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Sota
Omoigui's
Anesthesia Drug Handbook
3rd Edition:
:
Enflurane
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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 anesthesia
Elimination
pulmonary, hepatic, renal
How supplied
Volatile liquid 125 mls, 250 mls
Storage
Room temperature (15-30 degrees Celsius).
Pharmacology
Enflurane is a nonflammable fluorinated ethyl methyl ether. It has a vapor pressure of approximately 175 mm Hg at 20 degrees Celsius and boils at 56.5 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 1.7% atm and in 70% nitrous oxide of 0.65% atm. The blood/gas partition coefficient at 37 degrees Celsius is 1.91. This intermediate solubility in blood combined with a high potency means a rapid induction of anesthesia. After 30 minutes of administration, the ratios of alveolar concentrations to the inspired concentration is 0.65 compared with 0.99 for nitrous oxide and 0.73 for isoflurane. The intermediate tissue solubility of enflurane (fat/blood partition coefficient, 36.0) 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 0.24 compared with 0.22 for isoflurane. Enflurane is slowly metabolized by the hepatic mixed function oxidase system. Biotransformation releases fluoride ions by oxidative dehalogenation. Peak plasma fluoride concentrations following a 2.5 MAC hour exposure to enflurane are about 20 µMol/L,, which is approximately one-third the level considered to be potentially nephrotoxic. Enflurane is resistant to degradation by soda lime and thus can be used in low flow or closed systems anesthesia. Like isoflurane, enflurane 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. Enflurane inhibits the hypoxic pulmonary vasoconstrictor response (HPV) in a dose related manner. It has little or no effect on pulmonary vascular smooth muscle. Enflurane produces dose-dependent reductions of arterial blood pressure in part or whole, a consequence of decreases in myocardial contractility and cardiac output. It produces dose-dependent elevations in heart rate. Enflurane attenuates baroreceptor reflex responses (tachycardia) to hypotension and vasomotor reflex responses (increased peripheral resistance) to hypovolemia. Like isoflurane, enflurane does not sensitize the heart to catecholamines. In one study, the dose of submucosally injected epinephrine necessary to produce ventricular cardiac arrhythmias in 50% of patients anesthetized with a 1.25 MAC concentration of enflurane was 10.9 mcg/kg, compared with 1.5 mcg/kg for halothane and 6.5 mcg/kg for isoflurane. Unlike isoflurane, enflurane does not cause coronary artery vasodilation that may lead to coronary artery steal syndrome. Decrease in cerebral metabolic rate is closely linked to cerebral electrical activity. Increased anesthetic concentrations decrease EEG wave frequency and increases voltage. Electrical silence does not occur but a high voltage repetitive-spiking activity may be produced. This activity may be attenuated or abolished by decreasing the enflurane dose or increasing the arterial carbon dioxide partial pressure (PaCO2 >30 mm Hg). Enflurane does not enhance pre-existing epileptic foci with the possible exceptions being certain types of myoclonic epilepsy and photosensitive epilepsy. Enflurane compared with isoflurane or halothane produces the greatest dose-related decrease in the amplitude and increase in the latency of cortical components of somatosensory-evoked potentials. The latencies of certain peaks of brain stem auditory evoked potentials may be increased. Cerebral vasodilation produced by enflurane causes an increase in cerebral blood flow and cerebral blood volume. Elevation of intracranial pressure parallels increase in cerebral blood flow. Unlike isoflurane or halothane, hyperventilation does not attenuate such increase but on the contrary increases the risk of seizure activity, which could lead to an elevation in cerebral metabolic oxygen requirements, carbon dioxide production, increased cerebral blood flow and increased intracranial pressure. Enflurane increases both the rate of production and resistance to reabsorption of cerebrospinal fluid,, which may contribute to sustained increases in intracranial pressure associated with administration of this drug. Enflurane produces uterine vasodilation and dose dependent decrease in uterine blood flow. Enflurane has a direct muscle relaxant effect and potentiation of neuromuscular blocking drugs may involve desensitization of the postjunctional membrane. Enflurane, potentiates muscle relaxants to a similar extent as isoflurane or desflurane and a greater extent than halothane or nitrous oxide. Enflurane can trigger malignant hyperthermia in susceptible swine.
Pharmacokinetics
ONSET OF ACTION: Loss of eyelid reflex (2.4 MAC enflurane plus 66% N2O): 2.9 minutes
PEAK EFFECT: Surgical anesthesia: 2% to 4.5% produces anesthesia in 7-10 minutes
DURATION OF ACTION: Emergence time (response to commands) after thiopental for induction and 66% nitrous oxide plus 0.9 MAC enflurane : 15.1 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; decreases pulmonary extraction and increases serum levels of propofol, norepinephrine; 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. However the uterine response to oxytocic drugs is blocked only at high concentrations (> 1.0%)
(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 seizure disorders and known or suspected genetic susceptibility to malignant hyperthermia.
(7) Abrupt onset of malignant hyperthermia may be triggered by enflurane. 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: seizures, dizziness, euphoria, increased cerebral blood flow and intracranial pressure
GI: nausea, vomiting, hepatic dysfunction
GU: renal dysfunction, renal failure
MUSCULOSKELETAL: motor activity of various muscle groups
METABOLIC: malignant hyperthermia, glucose elevation
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.
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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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