Desflurane: Drug information

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Desflurane: Drug information


U.S. Brand Names :Suprane®

Pharmacologic Category

• General Anesthetic, Inhalation

Dosing: Adults
Inhalation: The minimum alveolar concentration (MAC), the concentration at which 50% of patients do not respond to surgical incision, ranges from 6.0% (45 years of age) to 7.3% (25 years of age). The concentration at which amnesia and loss of awareness occur (MAC - awake) is 2.4%. Surgical levels of anesthesia are achieved with concentrations between 2.5% to 8.5%.

Note:Because of the higher vapor pressure of desflurane, its vaporizer is heated in order to deliver a constant concentration

Dosing: Pediatric
Anesthesia maintenance: Children (intubated): Surgical levels of anesthesia range between 5.2% to 10%

Dosing: Elderly
MAC is reduced (5.2% at 70 years of age).

Dosage Forms
Liquid, for inhalation:
Suprane®: 100% (240 mL) [amber bottle]

Generic Equivalent Available
No

Administration
Via desflurane-specific calibrated heated vaporizer

Use
Induction and/or maintenance of general anesthesia in adults; maintenance of anesthesia in intubated children; Note: Use of desflurane for induction of general anesthesia is not recommended due to its irritant properties and unpleasant odor which causes coughing, breath holding, laryngospasm, oxygen desaturation, increased secretions, hypertension, and tachycardia.

Use - Unlabeled/Investigational
Intraoperative cardio- and neuroprotection (ischemic preconditioning)

Adverse Reactions Significant

>10%:
Gastrointestinal: Nausea (27%), vomiting (16%)
Respiratory: Cough (3% to 34%), breath-holding (>1% to 30%), apnea (3% to 15%)

1% to 10%:
Cardiovascular: Bradycardia, hypertension, nodal arrhythmia, tachycardia
Central nervous system: Emergence delirium, headache
Gastrointestinal: Salivation increased
Ocular: Conjunctivitis
Respiratory: Secretions increased (3% to 10%), laryngospasm (3% to 10%), oxyhemoglobin desaturation (3% to 10%), pharyngitis (>1% to 10%)
Miscellaneous: Shivering

<1% (Limited to important or life-threatening): Abdominal pain, agitation, ALT increased, ammonia increased, arrhythmia, AST increased, asthma, bigeminy, bronchospasm, cardiac arrest, cholestasis, coagulopathy, CPK increased, cytolytic hepatitis, dizziness, dyspnea, ECG changes, erythema, hemoptysis, hemorrhage, hepatic failure, hepatic necrosis, hepatitis, hyperglycemia, hyper-/hypokalemia, hypotension, hypoxia, jaundice, malaise, malignant hypertension, malignant hyperthermia, metabolic acidosis, MI, myocardial ischemia, myalgia, ocular icterus, pancreatitis (acute), pruritus, respiratory arrest, respiratory distress, respiratory failure, rhabdomyolysis, seizure, shock, torsade de pointes, urticaria, vasodilation, ventricular failure, ventricular hypokinesia, WBC increased, weakness

Adverse reactions with accidental occupational exposure: Dizziness, encephalopathy, headache, migraine, ocular hyperpalpitations, tachyarrhythmia, unconsciousness

Contraindications
Hypersensitivity to desflurane, other halogenated anesthetic agents, or any component of the formulation; known or suspected susceptibility to malignant hyperthermia
Warnings/Precautions

Concerns related to adverse effects:
• Decreased blood flow: May cause decrease in hepatic and/or renal blood flow.

• Hepatitis: May cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics.

• 
  Hyperkalemia: Use of other inhaled anesthetics has been associated with rare cases of perioperative hyperkalemia; concomitant use of succinylcholine was associated with many of the reported cases, but not all. Risk of hyperkalemia is increased in pediatric patients with underlying neuromuscular disease (eg, Duchenne muscular dystrophy). Other abnormalities may include elevation in CK and myoglobinuria. Monitor closely for arrhythmias. Aggressively identify and treat hyperkalemia.
• 
  • InIncreased intracranial pressure: May dilate the cerebral vasculature and may, in certain conditions, increase intracranial pressure. In patients with intracranial space-occupying lesions, administer at ≤0.8 MAC in conjunction with a barbiturate induction and hyperventilation in the period before cranial decompression; maintain cerebral perfusion pressure.
• 
  • Malignant hyperthermia: May trigger malignant hyperthermia (MH); contraindicated in patients susceptible to MH.
• 
  • Respiratory depression: Causes dose-dependent respiratory depression and blunted ventilatory response to hypoxia and hypercapnia. Hypoxic pulmonary vasoconstriction is blunted which may lead to increased pulmonary shunt. May produce elevated carbon monoxide levels in the presence of a dry carbon dioxide absorbent within the circle breathing system of an anesthetic machine; maintain fresh absorbent as per manufacturer guidelines regardless of state of colorimetric indicator.

