Aerrane

/ Baxter

In order to be able to accurately control the precise concentration of AERRANE, vaporisers that have been specially calibrated for isoflurane should be used.
For minimum alveolar concentration (MAC) of AERRANE in humans: please refer to prescribing information.
Induction of anaesthesia: If AERRANE is used for induction of anaesthesia, a starting concentration of 0.5% is recommended. Concentrations of 1.3 – 3.0% usually bring about surgical anaesthesia within 7 to 10 minutes.
It is recommended that use be made of a hypnotic dose of a short acting barbiturate or another product such as propofol, etomidate, or midazolam in order to avoid coughing or laryngospasm, which can arise if induction is carried out with AERRANE alone or in combination with oxygen or with an oxygen-nitrous oxide mixture.
Maintenance of anaesthesia: Anaesthesia can be maintained during surgery using a concentration of 1.0 – 2.5%, with the simultaneous administration of N20 and 02. A higher concentration of 1.5 – 3.5% of AERRANE is necessary if AERRANE is administered with pure oxygen.
Recovery: The concentration of AERRANE must be reduced to 0.5% at the end of the operation, or to 0% during closure of the wound to allow prompt recovery.
If all administration of anaesthetic agents has been stopped, the air passages of the patient should be ventilated several times with 100% oxygen until complete awakening occurs.
If the vector gas is a mixture of 50% 02 and 50% N20, the volume of the minimum alveolar concentration of AERRANE is approximately 0.65%.
See prescribing information for full details.

Isoflurane is a volatile halogenated anaesthetic for general inhalation anaesthesia.

Isoflurane is contraindicated in patients with known sensitivity to Isoflurane or other halogenated anaesthetics. It is also contraindicated in patients with known or suspected genetic susceptibility to malignant hyperthermia.          

As with any potent general anesthetic, Isoflurane should only be administered in an adequately equipped anesthetizing environment by those who are familiar with the pharmacology of the drug and qualified by training and experience to manage the anesthetized patient.Vaporizers specially calibrated for Isoflurane should be used so that the concentration of anesthetic delivered can be accurately controlled. Hypotension and respiratory depression increase as anesthesia is deepened. Since levels of anesthesia may be altered quickly and easily with Isoflurane, only vaporizers which deliver a predictable output with reasonable accuracy, or techniques during which inspired or expired concentrations can be monitored, should be used. The degree of hypotension and respiratory depression may provide some indication of anesthetic depth.Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal) have been received. Caution should be exercised when administering Isoflurane to patients at risk for QT prolongation.Caution should be exercised in administering general anesthesia, including Isoflurane, to patients with mitochondrial disorders. Reports demonstrate that Isoflurane can produce hepatic injury ranging from mild transient increases of liver enzymes to fatal hepatic necrosis in very rare instances.
It has been reported that previous exposure to halogenated hydrocarbon anesthetics, especially if the interval is less than 3 months, may increase the potential for hepatic injury. Cirrhosis, viral hepatitis, or other pre-existing liver disease can be a reason to select an anaesthetic other than a halogenated anaesthetic. Isoflurane is a profound respiratory depressing agent whose effect is accentuated by narcotic premedication or concurrent use of other respiratory depressants.  Respiration should be closely monitored, and assisted or controlled ventilation employed when necessary. Relatively little metabolism of Isoflurane occurs in the human body.  In the post operation period only 0.17% of the Isoflurane taken up can be recovered as urinary metabolites.  Peak serum inorganic fluoride values usually average less than 5 µmol/litre and occur about four hours after anaesthesia, returning to normal levels within 24 hours.  No signs of renal injury have been reported after Isoflurane administration.
There is insufficient experience of use in repeated anaesthesia to make a definitive recommendation in this regard. As with all halogenated anaesthetics repeat anaesthesia within a short period of time should be approached with caution. A potentiation of neuromuscular fatigue can be seen in patients with neuromuscular diseases, such as myasthenia gravis. Isoflurane should be used with caution in these patients Isoflurane markedly increases cerebral blood flow at deeper levels of anesthesia. There may be a transient rise in cerebral spinal fluid pressure which is fully reversible with hyperventilation.
Isoflurane must be used with caution in patients with increased intracranial pressure. In such cases hyperventilation may be necessary. Isoflurane should be administered with caution to patients who can develop bronchoconstriction since bronchospasms can occur. Use of Isoflurane in hypovolemic, hypotensive and debilitated patients has not been extensively investigated. A lower concentration of Isoflurane is recommended for use in these patients.Regardless of the anesthetics employed, maintenance of normal hemodynamics is important to the avoidance of myocardial ischemia in patients with coronary artery disease. In light of the fact that Isoflurane acts in an irritating manner on the mucous membranes, the product is difficult to use if inhalation anaesthesia is applied via mask.  During the induction of anaesthesia in children, saliva flow and tracheobronchial secretion can increase and can be the cause of laryngospasms. Increased blood losses comparable with those found following anaesthesia with other inhalation agents have been recorded with Isoflurane in patients undergoing induced abortion.Isoflurane relaxes the uterus muscle, and the lowest possible concentration of Isoflurane should be used in obstetrical operations.
Malignant hyperthermia: In the case of sensitive individuals, Isoflurane anaesthesia may trigger a skeletal hypermetabolic state in the skeletal muscles, which leads to a high oxygen demand and a clinical syndrome that is known as malignant hyperthermia.  The clinical syndrome includes nonspecific features such as muscle rigidity, tachycardia, tachypnoea, cyanosis, arrhythmias, and/or unstable blood pressure (it also should be noted that many of these nonspecific signs may appear with light anesthesia, acute hypoxia, etc.). Isolated cases of increased carboxyhemoglobin have been reported with the use of halogenated inhalation agents with a – CF₂H moiety (i.e., desflurane, enflurane and Isoflurane). No clinically significant concentrations of carbon monoxide are produced in the presence of normally hydrated absorbents. Care should be taken to follow manufacturers’ instructions for CO₂ absorbents.Rare cases of extreme heat, smoke and/or spontaneous fire in the anesthesia machine have been reported during administration of general anesthesia with drugs in this class when used in conjunction with desiccated CO₂ absorbents, specifically those containing potassium hydroxide (e.g. Baralyme). When a clinician suspects that the CO₂ absorbent may be desiccated, it should be replaced before administration of Isoflurane. The color indicator of most CO₂ absorbents does not necessarily change as a result of desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. CO₂ absorbents should be replaced routinely regardless of the state of the color indicator. Use of inhaled anaesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in paediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all of these cases. These patients also experienced significant elevations in serum creatine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalaemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
Isoflurane may cause a slight decrease in intellectual function for 2-4 days following anesthesia. Small changes in moods and symptoms may persist for up to 6 days after administration. This must be taken into account when patients resume normal daily activities, including driving or operating heavy machinery. All commonly used muscle relaxants are markedly potentiated by Isoflurane, the effect being most profound with non-depolarizing agents. During the induction of anesthesia, saliva flow and thracheobronchial secretion can increase and can be the cause of laryngospasm, particularly in children.
Children under Two Years of Age: Caution should be exercised when Isoflurane is used in small children due to limited experience with this patient-group.
For full details See prescribing information.

