experience dizziness or headaches, they should be moved to an area with fresh air. Individuals could also experience the following: Cardiovascular effects: may include fluctuations in heart rate, changes in blood pressure, chest pain. Respiratory effects: may include shortness of breath, bronchospasms, laryngospasms, respiratory depression. Gastrointestinal effects: may include nausea, upset stomach, loss of appetite. Nervous System effects: may include ataxia, tremor, disturbance of speech, lethargy, headache, dizziness, blurred vision.
The predicted effects of acute overexposure by inhalation of SUPRANE include headache, dizziness or (in extreme cases) unconsciousness [see OVERDOSE].
There are no documented adverse effects of chronic exposure to halogenated anesthetic vapors (Waste Anesthetic Gases or WAGs) in the workplace. Although results of some epidemiological studies suggest a link between exposure to halogenated anesthetics and increased health problems (particularly spontaneous abortion), the relationship is not conclusive. Since exposure to WAGs is one possible factor in the findings for these studies, operating room personnel, and pregnant women in particular, should minimize exposure. Precautions include adequate general ventilation in the operating room, the use of a well-designed and well-maintained scavenging system; work practices to minimize leaks and spills while the anesthetic agent is in use, and routine equipment maintenance to minimize leaks.
Consistent with clinical data, concentrations would need to reach 2-3% in inspired air before individuals would likely experience dizziness or other physiologic effects.
Store at room temperature, 15°-30°C (59°-86°F). SUPRANE has been demonstrated to be stable for the period defined by the expiration dating on the label. The bottle should be recapped after each use of SUPRANE.
Manufactured for: Baxter Healthcare Corporation Deerfield, IL 60015 USA. Revised: April 2017
The following serious adverse reactions with the use of STAXYN (vardenafil) are discussed elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Safety of STAXYN was evaluated in two identical multi-national, randomized, double-blind, placebo-controlled trials. In both pivotal studies, enrollment was stratified so that approximately 50% of patients were ≥ 65 years old. Approximately 8% (n=29) were ≥ 75 years old. An integrated analysis of both studies included a total of 355 subjects that received STAXYN compared to 340 subjects that received placebo (mean age was 61.7, range 21.0 to 88.0; 68% White, 5% Black, 6% Asian, 11% Hispanic and 11% Other). The discontinuation rates due to adverse reactions were 1.4% for STAXYN compared to 0.6% for placebo. Table 1 below details the most frequently reported adverse reactions.
Table 1: Adverse drug reactions reported by ≥ 2%
of the patients treated with STAXYN and more frequent on drug than placebo in
controlled trials
| Adverse Drug Reaction | STAXYN (n=355) |
Placebo (n=340) |
| Headache | 14.4% | 1.8% |
| Flushing | 7.6% | 0.6% |
| Nasal Congestion | 3.1% | 0.3% |
| Dyspepsia | 2.8% | 0% |
| Dizziness | 2.3% | 0% |
| Back Pain | 2% | 0.3% |
Adverse drug reactions reported in the STAXYN placebo controlled trials were comparable to the adverse drug reactions reported in earlier vardenafil film-coated tablets placebo controlled trials.
Vardenafil film-coated tablets and STAXYN has been administered to over 17,000 men (mean age 54.5, range 18 - 89 years; 70% White, 5% Black, 13% Asian, 4% Hispanic and 8% Other) during controlled and uncontrolled clinical trials worldwide. The number of patients treated for 6 months or longer was 3357, and 1350 patients were treated for at least 1 year.
In the placebo-controlled clinical trials for vardenafil film-coated tablets and STAXYN, the discontinuation rate due to adverse events was 1.9% for vardenafil compared to 0.8% for placebo. Placebo-controlled trials suggested a dose effect in the incidence of some adverse reactions (for example, dizziness, headache, flushing, dyspepsia, nausea, nasal congestion) over the 5 mg, 10 mg, and 20 mg doses of vardenafil film-coated tablets.
The following section identifies additional, less frequent adverse reactions (<2%) reported during the clinical development of vardenafil film-coated tablets and STAXYN. Excluded from this list are those adverse reactions that are infrequent and minor, those events that may be commonly observed in the absence of drug therapy, and those events that are not reasonably associated with the drug:
Body as a whole: allergic edema and angioedema, feeling unwell, allergic reactions, chest pain Auditory: tinnitus, vertigo
Cardiovascular: palpitation, tachycardia, angina pectoris, myocardial infarction, ventricular tachyarrhythmias, hypotension
Digestive: nausea, gastrointestinal and abdominal pain, dry mouth, diarrhea, gastroesophageal reflux disease, gastritis, vomiting, increase in transaminases
Musculoskeletal: increase in creatine phosphokinase (CPK), increased muscle tone and cramping, myalgia
Nervous: paresthesia and dysesthesia, somnolence, sleep disorder, syncope, amnesia, seizure
Respiratory: dyspnea, sinus congestion
Skin and appendages: erythema, rash
Ophthalmologic: visual disturbance, ocular hyperemia, visual color distortions, eye pain and eye discomfort, photophobia, increase in intraocular pressure, conjunctivitis
Urogenital: increase in erection, priapism
The following adverse reactions have been identified during post approval use of vardenafil in the film-coated tablet formulation. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.
Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors [see WARNINGS AND PRECAUTIONS and PATIENT INFORMATION].
Visual disturbances including vision loss (temporary or permanent), such as visual field defect, retinal vein occlusion, and reduced visual acuity, have also been reported rarely in postmarketing experience. It is not possible to determine whether these events are related directly to the use of vardenafil.
Seizure, seizure recurrence and transient global amnesia have been reported postmarketing in temporal association with vardenafil.
Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. In some cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of vardenafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors [see PATIENT INFORMATION].
The drug interaction studies described below were conducted using vardenafil film-coated tablets.
Concomitant use of STAXYN and nitrates is contraindicated. The blood pressure lowering effects of sublingual nitrates (0.4 mg) taken 1 and 4 hours after vardenafil and increases in heart rate when taken at 1, 4 and 8 hours after vardenafil were potentiated by a 20 mg dose of vardenafil in healthy middle-aged subjects. These effects were not observed when vardenafil 20 mg was taken 24 hours before the nitroglycerin (NTG). Potentiation of the hypotensive effects of nitrates for patients with ischemic heart disease has not been evaluated, and concomitant use of STAXYN and nitrates is contraindicated [see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY].
Patients taking alpha-blockers should not initiate vardenafil therapy with STAXYN. Patients treated with alpha-blockers who have previously used vardenafil film-coated tablets may be switched to STAXYN at the advice of their healthcare provider. Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including STAXYN and alpha-adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. Clinical pharmacology studies have been conducted with co-administration of vardenafil with alfuzosin, terazosin or tamsulosin. [See DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY]
STAXYN may add to the blood pressure lowering effect of antihypertensive agents. In a clinical pharmacology study of patients with erectile dysfunction, single doses of 20 mg vardenafil caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1.
Vardenafil 20 mg did not potentiate the hypotensive effects of alcohol during the 4-hour observation period in healthy volunteers when administered with alcohol (0.5 g/kg body weight: approximately 40 mL of absolute alcohol in a 70 kg person). Alcohol and vardenafil plasma levels were not altered when dosed simultaneously.
Studies in human liver microsomes showed that vardenafil is metabolized primarily by cytochrome P450 (CYP) isoforms 3A4/5, and to a lesser degree by CYP2C9. Therefore, inhibitors of these enzymes are expected to reduce vardenafil clearance [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
Do not use STAXYN with moderate and potent CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION].
Potent CYP3A4 inhibitors
Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil area under the curve (AUC) and a 4-fold increase in maximum concentration (Cmax) when co-administered with vardenafil 5 mg in healthy volunteers. [See DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]
Indinavir (800 mg t.i.d.) co-administered with vardenafil 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil Cmax and a 2-fold increase in vardenafil half-life. [See DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]
Ritonavir (600 mg b.i.d.) co-administered with vardenafil 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13fold increase in vardenafil Cmax. The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a HIV protease inhibitor and a highly potent CYP3A4 inhibitor, which also inhibits CYP2C9. [See DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]
Moderate CYP3A4 inhibitors
Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in vardenafil Cmax when co-administered with vardenafil 5 mg in healthy volunteers [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum hydroxide, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters.
Cimetidine (400 mg b.i.d.) had no effect on AUC and Cmax of vardenafil when co-administered with 20 mg vardenafil in healthy volunteers.
Vardenafil and its metabolites had no effect on CYP1A2, 2A6, and 2E1 (Ki >100 micromolar). Weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4) were found, but Ki values were in excess of plasma concentrations achieved following dosing. The most potent inhibitory activity was observed for vardenafil metabolite M1, which had a Ki of 1.4 micromolar toward CYP3A4, which is about 20 times higher than the M1 Cmax values after an 80 mg vardenafil dose.
Nifedipine
Vardenafil 20 mg (film-coated tablets), when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the relative AUC or Cmax of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil when taken in combination. STAXYN, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily in patients whose hypertension was controlled with nifedipine, produced mean additional supine systolic/diastolic blood pressure reductions of 3/4 mmHg (age group 65 to 69 years) and 5/5 mmHg (age group 70 to 80 years) compared to placebo.
Ritonavir And Indinavir
Upon concomitant administration of 5 mg vardenafil with 600 mg b.i.d. ritonavir, the Cmax and AUC of ritonavir were reduced by approximately 20%. Upon administration of 10 mg of vardenafil (film-coated tablets) with 800 mg t.i.d. indinavir, the Cmax and AUC of indinavir were reduced by 40% and 30%, respectively.
Aspirin
Vardenafil 10 mg and 20 mg did not potentiate the increase in bleeding time caused by aspirin (two 81 mg tablets).
Other Interactions
Vardenafil had no effect on the pharmacodynamics of glyburide (glucose and insulin concentrations) and warfarin (prothrombin time or other pharmacodynamic parameters).
