Digoxin Toxicity......Clinical diagnosis and Management

1. By:
Alaa Atteya AboDonia

2. Presonal history
 Female patient………
 Aged 70 years
 From ……………………, Alexandria
 Housewife
 Has……children
 Admitted on ………..
 The Complaint:
Persistent vomiting &
easy fatigability and dizziness since 1 1/2month

3. History of the present complain
 Condition started 1 and ½ month ago by acute onset of
attacks of persistent vomiting , associated with nausea
and epigastric pain, not related to food intake,
 no fever, no blood in stool, the pateint sought medical
advice and received medications for gastroenteritis
but no improvement
 Condtion progressed and easy fatigability and
dizziness associated with blurred vision occurs and
sometimes presyncope but no syncopal attack
 Sought medical advice again and IV fluids was given
with no improvement

4. History of the present complain
 Presented to our internal medicine clinic and was
admitted to our hospital for workup

5.  Family history: Irrelevant
 Past History
HTN since 1 y
Mild mitral regurgitation( degenerative)
No DM
Recurrent UTI
 Surgical history:
Lt Nephrectomy sine 7 years on top of pyelonephritis
Cataract surgery since 4 years
 Drug & transfusion history:
Coversyl 5 mg , Concor 5 mg, Lanoxin 0.25 , PPI, Motillium

6. Examination on admission
 General: concious , alert
 Vital signs:
 B.P = 110 / 70 , Rt=Lt
 Pulse:
 40 bpm, regular, equal bilateral, average force and volume
 Temp.=37 c
 Head and neck:
 No thyroid enlargement.
 No jaundice , No central cyanosis.
 Extremities:
 No odema
 No peripheral cyanosis
 No clubbing

7. Cardiac examination
 Neck veins:
 Normal pressure& pulsations
 Hepatojugular reflux -ve
 Emptying with inspiration
Inspection of the heart: The apical heartbeat visible in the mid-
clavicular line at the 5th intercostal space
Palpation of the heart: Apex located in the Lt mid-clavicular line at the
5th intercostal space, localized .
Percussion no dullness outside apex and Rt sternal border, reasonant
2nd Rt & Lt intercostal space parasternal line, impaired note on
lower 1/3 sternum.

8. Auscultation
 Apex:
1st heart sound of slightly reduced intensity, 2nd heart sound heard normal,
pansystolic murmur , 2/6 , that radiate to axilla
 Tricuspid area:
S1, S2 heard normal, no added sounds, no murmur
 Aortic area
A2 heard normal
no added sounds no murmur
 Pulmonary area
P2 heard normal
no added sounds no murmurs

9.  Chest
EBAE
no added sounds
 Abdomen
No hepatomegaly,
no spleenomegaly,
no ascites.

10.  ECG:
Sinus bradycardia,
HR= 40 bpm, normal axis,
scooping of ST segment I, Avl, V4-6
 Echo:
Mild LVH, calcific mitral annulus, sclerotic aortic valve,
mild mitral regurgitation.

11. Laboratory tests:
 ABG= PH: 7.38, Co2: 35, O2: 110, HCo3: 21, O2sat: 96%
 S.creatinine= 3.2 mg/dl
 S. urea= 119 mg/dl
 K = 4.4 mmol/l
 Ca= 8
 Uric acid= 10.1
 P = 4.1
 INR= 1
 S.albumin= 3.1
 Bil= 0.7
 HCV+ve
 Urine analysis: pus cells +ve
 Urine culture: E-coli

12. Lanoxin level= 4.9 ng/dl

13. Digoxin therapy and
toxicity
By :
Alaa Atteya AboDonia

14. More than 200 years with
Digoxin therapy & toxicity

15.  Cardiac actions of digitalis glycosides have been
recognized for centuries.
 The use of digoxin has decreased because of the
availability of agents with greater potency and a wider
therapeutic to toxic drug concentration range

17. Electrophysiologic Actions
 Enhancing both central and peripheral
vagal tone:
 Slowing of the sinus node discharge rate
 Shortening of atrial refractoriness
 Prolongation of AV nodal refractoriness
 Effects on the His-Purkinje system and ventricular
muscle are minimal, except in toxic concentrations
 In studies of denervated hearts, little effect on AVnode
and causes a mild increase in atrial refractoriness
 The characteristic ST and T wave abnormalities seen
with digoxin use do not represent toxicity.

