Isoflurane Fahrenheit

Isoflurane.

Isoflurane 100 Liquid for Inhalation: Each bottle contains: Isoflurane 100 mL.
Isoflurane 250 Liquid for Inhalation: Each bottle contains: Isoflurane 250 mL.

Pharmacology: Induction and, particularly, recovery are rapid. Although slight pungency may limit the rate of induction, excessive salivation and tracheobronchial secretions do not appear to be stimulated. Pharyngeal and laryngeal reflexes are diminished quickly. 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 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.
lsoflurane 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.
lsoflurane 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.

lsoflurane is used for general anesthesia. Data are not yet available to support its use in anesthesia for obstetrics or in children of less than 2 years.

Premedication: Drugs used for premedication should be selected for the individual patient, bearing in mind the respiratory depressant effect of lsoflurane. The use of anticholinergic drugs is a matter of choice.
Induction: lsoflurane with oxygen or with an oxygen/nitrous oxide may be used for induction, but more usually a short-acting barbiturate or other intravenous induction agent is administered followed by inhalation of the lsoflurane mixture.
It is recommended that induction with lsoflurane be initiated at a concentration of 0.5%. Concentrations of 1.5 to 3.0% usually produce surgical anesthesia in 7 to 10 minutes.
Maintenance: Surgical levels of anesthesia may be maintained with 1.0 - 2.5% lsoflurane in oxygen/nitrous oxide mixtures. An additional 0.5 - 1.0% lsoflurane may be required when given with oxygen alone.
Arterial pressure levels during maintenance tend to be inversely related to alveolar lsoflurane concentrations in the absence of other complicating factors. Excessive falls in blood pressure may be due to depth of anesthesia and in these circumstances, should be corrected by reducing the inspired lsoflurane concentration.
Recovery: The inspired concentration of Isoflurane may be reduced to 0.5% near the end of surgery or may be reduced to zero at the beginning of the skin closure.
Administration Equipment: It is recommended that Isoflurane should be vaporized using a flow-through vaporizer specifically calibrated for the agent, though non-calibrated vaporisers may be used, particularly with low flow or closed systems, in conjunction with equipment capable of monitoring inspired or expired concentrations.
lsoflurane does not contain stabilisers which, in other agents, may affect vaporizer output.
MAC (Minimum Alveolar Concentration) in man: (See table.)


Click on icon to see table/diagram/image

In the event of overdosage, or what may appear to be overdosage, stop drug administration, establish a clear airway and initiate assisted or controlled ventilation with pure oxygen.
Hypotension and respiratory depression have been observed. 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.

lsoflurane is contraindicated in patients with known sensitivity to isoflurane or other halogenated anesthetics. It is also contraindicated in patients with known or suspected genetic susceptibility to malignant hyperthermia.

lsoflurane 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.
Since levels of anesthesia may be altered easily and rapidly, only vaporizers producing predictable concentrations and flow rates should be used. 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.
Blood losses comparable with those found following anesthesia with other inhalation agents have been recorded with lsoflurane in patients undergoing induced abortion. Adequate data have not been developed to established the use of lsoflurane in obstetric anesthesia.
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 lsoflurane. 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.
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.
As with other halogenated agents, isoflurane must be used with caution in patients with increased intracranial pressure. In such cases hyperventilation may be necessary.
The action of non-depolarizing relaxants is markedly potentiated with isoflurane.
lsoflurane should be administered with caution to patients who can develop bronchoconstriction since bronchospasm can occur.
lsoflurane 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.
lsoflurane, 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 (see EFFECTS ON ABILITY TO DRIVE AND USE MACHINES as follows).
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.

Pregnancy: Reproduction studies have been carried out on animals after repeated exposure to anesthetic concentrations of isoflurane. lsoflurane has been shown to have a possible anesthetic-related fetotoxic effect in mice when given in doses six times the human dose. 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.
lsoflurane, 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.
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.

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, hyperkalemia, elevated serum creatinine kinase, and myoglobinuria (see PRECAUTIONS).
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. lsoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably nondepolarizing muscle relaxants, an 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).
lsoflurane, 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.

Concomitant use of succinylcholine with 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.
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 2 weeks prior to surgery.
Inducers of CYP2E1: 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 isoniazid can increase the risk of potentiation of the hepatotoxic effects.
lsoflurane 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.

Store below 30°C.

Anaesthetics - Local & General

N01AB06 - isoflurane ; Belongs to the class of halogenated hydrocarbons. Used as general anesthetics.

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