Professional Drug Information > Desflurane

Desflurane (Inhalation-Systemic)

VA CLASSIFICATION
Primary: CN201

Commonly used brand name(s): Suprane.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Anesthetic (general)—

Indications

Accepted

Anesthesia, general—Desflurane is indicated for the induction and maintenance of general anesthesia in adults and for maintenance of anesthesia in infants and children ^{01}. However, inhalation anesthetic agents are rarely used alone; other medications are frequently administered to induce or supplement anesthesia ^{03}.
—When desflurane is used for an inhalation induction in adults, it can cause complications such as coughing, increased secretions, laryngospasm, apnea, and oxyhemoglobin desaturation ^{{01} {08} {09} {15}}. The occurrence of such complications may not be decreased ^{{15} {25}}, and the risk of hypoxemia may be increased ^{44}, when nitrous oxide (60 to 66%) is administered concurrently with induction doses of desflurane. However, the risk of severe oxygen desaturation and apnea is decreased when desflurane is administered with 100% oxygen ^{56}. Therefore, administration of an intravenous induction agent and/or other intravenous adjuvant prior to or concurrently with desflurane, or administration of desflurane with 100% oxygen, should be considered ^{45}.

Unaccepted
Desflurane is not recommended for induction of anesthesia in infants and children because of an unacceptably high incidence of moderate to severe adverse effects, such as breath-holding, coughing, severe laryngospasm, increased secretions, oxyhemoglobin desaturation ^{01}, and excitement ^{15}. Although these complications may also occur when desflurane is used for an inhalation induction in adults, they occur more frequently ^{{01} {15}} and are more severe ^{15} in pediatric patients.


Pharmacology/Pharmacokinetics

Note: Concentration-response relationships for inhalation anesthetics are described in terms of the minimum alveolar concentration (MAC), which is defined as the alveolar concentration that prevents movement in 50% of patients subjected to a painful stimulus. The MAC decreases with increasing age (being highest in infants and young children), pregnancy, hypothermia, hypotension, and concurrent use of other CNS depressants, including other inhalation anesthetics ^{{03} {07}}. Average MAC values for desflurane (vaporized in oxygen or a mixture of oxygen and air) are 10%, 7.3%, and 5.2% in patients 9 months, 25 years, and 70 years of age, respectively ^{01}.


Physicochemical characteristics:

Chemical group—
    A halogenated hydrocarbon (methyl ethyl ether) anesthetic ^{{04} {05} {06}}, structurally related to isoflurane ^{{07} {08} {09}}.
Molecular weight—
    168.04 ^{10}


Blood-to-gas partition coefficient (37 °C)
    0.42 ^{01}

Note: The blood-to-gas partition coefficient is an indicator of the solubility of the anesthetic in blood, which affects the rate at which the partial pressure of the anesthetic in the blood (and therefore in the brain) equilibrates with that in the alveoli. Low solubility results in rapid rates of induction, changes in depth of anesthesia, and recovery ^{03}. Desflurane's blood-to-gas partition coefficient is lower than those of other halogenated hydrocarbon anesthetics currently in use ^{{05} {07}}.



Oil-to-gas partition coefficient (37 °C)
    18.7 ^{01}

Note: The oil-to-gas partition coefficient is an indicator of solubility in fatty tissues. High solubility increases anesthetic potency ^{03}. Desflurane's oil-to-gas partition coefficient is substantially lower than those of other halogenated hydrocarbon anesthetics currently in use ^{05}.



Boiling point (1 atm pressure)
    22.8 °C ^{01}

Mechanism of action/Effect:

The precise mechanisms by which inhalation anesthetics produce loss of perception of sensations and unconsciousness have not been established. Inhalation anesthetics probably act on nerve cell membranes to disrupt neuronal transmission in the brain ^{41}. These agents have been shown to bind to and alter membrane proteins ^{{41} {46}}, to alter cellular calcium ion processes ^{47}, and to augment the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) on synaptic transmission ^{{41} {47}}. The Meyer-Overton theory, which is based on the observation that there is a strong correlation between the potency of an inhalation anesthetic and its solubility in oil, suggests that the effects of these agents may be at least partially mediated via an action at the lipid matrix of the neuronal membrane ^{41}.


Other actions/effects:


Cardiovascular system effects:


Blood pressure—

Like other potent inhalation anesthetics, desflurane usually causes dose-dependent decreases in blood pressure ^{{01} {09} {11}} that may reflect the depth of anesthesia ^{{03} {48}}. However, in clinical studies, hypertension occasionally developed during or shortly following induction of anesthesia in patients receiving desflurane ^{{01} {44}}.



Cardiac function—

Desflurane depresses myocardial function ^{{11} {12}}; it may decrease contractility and possibly compliance ^{11}. However, after prolonged administration (several hours), some of the cardiovascular depressant effects may be attenuated ^{11}. Indirect stimulation induced by hypercarbia in spontaneously breathing patients may partially oppose the direct cardiopressant effects of the anesthetic ^{12}. During desflurane administration, indicators of cardiac function (e.g., cardiac index, stroke volume, and central venous pressure) are higher in spontaneously breathing patients than in mechanically ventilated patients ^{{01} {12}}.

Use of desflurane for induction of anesthesia may be associated with myocardial ischemia in patients with significant cardiovascular disease unless an agent that blunts the sympathetic response, e.g., an opioid, is administered concurrently ^{{01} {13} {49}}.

One study has shown that desflurane is not likely to sensitize the myocardium to the ventricular arrhythmogenic effects of catecholamines or other sympathomimetics ^{14}.



Heart/pulse rate—

May be increased by desflurane, especially when high concentrations are given ^{51} during induction ^{{01} {04} {09} {11} {12} {15} {16}}, when concentrations are increased rapidly ^{50}, or after prolonged administration ^{11}. An increase in heart rate therefore cannot be used as an indication of inadequate anesthesia ^{01}.