19. Pharmacokinetics
 Oral dosing: the peak effect occurs in 4 to 6 hrs.
 Tablet forms are 60% to 75% absorbed
 Intravenously administered: some effect within
minutes, with a peak effect occurring after 1.5 to 3
hours.
 Cholestyramine or antacids decreases absorption.
 The serum halflife is 36 to 48 hours
 Excreted unchanged by the kidneys

20. INDICATIONS
 Orally to control the ventricular rate in chronic atrial
fibrillation,
 At rest vagal tone predominates and rate controlled
in 40-60% pateints
 But even with mild exertion marked increase in
ventricular rate
 Rarely used as a single agent

21. Acute rate control in AF
 ESC Guidelines 2010 Atrial Fibrillation
In the acute setting, IV administration of digitalis or
amiodarone is recommended to control the heart rate
in pateints with AF and concomitant heart failure,
or in the setting of hypotension .( I B )

22. In heart failure
 ESC 2012 Guidelines of heart failure ,
Digoxin indications
 IIb B: May be considered to reduce the risk of HF hospitalization
in patients with an EF ≤45% and persisting symptoms (NYHA
class II–IV) despite treatment with a beta-blocker, ACE inhibitor
(or ARB), and an MRA (or ARB).
 IIb B: May be considered to reduce the risk of HF hospitalization
in patients in sinus rhythm with an EF ≤45% who are unable to
tolerate a beta-blocker (ivabradine is an alternative in patients
with a heart rate ≥70 b.p.m.). Patients should also receive an ACE
inhibitor (or ARB) and an MRA

23. DOSAGE
 Most patients require 0.125 to 0.25 mg/day as a single
dialy dose
 As little as 0.125 mg every other day in renal impairment
 Young patients may require as much as 0.5 mg/day
 In acute loading doses of 0.5 to 1.0 mg, digoxin may be given
intravenously or by mouth
 Serum digoxin levels for compliance & digitalis toxicity ,
but not routine if ventricular rate is controlled during
atrial fibrillation and no symptoms of toxicity

24. Digoxin Toxicity
 Narrow window between therapeutic and toxic concentrations
 Clinical picture:
 Headache, Generalized malaise
 Nausea and vomiting
 Altered color perception, halo vision
 More serious than these are digitalis-related arrhythmias,
 Bradycardias related to a markedly enhanced vagal effect
(e.g., sinus bradycardia or arrest, AV node block)
 Tachyarrhythmias that may be caused by delayed afterdepolarization
mediated triggered activity
(e.g., atrial, junctional, and ventricular tachycardia)
most common paroxysmal atrial tachycardia with block

25. Forms of toxicity
 Acute:
Accidental
Intentsional
 Chronic:
Therapeutic error
Decreased elimination
Drug interactions
Condition increasing pateint sensitivity to digoxin

27. Conditions increasing a patient’s
sensitivity to digoxin toxicity
 Worsening renal function
 Advanced age
 Hypokalemia
 Hypothyroidism
 Amyloidosis
 Chronic lung disease

28. Confirming diagnosis
Plasma digoxin level should
be measured at least 6 hours
after the last dose since this
is the time required for
attainment of the steady
state

29. Management
 Stop Digoxin and Diuretics
 Decreasing absorption: Charcol, Cholestyramine
 ?? Gastric lavage (acute overdose)
increases vagal tone and may precipitate arrhythmias,
Consider pretreatment with atropine if performed.
 Proper hydration to optimize renal clearance
 Estimate serum potassium

30. Management of dysrhythmias
 Depending on the presence or absence of:
hemodynamic instability
Nature of the arrhythmia
Electrolyte disturbances

31. Digoxin toxicity induced
Bradyarrhythmias :
 Hemodynamically stable :
Observation and discontinuation of the drug
 Hemodynamically unstable :
Digibind
Atropine (improves AV nodal conduction)(short acting)
Cardiac pacing (used successfully, but induce arrhythmias)

