Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use


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Desflurane should only be administered by persons trained in the administration of general anaesthesia using a vaporizer specifically designed and designated for use with desflurane. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment and circulatory resuscitation must be immediately available.

Warnings:

Malignant Hyperthermia (MH)
In susceptible individuals, potent inhalation anaesthetic agents may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. Desflurane was shown to be a potential trigger of 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 non-specific signs may also appear during light anaesthesia: acute hypoxia, hypercapnia, and hypovolemia. Treatment of malignant hyperthermia includes discontinuation of triggering agents, administration of intravenous dantrolene sodium, and application of supportive therapy. Renal failure may appear later, and urine flow should be monitored and sustained if possible.
Desflurane should not be used in subjects known to be susceptible to MH. Fatal outcome of malignant hyperthermia has been reported with desflurane.

Perioperative Hyperkalemia
Use of inhaled anaesthetic agents, has been associated with very rare increases in serum potassium levels that have resulted in cardiac arrhythmias, and death in children during the postoperative period. The condition has been described in patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy. Use of suxamethonium 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.


Paediatric Inhalation Induction
Desflurane is not indicated for use as an inhalation induction agent in children and infants because of the frequent occurrence of cough, breath holding, apnoea, laryngospasm and increased secretions.

Use in Children with Bronchial Hyperreactivity
Desflurane should be used with caution in children with asthma or a history of recent upper airway infection due to the potential for airway narrowing and increases in airway resistance.

Maintenance of Anaesthesia in Children
Desflurane is not approved for maintenance of anaesthesia in non-intubated children under the age of 6 years due to an increased incidence of respiratory adverse 4
reactions. Caution should be exercised when desflurane is used for maintenance anaesthesia with laryngeal mask airway (LMA) or face mask in children 6 years old or younger because of the increased potential for adverse respiratory events, e.g.
coughing and laryngospasm, especially with removal of the LMA under deep anaesthesia.

Obstetrics
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 uterine-placental blood-flow (See section 4.6).

Isolated reports of QT prolongation, very rarely associated with torsade de points (in exceptional cases, fatal), have been received (see section 4.8). Caution should be exercised when administering desflurane to susceptible patients (e.g. patients with congenital or acquired Long QT Syndrome, hypokalamia, congestive heart failure or patients taking drugs that can prolong with QT interval).

Precautions:
With the use of halogenated anaesthetics, disruption of hepatic function, icterus and fatal liver necrosis have been reported: such reactions appear to indicate hypersensitivity. As with other halogenated anaesthetic agents, 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.

Desflurane, as other volatile anaesthetics, 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 in patients with known or suspected increases in CSFP.
Appropriate attention must be paid to maintain cerebral perfusion pressure.

In patients with coronary artery diseases, maintenance of normal hemodynamics is important to avoid myocardial ischemia. Marked increases in pulse rate, mean arterial pressure and levels of epinephrine and norepinephrine are associated with a rapid increase in desflurane concentrations. Desflurane should not be used as the sole agent for anaesthetic induction in patients at risk of coronary artery disease or in patients where increases in the heart rate or blood pressure are undesirable. It should be used with other medications, preferably intravenous opioids and hypnotics.

During maintenance of anaesthesia, increases in heart rate and blood pressure occurring after rapid incremental increases in end-tidal concentration of desflurane may not represent inadequate anaesthesia. The changes due to sympathetic activation resolve in approximately 4 minutes. Increases in heart rate and blood pressure occurring before or in the absence of a rapid increase in desflurane concentration may be interpreted as light anaesthesia.
Hypotension and respiratory depression increase as anaesthesia is deepened.



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Use of desflurane in hypovolaemic, hypotensive and debilitated patients has not been extensively investigated. As with other potent inhaled anaesthetics, a lower concentration is recommended for use in these patients.

Desflurane, like some other inhalation anaesthetics, 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 desflurane.

As with other rapid-acting anesthetic agents, rapid emergence with desflurane should be taken into account in cases where post-anaesthesia pain is anticipated. Care should be taken that appropriate analgesia has been administered to the patient at the end of the procedure or early in the post-anaesthesia care unit stay. Emergence from anaesthesia in children may evoke a brief state of agitation that may hinder cooperation.

As with all halogenated anaesthetics, repeated anaesthesia within a short period of time should be approached with caution.

Facilities and equipment for maintenance of a patent airway, artificial ventilation, oxygen enrichment and circulatory resuscitation must be immediately available.

Glucose elevation
As with other halogenated anaesthetic agents, desflurane has been associated with some elevation of glucose intra-operatively.

Effects on Driving

4.7   Effects on ability to drive and use machines

There is no information on the effects of desflurane on the ability to drive or operate machinery. However, patients should be advised that the ability to perform tasks such as driving or operation of machinery may be impaired after general anaesthesia, and it is advisable to avoid such tasks for a period of 24 hours.