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Sota
Omoigui's
Anesthesia Drug Handbook
3rd Edition:
:
Flumazenil
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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
diagnostic and therapeutic reversal of
benzodiazepine receptor agonists.
Dosing
IV bolus: Adults 0.2-1 mg (4-20 mcg/kg) at rate of 0.2 mg per minute. Titrate to patient response. May repeat at 20 min intervals. Max single dose of 1 mg. Max total dose of 3 mg in any one hour.
Children 0.01 mg/kg (up to 0.2 mg). Administer over 15 seconds. Dose may be repeated after 45 seconds and then at 60 seconds intervals where necessary (up to a max. of 4 additional times) to a max. dose of 0.05 mg/kg or 1 mg whichever is lower. Average dose: 0.65 mg
infusion: Adult: 30-60 mcg/min. Max. total dose of 3 mg in any one hour.
Children: 0.5-1 mcg/kg/min. Max. total dose of 1 mg in any one hour.
Intratracheal: Adult: 1.0 mg. Dilute dose in10 mls normal saline and inject via an Endotracheal tube.
Lack of patient response at 5 minutes after cumulative dose above 5 mg implies that the major cause of sedation is unlikely to be due to benzodiazepines.
Elimination
hepatic
How supplied
Injection: 0.1 mg/ml
Storage
Room temperature (15-30 degrees Celsius).
DILUTION FOR INFUSION: IV: 3 mg in 50 mls D5W or NS (60 mcg/ml)
Pharmacology
Flumazenil is a benzodiazepine receptor antagonist with little or no agonist activity. It competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex in the central nervous system. It reverses sedation, respiratory depression, amnesia and psychomotor effects of benzodiazepines (e.g. midazolam, diazepam, flurazepam, lorazepam). Hypoventilation may not be fully reversed. Doses and plasma levels required to reverse each agonist depends on the particular benzodiazepine and the residual plasma level e.g. higher doses are required to reverse lorazepam than diazepam (a less potent benzodiazepine). The administration of flumazenil to patients given agonists is remarkably free of cardiovascular effects unlike opioid reversal with naloxone. Resedation may occur and is more common with larger doses of benzodiazepine (>20 mg of midazolam), long procedures (>60 minutes) and use of neuromuscular blocking agents. Flumazenil does not affect the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids. Flumazenil has no direct effects on cerebral blood flow, but may reverse the cerebral blood flow (CBF), cerebral metabolic rate (CMRO2) and intracranial pressure (ICP) lowering effects of midazolam. Flumazenil produces withdrawal symptoms (seizures, emergent confusion and agitation) in the presence of physical dependence.
Pharmacokinetics
ONSET OF ACTION: 1-2 minutes
PEAK EFFECT: 2-10 minutes
DURATION OF ACTION: 45-90 minutes ( variable depends on benzodiazepine plasma concentration)
Interactions
reversal of sedation; precipitation of benzodiazepine withdrawal (agitation, seizures, cardiac arrhythmias); increased risk of seizures in patients with concurrent tricyclic antidepressant poisoning; may provoke panic attacks in patients with a history of panic disorders.
Guidelines
(1) The reversal of benzodiazepine effects may be associated with the onset of seizures in certain high risk populations. Possible risk factors include: concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to flumazenil administration in overdose cases, or concurrent tricyclic antidepressant poisoning
(2) Flumazenil is not recommended in cases of serious tricyclic antidepressant poisoning. Such patients should be allowed to remain sedated (with ventilatory and circulatory support as needed) until the signs of antidepressant toxicity have subsided.
(3) Treat convulsions associated with flumazenil administration with benzodiazepines, phenytoin or barbiturates. Because of the presence of flumazenil, higher than usual doses of benzodiazepines may be required.
(4) Patients who have responded to flumazenil should be carefully monitored (up to 120 minutes) for resedation, respiratory depression, or other residual benzodiazepine effects since the duration of action of the benzodiazepine may exceed that of flumazenil. Overdose cases should always be monitored until the patients are stable and resedation is unlikely. The availability of flumazenil does not decrease the need for prompt detection of hypoventilation and the ability to effectively intervene by establishing an airway or assisting ventilation.
(5) Necessary measures should be instituted to secure airway, ventilation and intravenous access prior to administering flumazenil. Upon arousal patients may attempt to withdraw endotracheal tubes and/or intravenous lines as the result of confusion and agitation following awakening.
(6) Do not use flumazenil until the effects of neuromuscular blockade have been fully reversed.
(7) To minimize pain and inflammation at the injection site, administer flumazenil in a large vein. Local irritation may occur following extravasation.
(8) Flumazenil should be administered in a series of small injections described above (not as a single bolus injection) in order to control the reversal of sedation to the approximate endpoint desired and to minimize the possibility of adverse effects.
(9) The safety and efficacy of flumazenil in the reversal of conscious sedation in pediatric patients below the age of 1 year has not been established.
Principal Adverse Reactions
CVS: arrhythmias (atrial, nodal, ventricular extrasystoles), tachycardia, bradycardia, hypertension, angina, flushing.
CNS: reversal of sedation, seizures, agitation, emotional lability
GI: nausea, vomiting
OTHER: pain at injection site, thrombophlebitis, rash, shivering.
Reactions
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Toll-Free: (800) 9-MEDIC-9, Phone: (310) 675-9121,
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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
in any information storage or retrieval system, or within any
monitoring system without prior permission in writing from S.O.T.A.
Technologies (Electronic Publishers).
The Universal Drug Infusion Slide Ruler (patent pending) is now
available. It incorporates an infusion data guide and enables
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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