Included as part of the "PRECAUTIONS" Section
In susceptible individuals, potent inhalation anesthetic agents may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. In genetically susceptible pigs, desflurane induced malignant hyperthermia. The clinical syndrome is signaled by hypercapnia, and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and/or unstable blood pressure. Some of these nonspecific signs may also appear during light anesthesia: acute hypoxia, hypercapnia, and hypovolemia.
Treatment of malignant hyperthermia includes discontinuation of triggering agents, administration of intravenous dantrolene sodium, and application of supportive therapy. (Consult prescribing information for dantrolene sodium intravenous for additional information on patient management.) Renal failure may appear later, and urine flow should be monitored and sustained if possible.
Fatal outcome of malignant hyperthermia has been reported with desflurane.
Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
SUPRANE is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm and secretions [see Clinical Studies].
Children, particularly if 6 years old or younger, who are under an anesthetic maintenance of SUPRANE delivered via laryngeal mask airway (LMA™ mask) are at increased risk for adverse respiratory reactions, e.g., coughing and laryngospasm, especially with removal of the laryngeal mask airway under deep anesthesia [see Clinical Studies]. Therefore, closely monitor these patients for signs and symptoms associated with laryngospasm and treat accordingly.
When SUPRANE is used for maintenance of anesthesia in children with asthma or a history of recent upper airway infection, there is an increased risk for airway narrowing and increases in airway resistance. Therefore, closely monitor these patients for signs and symptoms associated with airway narrowing and treat accordingly.
Desflurane like some other inhalation anesthetics, can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide that may result in elevated levels of carboxyhemoglobin in some patients. Case reports suggest that barium hydroxide lime and soda lime become desiccated when fresh gases are passed through the CO2 canister at high flow rates over many hours or days. When a clinician suspects that CO2 absorbent may be desiccated, it should be replaced before the administration of SUPRANE.
With the use of halogenated anesthetics, disruption of hepatic function, icterus and fatal liver necrosis have been reported; such reactions appear to indicate hypersensitivity. As with other halogenated anesthetic agents, SUPRANE may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics [see CONTRAINDICATIONS]. Cirrhosis, viral hepatitis or other pre-existing hepatic disease may be a reason to select an anesthetic other than a halogenated anesthetic. As with all halogenated anesthetics, repeated anesthesia within a short period of time should be approached with caution.
Published animal studies demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. The clinical significance of these findings is not clear. However, based on the available data, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately three years of age in humans. [See Use In Specific Populations , Nonclinical Toxicology].
Some published studies in children suggest that similar deficits may occur after repeated or prolonged exposures to anesthetic agents early in life and may result in adverse cognitive or behavioral effects. These studies have substantial limitations, and it is not clear if the observed effects are due to the anesthetic/sedation drug administration or other factors such as the surgery or underlying illness.
Anesthetic and sedation drugs are a necessary part of the care of children needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks.
Transient elevations in glucose and white blood cell count may occur as with use of other anesthetic agents.
Emergence from anesthesia in children may evoke a brief state of agitation that may hinder cooperation.
Long-term studies in animals to evaluate the carcinogenic potential of desflurane have not been conducted.
In vitro and in vivo genotoxicity studies did not demonstrate mutagenicity or chromosomal damage by desflurane. Tests for genotoxicity included the Ames mutation assay, the metaphase analysis of human lymphocytes, and the mouse micronucleus assay.
In a study in which male animals were administered 8.2% desflurane (60% oxygen) for either 0.5, 1.0, or 4.0 hours per day beginning 63 days prior to mating and female animals were administered the same doses of desflurane for 14 days prior to mating through Lactation Day 21, there were no adverse effects on fertility in the 1.0 hour per day treatment group. However, reduced male and female fertility was noted in the 4 hour a day group. A dose dependent increase in mortality and decreased body weight gain was note in all treatment groups.
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, embryo-fetal toxicity (reduced viable fetuses and/or increased post-implantation loss) was noted in pregnant rats and rabbits administered 1 MAC desflurane for 4 hours a day (4 MAC-hours/day) during organogenesis.
Published studies in pregnant primates demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of peak brain development increases neuronal apoptosis in the developing brain of the offspring when used for longer than 3 hours. There are no data on pregnancy exposures in primates corresponding to periods prior to the third trimester in humans [See Data].
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 1520%, respectively.
Labor or Delivery
The safety of SUPRANE during labor or delivery has not been demonstrated. SUPRANE is a uterine-relaxant.
Animal Data
Pregnant rats were exposed to 8.2% desflurane (1 MAC; 60% oxygen) for 0.5, 1.0, or 4.0 hours (0.5, 1.0, or 4.0 MAC-hours) per day during organogenesis (Gestation Day 6-15).
Embryo-fetal toxicity (increased post-implantation loss and reduced viable fetuses) was noted in the 4 hour treatment group in the presence of maternal toxicity (reduced body weight gain). There was no evidence of malformations in any group.
Pregnant rabbits were exposed to 8.9% desflurane (1 MAC; 60% oxygen) for 0.5, 1.0, or 3.0 hours per day during organogenesis (Gestation Days 6-18). Fetal toxicity (reduced viable fetuses) was noted in the 3 hour treatment group in the presence of maternal toxicity (reduced body weight). There was no evidence of malformations in any group.