Disease-related concerns:
• Cardiovascular disease: Do not use as a single agent to induce anesthesia in patients with CAD or in whom an increase in heart rate or blood pressure should be avoided. Abrupt increases in inspired concentrations >1 MAC can produce a transient increase in blood pressure and heart rate due to increased plasma catecholamine levels. Hypotensive effect due to peripheral vasodilation is dose dependent and increases as anesthesia is deepened.
Special populations:
• Pediatrics: Due to higher incidences of airway irritation (eg, laryngospasm, coughing, breath-holding, increased secretions) in pediatric patients; do not use to induce and/or maintain anesthesia in nonintubated pediatric patients.

Drug Interactions:

• 
  EPINEPHrine: Inhalational Anesthetics may enhance the arrhythmogenic effect of EPINEPHrine. Risk D: Consider therapy modification
• Methylphenidate: May enhance the hypertensive effect of Inhalational Anesthetics. Risk X: Avoid combination
• Neuromuscular-Blocking Agents (Nondepolarizing): Inhalational Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy

Pregnancy Risk Factor
Pregnancy Implications
No adverse events observed in animal studies. There are no adequate and well-controlled studies in pregnant women.

Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Due to rapid washout, desflurane levels in milk most likely have no clinical importance 24 hours after anesthesia.

Monitoring Parameters
Blood pressure, heart rate and rhythm, temperature, oxygen saturation, end-tidal CO2 and end-tidal desflurane concentrations should be monitored prior to and throughout anesthesia.

Mechanism of Action
Although not completely defined, it is thought that desflurane enhances inhibitory postsynaptic channel activity and inhibits excitatory synaptic activity resulting in general anesthesia.

Pharmacodynamics/Kinetics
Onset of action: 1-2 minutes
Duration: Emergence time: Depends on blood concentration when desflurane is discontinued
The rate of change of anesthetic concentration in the lung is more rapid with desflurane because of its low blood/gas solubility (0.42), which is similar to nitrous oxide.
Metabolism: Hepatic (0.02%) to triflouroacetate (negligible) and inorganic fluoride
Excretion: Exhaled gases

REFERENCES

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2.
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3.
Ebert TJ and Muzi M, “Sympathetic Hyperactivity During Desflurane Anesthesia in Healthy Volunteers. A Comparison With Isoflurane,” Anesthesiology, 1993, 79(3):444-53. [PubMed 8363068]
4.
Guarracino F, Landoni G, Tritapepe L, et al, “Myocardial Damage Prevented by Volatile Anesthetics: A Multicenter Randomized Controlled Study,” J Cardiothorac Vasc Anesth, 2006, 20(4):477-83. [PubMed 16884976]
5.
Meco M, Cirri S, Gallazzi C, et al, “Desflurane Preconditioning in Coronary Artery Bypass Graft Surgery: A Double-Blinded, Randomised and Placebo-Controlled Study,” Eur J Cardiothorac Surg, 2007, 32(2):319-25. [PubMed 17574858]
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Sakai EM, Connolly LA, and Klauck J, “Inhalation Anesthesiology and Volatile Liquid Anesthetics: Focus on Isoflurane, Desflurane, and Sevoflurane,” Pharmacotherapy, 2005, 25(12):1773-88. [PubMed 16305297]
7.
Tritapepe L, Landoni G, Guarracino F, et al, “Cardiac Protection by Volatile Anaesthetics: A Multicentre Randomized Controlled Study in Patients Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass,” Eur J Anaesthesiol, 2007, 24(4):323-31. [PubMed 17156509]
8.
Wang L, Traystman RJ, and Murphy SJ, “Inhalational Anesthetics as Preconditioning Agents in Ischemic Brain,” Curr Opin Pharmacol, 2008, 8(1):104-10. [PubMed 17962069]
9.
Weiskopf RB, Eger EI 2nd, Noorani M, et al, “Fentanyl, Esmolol, and Clonidine Blunt the Transient Cardiovascular Stimulation Induced by Desflurane in Humans,” Anesthesiology, 1994, 81(6):1350-5. [PubMed 7992902]
10.
Weiskopf RB, Moore MA, Eger EI 2nd, et al, “Rapid Increase in Desflurane Concentration Is Associated With Greater Transient Cardiovascular Stimulation Than With Rapid Increase in Isoflurane Concentration in Humans,” Anesthesiology, 1994, 80(5):1035-45. [PubMed 8017643]
11.
Yasuda N, Lockhart SH, Eger EI 2nd, et al, “Kinetics of Desflurane, Isoflurane, and Halothane in Humans,” Anesthesiology, 1991, 74(3):489-98. [PubMed 2001028]


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