Peripheral vasculature—

Desflurane may cause vasodilatation ^{01}.


Note: Some of desflurane's cardiovascular effects may be at least partially reversed by surgical stimulation or stress (e.g., skin incision) ^{04}. Also, concurrent use of nitrous oxide (60%) reduces the requirement for desflurane and may therefore attenuate the cardiovascular effects observed with desflurane alone ^{{09} {12} {17}}, especially in mechanically ventilated patients ^{12}.




Central nervous system (CNS) effects:


Electroencephalogram (EEG)—

Desflurane produces a dose-dependent decrease in EEG activity ^{{18} {19}}. It does not produce convulsive activity in the EEG ^{19} (as has been observed with enflurane ^{03}).



Effect on intracranial pressure—

Desflurane dilates cerebral arterioles ^{{18} {20}}. In clinical trials, concentrations of 1 MAC ^{20} or higher ^{01} (but not 0.5 ^{{01} {18}} or 0.8 MAC ^{01}) increased cerebrospinal fluid pressure in patients undergoing craniotomy for removal of tumors despite use of measures that prevent or attenuate the increase in intracranial pressure induced by equivalent concentrations of other halogenated hydrocarbon anesthetics, i.e., establishment of hypocapnia and barbiturate administration ^{20}. However, in another study, 1 or 1.5 MAC of desflurane did not increase cerebral blood flow in patients undergoing craniotomies under hypocapnic conditions ^{01}.




Neuromuscular effects:

Desflurane impairs neuromuscular conduction and decreases muscle contractility ^{{07} {21} {22}}. Its neuromuscular blocking activity is equivalent to that of enflurane ^{07} or isoflurane ^{{15} {19}}. Like these other agents ^{03}, desflurane may produce muscle relaxation sufficient to permit many types of surgery to be performed without a neuromuscular blocking agent.



Respiratory system effects:


Respiration—

Desflurane produces dose-dependent respiratory depression ^{{01} {09} {23}}. It increases arterial carbon dioxide tension and respiratory rate and decreases tidal volume ^{{01} {09} {23}}. In concentrations higher than 1.5 MAC, desflurane may cause apnea ^{{01} {09}}. Respiratory depression induced by inhalation anesthetics may be partially reversed with surgical stimulation or stress ^{03}.



Effects on the airway—

Desflurane is an irritant to the airway ^{{08} {09} {15} {24}} and may cause breath-holding, coughing, increased secretions, and laryngospasm ^{{08} {09} {15}} as well as increased sympathetic nervous system activity ^{47} during induction. These effects may not be attenuated by increasing the inspired concentration slowly ^{15}, premedicating with an opioid (e.g., fentanyl) ^{{15} {25}}, and/or administering nitrous oxide concurrently ^{{15} {25}}.



Absorption:

Rapidly absorbed into the circulation via the lungs, as indicated by the low blood-to-gas partition coefficient ^{{05} {07}}.

Biotransformation:

Hepatic ^{01}; minimal ^{{01} {26} {27} {28}} (approximately 0.02% of the quantity absorbed) ^{28}. In studies performed to date, small quantities of trifluoroacetic acid appeared in the serum and urine of desflurane recipients, but concentrations of inorganic fluoride were not increased ^{{26} {28}}. The risk of postoperative renal function impairment, which has occurred in patients with high concentrations of fluoride resulting from administration of other halogenated hydrocarbon anesthetics (primarily methoxyflurane and occasionally enflurane) ^{27}, appears minimal with desflurane ^{26}.

Time to peak concentration:

The alveolar concentration increases very rapidly toward the inspired concentration ^{{01} {05}}. The ratios of the end-tidal alveolar concentration to the inspired concentration (washin ratio) after 10 and 30 minutes of administration are > 0.8 ^{05} and 0.9 ^{{01} {31}}, respectively.

Time to peak effect

Onset of anesthesia—End-tidal concentrations of 4 to 11% of desflurane, administered with or without nitrous oxide, produce anesthesia in 2 to 4 minutes ^{01}. Desflurane's pungent odor and the airway irritability it causes may limit the rate at which the administered concentration can be increased, resulting in a longer induction time than would be expected with an agent having desflurane's low blood-to-gas partition coefficient ^{{07} {09}}.

Duration of action:

Time to recovery—Recovery after administration is discontinued is rapid ^{{01} {07} {08} {15} {29} {30} {40}} but subject to interpatient variability ^{01}. Recovery time also depends on the administered concentration ^{{15} {24}} and on whether other CNS depressants have been used concurrently ^{{01} {08}}. Whether the duration of administration also affects recovery time has not been studied ^{52}, but, because of desflurane's rapid elimination, a significant lengthening of the recovery time after prolonged administration would not be expected ^{{49} {53}}. In clinical studies, mean emergence times have generally ranged from 5 to 16 minutes ^{{01} {08} {15} {30}}. Psychometric testing has shown that patients begin to recover more rapidly after desflurane than after isoflurane ^{{01} {15} {29} {30}}. However, other determinants of recovery (e.g., time to sit up or walk) and readiness for discharge from outpatient surgical facilities have not been shown to be significantly more rapid with desflurane than with comparison agents (isoflurane or propofol with nitrous oxide) ^{{01} {29} {40}}.

Elimination:
    Primarily as unchanged desflurane, via exhalation ^{31}. Less than 0.02% of a dose is eliminated in the urine as metabolites ^{01}. Also, very small quantities may be eliminated through the skin ^{{07} {32}}.
    A pharmacokinetic study determined that 5 minutes after discontinuation of desflurane the ratio of the end-tidal alveolar concentration to the last concentration during administration (washout ratio) is 0.14 ^{31}. In other studies, the end-tidal desflurane concentration decreased by about 85% within 2 minutes after discontinuation of administration to pediatric patients ^{15} and by about 50% within 2.5 minutes after discontinuation of administration to adult patients ^{{15} {30}}.