Pregnant rats were exposed to 8.2% desflurane (1 MAC; 60% oxygen) for 0.5, 1.0, or 4.0 hours per day from late gestation and through lactation (Gestation Day 15 to Lactation Day 21). Pup body weights were reduced in the 4 hours per day group in the presence of maternal toxicity (increased mortality and reduced body weight gain). This study did not evaluate neurobehavioral function including learning and memory or reproductive behavior in the first generation (F1) pups.
In a published study in primates, administration of an anesthetic dose of ketamine for 24 hours on Gestation Day 122 increased neuronal apoptosis in the developing brain of the fetus. In other published studies, administration of either isoflurane or propofol for 5 hours on Gestation Day 120 resulted in increased neuronal and oligodendrocyte apoptosis in the developing brain of the offspring. With respect to brain development, this time period corresponds to the third trimester of gestation in the human. The clinical significance of these findings is not clear; however, studies in juvenile animals suggest neuroapoptosis correlates with long-term cognitive deficits [See WARNINGS AND PRECAUTIONS, Pediatric Use and Nonclinical Toxicology].
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when SUPRANE is administered to a nursing woman.
SUPRANE is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than SUPRANE, and tracheal intubation.
Is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing (26%), laryngospasm (13%) and secretions (12%) [see Clinical Studies].
Children, particularly if 6 years old or younger, who are under an anesthetic maintenance of SUPRANE delivered via laryngeal mask airway (LMA™ mask) are at increased risk for adverse respiratory reactions, e.g., coughing and laryngospasm, especially with removal of the laryngeal mask airway under deep anesthesia [see Clinical Studies]. Therefore, closely monitor these patients for signs and symptoms associated with laryngospasm and treat accordingly.
When SUPRANE is used for maintenance of anesthesia in children with asthma or a history of recent upper airway infection, there is an increased risk for airway narrowing and increases in airway resistance. Therefore, closely monitor these patients for signs and symptoms associated with airway narrowing and treat accordingly.
Published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as SUPRANE, that either block NMDA receptors or potentiate the activity of GABA during the period of rapid brain growth or synaptogenesis, results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately 3 years of age in humans.
In primates, exposure to 3 hours of ketamine that produced a light surgical plane of anesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer of isoflurane increased neuronal cell loss. Data from isoflurane-treated rodents and ketamine-treated primates suggest that the neuronal and oligodendrocyte cell losses are associated with prolonged cognitive deficits in learning and memory. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in pregnant women, neonates, and young children who require procedures with the potential risks suggested by the nonclinical data [See WARNINGS AND PRECAUTIONS, Pregnancy and Nonclinical Toxicology].
The minimum alveolar concentration (MAC) of SUPRANE decreases with increasing patient age. The dose should be adjusted accordingly. The average MAC for SUPRANE in a 70 year old patient is two-thirds the MAC for a 20 year old patient [see DOSAGE AND ADMINISTRATION Table 1 and Clinical Studies].
Concentrations of 1-4% SUPRANE in nitrous oxide/oxygen have been used in patients with chronic renal or hepatic impairment and during renal transplantation surgery.
Because of minimal metabolism, a need for dose adjustment in patients with renal and hepatic impairment is not to be expected.
Nine patients receiving desflurane (N=9) were compared to 9 patients receiving isoflurane, all with chronic renal insufficiency (serum creatinine 1.5-6.9 mg/dL). No differences in hematological or biochemical tests, including renal function evaluation, were seen between the two groups. Similarly, no differences were found in a comparison of patients receiving either desflurane (N=28) or isoflurane (N=30) undergoing renal transplant.
Eight patients receiving SUPRANE were compared to six patients receiving isoflurane, all with chronic hepatic disease (viral hepatitis, alcoholic hepatitis, or cirrhosis). No differences in hematological or biochemical tests, including hepatic enzymes and hepatic function evaluation, were seen.
The symptoms of overdosage of SUPRANE can present as a deepening of anesthesia, cardiac and/or respiratory depression in spontaneously breathing patients, and cardiac depression in ventilated patients in whom hypercapnia and hypoxia may occur only at a late stage. In the event of overdosage, or suspected overdosage, take the following actions: discontinue administration of SUPRANE, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.
The use of SUPRANE is contraindicated in the following conditions:
Changes in the clinical effects of SUPRANE rapidly follow changes in the inspired concentration. The duration of anesthesia and selected recovery measures for SUPRANE are given in the following tables:
In 178 female outpatients undergoing laparoscopy, premedicated with fentanyl (1.5-2.0 μg/kg), anesthesia was initiated with propofol 2.5 mg/kg, desflurane/N2O 60% in O2 or desflurane/O2 alone. Anesthesia was maintained with either propofol 1.5-9.0 mg/kg/hr, desflurane 2.6-8.4% in N2O 60% in O2, or desflurane 3.1-8.9% in O2.
