Desflurane

Patients anaesthetized with different concentrations of desflurane and receiving increasing doses of fentanyl or midazolam showed a reduction in anaesthetic requirements or MAC. (Refer Table). It is anticipated that there will be a similar influence on MAC with other opioid and sedative medicinal products.

Effect of Fentanyl or Midazolam on Desflurane MAC:

* Patients aged 18-65 years

Nitrous oxide used concomitantly decreases the MAC of desflurane.

Commonly used muscle relaxants are potentiated by desflurane.

The table below shows the doses of pancuronium, atracurium, suxamethonium and vecuronium required to obtain a 95% depression (ED95) of neuromuscular transmission according to different concentrations of desflurane (these doses are identical to those required for isoflurane). The ED95 of vecuronium is lower than 14%, with desflurane than isoflurane. In addition, recovery from neuromuscular blockade is longer with desflurane than isoflurane.

Dose of myorelaxant (mg/kg) inducing 95% depression of neuromuscular transmission:

* ND = not determined

Relaxometry is recommended for the exact dosing.

With the use of halogenated anaesthetics, disruption of hepatic function, icterus and fatal liver necrosis have been reported: such reactions appear to indicate hypersensitivity. Desflurane may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anaesthetics. Cirrhosis, viral hepatitis or other pre-existing hepatic disease may be a reason to select an anaesthetic, other than a halogenated anaesthetic.

Use of inhaled anaesthetics, has been associated with very rare increases in serum potassium levels that have resulted in cardiac arrhythmias in patients, during the post-operative period, sometimes with a fatal outcome. The condition has been described in patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy. Use of suxamethonium (succinylcholine) has been associated with most, but not all, of these cases. These patients showed evidence of muscle damage with increased serum creatinine kinase concentration and myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state.

Prompt and vigorous treatment for hyperkalaemia and arrhythmias is recommended. Subsequent evaluation for latent neuromuscular disease is indicated. Likewise the possible presence of latent neuromuscular disease is subsequently clarified.

Desflurane may produce a dose-dependent increase in cerebrospinal fluid pressure (CSFP) when administered to patients with space occupying lesions. In such patients, desflurane should be administered at 0.8 MAC or less, and in conjunction with a barbiturate induction and hyperventilation (hypocapnia) until cerebral decompression. Appropriate attention must be paid to maintain cerebral perfusion pressure.

In cases of threatening intracranial hypertension, the use of desflurane is not recommended.

Due to the limited number of patients studied, the safety of desflurane has not been established for use in obstetric procedures. Desflurane is a uterine relaxant and reduces the utero-placental blood flow.

Desflurane has been associated with some elevation of glucose intra-operatively.

Due to the limited number of patients studied, the safety of desflurane has not been established for use in obstetric procedures. Desflurane is a uterine relaxant and reduces the utero-placental blood flow. Animal studies have shown reproductive toxicity. Desflurane should only be used in pregnant women when absolutely necessary.

There is insufficient information on the excretion of desflurane/metabolites in human milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from desflurane therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Breastfeeding should be avoided after anaesthesia until desflurane has been eliminated (around 24 hours).

Fertility

Data concerning potential effects of desflurane on human fertility are not available. In rats, effects on fertility were observed.

There are no data on the effects of desflurane following anaesthesia on the ability to drive or use machines. However, patients should be advised that the ability to perform such tasks may be impaired after general anaesthesia. It is therefore advisable to avoid such tasks for a period of 24 hours after anaesthesia.

Desflurane may cause dose-dependent cardiac and respiratory depression and a slight intraoperative increase in blood glucose levels. Most undesirable effects are mild to moderate. Nausea and vomiting have been observed in the postoperative period, common sequelae of surgery and general anaesthesia, which may be due to inhalational anaesthetic, other medicinal products administered intraoperatively or post-operatively and to the patient’s response to the surgical procedure.

The adverse reactions listed below are categorized using the following frequency convention:

Very common (≥1/10)
Common (≥1/ 100 to <1/10)
Uncommon (≥1/1000 to <1/100)
Rare (≥1/10 000 to <1/1000)
Very rare (<1/10 000)
Not known (frequency cannot be estimated from the available data)

The following adverse drug reactions are listed by system organ class according to MedDRA terminology and frequencies.

Adverse Drug Reactions:

Infections and infestations

Common: Pharyngitis

Blood and lymphatic system disorders

Not known: Coagulopathy

Metabolism and nutrition disorders

Not known: Hyperkalaemia, Hypokalaemia, Metabolic

Psychiatric disorders

Common: Breath

Uncommon: Holding

Nervous system disorders

Common: Headache

Uncommon: Somnolence

Not known: Seizure, Dizziness³, Migraine³, Encephalopathy³

Eye disorders

Common: Conjunctivitis

Not known: Ulcerative keratitis³, Ocular hyperaemia³, Visual acuity reduced³, Eye irritation³, Eye pain³

Cardiac disorders

Common: Nodal arrhythmia, Bradycardia, Tachycardia

Uncommon: Myocardial infarction, Myocardial ischaemia, Arrhythmia

Not known: Cardiac arrest, Torsade de Pointes, Ventricular failure, Ventricular hypokinesia, Atrial

Vascular disorders

Common: Hypertension

Uncommon: Vasodilation

Not known: Malignant hypertension, Haemorrhage, Hypotension

Respiratory, thoracic and mediastinal disorders

Common: Apnoea¹, Cough¹, Laryngospasm²

Uncommon: Hypoxia¹

Not known: Respiratory failure, Dyspnoea, Bronchospasm, Haemoptysis

Gastrointestinal disorders

Very common: Vomiting¹, Nausea¹

Common: Salivary hypersecretion¹, Pancreatitis acute

Hepatobiliary disorders

Not known: Hepatic failure, Hepatic necrosis, Hepatitis, Cholestasis, Jaundice, Hepatic function abnormal, Liver disorder, Ocular icterus³

Skin and subcutaneous tissue disorders

Not known: Urticaria, Erythema

Musculoskeletal and connective tissue disorders

Uncommon: Myalgia

Not known: Rhabdomyolys

General disorders and administration site conditions

Not known: Malignant, Hyperthermia, Asthenia, Discomfort

Investigations

Common: Blood creatine phosphokinase increased, Electrocardiogram abnormal, Electrocardiogram Prolongation of QTc interval

Not known: Electrocardiogram ST-T change, Electrocardiogram T wave inversion, Alanine aminotransferase increased, Aspartate aminotransferase increased, Coagulation test abnormal, Ammonia increased

Injury, poisoning and procedural complications³

Not known: Agitation postoperative

Ear and Labyrinth disorders

Not known: Vertigo

¹ Reported during induction and maintenance of anaesthesia.
² Reported during induction of anaesthesia.
³ Reported by non-patients after accidental exposure.

Paediatric population

The frequency, type, and intensity of these adverse reactions are considered identical for children and adults.