1. One drug, two stories
Dr FT Lee
PMH/YCH AED

2. History (Patient A) 8-1-05 02:12 F/49
:12
F/49
Known case of CRHD with MVR FU GH
On Digoxin, Lasix, Acertil, Slow K. Aldactone, Warfarin

3. 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

4. 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

6. 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

7. 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

8. Digitalis antidote was ordered but only available after prolonged resuscitation
RFT: Na: 131, K: 7.3, Urea: 7.4, Cr: 88
INR: 1.6

9. A sad story !!

10. 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

11. P/E GCS: 15 BP: 151/65, P: 93/min RR: 16/min, Sa O2: 99% (Rm air)
Temp: 37°C

13. Management in AED O2 NS Q4H Cardiac Monitor CXR: NAD
Activated charcoal 50g po
Consult ICU (Suggest admission to Medical ward)

14. 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

15. 11:25, 10 hrs postingestion
Digoxin Level
10.7 nmol/l ( )
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

16. (Day 2)
INR: 2.8
off pacing
Vit K1 10mg iv

17. Hours & days after ingestion
Digoxin Level
Digitalis antidote
Time & Date
05:40
8-1-05
11:25
12:17
11:28
Hours & days after ingestion
5 hours
post ingestion
10 hours
4 days
9 days
Serum Digoxin level
13.4nmol/l
10.7 nmol/l
3.5 nmol/l
1 nmol/l

18. 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

19. An happy ending !!

20. Acute Digoxin Overdose

21. the Na-K-ATPase pump (70%)
Mechanism
Inhibition of
the Na-K-ATPase pump (70%)

22. Normal depolarization & repolarization
Na-K-ATPase pump
Na & Ca Ca

23. Toxic Digoxin effect
Elevate the resting potential predispose to dysrhythmia

24. Toxic Digoxin effect
(Autonom & Anta Pharm, Vol 25(2) 35-52)

25. Rhythm disturbances
Increase automaticity particularly in the Purkinje fibre
Impaired conduction through
the SA & AV node

26. (Heart 2000;83: )

27. Extracardiac Nausea, vomiting almost always present
Confusion and delirium
Seizure (very rare)

28. Toxicokinetic Toxic dose: >3mg in Adults >1mg in Child
Large volume of distribution
(Vd: 5-10 l/kg)

29. Toxicokinetic Two-compartment system ka k12 Compartment 1
(Serum)
Compartment 2
(Tissue)
k21
kel

30. Toxicokinetic Peak effect occurs after a delay of 6-12 hours
Eliminated by kidney (60-80%)
Elimination half-life: 1.6 days

31. Pretreatment serum K(meq/l)
Hyperkalaemia
An accurate predictor of outcome
(Bismuth et al; J Toxicol Clin Toxicol 6: , 1973)
Pretreatment serum K(meq/l)
Mortality rate
<5 0%
5- 5.5
~50%
>5.5
100%

32. 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

33. Management
ABC
Decontamination
Antidote

34. Management of dysrhythmia

35. 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: , 1993)

36. 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

37. GI decontamination Orogastric larvage Activated Charcoal
increase vagal tone
Activated Charcoal
Multiple dose Activated Charcoal is effective
(Silva et al; Lancet 2003;361: )

38. Treatment of Hyperkalaemia
K>5mmol/l is an absolute indication for Digibind
(Elliot et al; Circulation 1990;81; )

39. 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: , 1973)

40. Antidote Digoxin Immune Fab

41. 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: hrs)

42. Serum & Intersitial free Digoxin
Pharmakokinetic
Creates a concentration gradient to dissociate digoxin from the heart
Compartment 2
Digoxin at
Myocardial receptor
Compartment 1
Serum & Intersitial free Digoxin
Increase renal clearance by 20-30%

43. 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)

44. Decrease mortality Pretreatment serum K (meq/l) Gaultier et al (1978)
Mortality rate
Antman et al
(1990)
<5 2% 3%
> 5 < 6.4
35%
25%
>6.4
90%
12.5%
(Antman et al; Circulation 1990;81; )

45. Improve survival rate in digitalis-induced cardiac arrest
(Gaultier et al La Rev d Practicien 1978; 28: )
(Elliot et al; Circulation 1990;81; )
Patients number
Gaultier et al
(1978)
Antman et al
(1990)
Experienced cardiac arrest 9 56
Died 26
Mortality (%)
100 46

46. 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

47. Factors affecting the efficacy
Time of administration
Dosage
Rate of administration

48. Dosage
Amount of ingestion and post distribution Digoxin level is unknown
Amount of ingestion is known
Post distribution Digoxin level is known

49. Dosage
The brand of Digoxin Fab

50. Digitalis Antidote
(Roche)
Available in PMH
80mg/vial
Each vial binds 1 mg digoxin
Digibind (Glaxo)
38mg/vial
Each vial binds 0.5mg digoxin

51. 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)

52. 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

53. Dosage of Digibind Tablets ingested 0.125mg/tabs 0.25mg/tabs
No of vials 5
2.5 1 10 2 20 4 50 25
100
Olson, Poisoning & Drug overdose 4th ediiton

54. Dosage The brand of Digoxin Fab Post distribution Digoxin level
nmol/l vs ng/ml

55. 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)

56. Dosage The brand of Digoxin Fab Post distribution Digoxin level
Serum Digoxin level (nmol/l vs ng/ml)
Use the highest calculated dose

57. Adverse reaction Allergy is rare Hypokalaemia
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

58. 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

59. Thank you