Emergence and Recovery After Outpatient Laparoscopy
178 Females, Ages 20-47 Times in Minutes: Mean ± SD (Range)
| Induction: | Propofol | Propofol | Desflurane/N2O | Desflurane/O2 |
| Maintenance: | Propofol/N2O | Desflurane/N2O | Desflurane/N2O | Desflurane/O2 |
| Number of Pts: | N = 48 | N = 44 | N = 43 | N = 43 |
| Median age | 30 (20 - 43) |
26 (21 - 47) |
29 (21 - 42) |
30 (20 - 40) |
| Anesthetic time | 49 ± 53 (8 - 336) |
45 ± 35 (11 - 178) |
44 ± 29 (14 - 149) |
41 ± 26 (19 - 126) |
| Time to open eyes | 7 ± 3 (2 - 19) |
5 ± 2* (2 - 10) |
5 ± 2* (2 - 12) |
4 ± 2* (1 - 11) |
| Time to state name | 9 ± 4 (4 - 22) |
8 ± 3 (3 - 18) |
7 ± 3* (3 - 16) |
7 ± 3* (2 - 15) |
| Time to stand | 80 ± 34 (40 - 200) |
86 ± 55 (30 - 320) |
81 ± 38 (35 - 190) |
77 ± 38 (35 - 200) |
| Time to walk | 110 ± 6 (47 - 285) |
122 ± 85 (37 - 375) |
108 ± 59 (48 - 220) |
108 ± 66 (49 - 250) |
| Time to fit for discharge | 152 ± 75 (66 - 375) |
157 ± 80 (73 - 385) |
150 ± 66 (68 - 310) |
155 ± 73 (69 - 325) |
| *Differences were statistically significant (p < 0.05) by Dunnett's procedure comparing all treatments to the propofol-propofol/N2O (induction and maintenance) group. Results for comparisons greater than one hour after anesthesia show no differences between groups and considerable variability within groups. | ||||
In 88 unpremedicated outpatients, anesthesia was initiated with thiopental 3-9 mg/kg or desflurane in O2. Anesthesia was maintained with isoflurane 0.7-1.4% in N2O 60%, desflurane 1.8-7.7% in N2O 60%, or desflurane 4.4-11.9% in O2.
Emergence and Recovery Times in Outpatient Surgery 46
Males, 42 Females, Ages 19-70 Times in Minutes: Mean ± SD (Range)
| Induction: | Thiopental | Thiopental | Thiopental | Desflurane/O2 |
| Maintenance: | Isoflurane/N2O | Desflurane/N2O | Desflurane/O2 | Desflurane/O2 |
| Number of Pts: | N = 23 | N = 21 | N = 23 | N = 21 |
| Median age | 43 (20 - 70) |
40 (22 - 67) |
43 (19 - 70) |
41 (21-64) |
| Anesthetic time | 49 ± 23 (11 - 94) |
50 ± 19 (16 - 80) |
50 ± 27 (16 - 113) |
51 ± 23 (19 - 117) |
| Time to open eyes | 13 ± 7 (5 - 33) |
9 ± 3* (4 - 16) |
12 ± 8 (4 - 39) |
8 ± 2* (4 - 13) |
| Time to state name | 17 ± 10 (6 - 44) |
11 ± 4* (6 - 19) |
15 ± 10 (6 - 46) |
9 ± 3* (5 - 14) |
| Time to walk | 195 ± 67 (124 - 365) |
176 ± 60 (101 - 315) |
168 ± 34 (119 - 258) |
181 ± 42 (92 - 252) |
| Time to fit for discharge | 205 ± 53 (153 - 365) |
202 ± 41 (144 - 315) |
197 ± 35 (155 - 280) |
194 ± 37 (134 - 288) |
| *Differences were statistically significant (p < 0.05) by Dunnett's procedure comparing all treatments to the thiopental-isoflurane/N2O (induction and maintenance) group. Results for comparisons greater than one hour after anesthesia show no differences between groups and considerable variability within groups. | ||||
Recovery from anesthesia was assessed at 30, 60, and 90 minutes following 0.5 MAC desflurane (3%) or isoflurane (0.6%) in N2O 60% using subjective and objective tests. At 30 minutes after anesthesia, only 43% of patients in the isoflurane group were able to perform the psychometric tests compared to 76% in the SUPRANE group (p < 0.05).
