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Sota
Omoigui's
Anesthesia Drug Handbook
3rd Edition:
:
Sevoflurane
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SECTION
ONE:
Uses, Dosing,
Elimination
SECTION TWO:
Preparation, Pharmacology, Pharmacokinetics
SECTION THREE:
Interactions, Toxicity
Guidelines/Precautions
Principal Adverse Reactions
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Uses
inhalation anesthesia
Dosing
Titrate to effect for induction or maintenance of anesthesia
Elimination
pulmonary, hepatic, renal
How supplied
Volatile liquid
Storage
Room temperature (15-30 degrees Celsius).
Pharmacology
Sevoflurane is a nonflammable fluorinated isopropyl ether. It has a vapor pressure of approximately 162 mm Hg at 20 degrees Celsius and boils at 58.5 degrees Celsius. In this respect it is similar to other volatile anesthetics and can be delivered by standard vaporizers. It is less potent than isoflurane with a MAC in100% oxygen of 3% atm, 2.6% atm and1.71% atm in patients 1-6 months, 25 yrs and 60 yrs of age respectively. For each 1% Nitrous oxide administered, sevoflurane MAC decreases by approximately 1% in all age groups. In adults, sevoflurane has a MAC in 63.5% nitrous oxide of 0.66% atm. The blood/gas partition coefficient at 37 degrees Celsius is 0.59. This low solubility in blood means a rapid induction of anesthesia. Sevoflurane is less of an irritant to the upper respiratory tract than desflurane, causing less coughing and laryngospasm on induction. After 30 minutes of administration, the ratio of alveolar concentrations to the inspired concentration is 0.85 compared with 0.9 for desflurane, 0.99 for nitrous oxide and 0.73 for isoflurane. The low tissue solubility of sevoflurane (fat/blood partition coefficient, 53.4) results in rapid elimination and awakening. After 5 minutes the ratio of the alveolar concentration relative to the concentration present at the conclusion of administration is 0.16 compared with 0.22 for isoflurane. Sevoflurane undergoes temperature dependent degradation by soda lime and baralyme. One of the byproducts is a substance called Compound A (pentafluoroisopropenyl fluoromethyl ether), which may be nephrotoxic at supraclinical doses. To decrease the production of Compound A, sevoflurane should not be used for closed systems anesthesia or at flow rates less than 2 liters/minute. Like isoflurane, sevoflurane causes a moderate increase in PaCO2 (approximately 20%) reflecting an increase in the rate of breathing insufficient to offset a decrease in tidal volume. Depression of ventilation reflects a direct depressant effect on the medullary ventilatory center and perhaps peripheral effects on intercostal muscle function. Bronchial smooth muscle relaxation may be produced by a direct effect or indirectly by reductions in afferent nerve traffic or central medullary depression of bronchoconstriction reflexes. Sevoflurane produces dose-dependent reductions of arterial blood pressure principally due to peripheral vasodilation. There is little effect on heart rate. Sevoflurane attenuates baroreceptor reflex responses (tachycardia) to hypotension and vasomotor reflex responses (increased peripheral resistance) to hypovolemia. At equipotent concentrations sevoflurane and isoflurane produce equivalent direct decreases in myocardial contractility. Like isoflurane, sevoflurane does not sensitize the heart to catecholamines. The arrhythmogenic threshold is intermediate between enflurane and isoflurane. In one study, the dose of submucosally injected epinephrine necessary to produce ventricular cardiac arrhythmias in 50% of patients anesthetized with a 1.3 MAC concentration of sevoflurane was 8.57 mcg/kg compared with 5.17 mcg/kg for enflurane and 9.81 mcg/kg for isoflurane. Unlike isoflurane, Sevoflurane may not cause coronary artery vasodilation that may lead to coronary artery steal syndrome. Sevoflurane undergoes oxidative metabolism in the liver with a serum fluoride concentration of approximately 22 µMol/L after a 1-MAC- hour exposure. The magnitude of sevoflurane metabolism resembles that of enflurane (peak plasma fluoride concentrations following a 2.5 MAC hour exposure to enflurane are about 20 µMol/L). Decrease in cerebral metabolic rate is closely linked to cerebral electrical activity. Increased anesthetic concentrations decrease EEG wave frequency and increases voltage with electrical silence at high concentrations. Sevoflurane like isoflurane may produce a dose-related decrease in the amplitude and increase in the latency of cortical components of visual and auditory evoked potentials. Cerebral vasodilation produced by sevoflurane causes an increase in cerebral blood flow and cerebral blood volume. Elevation of intracranial pressure parallels increase in cerebral blood flow. The increase in cerebral blood flow is attenuated with time and reflects a return of cerebral vascular autoregulation. Hyperventilation of the lungs (PaCO2 ?30) opposes the increase in intracranial pressure. Sevoflurane produces uterine vasodilation and dose dependent decrease in uterine blood flow. Sevoflurane has a direct muscle relaxant effect and potentiation of neuromuscular blocking drugs may involve desensitization of the postjunctional membrane. Sevoflurane can trigger malignant hyperthermia in susceptible swine.
