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FORANEŽ
Zeneca
Isoflurane
Inhalation Anesthetic
 
Action And Clinical Pharmacology: Isoflurane is an inhalation anesthetic whose low solubility (blood/gas partition coefficient equals 1.4), permits a rapid induction of and recovery from anesthesia. The mild pungency of isoflurane may limit the rate of induction, although excessive salivation or tracheobronchial secretions do not appear to be stimulated. The level of anesthesia may be changed rapidly with isoflurane. Pharyngeal and laryngeal reflexes are readily and easily obtunded. Isoflurane is a profound respiratory depressant. An increase in anesthetic dose will decrease tidal volume without changing respiratory rate. This depression is partially reversed by surgical stimulation, even at deeper levels of anesthesia. Isoflurane evokes a sigh response reminiscent of that seen with diethyl ether and enflurane.

Blood pressure decreases with induction of anesthesia but returns toward normal with surgical stimulation. Progressive increases in depth of anesthesia correspondingly decrease blood pressure. Nitrous oxide diminishes the inspired concentration of isoflurane required to reach a desired level of anesthesia and has a favorable effect on the parameters of the anesthetic process. With controlled ventilation and normal PaCO2, cardiac output is maintained despite increasing depth of anesthesia primarily through an increase in heart rate which compensates for a reduction in stroke volume. The hypercapnia which attends spontaneous ventilation during isoflurane anesthesia further increases heart rate and raises cardiac output above awake levels.

The cardiac rhythm during isoflurane anesthesia is stable. In dog studies, isoflurane has not been found to sensitize the myocardium to exogenously administered epinephrine. Limited data indicate that s.c. injection of 0.25 mg of epinephrine (50 mL of 1:200 000 solution) does not cause ventricular arrhythmias in patients anesthetized with isoflurane. Doubling this dose will produce ventricular extrasystoles in about half of patients anesthetized with 1.25 MAC isoflurane.

Muscle relaxation usually is adequate for intra-abdominal operations at normal levels of anesthesia. All commonly used muscle relaxants are compatible with isoflurane. Complete paralysis can be attained with small doses of muscle relaxants. Isoflurane potentiates all commonly used muscle relaxants, the effect being most profound with nondepolarizing relaxants. Neostigmine reverses the effect of nondepolarizing muscle relaxants in the presence of isoflurane but does not reverse the direct neuromuscular depression of isoflurane.

The metabolism of isoflurane is low in miniature swine, black C-57 mice and Fischer 344 rats. Less than 0.5% of isoflurane taken up in humans can be recovered as metabolites.

Indications And Clinical Uses: Induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia.

Contra-Indications: Known sensitivity to isoflurane or to other halogenated agents. tag_WarningWarnings

Manufacturers' Warnings In Clinical States: Levels of anesthesia may be altered easily and rapidly; therefore, only vaporizers producing predictable concentrations should be used. Hypotension and respiratory depression increase as anesthesia is deepened.

Respiration must be monitored closely and supported when necessary.

Isoflurane potentiates all commonly used muscle relaxants, the effect being most profound with the nondepolarizing type. Therefore, less than the usual amounts of such agents should be used. Neostigmine reverses the effects of nondepolarizing muscle relaxants, but does not reverse the direct neuromuscular depression of isoflurane.

Blood loss during abortion is increased when halogenated agents such as isoflurane are used for anesthesia.

Isoflurane may increase cerebral blood flow and hence cerebral spinal fluid pressure, and therefore should be used with special care in patients with pre-existing increases in cerebrospinal fluid pressure. This effect on flow and pressure is reversed by hyperventilation.

The safety of repeated anesthesia with isoflurane has not been established.

Pregnancy: The safety of isoflurane anesthesia to mother and fetus has not been established. Reproduction studies in rats and mice reveal no evidence of harm to the fetus. The relevance of these studies to the human is not known. There are no data on the use of isoflurane in pregnant women.

Precautions: Bromsulfalein (BSP) retention is mildly elevated postoperatively in some cases. There is some elevation of glucose and white blood count intraoperatively. Glucose elevation should be considered in diabetic patients.

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 pressure. (It should also be noted that many of these nonspecific signs may appear with light anesthesia, acute hypoxia, etc.) An increase in overall metabolism may be reflected in an elevated temperature (which may rise rapidly early or late in the case, but usually is not the first sign of augmented metabolism) and an increased usage of the CO2 absorption system (hot canister). PaO2 and pH may decrease, and hyperkalemia and a base deficit may appear. Treatment includes discontinuance of triggering agents (e.g., isoflurane), administration of i.v. 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 i.v. for additional information on patient management.) Renal failure may appear later, and urine flow should be sustained if possible.

Adverse Reactions: Hypotension, respiratory depression, arrhythmias, shivering, nausea, vomiting, and postoperative ileus have been reported. As with all other anesthetics, elevation of the white blood count has been observed following anesthesia even in the absence of surgical stress.

Elevation of AST, LDH, alkaline phosphatase and bilirubin with or without frank jaundice, have been reported in the postoperative period following isoflurane anesthesia in some patients. Hepatitis has been reported very rarely.

Delirium, hallucinations and hiccup occur rarely.

Symptoms And Treatment Of Overdose: Symptoms: Overdosage with isoflurane produces marked hypotension and may cause apnea. tag_Treatment

Treatment: In the event of overdosage, or what appears to be overdosage, the following should be done: Stop drug administration. Establish that the airway is clear. Instigate assisted or controlled ventilation with pure oxygen as the circumstances dictate.

Dosage And Administration: Preanesthetic Medication: Premedication should be selected according to the need of the individual patient, taking into account that secretions are weakly stimulated by isoflurane and that the heart rate tends to be increased. 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 use of a hypnotic dose of a short acting barbiturate preceding the isoflurane mixture. Inspired concentrations of 1.5 to 3.0% isoflurane with a background of 50 to 70% nitrous oxide usually produce surgical anesthesia in 7 to 10 minutes. If nitrous oxide is not used, an additional 1.0 to 1.5% isoflurane may be required for induction of anesthesia.

Maintenance: Surgical levels of anesthesia may be sustained with a 1.0 to 2.5% concentration when 50 to 70% nitrous oxide is used concomitantly. An additional 0.5 to 1.0% may be required when isoflurane is given in oxygen alone. Additional relaxation may be produced with supplemental doses of muscle relaxants.

In the absence of other complicating problems, blood pressure during maintenance varies inversely with isoflurane concentration. Excessive decreases may be due to depth of anesthesia and in such instances may be corrected by lightening anesthesia.

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 sodalime 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.

Administration Equipment: The delivered concentration of isoflurane should be known. Isoflurane may be vaporized from a flow-through vaporizer specifically calibrated for isoflurane. Vaporizers which deliver saturated vapor at reasonable flows but are not specifically calibrated for isoflurane may be used. The delivered concentration from such a vaporizer may be calculated using the formula:

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