AMIODARONE OR DIGOXIN

UNIT FARMASI KLINIKAL (UFK),
HUSM.
ATRIAL FIBRILLATION IN
CRITICAL CARE –
AMIODARONE
OR DIGOXIN ?
PRECEPTOR:
PN KHAIRUL BARIAH
KHOR KAH LOONG HUSM PRP 2011/12

Presentation Outline
Objectives
Introduction
Discussion
Conclusion
Reference

OBJECTIVES

OBJECTIVES
To present on management of atrial fibrillation in
critical care
To discuss on the comparison between Digoxin and
Amiodarone in management of acute atrial
fibrillation.

INTRODUCTION
DEFINTION
CLASSIFICATION
MANAGEMENT

DEFINITION 1,2
Supraventricular tachyarrhythmia
Uncoordinated atrial activation
Atrial
Rapid
Irregular
Chaotic
Deterioration in atrial mechanical function
Irregular-rapid ventricular response
Irregularly-irregular

CLASSIFICATION 1 (1)
First Detected
(One-Diagnosed Episode)
Paroxymal
(< 7days)
Persistent
(> 7days)
Permanent
(>1 year)

CLASSIFICATION 1 (2)
Lone AF
No clinical or echocardiographic evidence of
cardiopulmonary disease (including HPT)
Young patient (

CLASSIFICATION 2,3 (3)
CLASS ACTIONS DRUGS CAUTIONS
IA
IB
IC
Na + channel inhibition:
prolong repolarization
Na + channel inhibition:
shorten repolarization
Na + channel inhibition: no
effect on repolarization but
reduce conductivity
Quinidine, procainamide,
disopyramide
Lidocaine
Flecainide, propafenone
II β-Adrenergic inhibition Timolol, esmolol, atenolol,
bisoprolol
III
K + channel inhibition: prolong
repolarization
Vaughan-Williams Classification
Amiodarone, sotalol*
History of myocardial infarction,
congestive heart failure, renal
disease
Proarrhythmias
Structural heart disease, history of
myocardial infarction, congestive
heart failure
Acute heart failure, bronchospasm
Renal disease, pulmonary disease
IV Ca 2+ channel inhibition Verapamil, diltiazem Not in conjunction with β-blockers
Misc
Na-K ATPase inhibition:
parasympathetic response
Digoxin
Renal disease, hypokalemia

CLASSIFICATION (4)
Critical Care ?
Acute Atrial Fibrillation
Onset < 48 h
Includes:
• Paroxysmal AF
• First symptomatic presentation of Persistent AF

MANAGEMENT 1,2 (1)
3 Objectives:
Rate control
Prevention of Thromboembolism
Correction of the rhythm disturbance
Rate control ? Rhythm control ?

RHYTHM CONTROL 1
Conversion to NSR either by electrical (DCC) or
pharmacological (AAD) cardioversion.
Haemodynamically unstable: Electrical
Haemodynamically stable: Either
Electrical conversion
Preferred: greater efficacy (85% vs 45%) and low
proarrhythmic risk.
But required generalized anaethesia

RATE CONTROL 1
Slowing AV conduction
Slow ventricular response rate → better
ventricular filling with blood.
If intolerable to S/E of rate-control agent
Combining lower-dose digoxin + B-blockers/CCBs
Amiodarone effective for patient who are not
cardioverted to NSR.
Good control:
Rest: 60-80 bpm,
Moderate: 90-115 bpm

MANAGEMENT 2 (2)

MANAGEMENT 2 (3)
Haemodynamically Instability
Ventricular rates > 150
Ongoing chest pain
Evidence of critical perfusion
• Systolic BP < 90 mm Hg
• Heart failure
• Reduced consciousness
To anticoagulate prior conversion if high risk
Heparin

MANAGEMENT 2 (4)

MANAGEMENT 2 (5)

MANAGEMENT 1,2 (6)
Focus:
Symptom relief
Prevention of complications
Pharmacotherapy
Rate Control
• Class II, Class IV, Digoxin
Rhythm Control
• Class I, Class III, Amiodarone
Anticoagulation

