Desflurane

Inhalation/Respiratory
Induction and maintenance of general anaesthesia

Hypovolaemic, hypotensive, or debilitated patients: Lower concentrations may be needed.

Pharmacogenomics:

Desflurane is identified as a triggering agent of malignant hyperthermia (MH) Individuals with malignant hyperthermia susceptibility (MHS) or those carrying certain genetic variants of ryanodine receptor isoform 1 gene (RYR1) and CACNA1S gene are predisposed to possible life-threatening hypermetabolic reactions triggered by potent volatile anaesthetics like desflurane. The prevalence of MHS genetic trait is estimated to be between 1/2,000 and 1/3,000, and approx 70% of individuals with MHS have the RYR1 pathogenic variants as the primary pharmacogenetic trait, while approx 1% of patients with MHS have the CACNA1S pathogenic variants.

The European Malignant Hyperthermia Group (EMHG) consortium has identified 50 MH-causative variants in the RYR1 or CACNA1S gene. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends performing genetic testing and considering the personal family history of individuals in relation to MH and their susceptibility before initiation of therapy.

Malignant hyperthermia susceptible (MHS)

Patients who are carriers of at least 1 of the 50 identified MH-causative variants are at increased risk of developing MH if administered with desflurane.

Recommendation:
Desflurane is contraindicated in these individuals, except in instances where the benefits outweigh the risks. Use alternative non-triggering anaesthetic agents (e.g. non-depolarising neuromuscular blockers, IV inducing agents, or regional anaesthesia [e.g. neuraxial, peripheral nerve block or local anaesthesia] or non-triggering agent general anaesthesia).

Uncertain MH susceptibility

Patients who are negative for RYR1 or CACNA1S MH-causative variant. Negative or inconclusive results do not eliminate the risk of susceptibility to MH.

Recommendation:
CPIC recommends monitoring the individual’s clinical findings, family history, and other laboratory data, and perform further genetic testing to guide the use of desflurane.

Chronic impairment and during renal transplantation surgery: 1-4% v/v in oxygen and nitrous oxide given via calibrated vaporiser.

Chronic impairment: 1-4% v/v in oxygen and nitrous oxide given via calibrated vaporiser.

Known or suspected genetic susceptibility to malignant hyperthermia (e.g. presence of RYR1 or CACNA1S pathogenic variants); in whom general anaesthesia is contraindicated; risk factors for coronary artery disease, or where increases in heart rate or blood pressure are undesirable. History of moderate to severe hepatic impairment, or in whom liver dysfunction, jaundice or unexplained fever, leucocytosis or eosinophilia occurred after previous desflurane or other halogenated anaesthetic use. Induction of anaesthesia in children.

Patient with underlying neuromuscular disease (e.g. Duchenne muscular dystrophy); risk factors for QT prolongation (e.g. congenital long QT syndrome, taking QT prolonging drugs); cirrhosis, viral hepatitis, or other pre-existing hepatic disease; intracranial space-occupying lesions; asthma or history of recent upper airway infection (particularly in children). Hypovolaemic, hypotensive, or debilitated patients. Not indicated for maintenance of anaesthesia in non-intubated children <6 years. Chronic renal and hepatic impairment. Children and elderly. Pregnancy and lactation.

