Sevoflex

Sevoflurane.

Sevoflurane is fluoromethyl 2,2,2,-trifluoro-1-(trifluoromethyl) ethyl ether, a volatile liquid for inhalation, a nonflammable and non-explosive liquid administered by vaporization and is a halogenated general inhalation anesthetic drug.

Pharmacology: Pharmacodynamics: Cardiovascular Effects: As with all other inhalation agents, sevoflurane depresses cardiovascular function in a dose related fashion. In one volunteer study, increase in sevoflurane concentration resulted in decrease in mean arterial pressure, but there was no change in heart rate. Sevoflurane did not alter plasma noradrenaline concentrations in this study.
Nervous System Effects: In patients with normal intracranial pressure (ICP), sevoflurane had minimal effect on ICP and preserved CO₂ responsiveness. The safety of sevoflurane has not been investigated in patients with a raised ICP. In patients at risk for elevations of ICP, sevoflurane should be administered cautiously in conjunction with ICP-reducing maneuvers such as hyperventilation.
Pharmacokinetics: In humans <5% of the absorbed sevoflurane is metabolized. The rapid and extensive pulmonary elimination of sevoflurane minimizes the amount of anesthetic available for metabolism. Sevoflurane is defluorinated via cytochrome P450 (CYP)2E1 resulting in the production of hexafluoroisopropanol (HFIP) with release of inorganic fluoride and carbon dioxide (or a one carbon fragment).
HFIP is then rapidly conjugated with glucuronic acid and excreted in the urine.
The metabolism of sevoflurane may be increased by known inducers of CYP2E1 (e.g. isoniazid and alcohol), but it is not inducible by barbiturates.

Sevoflurane is indicated for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery.

The concentration of sevoflurane being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using a vaporizer calibrated specifically for sevoflurane.
The administration of general anesthesia must be individualized based on the patient's response.
Replacement of Desiccated CO₂ Absorbents: When a clinician suspects that the CO₂ absorbent may be desiccated, it should be replaced. The exothermic reaction that occurs with sevoflurane and CO₂ absorbents is increased when the CO₂ absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO₂ absorbent canisters.
Pre-anesthetic Medication: No specific premedication is either indicated or contraindicated with sevoflurane. The decision to whether or not to premedicate and the choice of premedication is left to the discretion of the anesthesiologist.
Induction: Sevoflurane has a non-pungent odor and does not cause respiratory irritability; it is suitable for mask induction in pediatrics and adults.
Maintenance: Surgical levels of anesthesia can usually be achieved with concentrations of 0.5-3% sevoflurane with or without the concomitant use of nitrous oxide. Sevoflurane can be administered with any type of anesthesia circuit. (See table.)

Click on icon to see table/diagram/image

In the event of over dosage, the following action should be taken: Stop drug administration, establish a clear airway and initiate assisted or controlled ventilation with pure oxygen and maintain adequate cardiovascular function.

Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known hypersensitivity to the drug or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.

Malignant Hyperthermia: In susceptible individuals, potent inhalation anesthetic agents, including sevoflurane, may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. Sevoflurane can induce malignant hyperthermia in genetically susceptible individuals, such as those with certain inherited ryanodine receptor mutations. The clinical syndrome is signaled by hypercapnia, and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and/or unstable blood pressure. Some of these nonspecific signs may also appear during light anesthesia, acute hypoxia, hypercapnia, and hypovolemia. In clinical trials, one case of malignant hyperthermia was reported. In addition, there have been postmarketing reports of malignant hyperthermia. Some of these cases have been fatal. Treatment of malignant hyperthermia includes discontinuation of triggering agents (e.g., sevoflurane), administration of intravenous dantrolene sodium (consult prescribing information for intravenous dantrolene sodium for additional information on patient management), and application of supportive therapy. Supportive therapy may include efforts to restore body temperature, respiratory and circulatory support as indicated, and management of electrolyte fluid-acid-base abnormalities. Renal failure may appear later, and urine flow should be monitored and 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.

During the maintenance of anesthesia, increasing the concentration of sevoflurane produces dose-dependent decreases in blood pressure. Due to sevoflurane's insolubility in blood, these hemodynamic changes may occur more rapidly than with other volatile anesthetics. Excessive decreases in blood pressure or respiratory depression may be related to depth of anesthesia and may be corrected by decreasing the inspired concentration of sevoflurane.
Rare cases of seizures have been reported in association with sevoflurane use. The recovery from general anesthesia should be assessed carefully before a patient is discharged from the post-anesthesia care unit.

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, sevoflurane should be used during pregnancy only if clearly needed.
The concentrations of sevoflurane in milk are probably of no clinical importance 24 hours after anesthesia. Because of rapid washout, sevoflurane concentrations in milk are predicted to be below those found with many other volatile anesthetics.

As with all potent inhaled anesthetics, sevoflurane may cause dose-dependent cardio-respiratory depression. Most adverse reactions are mild to moderate in severity and are transient in duration. Nausea and vomiting are commonly observed in the post-operative period, at a similar incidence to those found with other inhalation anesthetics. These effects are common sequelae of surgery and general anesthesia which may be due to the inhalational anesthetic, other agents administered intra-operatively or post-operatively and to the patient's response to the surgical procedure. The most frequent adverse events associated with sevoflurane overall were nausea and vomiting. Agitation occurred frequently in children.

The action of non-depolarising muscle relaxants is potentiated with sevoflurane, therefore, when administered with sevoflurane, dosage adjustments of these agents should be made. Sevoflurane is similar to isoflurane in the sensitization of the myocardium, to the arrhythmogenic effect of exogenously administered adrenaline.
Benzodiazepines and opiates are expected to reduce sevoflurane MAC. Opioids (e.g. alfentanil and sufentanil), used concomitantly with sevoflurane, may lead to a synergistic fall in heart rate, blood pressure and respiratory rate.
The metabolism of sevoflurane may be increased by known inducers of CYP2E1 (e.g. isoniazid and alcohol), but it is not inducible by barbiturates.

Store at temperatures not exceeding 30°C.

Anaesthetics - Local & General

N01AB08 - sevoflurane ; Belongs to the class of halogenated hydrocarbons. Used as general anesthetics.

Rx