MANAGEMENT 2 (7)

RATE CONTROL AGENT 1
Drug
Esmolol
(II)
Metoprolol
(II)
Propranolol
(II)
Diltiazem
(IV)
Verapamil
(IV)
Recommendation
/ LOE
I / C
I / C
LD Onset MD Major S/E
500 mcg/kg IV
over 1 min
2.5 to 5 mg IV
bolus over 2 min;
up to 3 doses
5 mins 60 to 200
mcg/kg/min IV
↓BP, HB, ↓HR,
asthma, HF
5 mins - ↓BP, HB, ↓HR,
asthma, HF
I / C 0.15 mg/kg IV 5 mins - ↓BP, HB, ↓HR,
asthma, HF
I / B
Rate Control (No accessory pathway)
0.25 mg/kg IV
over 2 min
I / B 0.075 to 0.15
mg/kg IV over 2
min
2-7
mins
3-5
mins
5 to 15 mg/h
IVI
↓BP, HB, HF
- ↓BP, HB, HF

Drug
Digoxin
(Misc)
RATE CONTROL AGENT 1
Rate Control in HEART FAILURE (No accessory pathway)
Recommendation
/ LOE
I / B
LD Onset MD Major S/E
0.25 mg
IV each 2
h, up to
1.5 mg
Amiodarone IIa / C 150 mg
over 10
min
60
mins or
more
0.125 to
0.375 mg
daily IV
or orally
Days 0.5 to 1
mg/min IV
Digitalis toxicity, HB, ↓HR
↓BP, HB, pulmonary toxicity,
skin discoloration,
hypothyroidism,
hyperthyroidism, corneal
deposits, optic neuropathy,
warfarin interaction, sinus
bradycardia

Drug
RATE CONTROL AGENT 1
Recommendation
/ LOE
Amiodarone IIa / C 150 mg
over 10
min
Rate Control (With accessory pathway)
LD Onset MD Major S/E
Days 0.5 to 1
mg/min
IV
↓BP, HB, pulmonary toxicity, skin
discoloration, hypothyroidism,
hyperthyroidism, corneal deposits,
optic neuropathy, warfarin
interaction, sinus bradycardia
*Intravenous administration of drugs such as digitalis, verapamil, or diltiazem, which
lengthen refractoriness and slow conduction across the AV node, does not block conduction
over the accessory pathway and may accelerate the ventricular rate. Hence
CONTRAINDICATED in AF with accessory pathway. Caution in B-Blockers*

RHYTHM CONTROL AGENT 1,2
Drug Recomm’ /
LOE
Flecainide
(Ic)
Propafenone
(Ic)
Amiodarone
(III)
Sotalol
(III)
Conversion Dose Onset MD Comments
I / A IV 2mg/kg OR 200
mg orally, repeat
after 3–4 h
I / A IV 2mg/kg OR 600
mg orally
IIa / A
Not recomm’
COMMON PHARMACOLOGIC Rhythm Conversion
6 mg/kg bolus over
30–60 min, then
1,200 mg IV over 24
h
5–10 mg slowly IV,
may be repeated
50–150 mg
bid
150–300 mg
bid
600 mg/d x
1/52, follow
by 400 mg/d
x 1/52, then
200 mg daily
120–160 mg
bid
Only for without
structural heart
disease
Only for without
structural heart
disease
Moderately
effective, slow
onset, good HR
control;
hypotension
(bolus dose)
Slow Conversion
rate; High
proarrhythmia

SR MAINTAINENCE AGENT 1

MANAGEMENT 2 (8)
HEPARIN
LMWH
HEPARIN-
WARFARIN

MANAGEMENT 1 (9)
Anticoagulation
In emergency electric conversion (48h):
LD Heparin followed by continuous infusion to keep 1.5-
2 x control.
Follow by warfarin for at least 3-4weeks to maintain
INR of 2-3.
In elective conversion:
For AF >48hr & haemodynamically stable,
anticoagulate for at least 3-4 weeks before & after
conversion
Transoesophageal echocardiography (TEE)
performed prior to exclude left atrial appendage
clot (↑risk of stroke).

