One drug, two stories
Dr FT Lee
PMH/YCH AED
History (Patient A)
8-1-05
02:12
F/49
Known case of CRHD with MVR FU GH
On Digoxin, Lasix, Acertil, Slow K.
Aldactone, Warfarin
Attempt suicide with her husband by
taking
Digoxin >100 tablets (0.25mg/tablet) &
Acertil > 60 tablets at around 01:00
(1 hour before arrival)
Vomit twice
P/E:
GCS: 14-15, refused to cooperate
BP: 152/49, P:49/min
RR:22/min, SaO2: 98% (Rm air)
Temp: 36°C
H’stix: 8.3
Management in AED
100%O2
Cardiac monitor
NS Q4H
CXR: cardiomegaly
Consult ICU
Standby pacing
Transfer to ICU at 02:30 (13 mins)
BP:166/70, P:30/min
Progress in ICU
Cardiac arrest at 02:50(38 mins)
Pulseless VT
Defibrillate 150J then 200J
Asystole
TCP given but no cardiac output
Certified dead after 1 hr of active
resuscitation



Adrenaline 1mg x 7
Atropine 0.6mg x2
NaHCO3 100ml
Digitalis antidote was ordered but only
available after prolonged resuscitation
RFT: Na: 131, K: 7.3, Urea: 7.4, Cr: 88
INR: 1.6
A sad story !!
History (Patient B)
M/58 (Husband)
Good past health
Attempt suicide with his wife by taking
Digoxin > 60 tabs, Acertil > 100 Tabs,
Warfarin > 100 tabs, Piriton> 60 Tabs
at 01:00
Vomit
P/E
GCS: 15
BP: 151/65, P: 93/min
RR: 16/min, Sa O2: 99% (Rm air)
Temp: 37°C
Management in AED
O2
NS Q4H
Cardiac Monitor
CXR: NAD
Activated charcoal 50g po
Consult ICU (Suggest admission to
Medical ward)
Progress
Transfer to ICU at 05:40
(BP: 160/80, P: 100/min)
RFT: Na: 135, K: 4.8, Urea: 7.2, Cr: 90
INR: 1.5
11:20 (10 hrs postingestion)
P: 35-40/min, BP: 140/60,
ECG: Complete Heart Block
Atropine 0.6mg iv
Transvenous pacing
11:25, 10 hrs postingestion
Digoxin Level
10.7 nmol/l (1.3-2.6)
13:45 (12 hrs postingestion)
Digitalis Fab 480mg(6 vials) was given
over ½ hour
20:40 (7 hrs after Fab)
Urticaria
Piriton 10mg iv
ECG: SR, 100/min
09-01-2005 (Day 2)
INR: 2.8
off pacing
Vit K1 10mg iv
Digoxin Level
Digitalis antidote
Time &
Date
05:40
8-1-05
11:25
8-1-05
12:17
12-1-05
11:28
17-1-05
Hours &
days
after
ingestion
5 hours
post
ingestion
10 hours
post
ingestion
4 days
post
ingestion
9 days
post
ingestion
Serum
Digoxin
level
13.4nmol/l
10.7 nmol/l
3.5 nmol/l
1 nmol/l
Progress
To general medical ward on D3
Claimed that he would commit suicide
again
Psychiatric assessment: Adjustment
disorder
Transfer to KCH by Vol form on D16
An happy ending !!
Acute Digoxin Overdose
Mechanism
Inhibition of
the Na-K-ATPase pump (70%)
Normal depolarization & repolarization
Depolarization
Na-K-ATPase
pump
Na & Ca
Ca
Toxic Digoxin effect
Elevate the resting potential
predispose to dysrhythmia
Toxic Digoxin effect
(Autonom & Anta Pharm, Vol 25(2) 35-52)
Rhythm disturbances
Increase automaticity particularly in the
Purkinje fibre
Impaired conduction through
the SA & AV node
(Heart 2000;83:301-306)
Extracardiac
Nausea, vomiting almost always
present
Confusion and delirium
Seizure (very rare)
Toxicokinetic
Toxic dose: >3mg in Adults
>1mg in Child
Large volume of distribution
(Vd: 5-10 l/kg)
Toxicokinetic
Two-compartment system
ka
Compartment 1
(Serum)
kel
k12
k21
Compartment 2
(Tissue)
Toxicokinetic
Peak effect occurs after a delay of 6-12
hours
Eliminated by kidney (60-80%)
Elimination half-life: 1.6 days
Hyperkalaemia
An accurate predictor of outcome
Pretreatment serum K(meq/l)
Mortality rate
<5
0%
5- 5.5
~50%
>5.5
100%
(Bismuth et al; J Toxicol Clin Toxicol 6: 153-162, 1973)
Digoxin Level
Tissue distribution completes in 6-12
hours
Not correlate accurately with severity of
intoxication
Other metabolic abnormalities must
take into consideration
Falsely elevated after Digibind
Management
ABC
Decontamination
Antidote
Management of dysrhythmia
Treatment of dysrhythmia
Bradydysrhythmias