Precautions to Consider

Cross-sensitivity and/or related problems

Although this problem has not been documented to date ^{53}, the possibility exists that patients sensitive to other halogenated hydrocarbon anesthetics (enflurane, halothane, isoflurane, or methoxyflurane) may be sensitive to desflurane also ^{01}.

Mutagenicity

No mutagenicity or chromosomal damage was found in in vitro and in vivo studies, including the Ames mutation assay, metaphase analysis of human lymphocytes, and mouse micronucleus assay ^{01}.

Pregnancy/Reproduction
Fertility—
Fertility was not affected after exposure of test animals to the equivalent of 1 minimum alveolar concentration (MAC) of desflurane for 1 hour (1 MAC-hour) per day. The cumulative exposure was 63 MAC-hours for males and 14 MAC-hours for females. At higher doses, mortalities and other manifestations of parental toxicity that could affect fertility (e.g., decreased weight gain) occurred ^{01}.

Pregnancy—

First trimester

Adequate and well-controlled studies in humans have not been done ^{01}. Studies (by retrospective survey) of operating room personnel chronically exposed to low concentrations of inhalation anesthetics in use at the time the studies were done indicate that pregnancies in female personnel and wives of male personnel may be subject to an increased incidence of spontaneous abortions ^{{58} {59}}, stillbirths ^{59}, and possibly birth defects. However, the methods used in obtaining and interpreting the data in these studies have been questioned ^{03}. Also, several animal studies (in which operating room conditions were simulated) failed to show fetotoxic or teratogenic effects following chronic exposure of male and/or female animals to low concentrations of inhalation anesthetics prior to and/or during gestation ^{03}.

Studies in rats and rabbits exposed to 1 MAC-hour per day for 10 and 13 days, respectively, during organogenesis failed to detect evidence of teratogenicity. At higher doses, increased incidences of post-implantation loss and maternal toxicity were observed. Also, at 10 MAC-hours cumulative exposure in rats, the weight of male pups was decreased by about 6% at preterm cesarean delivery ^{01}.



Third trimester

Rats exposed to 1 MAC-hour of desflurane per day from gestation Day 15 did not show signs of dystocia at delivery. The body weights of the exposed pups were comparable to those of controls ^{01}.

FDA Pregnancy Category B ^{01}.



Labor and delivery—

The safety of desflurane during labor and delivery has not been established ^{01}.

Breast-feeding

Because of its rapid elimination from the body, concentrations of desflurane in breast milk are predicted to be lower than those found with other volatile anesthetics. Concentrations in breast milk are not likely to be of clinical importance 24 hours after anesthesia ^{01}.

Pediatrics

Induction—Desflurane is not recommended for induction of anesthesia in pediatric patients because of an unacceptably high incidence of moderate to severe adverse effects, such as breath-holding (68%), coughing (72%), laryngospasm (50%), increased secretions (21%), oxyhemoglobin desaturation (26%) ^{01}, and excitement ^{15}.

Maintenance—The MAC of desflurane is age-dependent; it is higher in infants and children 2 years of age and younger than in older children ^{{01} {04}} and adults ^{01}. MAC values are highest (about 10% ^{01}) in infants 6 to 12 months of age, although values in neonates and infants younger than 6 months of age also exceed 9% ^{{01} {04}}. In contrast, the MAC values of halothane and isoflurane are highest in infants 1 to 6 months of age ^{04}. Also, the difference between MAC values in neonates and those in older infants is not as great for desflurane (about 7.7%) as for halothane (25%) or isoflurane (17%) ^{04}. MAC values decrease to approximately 8.7 ^{04} to 9.1% ^{01} in children 1 to 3 years of age and to 8.1% in children 7 to 12 years of age ^{{01} {04}}.


Geriatrics


Desflurane has been studied in patients up to 91 years of age ^{01}. The MAC is lower in geriatric patients than in younger adults ^{{01} {33} {60}}, about 5.2% for a patient 70 years of age (compared with 6% and 7.3% for patients 45 and 25 years of age, respectively) ^{01}. Also, although emergence in geriatric patients is approximately 20% more rapid after desflurane than after isoflurane, the difference is not as great as in younger adults ^{15}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Many of the following interactions have not been documented with desflurane. However, because they have been reported to occur with other halogenated hydrocarbon anesthetics, the possibility of a significant interaction with desflurane must be considered.

Alcohol, chronic abuse^{03}    (anesthetic requirement may be increased)


» Aminoglycosides, systemic, possibly including oral neomycin (if significant quantities are absorbed by patients with renal function impairment) or
Anesthetics, parenteral-local (large doses leading to significant plasma concentrations) or
Bacitracin or
» Capreomycin or
» Citrate-anticoagulated blood, massive transfusions of or
» Clindamycin or
Colistimethate sodium or
Colistin or
Lidocaine (systemic use, with intravenous doses > 5 mg per kg of body weight) or
» Lincomycin, systemic or
» Neuromuscular blocking agents or
» Polymyxins, systemic or
Procaine (systemic use) or
Tetracyclines or
Trimethaphan (large doses)    (neuromuscular blocking activity of these medications may be additive to that of desflurane, with the degree of potentiation being increased as the concentration of desflurane is increased; although increased and/or prolonged skeletal muscle weakness and respiratory depression or paralysis [apnea] may occur, clinical significance is minimal if the patient is being mechanically ventilated ^{{03} {39}})