Pharmacokinetics
ONSET OF ACTION: Loss of eyelid reflex (1.8 MAC sevoflurane plus 66% N2O): 1.6 minutes
PEAK EFFECT: dose dependent
DURATION OF ACTION: Emergence time (response to commands) after thiopental for induction and 66% nitrous oxide plus 0.9 MAC sevoflurane : 14.3 minutes.
Interactions
ventilatory and circulatory depressant effects decreased by nitrous oxide substitution; circulatory depressant effects potentiated by arterial hypoxemia, antihypertensives, beta adrenergic antagonists, calcium channel blockers; potentiates depolarizing and non depolarizing muscle relaxants; Minimum alveolar concentration (MAC) decreased by nitrous oxide, clonidine, lithium, ketamine, pancuronium, narcotic agonists, narcotic agonist-antagonist, physostigmine, neostigmine, sedative-hypnotics, chlorpromazine, verapamil, hypothermia, hyponatremia, hypo-osmolality, pregnancy, ?-9-Tetrahydrocannabinol; Minimum alveolar concentration (MAC) increased by MAO inhibitors, ephedrine, levodopa, chronic ethanol abuse, hypernatremia, hyperthermia, acute cocaine and acute amphetamine ingestion.
Guidelines
(1) Patients with stenotic lesions of the aortic or mitral valves poorly tolerate changes in blood pressure and systemic vascular resistance.
(2) The minimum alveolar concentration (MAC) is highest in the first 6 months of life and is slightly lower in neonates. Beyond adolescence, anesthetic requirements decrease with age so that an 80 year old patient should require only three-fourths the alveolar concentration for anesthesia required for a young adult
(3) Produces dose related depression of uterine contractility and tone, which can contribute to perioperative blood loss.
(4) Crosses the placental barrier and the degree of fetal and neonatal depression (hypotension, hypoxia, acidosis) is directly proportional to the depth and duration of maternal anesthesia.
(5) Changes in mental function may persist beyond the period of anesthetic administration and the immediate postoperative period. There may be altered psychomotor performance and driving skills.
(6) Contraindicated in patients with known or suspected genetic susceptibility to malignant hyperthermia.
(7) Abrupt onset of malignant hyperthermia may be triggered by sevoflurane. Early premonitory signs include muscle rigidity especially jaw muscles, tachycardia and tachypnea unresponsive to increased depth of anesthesia, evidence of increased oxygen consumption and carbon dioxide production, (change in color and increased temperature of the CO2 absorber), rising body temperature and metabolic acidosis.
Principal Adverse Reactions
CVS: hypotension, arrhythmias.
PULM: respiratory depression, apnea
CNS: dizziness, euphoria, increased cerebral blood flow and intracranial pressure
GI/HEPATIC: nausea, vomiting, ileus
GU: renal dysfunction
METABOLIC: malignant hyperthermia
Reactions
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NOTICE:
Every effort has been made to ensure that the drug dosage schedules
herein are accurate and in accord with the standards accepted
at the time of publication. As new research and experience broaden
our knowledge, changes in treatment and drug therapy occur. The
medications described do not necessarily have specific approval
by the Food and Drug Administration for use in the situations
and the dosages for which they are recommended. This information
is advisory only. The package insert should be consulted for use
and dosage as approved by the FDA, for any changes in indications
and dosages and for added warnings and precautions. The ultimate
responsibility lies with the prescribing physician.
No part of this information may be reproduced or transmitted electronically
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monitoring system without prior permission in writing from S.O.T.A.
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infusion calculations for any drug at any dose and at any concentration.
It may be obtained by calling S.O.T.A Technologies (800 9-MEDIC-9)
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COMPOUNDED
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Copyright 2000. Sota Omoigui, M.D. All rights reserved.
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