Recovery Tests: Percent of Preoperative Baseline
Values 16 Males, 22 Females, Ages 20-65 Percent: Mean ± SD
| Maintenance: | 60 minutes After Anesthesia | 90 minutes After Anesthesia | ||
| Desflurane/N2O | Isoflurane/N2O | Desflurane/N2O | Isoflurane/N2O | |
| Confusion Δ | 66 ± 6 | 47 ± 8 | 75 ± 7* | 56 ± 8 |
| Fatigue Δ | 70 ± 9* | 33 ± 6 | 89 ± 12* | 47 ± 8 |
| Drowsiness Δ | 66 ± 5* | 36 ± 8 | 76 ± 7* | 49 ± 9 |
| ClumsinessΔ | 65 ± 5 | 49 ± 8 | 80 ± 7* | 57 ± 9 |
| ComfortΔ | 59 ± 7* | 30 ± 6 | 60 ± 8* | 31 ± 7 |
| DSST+ score | 74 ± 4* | 50 ± 9 | 75 ± 4* | 55 ± 7 |
| Trieger Tests++ | 67 ± 5 | 74 ± 6 | 90 ± 6 | 83 ± 7 |
| Δ Visual analog scale (values from 0-100; 100 = baseline) + DSST = Digit Symbol Substitution Test ++ Trieger Test = Dot Connecting Test * Differences were statistically significant (p < 0.05) using a two-sample t-test |
||||
SUPRANE was studied in twelve volunteers receiving no other drugs. Hemodynamic effects during controlled ventilation (PaCO2 38 mm Hg) were:
Hemodynamic Effects of Desflurane During Controlled
Ventilation 12 Male Volunteers, Ages 16-26 Mean ± SD (Range)
| Total MAC Equivalent | End-Tidal % Des/O2 | End-Tidal % Des/N2O | Heart Rate (beats/min) |
Mean Arterial Pressure (mm Hg) |
Cardiac Index (L/min/m²) |
|||
| O2 | N2O | O2 | N2O | O2 | N2O | |||
| 0 | 0% / 21% | 0% / 0% | 69 ± 4 (63 - 76) |
70 ± 6 (62 - 85) |
85 ± 9 (74 - 102) |
85 ± 9 (74 - 102) |
3.7 ± 0.4 (3.0 - 4.2) |
3.7 ± 0.4 (3.0 - 4.2) |
| 0.8 | 6% / 94% | 3% / 60% | 73 ± 5 (67 - 80) |
77 ± 8 (67 - 97) |
61 ± 5* (55 - 70) |
69 ± 5* (62 - 80) |
3.2 ± 0.5 (2.6 - 4.0) |
3.3 ± 0.5 (2.6 - 4.1) |
| 1.2 | 9% / 91% | 6% / 60% | 80 ± 5* (72 - 84) |
77 ± 7 (67 - 90) |
59 ± 8* (44 -71) |
63 ± 8* (47 - 74) |
3.4 ± 0.5 (2.6 - 4.1) |
3.1 ± 0.4* (2.6 - 3.8) |
| 1.7 | 12% / 88% | 9% / 60% | 94 ± 14* (78 - 109) |
79 ± 9 (61 -91) |
51 ± 12* (31 -66) |
59 ± 6* (46 - 68) |
3.5 ± 0.9 (1.7 - 4.7) |
3.0 ± 0.4* (2.4 - 3.6) |
| *Differences were statistically
significant (p < 0.05) compared to awake values, Newman-Keul's method of multiple comparison. |
||||||||
When the same volunteers breathed spontaneously during desflurane anesthesia, systemic vascular resistance and mean arterial blood pressure decreased; cardiac index, heart rate, stroke volume, and central venous pressure (CVP) increased compared to values when the volunteers were conscious. Cardiac index, stroke volume, and CVP were greater during spontaneous ventilation than during controlled ventilation.
During spontaneous ventilation in the same volunteers, increasing the concentration of SUPRANE from 3% to 12% decreased tidal volume and increased arterial carbon dioxide tension and respiratory rate. The combination of N2O 60% with a given concentration of desflurane gave results similar to those with desflurane alone. Respiratory depression produced by desflurane is similar to that produced by other potent inhalation agents.
The use of desflurane concentrations higher than 1.5 MAC may produce apnea.
Figure 1:PaCO2 During
Spontaneous Ventilation in Unstimulated Volunteers
 |
Due to the volatile nature of desflurane in plasma samples, the washin-washout profile of desflurane was used as a surrogate of plasma pharmacokinetics. SUPRANE is a volatile liquid inhalation anesthetic minimally biotransformed in the liver in humans. Less than 0.02% of the desflurane absorbed can be recovered as urinary metabolites (compared to 0.2% for isoflurane). Eight healthy male volunteers first breathed 70% N2O/30% O2 for 30 minutes and then a mixture of desflurane 2.0%, isoflurane 0.4%, and halothane 0.2% for another 30 minutes. During this time, inspired and end-tidal concentrations (FI and FA) were measured. The FA/FI (washin) value at 30 minutes for desflurane was 0.91, compared to 1.00 for N2O, 0.74 for isoflurane, and 0.58 for halothane (see Figure 2). The washin rates for halothane and isoflurane were similar to literature values. The washin was faster for desflurane than for isoflurane and halothane at all time points. The FA/FAO (washout) value at 5 minutes was 0.12 for desflurane, 0.22 for isoflurane, and 0.25 for halothane (see Figure 3). The washout for desflurane was more rapid than that for isoflurane and halothane at all elimination time points. By 5 days, the FA/FAO for desflurane is 1/20th of that for halothane or isoflurane.
Figure 2: Desflurane Washin
 |
Figure 3: Desflurane Washout
 |
The efficacy of SUPRANE was evaluated in 1,843 patients including ambulatory (N=1,061), cardiovascular (N=277), geriatric (N=103), neurosurgical (N=40), and pediatric (N=235) patients. Clinical experience with these patients and with 1,087 control patients in these studies not receiving SUPRANE is described below. Although SUPRANE can be used in adults for the inhalation induction of anesthesia via mask, it produces a high incidence of respiratory irritation (coughing, breathholding, apnea, increased secretions, laryngospasm). Oxyhemoglobin saturation below 90% occurred in 6% of patients (from pooled data, N = 370 adults).