    (administration of desflurane for 15 minutes has been shown to decrease the ED ₉₅ [dose of a neuromuscular blocking agent required to produce 95% suppression of the adductor pollicis muscle twitch response to ulnar nerve stimulation] of subsequently administered succinylcholine by about 30% and the ED ₉₅ of subsequently administered atracurium or pancuronium by about 50%; ^{{01} {21}} desflurane's effects on ED ₉₅ values of other nondepolarizing neuromuscular blocking agents and on the duration of action of any neuromuscular blocking agent have not been established; a reduction of dosage, as determined by response to peripheral nerve stimulation, may be needed when a neuromuscular blocking agent is administered after steady-state anesthesia with desflurane has been established ^{01})

    (concurrent use of succinylcholine with halogenated hydrocarbon anesthetics may increase the risk of malignant hyperthermia; also, repeated concurrent use may increase the risk of bradycardia ^{03})


Amiodarone^{03}    (concurrent use with inhalation anesthetics may potentiate hypotension and increase the risk of atropine-resistant bradycardia)


Antihypertensive agents, especially diazoxide or ganglionic blockers such as guanadrel, guanethidine, mecamylamine, or trimethaphan or^{03}
Chlorpromazine or^{03}
Diuretics or^{03}
Hypotension-producing medications, other (see Appendix II )^{03}    (hypotensive effects may be potentiated when these medications are used concurrently with an inhalation anesthetic; patients should be monitored for excessive fall in blood pressure during and following concurrent use)


Antimyasthenics^{03}    (antimyasthenics, especially neostigmine and pyridostigmine, may decrease the neuromuscular blocking activity of halogenated hydrocarbon anesthetics; also, the neuromuscular blocking activity of the anesthetic may interfere with the efficacy of antimyasthenics, and temporary dosage adjustment may be required to control symptoms of myasthenia gravis postoperatively)


Beta-adrenergic blocking agents, including ophthalmic dosage forms^{03}    (concurrent use with hydrocarbon inhalation anesthetics may result in prolonged, severe hypotension because beta-blockade reduces the ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli; if necessary to reverse the effects of beta-adrenergic blocking agents during surgery, agonists such as dobutamine, dopamine, isoproterenol, or norepinephrine may be administered)

    (it is recommended that high concentrations of halogenated hydrocarbon anesthetics not be administered when labetalol is used to produce controlled hypotension during surgery; possible additive effects may lead to excessive hypotension, large reduction in cardiac output, and increased central venous pressure)


» Catecholamines such as dopamine, epinephrine, or norepinephrine or
» Cocaine or
» Ephedrine or
» Levodopa or
» Metaraminol or
» Methoxamine or
Other sympathomimetic agents    (the increase in heart rate and/or blood pressure induced by these agents may be intensified if desflurane causes the same effects; caution in concurrent use is recommended, especially in patients who are at risk of cardiac ischemia ^{49}; however, desflurane does not significantly sensitize the myocardium to the ventricular arrhythmogenic effects of catecholamines or other sympathomimetics ^{14})


CNS depression–producing medications, other, including those commonly used for pre-anesthetic medication or induction or supplementation of anesthesia (see Appendix II )^{01} , especially
Benzodiazepines or
Nitrous oxide or
Opioid analgesics    (concurrent administration with an inhalation anesthetic may cause increased CNS depression, respiratory depression, and/or hypotension, decrease the anesthetic requirement, and prolong recovery from anesthesia; careful attention to the dosage of each agent is required ^{03})

    (concurrent administration of benzodiazepines and/or opioid analgesics decreases the MAC of desflurane ^{{01} {07}}; specifically, midazolam [25 to 50 mcg per kg of body weight (mcg/kg)] decreases the MAC of desflurane by about 16 ^{01} to 22% ^{{07} {34}} and fentanyl [3 to 6 mcg/kg] decreases the MAC of desflurane by 50% ^{01} or more ^{35})

    (concurrent administration of nitrous oxide [60%] decreases the MAC of desflurane by about 50% in adult patients ^{{06} {07}} [in one study, MAC was decreased from 6% to 3% ^{06}] and by about 25% in pediatric patients ^{{16} {36}}; also, concurrent use of 60% nitrous oxide may attenuate many of the cardiovascular effects observed with desflurane alone ^{{09} {12} {17}}, especially in mechanically ventilated patients ^{12}, reduce struggling by patients during induction ^{08}, and decrease postoperative patient recall of induction ^{08})

    (two or more CNS depressants may decrease the MAC of desflurane to a greater extent than a single CNS depressant when used concurrently; in one study, MAC values for desflurane were 3.7% when 60% nitrous oxide was given concurrently and 3%, 1.2%, and 0.1% when 3, 6, or 9 mcg/kg, respectively, of fentanyl was added to the desflurane–nitrous oxide regimen ^{06})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Glucose concentrations, blood and
White blood cell count    (may be transiently increased ^{{01} {02} {37}})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Malignant hyperthermia, history of or suspected genetic predisposition to    (risk of malignant hyperthermic crisis during or following anesthesia; although this complication has not yet been documented in humans receiving desflurane, the anesthetic has induced malignant hyperthermia in genetically susceptible swine ^{01}; although prophylactic administration of dantrolene prior to administration of a potent inhalation anesthetic may prevent the occurrence of a malignant hyperthermic crisis during or shortly following surgery in susceptible patients, this use of dantrolene is controversial and should be undertaken with caution [see Dantrolene (Systemic) ] ^{03})


Risk-benefit should be considered when the following medical problems exist
» Coronary artery disease or other conditions in which increases in heart rate and/or blood pressure would be undesirable    (desflurane increased heart rate, arterial blood pressure, and pulmonary blood pressure; decreased stroke volume; and caused ischemia when used as the sole induction agent in patients undergoing cardiovascular surgery ^{{01} {13}}; however, ischemia did not occur in studies in patients undergoing cardiovascular surgery when supplemental opioid analgesic was administered concurrently ^{{01} {38}}; use of desflurane as the sole induction agent, without premedication with or supplemental administration of an opioid analgesic and/or an appropriate intravenous hypnotic, is not recommended ^{01})


