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Administration of amiodarone during resuscitation of ventricular arrhythmias
Authors: Heather D. Eppert, PharmD, BCPS, and Kara B. Goddard, BS, Maryville and Knoxville, TN
the treatment of ventricular arrhythmias. Early
dose. In the typical medical setting, the preferred standard
studies evaluating amiodarone for the management
of practice is to prepare an infusion of amiodarone diluted
of ventricular arrhythmias demonstrated the efficacy of amio-
in 5% dextrose in water placed in a polyolefin bag, admi-
darone in patients who were refractory to treatment with
nistered through an in-line filter via a central vein or large
multiple antiarrhythmic drugs.1-13 More recently, 2 major
peripheral vein.However, in the setting of cardiac emer-
trials, published in 1999 and 2002, described the efficacy
gency, administration by prolonged infusion is not desir-
of amiodarone as a primary treatment modality in the treat-
able. The vast differences in the recommendations for
ment of ventricular arrhythmias compared with another
administration of amiodarone in this setting have raised
antiarrhythmic drug, lidocaine, and placebo.14,15 As a
significant questions in the medical community.
result of this literature, the American Heart AssociationAdvanced Cardiac Life Support (ACLS) guidelines recom-
Amiodarone: A Complex Antiarrhythmic Drug
mend amiodarone as the antiarrhythmic of choice in theresuscitation of patients with ventricular arrhythmias.
Amiodarone is a Vaughn Williams class III antiarrhythmic
The use of amiodarone for the emergent treatment of
drug. It has a complex mechanism of action, with mecha-
ventricular arrhythmias, including ventricular tachycardia
nistic properties that include action at α- and β-adrenergic
and ventricular fibrillation, has steadily increased in recent
receptors, as well as action on the potassium, sodium, and
years. This increased use is a result of emerging literature
calcium channels in the In general, the beneficial
relating to the efficacy of amiodarone, combined with the
effects of amiodarone are due to its ability to prolong the
updated ACLS treatment guidelines available from the
cardiac action potential and refractory period. The efficacy
American Heart AIn the setting of cardiac
of amiodarone in the treatment of ventricular arrhythmias
emergency (eg, ventricular tachycardia with a palpable
is thought to be due to suppression of premature ventricular
pulse), the recommended dose of intravenous amiodarone
depolarization and the occurrence of further arrhythmias.
is 150 mg. In cardiac arrest (eg, ventricular fibrillation),the recommended dose of amiodarone is 300 mg adminis-
Amiodarone: Administration and Adverse Events
tered intravenously, followed by a subsequent dose of 150mg as needed for sustained arrhythmia. In the 2005 Amer-
In the clinical trials that have evaluated the use of amiodarone
ican Heart Association guidelines, the recommendation for
for the treatment of ventricular arrhythmias, there has beena wide range of variability in the dose, rate of administra-tion, and dilution of amiodarone.1-14,18,19 The range of
Heather D. Eppert is Clinical Specialist, Emergency Medicine, Blount Me-
amiodarone doses reported has ranged from 18.75 mg to
morial Hospital, Department of Pharmacy, Maryville, TN, and Assistant
600 mg. Similarly, the rate of administration has varied
Professor, University of Tennessee College of Pharmacy, Department of Clin-
widely, from rapid intravenous administration to infusion of
up to 30 minutes. Based on all of the available literature to
Kara B. Goddard is Doctor of Pharmacy Candidate, 4th Professional Year,
date, only 3 studies have reported rapid intravenous infusion
University of Tennessee College of Pharmacy, Knoxville, TN.
of amiodarone.14,15,18 Each of these 3 protocols varied in the
For correspondence, write: Heather D. Eppert, PharmD, BCPS, 1924 Alcoa
dilution of amiodarone, ranging from undiluted solution to
Highway, Box 117, Knoxville, TN 37920; E-mail:
dilution in either 20 or 30 mL of 5% dextrose in water.
Concerns have been raised regarding the rapid adminis-
Available online 25 June 2009.
tration of intravenous amiodarone. This concern results fromreports of numerous adverse events associated with the admin-
Copyright 2010 Emergency Nurses Association. Published by Elsevier Inc.
All rights reserved.
istration of amiodarone, the most notable of these adverse
events being hypotension, bradycardia, and phlebitiIn
clinical studies reported to date, the incidence of these adverse
be administered in a central vein; if central venous access
events has been highly variable, with the incidence of hypo-
is not available, administration should occur through the
tension ranging from 7% to 59%, bradycardia ranging from
0% to 41%, and phlebitis ranging from 0% to 27%.1-15,18,19However, an in-depth evaluation of the clinical studies that
have evaluated the use of amiodarone for the treatment of
Recent literature has found amiodarone to be the anti-
ventricular arrhythmias reveals that the incidence of adverse
arrhythmic of choice in the resuscitation of cardiac emer-
events from administration of amiodarone appears to be rela-
gencies due to ventricular arrhythmias. As a result, the use
tively varied, regardless of the rate of administration or dilu-
of intravenous amiodarone has steadily increased. How-
ever, amiodarone has been associated with multiple adverse
It is difficult to define the occurrence of adverse drug
events, raising concerns regarding the appropriate adminis-
events in resuscitation trials and even more difficult to deter-
tration of amiodarone in this setting. When administrating
mine an association of adverse events with a specific drug
intravenous amiodarone, the need for rapid administration,
therapy. For example, several clinical studies resorted to
the risk for adverse events, and the clinical condition of the
the definition of hypotension in the clinical trial as the need
patient must be considered. In the case of life-threatening
for vasopressor therapy (eg, dopamine) after the resuscita-
ventricular arrhythmias, rapid achievement of therapeutic
tion.1-11,14 This definition is tenuous, because vasopressor
drug concentrations and the suppression of further arrhyth-
supportive therapy of blood pressure is commonly required
mia is a high priority. Therefore, in the setting of cardiac
in post-cardiac arrest victims.The protective effect of
emergency (eg, hemodynamic instability with a palpable
simultaneous administration of potent vasoconstrictive drugs
pulse), a recommended dose of intravenous amiodarone,
commonly used during resuscitation, such as epinephrine or
150 mg administered over 10 minutes with continuous car-
dopamine, against the development of hypotension and bra-
diac monitoring, is appropriate. In the setting of cardiac
dycardia in this setting has been debated.3,15,18 Therefore, it
arrest (eg, ventricular fibrillation), rapid intravenous
would be difficult to deduce whether the hypotension, bra-
administration of amiodarone, 300 mg, is reasonable. This
dycardia, or proarrhythmia observed in the clinical trials of
method of administration can be accomplished in 1 of
amiodarone during cardiac arrest are in fact due to the pri-
2 ways: either via direct injection of the undiluted drug,
mary cause of the arrest (eg, myocardial infarction), the loss
followed by a minimum of 10-mL flush, or by minimally
of cardiac output during the arrest, or as the result of an
diluting each of two 150-mg doses within two 10-mL
adverse effect from amiodarone therapy.