32. Digoxin toxicity induced
supraventricular arrhythmias
 Hemodynamically stable: observation
 Short-acting beta blockers (eg, esmolol) may be helpful
for supraventricular tachyarrhythmias with rapid
ventricular rates, but advanced or complete atrioventricular
(AV) block may be precipitated.
 If rate-related ischemia or hemodynamic instability,
Digibind is the treatment of choice
 Calcium channel blockers are contraindicated because
they may increase digoxin levels

33.  Premature ventricular contractions (PVCs), bigeminy,
or trigeminy may be observed unless the patient is
hemodynamically unstable, in which case lidocaine
may be effective.

34. Digoxin toxicity induced
Ventricular tachycardia
 Responds best to Digibind
 Lidocaine and phenytoin may be useful because they depress the
enhanced ventricular automaticity without slowing AV conduction
 Lidocaine : boluses of 100 mg & If successful, infusion 1-4 mg/min
 Phenytoin :
 May reverse digitalis-induced prolongation of AV nodal conduction
 Dissociate the inotropic and dysrhythmic action of digitalis
 Can terminate supraventricular dysrhythmias induced by digitalis
 Phenytoin administered in boluses of 100 mg every 5-10 minutes
up to a loading dose of 15 mg/kg

35. Direct-Current Electrical
Cardioversion
 Relatively Contraindicated
 Performed only when absolutely necessary in the
digitalis-toxic patient because life-threatening VT or VF
can result, which can be very difficult to control.

36. Correction of Hypokalemia
Mild toxicty:
potassium salts 5-7.5 g KCL
Serious arrhythmias:
40 mEq of KCL in 500ml of G 5% glucose IV over 2-4 hours

37. Role of
Magnesium therapy
 As temporizing antiarrhythmic agent until fab available.
 Life saving when VT or VF
 IV magnesium sulfate, 2 g over 5 minutes
 Aside from successful replacement of intracellular
magnesium, act as an indirect antagonist of digoxin at the
supraphysiologic level
 After an initial bolus of 2 g intravenously, a maintenance
infusion at 1-2 g/h is initiated.
 Monitor magnesium levels approximately every 2hours, The
therapeutic goal between 4 and 5 mEq/L

38. For hyperkalemia
 Calcium is not recommended to treat hyperkalemia,
because ventricular tachycardia or ventricular fibrillation
may be precipitated.
 Sodium bicarbonate and/or glucose and insulin are
indicated.
 Digoxin-fab fragments for K+ > 5 mEq/L
 Kayexalate (0.5 g/kg PO) binding potassium and
enterohepatically recycled digitalis.
 However, digoxin-induced hyperkalemia reflects an
extracellular shift, not an increase in total body potassium

39. AntiDigoxin Antibodies
Digibind
 Indications:
For severe toxicity
Life threatening arrhythmias
Hemodynamic instability
Hyperkalemia > 5
Digoxin level more than 10 ng/ml
 Altered mental status
Ingestion greater than 10 mg in adults (40 x 0.25 mg
tablets) or greater than 0.3 mg/kg in children

40. Dosing of Digibind:
 No. Vials=
digoxin level (ng/ml) x Wt (Kg) / 100
 1 vial of Digibind= 40 mg
= neutralize 0.6 mg of digoxin

41. Home message
 Donot prescribe lanoxin unless guideliness-indicated
 Narrow window between therapeutic and toxic concentrations
 Suspect toxicity in elderly, renally impaired pateints on lanoxin
with (GIT+CNS+Vision+Rhythm) abnormalities

42. Home message
 Management of lanoxin induced dysrhysmias
 Atropine and pacing for unstable bradyarrhythmias
 Lidocaine or phenytoin + Magnesium for VT, VF
 B-Blockers may induce advanced AV block
 Calcium channel blockers are contraindicated
 Importance of electrolyte imbalance correction
 Importance of hypokalemia correction
 Indications and dosing of digibind
 DC relative contraindication