SUPRANE plus N2O was compared to isoflurane plus N2O in multicenter studies (21 sites) of 792 ASA physical status I, II, or III patients aged 18-76 years (median 32).
Anesthetic induction begun with thiopental and continued with SUPRANE was associated with a 7% incidence of oxyhemoglobin saturation of 90% or less (from pooled data, N = 307) compared with 5% in patients in whom anesthesia was induced with thiopental and isoflurane (from pooled data, N = 152).
SUPRANE (desflurane, USP) with or without N2O or other anesthetics was generally well tolerated. There were no differences between SUPRANE and the other anesthetics studied in the times that patients were judged fit for discharge.
In one outpatient study, patients received a standardized anesthetic consisting of thiopental 4.2-4.4 mg/kg, fentanyl 3.5-4.0 μg/kg, vecuronium 0.05-0.07 mg/kg, and N2O 60% in oxygen with either desflurane 3% or isoflurane 0.6%. Emergence times were significantly different; but times to sit up and discharge were not different (see Table 5).
Table 5 : Recovery Profiles After Desflurane 3% in N2O
60% vs Isoflurane 0.6% in N2O 60% in Outpatients 16 Males, 22 Females, Ages
20-65 Mean ± SD
| Isoflurane | Desflurane | |
| Number | 21 | 17 |
| Anesthetic time (min) | 127 ± 80 | 98 ± 55 |
| Recovery time to: | ||
| Follow commands (min) | 11.1 ± 7.9 | 6.5 ± 2.3* |
| Sit up (min) | 113 ± 27 | 95 ± 56 |
| Fit for discharge (min) | 231 ± 40 | 207 ± 54 |
| *Difference was statistically significant from the isoflurane group (p < 0.05), unadjusted for multiple comparisons. | ||
SUPRANE was compared to isoflurane, sufentanil or fentanyl for the anesthetic management of coronary artery bypass graft (CABG), abdominal aortic aneurysm, peripheral vascular and carotid endarterectomy surgery in 7 studies at 15 centers involving a total of 558 patients. In all patients except the desflurane vs. sufentanil study, the volatile anesthetics were supplemented with intravenous opioids, usually fentanyl. Blood pressure and heart rate were controlled by changes in concentration of the volatile anesthetics or opioids and cardiovascular drugs if necessary. Oxygen (100%) was the carrier gas in 253 of 277 desflurane cases (24 of 277 received N2O/O2).
Cardiovascular Patients by
Agent and Type of Surgery 418 Males, 140 Females, Ages 27-87 (Median 64)
| Type of Surgery | 13 Centers | 1 Center | 1 Center | |||
| Isoflurane | Desflurane | Sufentanil | Desflurane | Fentanyl | Desflurane | |
| CABG | 58 | 57 | 100 | 100 | 25 | 25 |
| Abd Aorta | 29 | 25 | - | - | - | - |
| Periph Vasc | 24 | 24 | - | - | - | - |
| Carotid Art | 45 | 46 | - | - | - | - |
| Total | 156 | 152 | 100 | 100 | 25 | 25 |
No differences were found in cardiovascular outcome (death, myocardial infarction, ventricular tachycardia or fibrillation, heart failure) among desflurane and the other anesthetics.
SUPRANE should not be used as the sole agent for anesthetic induction in patients with coronary artery disease or any patients where increases in heart rate or blood pressure are undesirable. In the desflurane vs. sufentanil study, anesthetic induction with desflurane without opioids was associated with new transient ischemia in 14 patients vs. 0 in the sufentanil group. In the desflurane group, mean heart rate, arterial pressure, and pulmonary blood pressure increased and stroke volume decreased in contrast to no change in the sufentanil group. Cardiovascular drugs were used frequently in both groups: especially esmolol in the desflurane group (56% vs. 0%) and phenylephrine in the sufentanil group (43% vs. 27%). When 10 μg/kg of fentanyl was used to supplement induction of anesthesia at one other center, continuous 2-lead ECG analysis showed a low incidence of myocardial ischemia and no difference between desflurane and isoflurane. If desflurane is to be used in patients with coronary artery disease, it should be used in combination with other medications for induction of anesthesia, preferably intravenous opioids and hypnotics.
In studies where SUPRANE or isoflurane anesthesia was supplemented with fentanyl, there were no differences in hemodynamic variables or the incidence of myocardial ischemia in the patients anesthetized with desflurane compared to those anesthetized with isoflurane.
During the precardiopulmonary bypass period, in the desflurane vs. sufentanil study where the desflurane patients received no intravenous opioid, more desflurane patients required cardiovascular adjuvants to control hemodynamics than the sufentanil patients. During this period, the incidence of ischemia detected by ECG or echocardiography was not statistically different between desflurane (18 of 99) and sufentanil (9 of 98) groups. However, the duration and severity of ECG-detected myocardial ischemia was significantly less in the desflurane group. The incidence of myocardial ischemia after cardiopulmonary bypass and in the ICU did not differ between groups.