0.9% sodium chloride–filled syringes.
Recommendations for Amiodarone Administration
Based on the results of recent research, amiodarone is the
Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of
intravenous antiarrhythmic drug of choice for the resuscita-
intravenous amiodarone in patients with life-threatening ventricular
tion of patients with ventricular arrhythmias.Amiodarone
tachyarrhythmias. Circulation. 1995;92:3264-72.
is commercially available as a 150-mg, 3-mL vial.In the
Levine JH, Massumi A, Scheinman MM, et al. Intravenous amiodarone
urgent treatment setting (eg, ventricular tachycardia with
for recurrent sustained hypotensive ventricular tachyarrhythmias. J Am
palpable pulses), a loading dose of amiodarone, 150 mg,
is preferably administered in 100 mL of 5% dextrose in
Helmy I, Herre JM, Gee G, et al. Use of intravenous amiodarone foremergency treatment of life-threatening ventricular arrhythmias. J Am Coll
water over 10 minutes, as per the manufacturer’s recom-
mendations.In the setting of cardiac arrest, some refer-
Morady F, Scheinman MM, Shen E, Shapiro W, Sung RJ, DiCarlo L.
ences have recommended rapid administration of undiluted
Intravenous amiodarone in the acute treatment of recurrent sympto-
amiodarone, followed immediately by a 10-mL flush with
matic ventricular tachycardia. Am J Cardiol. 1983;51:156-9.
either 5% dextrose in water or 0.9% normal saline solu-
Mostow ND, Rakita L, Vrobel TR, et al. Amiodarone: intravenous load-
tion.18,20 Anecdotally, one practical method for rapid admin-
ing for rapid suppression of complex ventricular arrhythmias. J Am Coll
istration of amiodarone during cardiac arrest (eg, ventricular
fibrillation) is to withdraw the contents of one 150-mg vial
Leak D. Intravenous amiodarone in the treatment of refractory life-threatening cardiac arrhythmias in the critically ill patient. Am Heart
into each of two 10-mL syringes filled with 0.9% sodium
chloride. These 2 syringes, for a total of 300 mg, could
Klein RC, Machell C, Rushforth N, Standefur J. Efficacy of intravenous
be administered via rapid intravenous infusion in the set-
amiodarone as short-term treatment for refractory ventricular tachycar-
ting of cardiac emergency. Amiodarone should preferably
Schutzenberger W, Leisch F, Kerschner K, et al. Clinical efficacy of in-
14. Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A. Amio-
travenous amiodarone in the short term treatment of recurrent sustained
darone as compared with lidocaine for shock-resistant ventricular fibrilla-
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tion. N Engl J Med. 2002;346:884-90.
15. Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resusci-
Williams ML, Woelfel A, Cascio W, et al. Intravenous amiodarone dur-
tation after out-of-hospital cardiac arrest due to ventricular fibrillation.
ing prolonged resuscitation from cardiac arrest. Ann Intern Med.
16. Emergency Cardiovascular Care Committee, Subcommittees, and Task
10. Ochi RP, Goldenberg IF, Almquist A, et al. Intravenous amiodarone for
Forces of the American Heart Association. 2005 Guidelines for cardiopul-
the rapid treatment of life-threatening ventricular arrhythmias in criti-
monary resuscitation and emergency cardiovascular care. Circulation.
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phia, PA: Wyeth-Ayerst Company; 2001.
high-dose intravenous amiodarone for recurrent, refractory ventricular
18. Skrifvars MB, Kuisma M, Boyd J, et al. The use of undiluted amiodar-
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12. Nalos PC, Ismail Y, Pappas JM, et al. Intravenous amiodarone for short-
term treatment of refractory ventricular tachycardia or fibrillation. Am
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13. Kowey PR, Levine JG, Herre JM, et al. Randomized, double-blind
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CV Dr. Giovanni Blandino, M.D., MSc - Page 2 Dr. Giovanni Blandino, M.D., M.Sc. Personal Information Languages: Italian, English Married: Two children Home Address: Via Apuania 31, 00162 Rome : +39 (06) 4420 2177 +39-339-6825451 Office Address: Translational Oncogenomics Unit Italian National Cancer Institute, Rome “Regina Elena” Via Elio Chianesi 53 00144-Rome Italy : +39