28% in the mid-twenties to 1.15% in the mid-forties, to 1.05% in the mid-sixties age group. The MAC values of isoflurane as per age are as follows:

As with other agents, lesser concentrations of isoflurane are normally required to maintain surgical anesthesia in elderly patients.
Premedication Drugs used for premedication should be selected based on the needs of the individual patient, bearing in mind the fact that secretions are weakly stimulated and heart rate tends to be increased by isoflurane. The use of anticholinergic drugs is a matter of choice. Induction Induction with isoflurane in oxygen or in combination with oxygen-nitrous oxide mixtures may produce coughing, breath holding, or laryngospasm. These difficulties may be avoided by the use of a hypnotic dose of an ultra-short-acting barbiturate. Concentrations of 1.5 to 3.0% usually produce surgical anesthesia in seven to ten minutes. Maintenance Surgical levels of anesthesia may be maintained with 1.0 to 2.5% isoflurane in oxygen/nitrous oxide mixtures. An additional 0.5 to 1.0% isoflurane may be required when given with oxygen alone. If added relaxation is required, supplemental doses of muscle relaxant may be used. Induction of and recovery from isoflurane anesthesia are rapid. Isoflurane has a mild pungency which limits the rate of induction, although excessive salivation or tracheobronchial secretions do not appear to be stimulated. Pharyngeal and laryngeal reflexes are readily obtunded. The level of anesthesia may be changed rapidly with isoflurane. Isoflurane is a profound respiratory depressant. Respiration must be monitored closely and supported when necessary. Arterial pressure levels during maintenance tend to be inversely related to alveolar isoflurane concentrations in the absence of other complicating factors. Increased depth of anesthesia may lead to excessive falls in blood pressure; this should be corrected by reducing the inspired isoflurane concentration. Muscle relaxation is often adequate for intra-abdominal operations at normal levels of anesthesia. Complete muscle paralysis can be attained with small doses of muscle relaxants. All commonly used muscle relaxants are markedly potentiated with isoflurane, the effect being most profound with the nondepolarizing type. Neostigmine reverses the effect of nondepolarizing muscle relaxants in the presence of isoflurane. All commonly used muscle relaxants are compatible with isoflurane.

Hypotension and respiratory depression increase as anesthesia is deepened.
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.
Isoflurane, like other inhalational agents, has relaxant effects on the uterus with the potential risk for uterine bleeding. Clinical judgment should be observed when using isoflurane during obstetric anesthesia. Consideration should be taken to use the lowest possible concentration of isoflurane in obstetrical operations.
Isolated cases of increased carboxyhemoglobin have been reported with the use of fluorinated inhalation agents (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 because 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.
General
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.
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 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.
Regardless of the anesthetics employed, maintenance of normal hemodynamics is important to the avoidance of myocardial ischemia in patients with coronary artery disease. As with other halogenated agents, isoflurane must be used with caution in patients with increased intracranial pressure. In such cases hyperventilation may be necessary.
Isoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably nondepolarizing muscle relaxants, and MAC (minimum alveolar concentration) is reduced by concomitant administration of N2O.
Isoflurane should be administered with caution to patients who can develop bronchoconstriction since bronchospasm can occur.
Isoflurane may cause respiratory depression, which may be augmented by narcotic premedication or other agents causing respiratory depression. Respiration should be supervised and if necessary, assisted.
Isoflurane, as well as other general anesthetics, may cause a slight decrease in intellectual function for 2-4 days following anesthesia. As with other anesthetics, small changes in moods and symptoms may persist for up to 6 days after administration.
Isoflurane, like some other inhalational anesthetics, can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide, which 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 absorber cannister 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 isoflurane.
Malignant Hyperthermia
In susceptible individuals, isoflurane anesthesia may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. The syndrome includes nonspecific features such as muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and unstable blood pressures (It should also be noted that many of these nonspecific signs may appear with light anesthesia, acute hypoxia, etc.). PaO2 and pH may decrease, and hyperkalemia and a base deficit may appear. There have been postmarketing reports of malignant hyperthermia. Some of these reports have been fatal. Treatment includes discontinuance of triggering agents (e.g. isoflurane), intravenous administration of dantrolene sodium, and application of supportive therapy. Such therapy includes vigorous efforts to restore body temperature to normal, respiratory and circulatory support as indicated, and management of electrolyte-fluid-acid-base derangements (Consult prescribing information for dantrolene sodium intravenous for additional information on patient management). Renal failure may appear later, and urine flow should be sustained if possible.
Perioperative Hyperkalemia
Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric 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 hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease.
Effects on ability to drive and use machines
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 anesthesia with isoflurane. As with other anesthetics, small changes in moods and symptoms may persist for up to 6 days after administration.
Pediatric Clinical Safety
Some published studies in children have observed cognitive deficits after repeated or prolonged exposures to anesthetic agents early in life. These studies have substantial limitations, and it is not clear if the observed effects are due to the anesthetic/sedation drug administration or other factors such as the surgery or underlying illness. In addition, more recent published registry studies did not confirm these findings. Published animal studies of some anesthetic/sedation drugs have reported adverse effects on brain development in early life.

