Севофлуран

Uses

Севофлуран is used for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery. Севофлуран should be administered only by persons trained in the administration of general anesthesia. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, and circulatory resuscitationmust be immediately available. Since level of anesthesia may be altered rapidly, only vaporizers producing predictable concentrations of sevoflurane should be used.

Севофлуран is also used to associated treatment for these conditions: General Anesthesia, Induction and Maintenance of General Anesthesia

How Севофлуран works

Севофлуран induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Севофлуран also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase and also binds to the GABA receptor, the large conductance Ca²⁺ activated potassium channel, the glutamate receptor, and the glycine receptor.

Dosage

Севофлуран dosage

he 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 CO2Absorbents: When a clinician suspects that the CO2absorbent may be desiccated, it should be replaced. The exothermic reaction that occurs with sevoflurane and CO2absorbents is increased when the CO2absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2absorbent canisters

Pre-anesthetic Medication: No specific premedication is either indicated or contraindicated with sevoflurane. The decision as to whether or not to premedicate and the choice of premedication is left to the discretion of theanesthesiologist

Induction: Севофлуран has a nonpungent odor and does not cause respiratory irritability; it is suitable for mask induction inpediatricsand adults

Maintenance: Surgical levels of anesthesia can usually be achieved with concentrations of 0.5-3% sevoflurane with or without the concomitant use ofnitrous oxide. Севофлуран can be administered with any type of anesthesia circuit

Side Effects

Cardiorespiratory depression, hypotension, bradycardia; laryngospasm, increased cough and salivation; urinary retention, acute renal failure, changes in liver enzyme values, liver damage; nausea, vomiting, delirium, seizure; rash, urticaria, pruritus, dyspnoea, wheezing, chest discomfort, bronchospasm, anaphylactic/anaphylactoid reaction; agitation, dystonic movements (childn).

Toxicity

LC₅₀=49881 ppm/hr (rat), LD₅₀=10.8 g/kg (rat)

Precaution

Patient with increased intracranial pressure, neuromuscular disease (esp Duchenne muscular dystrophy), mitochondrial disorders. Patient who are hypovolaemic, hypotensive, haemodynamically compromised, at risk of QT prolongation. Hepatic and renal impairment. Childn. Pregnancy and lactation.

Interaction

Increased metabolism and toxicity with drugs that induce CYP2E1 isoenzyme (e.g. isoniazid). Reduced MAC with benzodiazepines, opioids. May cause ventricular arrhythmia with β-sympathomimetic agents (e.g. isoprenaline), and α- and β-sympathomimetic agents (e.g. adrenaline, noradrenaline). May cause crisis during operation with nonselective MAO inhibitors. May lead to marked hypotension and risk of additive negative inotropic effect with Ca antagonists (esp dihydropyridines).

Food Interaction

Севофлуран Drug Interaction

Major: epinephrineModerate: azithromycin, ciprofloxacin, hydromorphone, ondansetronUnknown: aspirin, charcoal, amoxicillin, multivitamin, dexamethasone, heparin, acetaminophen, procaine penicillin, vitamin a topical, bioflavonoids, ketorolac, valproic acid, cyanocobalamin, cholecalciferol, phytonadione

Севофлуран Disease Interaction

Major: hyperthermiaModerate: hepatic dysfunction, hyperkalemia, intracranial pressure, renal impairment, seizures

Elimination Route

Rapidly absorbed into circulation via the lungs, however solubility in the blood is low.

Half Life

15-23 hours

Elimination Route

The low solubility of sevoflurane facilitates rapid elimination via the lungs. In vivo metabolism studies suggest that approximately 5% of the sevoflurane dose may be metabolized. Up to 3.5% of the sevoflurane dose appears in the urine as inorganic fluoride.

Pregnancy & Breastfeeding use

Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 1 MAC (minimum alveolar concentration) without CO2 absorbent and have revealed no evidence of impaired fertility or harm to the fetus due to sevoflurane at 0.3 MAC, the highest nontoxic dose. Developmental and reproductive toxicity studies of sevoflurane in animals in the presence of strong alkalies (i.e., degradation of sevoflurane and production of Compound A) have not been conducted. 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.

Labor And Delivery: Севофлуран has been used as part of general anesthesia for elective cesarean section in 29 women. There were no untoward effects in mother or neonate (see Pharmacodynamics - Clinical Trials). The safety of sevoflurane in labor and delivery has not been demonstrated.

Nursing Mothers: 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.

Contraindication

Севофлуран can cause malignant hyperthermia. It should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.

Special Warning

Geriatric Use: MAC decreases with increasing age. The average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old.

Pediatric Use: Induction and maintenance of general anesthesia with sevoflurane have been established in controlled clinical trials in pediatric patients aged 1 to 18 years. Севофлуран has a nonpungent odor and is suitable for mask induction in pediatric patients.

The concentration of sevoflurane required for maintenance of general anesthesia is age dependent. When used in combination with nitrous oxide, the MAC equivalent dose of sevoflurane should be reduced in pediatric patients. MAC in premature infants has not been determined.

The use of sevoflurane has been associated with seizures. The majority of these have occurred in children and young adults starting from 2 months of age, most of whom had no predisposing risk factors. Clinical judgement should be exercised when using sevoflurane in patients who may be at risk for seizures.

Acute Overdose

In the event of overdosage, or what may appear to be overdosage, the following action should be taken: discontinue administration of sevoflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.

Storage Condition

Store between 15-30° C. Protect from light.

Innovators Monograph

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