SUPRANE plus N2O was compared to isoflurane plus N2O in a multicenter study (6 sites) of 203 ASA physical status II or III elderly patients, aged 57-91 years (median 71).
Most patients were premedicated with fentanyl (mean 2 μg/kg), preoxygenated, and received thiopental (mean 4.3 mg/kg IV) or thiamylal (mean 4 mg/kg IV) followed by succinylcholine (mean 1.4 mg/kg IV) for intubation.
Heart rate and arterial blood pressure remained within 20% of preinduction baseline values during administration of SUPRANE 0.5-7.7% (average 3.6%) with 50-60% N2O. Induction, maintenance, and recovery cardiovascular measurements did not differ from those during isoflurane/N2O administration nor did the postoperative incidence of nausea and vomiting differ. The most common cardiovascular adverse event was hypotension occurring in 8% of the desflurane patients and 6% of the isoflurane patients.
SUPRANE was studied in 38 patients aged 26-76 years (median 48 years), ASA physical status II or III undergoing neurosurgical procedures for intracranial lesions.
Induction consisted of standard neuroanesthetic techniques including hyperventilation and thiopental.
No change in cerebrospinal fluid pressure (CSFP) was observed in 8 patients who had intracranial tumors when the dose of SUPRANE was 0.5 MAC in N2O 50%. In another study of 9 patients with intracranial tumors, 0.8 MAC desflurane/air/O2 did not increase CSFP above post induction baseline values. In a different study of 10 patients receiving 1.1 MAC desflurane/air/O2, CSFP increased 7 mm Hg (range 3-13 mm Hg increase, with final values of 11-26 mm Hg) above the pre-drug values.
All volatile anesthetics may increase intracranial pressure in patients with intracranial space occupying lesions. In such patients, SUPRANE should be administered at 0.8 MAC or less, and in conjunction with a barbiturate induction and hyperventilation (hypocapnia) in the period before cranial decompression. Appropriate attention must be paid to maintain cerebral perfusion pressure. The use of a lower dose of SUPRANE (desflurane, USP) and the administration of a barbiturate and mannitol would be predicted to lessen the effect of desflurane on CSFP.
Under hypocapnic conditions (PaCO2 27 mm Hg) SUPRANE 1 and 1.5 MAC did not increase cerebral blood flow (CBF) in 9 patients undergoing craniotomies. CBF reactivity to increasing PaCO2 from 27 to 35 mm Hg was also maintained at 1.25 MAC desflurane/air/O2.
In a clinical safety trial conducted in children aged 2 to 16 years (mean 7.4 years), following induction with another agent, SUPRANE and isoflurane (in N2O/O2) were compared when delivered via face mask or laryngeal mask airway (LMA™ mask) for maintenance of anesthesia, after induction with intravenous propofol or inhaled sevoflurane, in order to assess the relative incidence of respiratory adverse events.
Maintenance in Nonintubated Pediatric Patients (Face
Mask or LMA™ mask Used; N=300) All Respiratory Events* ( > 1% of All Pediatric
Patients)
| All Ages (N=300) | 2-6 yr (N=150) | 7-11 yr (N=81) | 12-16 yr (N=69) | |
| Any respiratory events | 39% | 42% | 33% | 39% |
| Airway obstruction | 4% | 5% | 4% | 3% |
| Breath-holding | 3% | 2% | 3% | 4% |
| Coughing | 26% | 33% | 19% | 22% |
| Laryngospasm | 13% | 16% | 7% | 13% |
| Secretion | 12% | 13% | 10% | 12% |
| Non-specific desaturation | 2% | 2% | 1% | 1% |
| *Minor, moderate and severe respiratory events | ||||
SUPRANE was associated with higher rates (compared with isoflurane) of coughing, laryngospasm and secretions with an overall rate of respiratory events of 39%. Of the pediatric patients exposed to desflurane, 5% experienced severe laryngospasm (associated with significant desaturation; i.e. SpO2 of < 90% for > 15 seconds, or requiring succinylcholine), across all ages, 2-16 years old. Individual age group incidences of severe laryngospasm were 9% for 2-6 years old, 1% for 7-11 years old, and 1% for 12-16 years old. Removal of LMA™ mask under deep anesthesia (MAC range 0.6 – 2.3 with a mean of 1.12 MAC) was associated with a further increase in frequency of respiratory adverse events as compared to awake LMA™ mask removal or LMA™ mask removal under deep anesthesia with the comparator. The frequency and severity of non-respiratory adverse events were comparable between the two groups.
The incidence of respiratory events under these conditions was highest in children aged 2-6 years. Therefore, similar studies in children under the age of 2 years were not initiated.
Anesthesia providers need to obtain the following information from patients prior to administration of anesthesia:
Anesthesia providers should inform patients of the risks associated with SUPRANE:
Studies conducted in young animals and children suggest repeated or prolonged use of general anesthetic or sedation drugs in children younger than 3 years may have negative effects on their developing brains. Discuss with parents and caregivers the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs [See WARNINGS AND PRECAUTIONS].