DISCUSSION
AMIODARONE OR DIGOXIN ?

AMIODARONE 3 (1)
Benzofuran derivative
Class III AAD
IV / Oral
MOA
Potassium channel inhibition
• Prolongation of the myocardial cell-action potential duration
and refractory period
• All cardiac tissues
Noncompetitive α- and β-adrenergic inhibition

AMIODARONE (2)
Study
Peuhkurinen
4
et al
Year Design AF
Onset
2000 RCT,
p=62
Comparison/Subject Result / Conclusion

AMIODARONE (3)
Study
Chevaliar 7
et al
Year Design AF
Onset
2003 Metaanalysis
13 RCT
Comparison/Subject Result / Conclusion
- 1. Amiodarone vs
Placebo
2. Amiodarone vs
Class Ic AAD
1) 24h = RR 1.44, p

DIGOXIN 8 (1)
Digitalis glycosides
Indications:
Atrial Fibrillation
• Ventricular rate control
Heart Failure
MOA
• LV Ejection Fraction
• Improve symptoms, reduced hospitalisation
Na-K ATPase inhibitor
Vagomimetic effect – HR & AV conduction
Sympathetic activity – baroreceptor sensitization

DIGOXIN (2)
Study Year Design AF
Onset
Falk 9 et al
Jordaens 10
et al
1987 RCT
p=36
1997 DB-RCT
p=40
Comparison/
Subject

AMIODARONE VS DIGOXIN (1)
Study
Year Design AF
Onset
Hou 12 et al 1995 R-
control
study
p=50
Comparison/
Subject

AMIODARONE VS DIGOXIN (2)
Study Year Design AF
Onset
Joseph 1
3
et al
2000 Prospective
RCT,
p=120
Comparison/
Subject

AMIODARONE VS DIGOXIN (3)
Study Year Design AF
Onset
Thomas
14
et al
2004 R-Digoxin
controlled
trial.
p=140
Comparison/
Subject
- Amiodarone
(10mg/kg in
30mins)
or
Sotalol
(1.5mg/kg in
10mins)
vs
Digoxin
(500ug in
20mins)
(placebo)
Result / Conclusion
Similar rates of pharmocological conversion to
sinus rhythm
51% vs 44% vs 50%, p=not significant
“The overall rates of cardioversion after trial
drug infusion and defibrillation were high for all
groups (amiodarone, 94%; sotalol, 95%,;
digoxin, 98%; P = not significant), but there was
a trend toward a higher incidence of serious
adverse reactions in the amiodarone group.”

AMIODARONE VS DIGOXIN (4)
Study Year Design AF
Onset
Hofmann
15
et al
2006 R-Digoxin
controlled
trial.
p=140
Comparison/
Subject
- IV bolus
amiodarone
vs IV bolus
digoxin
Result / Conclusion
Baseline HR = 144 ± 19 vs 145 ± 15
30mins = 104 ± 25 vs 116 ± 23 (p=0.02)
60mins = 94 ± 22 vs 105 ± 22 (p=0.03)
Better HR reduction
SR conversion:
30mins = 28% vs 6% (p=0.003)
60mins = 42% vs 18% (p=0.012)
Amiodarone S/E:
Asymptomatic hypotension (p=4), Superficial
phlebitis (p=1)
“Amiodarone, given as an intravenous bolus is
relatively safe and more effective than
digoxin for heart rate control and conversion
to sinus rhythm in patients with atrial
fibrillation and a rapid ventricular rate.”

CONCLUSION

CONCLUSION
Based on current evidence, amiodarone appears to
be more effective and fast in terms of SR
restoration in comparison with digoxin.
Important in critical care setting
Digoxin is not recommended for SR conversion
Amiodarone also effective in rate control when
other agent fails or contraindicated.
However, amiodarone associated with various
adverse effect
Close monitoring and precaution is needed

REFERENCES

REFERENCES
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