Studies with the rat demonstrated no effect on fertility, pregnancy or delivery or on the viability of the offspring. No evidence of teratogenicity was revealed. Comparable experiments in rabbits produced similar negative results. The relevance of these studies to the human is not known, as there are no adequate and well-controlled studies in pregnant women.
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 judgment should be observed when using isoflurane during obstetric anesthesia. Consideration should be taken to use the lowest possible concentration of isoflurane in obstetrical operations.
Published animal studies of some anesthetic/sedation drugs have reported adverse effects on brain development in early life. Published studies in pregnant and juvenile animals suggest that the use of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of rapid brain growth or synaptogenesis may result in neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis when used for longer than 3 hours. These studies included anesthetic agents from a variety of drug classes. The clinical significance of these nonclinical findings is yet to be determined.
Use in Cesarean Section
The use of isoflurane as part of general anesthesia for elective cesarean section has been described in the literature. Isoflurane should be used only if the potential benefit justifies the potential risk.
Isoflurane exerts a relaxant effect on uterine smooth muscle. This can lead to increased blood loss in situations where uterine muscle contraction aids hemostasis, such as in obstetric surgery and in patients undergoing intrauterine procedures. Clinical judgment should be observed when using isoflurane during obstetric anesthesia. Consideration should be taken to use the lowest possible concentration of isoflurane in obstetrical operations.
Lactation
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isoflurane is administered to a nursing woman.
Pediatric Use
Published juvenile animal studies have shown neuronal loss with usage of isoflurane. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in pregnant women, neonates, and young children who require procedures with the potential risks suggested by the nonclinical data.

All commonly used muscle relaxants are markedly potentiated by isoflurane, the effect being most profound with nondepolarizing agents. Neostigmine reverses the effects of nondepolarizing muscle relaxants but has no effect on the relaxant properties of isoflurane itself. All commonly used muscle relaxants are compatible with isoflurane.
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. Non-selective MAO-inhibitors: Risk of crisis during the operation. It is generally recommended that treatment should be stopped two weeks prior to surgery.
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.
Concomitant use of isoflurane and isoniazide can increase the risk of potentiation of the hepatotoxic effects.
Isoflurane may lead to marked hypotension in patients treated with calcium antagonists, in particular, dihydropyridine derivates.
Caution should be exercised when calcium antagonists are used concomitantly with inhalation anesthetics due to the risk of additive negative inotropic effect.
Opioids, benzodiazepines and other sedative agents are associated with respiratory depression. Caution should be exercised when these agents are concomitantly administered with isoflurane.