Familial periodic paralysis, hypokalemic or hyperkalemic^{39} or
» Muscular dystrophy^{39} or
» Myasthenia gravis^{03}{39} or
Myasthenic syndrome (Eaton-Lambert syndrome)^{39} or
Other neuromuscular disease leading to muscle weakness^{39}    (the neuromuscular blocking activity of desflurane may cause increased risk of severe muscle weakness or paralysis in patients with these conditions, which may lead to respiratory and other complications; although use of an inhalation anesthetic with substantial neuromuscular blocking activity may be safer than [and may eliminate the need for] a neuromuscular blocking agent in these patients, caution is recommended)


» Head injury or
» Increased intracranial pressure, pre-existing or
» Intracranial lesions, space occupying, or tumors    (desflurane may increase intracranial and/or cerebrospinal fluid [CSF] pressure; in patients undergoing neurosurgery, it is recommended that desflurane be administered in a dose of 0.8 MAC or lower, in conjunction with a barbiturate and hyperventilation [hypocapnia] prior to cranial decompression, and in conjunction with measures to maintain cerebral perfusion; administration of mannitol, in addition to barbiturate administration and reduction of desflurane dosage, may also attenuate the effect of desflurane on CSF pressure ^{01})


Sensitivity to desflurane or other halogenated hydrocarbon anesthetics, history of

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


Note: Various organizations, including medical specialty societies, and institutions, have established standards for the pre-, intra-, and post-procedure care, evaluation, and monitoring of patients receiving various forms of anesthesia and/or sedation. The following recommendations represent the minimum standards established by the American Society of Anesthesiologists for monitoring the status of patients receiving general anesthesia ^{42}. Individual patients may require additional monitoring.

» Blood pressure and
» Body temperature and
» Cardiac/pulse rate and
» Electrocardiographic evaluation and
» Oxygenation and
» Respiratory and ventilatory status    (it is recommended that the patient's blood and tissue oxygenation, ventilation, circulation, and body temperature be monitored continuously during anesthetic administration and as required during the recovery period ^{41})






Side/Adverse Effects

Note: The possibility that malignant hyperthermia may develop during or following anesthesia must be considered. Although this problem has not been documented to date in humans receiving desflurane, the anesthetic has induced malignant hyperthermia in genetically susceptible swine ^{01}.
Sixty-four percent of adults in clinical studies who received induction of anesthesia with desflurane in oxygen, but a significantly smaller percentage of adults who received nitrous oxide concurrently during induction, reported postoperative recall of induction and of a strong or disagreeable odor ^{08}.
In addition to the adverse effects reported below, fever, hemorrhage, myalgia, myocardial infarction, and pruritus occurred rarely (incidence of each < 1%) in clinical trials. A causal relationship to use of desflurane has not been established ^{01}.
Some of the adverse effects that developed during clinical trials, as reported below, may reflect the surgical procedures performed, patient characteristics (including disease), and/or other medications administered concurrently ^{01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent (3 to 10%, or as specified)
During induction by mask (adults only)
    
Apnea^{01} —incidence 15%
    
breath-holding^{01} —incidence 30%
    
coughing^{01} —incidence 34%
    
excitement/struggling^{08}{25}
    
increased secretions^{01}
    
laryngospasm^{01}
    
oxyhemoglobin desaturation^{01}
    
pharyngitis^{01}

During maintenance or recovery (adult and pediatric patients)
    
Apnea^{01}
    
laryngospasm^{01}


Incidence less frequent (1 to 3%)
During maintenance or recovery (adult and pediatric patients)
    
Breath-holding
    
cardiovascular effects, such as bradycardia^{01}
hypertension
nodal arrhythmia
and tachycardia


Incidence rare (less than 1%)
During maintenance or recovery (adult and pediatric patients)
    
Cardiovascular effects, such as arrhythmias, including
bigeminy and other cardiographic abnormalities
myocardial ischemia
    
respiratory effects, such as asthma
dyspnea
and hypoxia




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent (3 to 10%, or as specified)
During maintenance or recovery (adult and pediatric patients)
    
Coughing
    
nausea —incidence 27%
    
vomiting ^{01}—incidence 16%


Incidence less frequent (1 to 3%) or rare (less than 1%)
During maintenance or recovery (adult and pediatric patients)
    
Agitation (nervousness or restlessness)
    
conjunctivitis or conjunctival hyperemia (red or irritated eyes)
    
dizziness
    
excessive salivation
    
headache
    
sore throat^{01}






Overdose
For specific information on the agents used in the management of a desflurane overdose, see:    • Atropine in Anticholinergics/Antispasmodics (Systemic) monograph; and/or
   • Sympathomimetic Agents—Cardiovascular Use (Parenteral-Systemic) monograph.


For more information on the management of overdose, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute
    
Bradycardia
    
circulatory depression or hypotension, severe
    
respiratory depression


Specific treatment
For bradycardia—Administering atropine ^{{03} {44}}.

For circulatory depression or severe hypotension—Discontinuing or lightening anesthesia (if still being administered) and administering plasma and/or intravenous fluids. If surgical or postsurgical conditions permit, positioning the patient to improve venous return to the heart (i.e., in the Trendelenburg position) is recommended. If necessary, a vasopressor may be administered ^{03}.

