Chemical formula: C₃H₂ClF₅O Molecular mass: 184.492 g/mol PubChem compound: 3763
Isoflurane interacts in the following cases:
Risk of crisis during the operation. Treatment should be stopped 15 days prior to surgery.
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.
Indirect-acting sympathomimetics (amphetamines and their derivatives, psychostimulants, appetite suppressants, ephedrine and its derivatives): Risk of peri-operative hypertension. In patients undergoing elective surgery, treatment should ideally be discontinued several days before surgery.
All commonly used muscle relaxants are markedly potentiated by isoflurane. Neostigmine has an effect on the non-depolarising relaxants, but has no effect on the relaxing action of isoflurane itself.
Cardiovascular compensation reactions may be impaired by beta-blockers.
Isoflurane may lead to marked hypotension in patients treated with calcium antagonists.
Caution should be exercised when calcium antagonists are used concomitantly with inhalation anaesthetics due to risk of additive negative inotropic effect.
Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with isoflurane.
Isoflurane has been reported to interact with dry carbon dioxide absorbents during closed circuit anaesthesia, to form carbon monoxide. In order to minimize the risk of formation of carbon monoxide in rebreathing circuits and the possibility of elevated carboxyhaemoglobin levels, carbon dioxide adsorbents should not be allowed to dry out.
Beta-sympathomimetic agents like isoprenaline, and alpha and beta- sympathomimetic agents like adrenaline and noradrenaline should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.
Medicinal products and compounds that increase the activity of cytochrome P450 isoenzyme CYP2E1, such as isoniazid and alcohol, may increase the metabolism of isoflurane and lead to significant increases in plasma fluoride concentrations.
Use of isoflurane and isoniazid can increase the risk of potentiation of the hepatotoxic effects.
Concomitant use of succinylcholine with 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 post-operative period.
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 age group 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, these patients did NOT have classical signs or symptoms of malignant hyperthermia such as muscle rigidity or hypermetabolic state. Prompt and vigorous treatment for hyperkalaemia and resistant arrhythmias is recommended as is subsequent evaluation for latent neuromuscular disease.
Caution should be exercised in administering general anaesthesia, including isoflurane, to patients with mitochondrial disorders.
Isoflurane markedly increases cerebral blood flow at deeper levels of anaesthesia. 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.
There are no or limited amount of data from the use of isoflurane in pregnant women. Studies in animals have shown reproductive toxicity.
Isoflurane should only be used during pregnancy if the benefit outweighs the potential risk.
Isoflurane, like other inhalational agents, has relaxant effects on the uterus with the potential risk for uterine bleeding. Clinical judgement should be observed when using isoflurane during obstetric anaesthesia. Consideration should be taken to use the lowest possible concentration of isoflurane in obstetrical operations.
Isoflurane, in concentrations up to 0.75%, has been shown to be safe for the maintenance of anaesthesia for caesarean section.
It is not known whether isoflurane/metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isoflurane is administered to a nursing woman.
Patients should be advised that performance of activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, may be impaired for 2-4 days after anaesthesia with isoflurane. As with other anaesthetics, small changes in moods and symptoms may persist for up to 6 days after administration.
Adverse reactions encountered in the administration of Isoflurane are in general dose dependent extensions of pharmaco-physiological effects and include hypotension, respiratory depression and arrhythmias. Potential serious undesirable effects include malignant hyperthermia, hyperkalaemia, elevated serum creatine kinase, myoglobinuria, anaphylactic reactions and liver adverse reactions. Shivering, nausea, vomiting, ileus, agitation and delirium have been observed in the post-operative period.
Cardiac arrest, bradycardia and tachycardia have been observed with general inhalation anaesthetic drugs including isoflurane.
Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal) have been received.
The following list displays adverse reactions reported in clinical trials and from post-marketing experience. Frequency cannot be estimated from the available data, therefore it is “not known”.
Not known: Carboxyhaemoglobinaemia
Not known: Anaphylactic reaction1, Hypersensitivity1
Not known: Hyperkalaemia, Blood glucose increased1
Not known: Agitation, Delirium, Mood altered4
Not known: Convulsion, Mental impairment3
Not known: Arrhythmia
Not known: Hypotension, Haemorrhage2
Not known: Bronchospasm, Dyspnoea1, Wheezing1, Respiratory depression, Laryngospasm
Not known: Ileus, Vomiting, Nausea
Not known: Hepatic necrosis, Hepatocellular injury, Blood bilirubin increased1
Not known: Swelling face1, Dermatitis contact1, Rash1
Not known: Blood creatinine increased1, Blood urea decreased1
Not known: Hyperthermia malignant, Chest discomfort1, Chills
Not known: White blood cell count increased1, Hepatic enzyme increased, Fluoride increased1, Electroencephalogram abnormal, Blood cholesterol decreased1, Blood alkaline phosphatase decreased1
1 See c.
2 In patients undergoing induced abortion.
3 May cause a slight decrease in intellectual function for 2-4 days after anaesthesia.
4 Small changes in moods and symptoms may persist for up to 6 days.
Transient increases in blood bilirubin, blood glucose and serum creatinine with decrease in BUN, serum cholesterol and alkaline phosphatase have been observed. As with other general anaesthetics, transient elevations in white blood count have been observed even in the absence of surgical stress.
Rare reports of hypersensitivity (including dermatitis contact, rash, dyspnoea, wheezing, chest discomfort, swelling face, or anaphylactic reaction) have been received, especially in association with long-term occupational exposure to inhaled anaesthetic agents, including isoflurane. These reactions have been confirmed by clinical testing (e.g., methacholine challenge). The etiology of anaphylactic reactions experienced during inhalational anaesthetic exposure is, however, unclear because of the exposure to multiple concomitant drugs, many of which are known to cause such reactions. Minimally raised levels of serum inorganic fluoride occur during and after isoflurane anaesthesia, due to biodegradation of the agent. It is unlikely that the low levels of serum inorganic fluoride observed (mean 4.4 µmol/l in one study) could cause renal toxicity, as these are well below the proposed threshold levels for kidney toxicity.
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 post-operative period.
During the induction of anaesthesia, saliva flow and tracheobronchial secretion can increase and can be the cause of laryngospasm.
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 post-operative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Early and aggressive intervention to treat the hyperkalaemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
Lesser concentrations of isoflurane are normally required to maintain surgical anaesthesia in elderly patients.
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