Atropine
Caution with electrical pacing
 Trigger fatal arrhythmia or delay Fab
 Failed in 23% of patient
(vs 8% treated with Digibind)
 Iatrogenic accidents in 36%
vs 0% in Digibind (p<0.05)
(Taboulet et al; J Toxicol Clin Toxicol 31: 261-273, 1993)
Treatment of dysrhythmia
Tachydysrhythmia




Cardioversion may precipitate refractory VT,
VF or asystole
Start with very low energy (10-25J)
Pretreated with Lidocaine or Amiodarone
Digitalis Fab
GI decontamination
Orogastric larvage

increase vagal tone
Activated Charcoal
Multiple dose Activated Charcoal is
effective
(Silva et al; Lancet 2003;361:1935-38)
Treatment of Hyperkalaemia
K>5mmol/l is an absolute indication for
Digibind
(Elliot et al; Circulation 1990;81;1744-52)
Treatment of Hyperkalaemia
Insulin/glucose, NaHCO3
Ca must not be given except after
Digibind
Correction of hyperkalaemia does not
improve survival
(Bismuth et al; J Toxicol Clin Toxicol 6: 153-162, 1973)
Antidote
Digoxin Immune Fab
Digoxin Immune Fab
Produced in immunize sheep
Greater binding affinity for digoxin than
Na-K ATPase
Fab fragment-digoxin complex
eliminated through kidney
(T1/2: 15-20 hrs)
Pharmakokinetic
Creates a concentration gradient to
dissociate digoxin from the heart
Compartment 1
Compartment 2
Serum & Intersitial
free Digoxin
Digoxin at
Increase renal
clearance by 20-30%
Myocardial receptor
Effectiveness
Resolution of all signs/symptoms (80%)
Improvement (10%)
No response (10%)
Response within 1 hour (mean:19 mins)
and complete within 4 hours
(TW. Smith American J of Emerg Med, March 191:1-6)
Decrease mortality
Pretreatment
serum K
(meq/l)
Gaultier et al
(1978)
Mortality rate
Antman et al
(1990)
Mortality rate
<5
2%
3%
> 5 < 6.4
35%
25%
>6.4
90%
12.5%
(Antman et al; Circulation 1990;81;1744-52)
Improve survival rate in
digitalis-induced cardiac arrest
Gaultier et al
(1978)
Antman et al
(1990)
Experienced
cardiac arrest
9
56
Died
9
26
Mortality (%)
100
46
Patients number
(Gaultier et al La Rev d Practicien 1978; 28:4565-4579)
(Elliot et al; Circulation 1990;81;1744-52)
Indications
Rhythm & Conduction disturbances
Hyperkalaemia (>5mmol/l)
Digoxin ingestion >10mg
(>4mg in child)
Serum digoxin level
15ng/ml (19nmol/l) at any time
or >10ng/ml (13nmol/l) 6h postingestion
Factors affecting the efficacy
Time of administration
Dosage
Rate of administration
Dosage
Amount of ingestion and post
distribution Digoxin level is unknown
Amount of ingestion is known
Post distribution Digoxin level is known
Dosage
The brand of Digoxin Fab
Digitalis Antidote
(Roche)
Available in PMH
80mg/vial
Each vial binds 1 mg
digoxin
Digibind (Glaxo)
38mg/vial
Each vial binds
0.5mg digoxin
Amount ingested or post distribution level
is unknown
Digibind (38mg/vial)
Recommendations vary from 5-20 vials
10 vials for both adult or child
Administered ivi over 30 mins
Given as a bolus injection in cardiac
arrest
(Glaxo Wellcome)
Amount ingested is known
No. of vials
=
Total digitalis body load in mg
0.5mg of digoxin bound per vial
Mulitply amount ingested in mg by 0.8 if
Digoxin tablets involved
Dosage of Digibind
Tablets
ingested
0.125mg/tabs
5
Tablets
ingested
0.25mg/tabs
2.5
No of vials
10
5
2
20
10
4
50
25
10
100
50
20
1
Olson, Poisoning & Drug overdose 4th ediiton
Dosage
The brand of Digoxin Fab
Post distribution Digoxin level
nmol/l vs ng/ml
Postdistribution level is known
Calculations Based on Steady-State
Serum Digoxin Concentrations
No. of vials
=
serum digoxin level (nmol/l X 0.781) X body wt (kg)
100
Conversion factor
= Serum Digoxin Concentration (SDC) nmol/L x 0.78
= SDC ng/mL.
(Glaxo Wellcome)
Dosage
The brand of Digoxin Fab
Post distribution Digoxin level
Serum Digoxin level (nmol/l vs ng/ml)
Use the highest calculated dose
Adverse reaction
Allergy is rare

Skin test for patients with known sensitivity to
sheep products
Hypokalaemia
Withdrawal of digoxin effects


CHF
Atrial fibrillation or flutter
Digoxin levels are not meaningful

Falsely elevated
Bring home messages
Digoxin Fab is cost effective
Electrical therapy has to be used
cautiously
Serum K is a accurate prognostic
pointer
Hyperkalaemia is an indication for
Digoxin Fab
Thank you