For respiratory depression—Decreasing anesthetic dosage (if still being administered), establishing a clear airway, and instituting assisted or controlled respiration with 100% oxygen ^{03}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Desflurane (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to desflurane or other halogenated hydrocarbon anesthetics





Use in children—Not recommended for induction because of the high incidence of severe adverse effects

Other medications, including use of “street” drugs
Other medical problems, especially history of or genetic susceptibility to malignant hyperthermia and neuromuscular diseases leading to muscle weakness (e.g., familial periodic paralysis, muscular dystrophy, myasthenia gravis, myasthenic syndrome [Eaton-Lambert syndrome])

Precautions after receiving this medication

For patients receiving anesthesia in an outpatient facility
» Possibility of psychomotor impairment following anesthesia; using caution in driving or performing other tasks requiring alertness and coordination for about 24 hours postanesthesia

» Avoiding use of alcohol or central nervous system (CNS) depressants within 24 hours following anesthesia, unless specifically prescribed or otherwise authorized by physician or dentist


Side/adverse effects
Notifying physician if nausea or vomiting, conjunctivitis, coughing, headache, or pharyngitis occurs or persists after discharge from outpatient surgical unit


General Dosing Information
Inhalation anesthetics are to be administered only by individuals experienced in airway management and respiratory support. Equipment, medications, and personnel for support of ventilation and circulatory resuscitation must be immediately available ^{01}.

Desflurane is to be administered only via a vaporizer specifically designed and designated for use with this agent ^{01}. The anesthetic may be vaporized in oxygen, a mixture of oxygen and air, or a mixture of nitrous oxide and oxygen ^{01}.

The stated dosages are given as a guideline. The dosage of inhaled anesthetics must be individualized according to surgical requirements; concurrent use of adjuvant medications and/or nitrous oxide; patient variables, especially age, body temperature, and physical condition ^{03}; and patient response ^{01}.

Anesthetic requirements are increased in very young children and decreased in geriatric patients ^{03}.

Preanesthetic medications should be selected according to the needs of the individual patient and surgical requirements ^{03}.

Because awakening from desflurane anesthesia may be rapid, the analgesic needs of the patient should be considered before the end of the procedure ^{02}. Rapid awakening with pain may cause agitation, especially in pediatric patients ^{02}.

An intravenous induction agent often is administered prior to an inhalation anesthetic to facilitate induction of anesthesia and prevent the transient initial CNS excitation that may occur during induction with the inhalation anesthetic ^{03}.

During maintenance of anesthesia, the concentration of inhaled anesthetic may be decreased progressively as necessary to prevent further increases in depth of anesthesia and/or hypotension ^{03}.

Assisted or controlled respiration may be necessary, especially during deep levels of anesthesia, to control respiratory depression and/or respiratory acidosis ^{03}.

Desiccation of carbon dioxide (CO ₂) absorbents may occur, especially with the use of high flow-rates of gases. Desflurane can react with desiccated CO ₂ absorbents to produce carbon monoxide. This reaction may result in elevated levels of carboxyhemoglobin in some patients ^{{01} {61}}.

Safety considerations for handling this medication
Predicted effects in operating room personnel of acute overexposure to anesthetic gases include headache, dizziness, and, in extreme cases, unconsciousness ^{01}.

The results of some epidemiological studies suggest a link between chronic exposure of operating room personnel to low concentrations of inhalation anesthetics (waste anesthetic gases [WAGs]) and increased health problems ^{01}, including reproductive problems (increases in spontaneous abortions ^{{01} {43}}, stillbirths ^{43}, and possibly birth defects). Although a causal relationship has not been established, measures to minimize exposure are recommended ^{01}. Such measures include maintaining adequate general ventilation in the operating room, using a well-designed and well-maintained scavenging system, and minimizing leaks and spills while the anesthetic agent is in use via careful work practices and routine equipment maintenance ^{01}.

Although no specific work exposure limit has been established for desflurane, the National Institute for Occupational Safety and Health Administration has recommended an 8-hour, time-weighted average limit of 2 parts per million (ppm) for halogenated anesthetic agents in general. The limit for halogenated anesthetics coupled with nitrous oxide is 0.5 ppm ^{01}.

For treatment of adverse effects
Recommended treatment includes

   • For cardiac arrhythmias ^{03}—Determining whether the level of anesthesia is adequate for the given surgical stimulus and adjusting (deepening or lightening) the level of anesthesia accordingly or discontinuing anesthesia. Also, determining whether the arrhythmia is caused by electrolyte disturbances (e.g., hypokalemia) ^{54}, hypercarbia, hypocarbia, or hypoxia and correcting as required.
   • For malignant hyperthermic crisis—Discontinuing possible triggering agents (e.g., potent inhalation anesthetics, succinylcholine, or stress), managing increased oxygen requirement, cooling the patient, and correcting fluid and electrolyte imbalances and metabolic acidosis. If necessary, administering dantrolene ^{03} until the symptoms subside or the maximum total dose of 10 mg/kg has been administered. Intravenous dantrolene administration may be repeated if symptoms recur. Dantrolene may be administered orally or intravenously, with caution, for 1 to 3 days postoperatively to prevent recurrence of symptoms.
   • For inadequate postoperative ventilation—Decreasing anesthetic dosage (if still being administered), establishing a clear airway, and instituting assisted or controlled respiration with oxygen ^{03}.
   • For emergence delirium—Administering small doses of an opioid (narcotic) analgesic ^{03}, provided that hypoxemia or hypercarbia is not present ^{46}.


Inhalation Dosage Forms

DESFLURANE USP

Usual adult and adolescent dose


Anesthetic (general):
Inhalation, vaporized in a flow of oxygen or oxygen and air, or in a flow of nitrous oxide and oxygen:


Induction¹—
For administration as sole induction agent: 0.5 to ^{55} 3% initially, to be increased by 0.5 to 1% every two to three breaths, or as tolerated, until onset of anesthesia ^{01}.