Potential serious undesirable effects include malignant hyperthermia, hyperkalemia, elevated serum creatine kinase, and myoglobinuria. Cardiac arrest, bradycardia, and tachycardia have been observed with general inhalation anesthetic drugs including isoflurane.
Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal), have been received.
Bronchospasm and laryngospasm due to airway irritation have been reported with volatile anesthetics during inhalation. Electroencephalographic changes and convulsions have been observed with isoflurane.
Isoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably non-depolarizing muscle relaxants, and MAC (minimum alveolar concentration) is reduced by concomitant administration of N2O in adults.
Isolated cases of increased carboxyhemoglobin have been reported with the use of fluorinated inhalation agents (i.e., desflurane, enflurane and isoflurane).
Isoflurane, like other inhalational agents, has relaxant effects on the uterus with the potential risk for uterine bleeding. Shivering, nausea, vomiting, ileus, agitation, and delirium have been observed in the postoperative period.
Transient increases in blood bilirubin, blood glucose and serum creatinine with decrease in BUN, serum cholesterol and alkaline phosphatase have been observed. As with all other general anesthetics, transient elevations in white blood count have been observed even in the absence of surgical stress. Reports demonstrate that isoflurane can produce hepatic injury ranging from mild transient increases of liver enzymes to fatal hepatic necrosis in very rare instances.
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 anesthetic agents, including isoflurane. These reactions have been confirmed by clinical testing (e.g., methacholine challenge). The etiology of anaphylactic reactions experienced during inhalational anesthetic 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 anesthesia, due to biodegradation of the agent. It is unlikely that the low levels of serum inorganic fluoride observed could cause renal toxicity, as these are well below the proposed threshold levels for kidney toxicity.

Close monitoring of blood pressure and respiration is recommended. Supportive measures may be necessary to correct hypotension and respiratory depression resulting from excessively deep levels of anesthesia.

Levels of anesthesia may be changed rapidly with isoflurane. Heart rhythm remains stable. Spontaneous respiration becomes depressed as depth of anesthesia increases and should be closely monitored and supported when necessary.
During induction there is a decrease in blood pressure which returns towards normal with surgical stimulation. Blood pressure tends to fall during maintenance in direct relation to depth of anesthesia, but cardiac rhythm remains stable. With controlled respiration and normal PaCO2, cardiac output tends to be maintained despite increasing depth of anesthesia primarily through a rise in heart rate which compensates for a reduction in stroke volume. With spontaneous respiration, the resulting hypercapnia may increase heart rate and cardiac output above awake levels. Cerebral blood flow remains unchanged during light isoflurane anesthesia but tends to rise at deeper levels. Increases in cerebrospinal fluid pressure may be prevented or reversed by hyperventilating the patient before or during anesthesia. Electroencephalographic changes and convulsions are extremely rare with isoflurane. In general, isoflurane produces an EEG pattern similar to that seen with other volatile anesthetics.
Isoflurane appears to sensitize the myocardium to adrenaline. Limited data suggest that subcutaneous infiltration of up to 50 mL of 1:200,000 solution adrenaline does not induce ventricular arrhythmias in patients anesthetized with isoflurane.
Muscular relaxation may be adequate for some intra-abdominal operations at normal levels of anesthesia, but should greater relaxation be required small doses of intravenous muscle relaxants may be used.
Isoflurane may be used for the induction and maintenance of general anesthesia. Adequate data are not available to establish its place in pregnancy.
Relatively little metabolism of isoflurane occurs in the human body. In the postoperative 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 micromole/litre and occur about four hours after anesthesia, returning to normal levels within 24 hours. No signs of renal injury have been reported after isoflurane administration. Known metabolites of isoflurane have been found to be either nontoxic or present in too low a concentration to be harmful. Isoflurane can produce coronary vasodilation at the arteriolar level in selected animal models; the drug is probably also a coronary dilator in humans. Isoflurane, like some other coronary arteriolar dilators, has been shown to divert blood from collateral dependent myocardium to normally perfused areas in an animal model (“coronary steal”). Clinical studies to date evaluating myocardial ischemia, infarction and death as outcome parameters have not established that the coronary arteriolar dilation property of isoflurane is associated with coronary steal or myocardial ischemia in patients with coronary artery disease.