Significant: Respiratory depression, disrupted hepatic function, icterus, sensitivity hepatitis (in patients previously sensitised with halogenated anaesthetic), decreased hepatic or renal blood flow, increased intracranial pressure, increased heart rate and blood pressure, hypotension. In children: postoperative agitation, adverse respiratory reactions (e.g. frequent cough, breath-holding, apnoea, laryngospasm, increased secretions).
Blood and lymphatic system disorders: Coagulopathy.
Cardiac disorders: Nodal arrhythmia, bradycardia, tachycardia, dyspnoea, myocardial ischaemia.
Eye disorders: Conjunctivitis, ocular icterus.
Gastrointestinal disorders: Nausea, vomiting, abdominal pain, salivary hypersecretion.
General disorders and administration site conditions: Asthenia, malaise, fever.
Hepatobiliary disorders: Jaundice, cholestasis.
Investigations: Increased creatine phosphokinase, abnormal ECG, transient elevations in WBC count and glucose.
Metabolism and nutrition disorders: Hypokalaemia, metabolic acidosis.
Musculoskeletal and connective tissue disorders: Myalgia.
Nervous system disorders: Headache, dizziness, convulsions.
Respiratory, thoracic and mediastinal disorders: Pharyngitis, hypoxia.
Skin and subcutaneous tissue disorders: Erythema, pruritus, urticaria.
Vascular disorders: Hypertension, vasodilation, haemorrhage.
Potentially Fatal: Malignant hyperthermia, torsade de pointes, liver necrosis. Rarely, perioperative hyperkalaemia resulting in cardiac arrhythmias in children.

Inhalation/Respiratory: B

This drug may impair your ability to perform some tasks for a certain period, if affected, do not drive or operate machinery.

Monitor blood pressure, heart rate and rhythm, temperature, oxygen saturation, end-tidal CO₂ and end-tidal desflurane levels prior to and throughout procedure; renal function tests, urinary output, serum electrolytes and glucose (in diabetic patients) as necessary. Assess for signs and symptoms of malignant hyperthermia, hypercarbia, muscle rigidity, tachycardia, cyanosis, arrhythmias, and hypo- or hypertension; airway narrowing and adverse respiratory symptoms in children.

Symptoms: Deepening of anaesthesia, cardiac and/or respiratory depression (in spontaneous breathing patients); hypotension, hypercarbia, and hypoxia (ventilated patients). Management: Discontinue administration, establish clear airway, and start assisted or controlled ventilation with pure oxygen. Maintain adequate CV function and haemodynamics.

Reduced minimum alveolar concentration (MAC) with nitrous oxide, opioids and benzodiazepines. May potentiate the effects of neuromuscular blocking agents (e.g. atracurium, pancuronium). May cause elevated carboxyhaemoglobin levels due to carbon monoxide production with desiccated CO₂ absorbents. Increased risk of perioperative hyperkalaemia with suxamethonium.

May enhance CNS depressant effects of alcohol.

Description:
Mechanism of Action: Desflurane is a volatile, halogenated methylethylether anaesthetic which is thought to enhance the inhibitory postsynaptic channel activity and inhibit the excitatory synaptic activity. These effects lead to the reversible loss of consciousness and of pain sensations, suppression of voluntary motor activity, reduction of autonomic reflexes, and sedation of the respiratory and CV system.
Onset: 1-2 minutes.
Pharmacokinetics:
Absorption: Low blood/gas partition coefficient.
Distribution: Diffuses through the skin (small amount).
Metabolism: Metabolised in the liver (approx 0.02%) to form trifluoroacetate and inorganic fluoride.
Excretion: Mainly via exhaled gases (as unchanged drug).

Source: National Center for Biotechnology Information. PubChem Database. Desflurane, CID=42113, https://pubchem.ncbi.nlm.nih.gov/compound/Desflurane (accessed on Jan. 20, 2020)

Store between 15-30°C.

Thuốc gây mê-gây tê

N01AB07 - desflurane ; Belongs to the class of halogenated hydrocarbons. Used as general anesthetics.

Gonsalves SG, Dirksen RT, Sangkuhl K et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. CPIC Guideline. 2019 Jun;105(6):1338-1344. doi: 10.1002/cpt.1319. Accessed 19/12/2019

Annotation of CPIC Guideline for Desflurane, Enflurane, Halothane, Isoflurane, Methoxyflurane, Sevoflurane, Succinylcholine and CACNA1S, RYR1. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 19/12/2019.

Anon. Desflurane. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/12/2019.

Buckingham R (ed). Desflurane. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/12/2019.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org. Accessed 19/12/2019.

Joint Formulary Committee. Desflurane. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/12/2019.

Suprane Liquid (Baxter Healthcare Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 19/12/2019.