For administration after induction with an intravenous induction agent: 0.5 to 1 minimum alveolar concentration (MAC) initially, then adjusted as necessary ^{01}.



Maintenance—
To be adjusted according to patient response and surgical requirements, usually 2.5 to 8.5% ^{01}.



Note: Anesthetic requirements, in terms of administered concentration or of MAC, decrease with increasing age. When the anesthetic is vaporized in 100% oxygen or a mixture of oxygen and air, 1 MAC of desflurane is 7.3% for a 25-year-old adult, 6% for a 45-year-old adult, and 5.2% for a 70-year-old adult ^{01}. Geriatric patients should require lower total doses of desflurane for induction and maintenance than younger adults.
Concentrations higher than 12% have been administered safely, usually during induction of anesthesia. However, administration of high concentrations of desflurane will reduce proportionately the quantity of oxygen administered. A decrease in the concentration of nitrous oxide and/or air given concurrently may be necessary to ensure adequate oxygenation ^{01}.


Usual pediatric dose


Anesthetic (general):
Inhalation, vaporized in a flow of oxygen or oxygen and air, or in a flow of nitrous oxide and oxygen:


[Induction]¹—
Use is not recommended.



Maintenance—
To be adjusted according to patient response and surgical requirements, usually 5.2 to 10% ^{01}.



Note: Anesthetic requirements, in terms of administered concentration or of minimum alveolar concentration (MAC), are highest in infants 6 to 12 months of age. When desflurane is vaporized in a flow of 100% oxygen, the value of 1 MAC in infants and children of various ages is approximately ^{{01} {02}}:
2-week-old neonates—9.2%.
10-week-old infants—9.4%.
9-month-old infants—10%.
2-year-old children—9.1%.
4-year-old children—8.6%.
7-year-old children—8.1%.


Usual geriatric dose
See Usual adult and adolescent dose .

Product(s) usually available:
U.S.—


[Suprane^{01}]

Canada—


[Suprane^{01}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Stability:
Stable at room temperature. The only known degradation reaction occurs through prolonged direct contact with soda lime. Small quantities of fluoroform (CHF ₃) are formed by this reaction. Strong acids do not produce discernible degradation ^{01}.

¹ Not included in Canadian product labeling.

Revised: 06/08/1999

References

1. Desflurane package insert (Suprane, Ohmeda—US), Rev 3/98, Rec 5/99.
   

2. Suprane product monograph (Zeneca Pharma—Canada), Rev 11/97, Rec 1/99.
   

3. Panel Consensus, Anesthetics, Inhalation (Systemic) monograph, draft for USP DI 1985.
   

4. Taylor RH, Lerman J. Minimum alveolar concentration of desflurane and hemodynamic responses in neonates, infants, and children. Anesthesiology 1991; 75(4S): 975-9.
   

5. Jones RM, Cashman JN, Eger EI II, et al. Kinetics and potency of desflurane (I-653) in volunteers. Anesth Analg 1990; 70: 3-7.
   

6. Ghouri AF, White PF. Effect of fentanyl and nitrous oxide on the desflurane anesthetic requirement. Anesth Analg 1991; 72: 377-81.
   

7. Eger EI II. Desflurane animal and human pharmacology: aspects of kinetics, safety, and MAC. Anesth Analg 1992; 75(4S): S3-S9.
   

8. Rampil IJ, Lockhart SH, Zwass MS, et al. Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration. Anesthesiology 1991: 74: 429-33.
   

9. Warltier DC, Pagel PS. Cardiovascular and respiratory actions of desflurane: is desflurane different from isoflurane? Anesth Analg 1992; 75(4S): S17-S31.
   

10. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 219.
    

11. Weiskopf RB, Calahan MK, Eger EI II, et al. Cardiovascular actions of desflurane in normocarbic volunteers. Anesth Analg 1991; 73: 143-56.
    

12. Weiskopf RB, Calahan MK, Ionescu P, et al. Cardiovascular actions of desflurane with and without nitrous oxide during spontaneous ventilation in humans. Anesth Analg 1991; 73: 165-74.
    

13. Helman JD, Leung JM, Bellows WH, et al. The risk of myocardial ischemia in patients receiving desflurane versus sufentanil anesthesia for coronary artery bypass graft surgery. Anesthesiology 1992; 77: 47-62.
    

14. Moore MA, Weiskopf RB, Eger EI II, et al. Arrhythomogenic doses of epinephrine during desflurane or isoflurane anesthesia in humans [abstract]. Anesthesiology 1993; 79(3A): A121.
    

15. Smiley RM. An overview of induction and emergence characteristics of desflurane in pediatric, adult, and geriatric patients. Anesth Analg 1992; 75(4S): S38-S46.
    

16. Zwass MS, Fisher DM, Welborn LG, et al. Induction and maintenance characteristics of anesthesia with desflurane and nitrous oxide in infants and children. Anesthesiology 1992; 76: 373-8.
    

17. Calahan MK, Weiskopf RB, Eger EI II, et al. Hemodynamic effects of desflurane/nitrous oxide anesthesia in volunteers. Anesth Analg 1991; 73: 157-64.
    

18. Young WL. Effects of desflurane on the central nervous system. Anesth Analg 1992; 75(4S): S32-S37.
    

19. Rampil IJ, Lockhart SH, Eger EI II, et al. The electroencephalographic effects of desflurane in humans. Anesthesiology 1991; 74: 434-9.
    

20. Muzzi DA, Losasso TH, Dietz NM, et al. The effect of desflurane and isoflurane on cerebrospinal fluid pressure in humans with supratentorial mass lesions. Anesthesiology 1992; 76: 720-4.
    