Adverse reactions encountered in the administration of Isoflurane are in general dose dependent extensions of pharmacophysiologic effects and include respiratory depression, hypotension and arrhythmias. Potential serious undesirable effects include malignant hyperthermia, anaphylactic reactions and liver adverse reactions. Shivering, nausea, vomiting and ileus have been observed in the postoperative period. Cardiac arrest has been observed with general inhalation anesthetic drugs including Isoflurane.
For full details See prescribing information.

The simultaneous administration of Isoflurane and the following products requires strict supervision of the clinical and biologic condition of the patient.
Combinations advised against: Beta-sympathomimetics (isoprenaline) and alpha- and beta-sympathomimetics (epinephrine or adrenaline; norepinephrine or noradrenaline) should be administered with caution during Isoflurane narcosis, due to a potential  risk of ventricular arrhythmia. Nonselective MAOI:  Risk of crisis and hemodynamic instability during the surgery or medical procedures.  Treatment should be stopped 15 days prior to surgery.
Combinations requiring precautions in using: Beta-blockers: Concomitant use of beta blockers may exaggerate the cardiovascular effects of inhalational anesthetics, including hypotension and negative inotropic effects. Risk of blockage of the cardiovascular compensation mechanism, as a result of which negative inotropic effects are intensified. The action of beta-blockers can be suppressed during the operation with the use of beta-sympathomimetic agents.  In general, any medication with a beta-blocker need not be stopped and an abrupt reduction of the dosage should be avoided.
Isoniazid: Risk of potentiating the hepatotoxic effect, with increased formation of toxic metabolites of isoniazid.  Treatment with isoniazid should be suspended one week before the operation and should not be resumed until 15 days afterward. Epinephrine (adrenaline) utilised for its local haemostatic action, by subcutaneous or gingival injections: risk of serious ventricular arrhythmia as a consequence of increased heart rate, although the myocardial sensitivity with respect to adrenaline is lower with the use of Isoflurane than in the case of halothane.  Thus, the dosage should be limited to, for example, 0.1 mg epinephrine (adrenaline) within 10 minutes or 0.3 mg within one hour in adults. Doses of adrenaline greater than 5 mcg/kg, when administered submucosally, may produce multiple ventricular arrhythmias.  Indirect sympathomimetics (amphetamines and their derivatives; psychostimulants, appetite suppressants, ephedrine and its derivatives): risk of perioperative hypertension. In patients undergoing elective surgery, treatment should ideally be discontinued several days before surgery.  In the majority of cases where a drug treatment is indispensable, there is no reason to suspend it before general anaesthesia.  It suffices to inform the anaesthetist about it.
Muscle relaxing agents: All commonly used muscle relaxants are markedly potentiated by Isoflurane, the effect being most profound with nondepolarizing agents. Thus it is recommended that approximately one third to one half of the usual dose of these substances be administered.  The disappearance of the myoneural effect takes longer with Isoflurane than with other conventional anaesthetics.  Neostigmine has an effect on the nondepolarising relaxants, but has no effect on the relaxing action of Isoflurane itself. Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with Isoflurane.
Calcium antagonists: Isoflurane may lead to marked hypotension in patients treated with calcium antagonists, particularly dihydropyridine derivatives. Caution should be exercised when calcium antagonists are used concomitantly with inhalation anaesthetics due to the risk of additive negative inotropic effect. MAC (minimum alveolar concentration) is reduced by concomitant administration of N20 in adults.
For full details please see prescribing information.    

Concerning the use of this substance in pregnancy in the case of humans, adequate data do not exist in order to judge possible injuriousness. In regard to effects in animal tests, adequate data do not exist in order to judge possible injuriousness. In light of the fact that it has not been established that AERRANE can be used safely in pregnant women, the use of this product must be avoided during pregnancy. Insufficient information is available to recommend use in pregnancy or obstetrics. Breast feeding should not be given for up to 12 hours after the termination of anaesthesia. Increased blood loss has been observed in patients undergoing uterine curettage.
For full details please see prescribing information.   

In case of overdose, stop administration of the anaesthetic agent, check whether air passages are open, and depending on the circumstances, continue with assisted or controlled respiration using pure oxygen. Support and maintain adequate haemodynamics.
For full details please see prescribing information.