21. Caldwell JE, Laster MJ, Magorian T, et al. The neuromuscular effects of desflurane, alone and combined with pancuronium or succinylcholine in humans. Anesthesiology 1991; 74: 412-8.
    

22. Caldwell JE, Laster MJ, Heier T, et al. The neuromuscular effects of desflurane (I-653) in human volunteers [abstract]. Anesth Analg 1990; 70: S47.
    

23. Lockhart SH, Rampil IJ, Yasuda N, et al. Depression of ventilation by desflurane in humans. Anesthesiology 1991; 74: 484-8.
    

24. Smiley RM, Ornstein E, Matteo RS, et al. Desflurane and isoflurane in surgical patients: comparison of emergence time. Anesthesiology 1991; 74: 425-8.
    

25. Rapp SE, Conahan TJ, Pavlin DJ, et al. Comparison of desflurane with propofol in outpatients undergoing peripheral orthopedic surgery. Anesth Analg 1992; 75: 572-9.
    

26. Koblin DD. Characteristics and implications of desflurane metabolism and toxicity. Anesth Analg 1992; 75(4S): S10-S16.
    

27. Smiley RM, Ornstein E, Pantuck EJ, et al. Metabolism of desflurane and isoflurane to fluoride ion in surgical patients. Can J Anaesth 1991; 38: 965-8.
    

28. Sutton RS, Koblin DD, Gruenke LD, et al. Fluoride metabolites after prolonged exposure of volunteers and patients to desflurane. Anesth Analg 1991; 73: 180-5.
    

29. White PF. Studies of desflurane in outpatient anesthesia. Anesth Analg 1992; 75(4S): S47-S54.
    

30. Ghouri AF, Bodner M, White PF. Recovery profile after desflurane–nitrous oxide versus isoflurane–nitrous oxide in outpatients. Anesthesiology 1991; 74: 419-24.
    

31. Yasuda N, Lockhart SH, Eger EI II, et al. Kinetics of desflurane, isoflurane, and halothane in humans. Anesthesiology 1991; 74: 489-98.
    

32. Fassoulaki A, Lockhart SH, Freire BA, et al. Percutaneous loss of desflurane, isoflurane, and halothane in humans. Anesthesiology 1991; 74: 479-83.
    

33. Rampil IJ, Lockhart SH, Zwass MS, et al. Effects of age or nitrous oxide on the MAC of desflurane [abstract]. Anesth Analg 1990; S319.
    

34. Glosten B, Faure EAM, Lichtor JL, et al. Desflurane MAC is decreased but recovery time is unaltered following premedication with midazolam (0.05 mg/kg) [abstract]. Anesthesiology 1990; 73: A346.
    

35. Sebel PS, Glass PSA, Fletcher JE, et al. Reduction of the MAC of desflurane with fentanyl. Anesthesiology 1992; 76: 52-9.
    

36. Fisher DM, Zwass MS. MAC of desflurane in 60% nitrous oxide in infants and children. Anesthesiology 1992; 76: 354-6.
    

37. Weiskopf RB, Eger EI II, Ionescu P, et al. Desflurane does not produce hepatic or renal injury in human volunteers. Anesth Analg 1992; 74: 570-4.
    

38. Thomson IR, Bowering JB, Hudson RJ, et al. A comparison of desflurane and isoflurane in patients undergoing coronary artery surgery. Anesthesiology 1991; 75: 776-81.
    

39. Panel Consensus, Mivacurium (Systemic) monograph, draft for USP DI 1993 Update.
    

40. Lebenbom-Mansour MH, Pandit SK, Kothary SP, et al. Desflurane versus propofol anesthesia: a comparative analysis in outpatients. Anesth Analg 1993; 76: 936-41.
    

41. Koblin DD. Mechanisms of action. In: Miller RD, editor. Anesthesia. 4th ed. New York: Churchill Livingston, Inc; 1994. p. 67-99.
    

42. American Society of Anesthesiologists. Position on Monitored Anesthesia (approved October 1986); Guidelines for Patient Care in Anesthesiology (approved October 1967, amended October 1985, October 1996); Standards for Basic Intra-Operative Monitoring (approved October 1986, amended October 1990, October 1992, October 1998); Standards for Postanesthesia Care (approved October 1988, amended October 1990, October 1994). Park Ridge, IL: American Society of Anesthesiologists.
    

43. Hold.
    

44. Panel comment, 6/93.
    

45. Panel comments, 6/93.
    

46. Panel comment, 6/93.
    

47. Panel comment, 6/93.
    

48. Panel comments, 6/93.
    

49. Panel comments, 11/93.
    

50. Pane comment, 6/93.
    

51. Panel comment, 6/93.
    

52. Panel comment, 6/93.
    

53. Panel comment, 6/93.
    

54. Panel comment, 6/93.
    

55. Panel comment, 6/93.
    

56. Panel comment, 11/93.
    

57. Tinker JH, editor. Clinical pharmacology of desflurane. Anesth Analg 1992; 75(4S): 1-54.
    

58. Rosenberg P, Kirves A. Miscarriages among operating theatre staff. Acta Anaesthesiol Scand 1973; 53: 37-42.
    

59. Holmberg K, Lambert B, Lindstein J, et al. DNA and chromosomal alterations in lymphocytes of operating room personnel and inpatients before and after inhalational anaesthesia. Acta Anaesthesiol Scand 1982; 26: 531-9.
    

60. Gold MI, Abello D, Herrington C. Minimum alveolar concentration of desflurane in patients older than 65 yr. Anesthesiology 1993; 79: 710-4.
    

61. Frink EJ Jr, Nogami WM, Morgan SE, et al. High carboxyhemoglobin concentrations occur in swine during desflurane anesthesia in the presence of partially dried carbon dioxide absorbents. Anesthesiology 1997; 87: 308-16.
    

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