History
- Accidental adult or pediatric overdose of a known amount
- Intentional acute overdose in a patient not taking digoxin chronically
- Intentional acute or chronic overdose in a patient taking digoxin chronically
- Unintentional chronic ingestion of digoxin in which renal clearance decreases or the dose chronically increases
- Unintentional toxicity from recent antibiotic use (esp. macrolides) that alter GI flora, primarily by decreasing
Eubacterium lentum
, increasing absorption
Physical-Exam
- Altered mental status
- Bradycardia
- Tachycardia
- Irregular rhythm
- Hypotension
ESSENTIAL WORKUP
- ECG:
- Digoxin level:
- Normal range: 0.5–2 ng/mL
- Distribution after oral intake not complete until 6 hr; therefore, >6-hr level is most accurate steady state concentration.
- False elevations possible with spironolactone use, pregnancy, hyperbilirubinemia, chronic renal failure, liver failure, CHF
- May be falsely elevated after digoxin-specific Fab fragments given
DIAGNOSIS TESTS & NTERPRETATION
Lab
- Electrolytes, BUN, creatinine, glucose:
- Hypokalemia contributes to digitalis toxicity.
- Hyperkalemia seen in acute toxicity and correlates with acute digitalis mortality better than digoxin serum levels.
- Follow K
+
serially
- Calcium, magnesium
ALERT
Serum digoxin concentration (SDC) should not be obtained after digoxin-specific antibody Fab fragments have been administered because it will be inaccurate.
DIFFERENTIAL DIAGNOSIS
- Overdoses:
- Calcium channel blockers
- β-Blockers
- Quinidine, procainamide
- Clonidine
- Organophosphates
- Antidysrhythmics
- Other antihypertensives
- Primary cardiac dysrhythmias
- Acute gastroenteritis
TREATMENT
PRE HOSPITAL
- Establish IV access
- Continuous cardiac monitoring
- Apply pads for potential cardioversion
ALERT
- If cardioversion is necessary for tachydysrhythmias, use low levels (50 J)
- May precipitate refractory tachydysrhythmias
INITIAL STABILIZATION/THERAPY
ABCs:
- IV, oxygen, monitor:
- IV fluid bolus if hypovolemic
- Administer naloxone, thiamine, dextrose for altered mental status.
ED TREATMENT/PROCEDURES
- Cardiac arrest resuscitation:
- Defibrillate for ventricular fibrillation, pulseless VT.
- Standard advanced cardiac life support (ACLS) protocol
- Administer digoxin-specific antibody Fab fragments (Digibind), up to 5–20 vials IV push (IVP).
- MgSO
4
, 2 g IVP
- Continue resuscitation for 30 min after digoxin-specific antibody Fab fragments.
- General measures:
- Activated charcoal if acute ingestion
- Replenish magnesium.
- Treat hyperkalemia with insulin, dextrose, bicarbonate, sodium polystyrene sulfonate.
- Calcium can probably be used to treat hyperkalemia, but because other safer alternatives exist it is not recommended, unless life-saving membrane stabilization is needed secondary to hyperkalemia, in the unstable patient.
- If the patient has hyperkalemia from digoxin toxicity treatment with digoxin-specific Fab fragments are indicated 1st in the hemodynamically stable patient.
DYSRHYTHMIA MANAGEMENT
- 1st choice: Digoxin-specific antibody Fab fragments (Digibind, DigiFab)
- Indications:
- SDC ≥15 ng/mL at any time or ≥10 ng/mL at steady state (6 hr)
- Ingestion of >10 mg in adults or 0.2 mg/kg or 4 mg in children
- Hyperkalemia >5–5.5 mEq/L
- Hemodynamically unstable or life-threatening dysrhythmias
- VT, ventricular fibrillation
- Atrial tachycardia
- Variable AV block
- Bradycardia with no response to atropine
- Hypotension
- Onset: 20–30 min
- Digoxin levels may increase, decrease, or stay in therapeutic range after therapy owing to Fab digoxin complexes and redistribution.
- Renal clearance of drug–antibody complexes:
- Too large to be removed by dialysis
- 2nd dose if rebound toxicity
- Complications:
- Exacerbation of CHF
- Hypokalemia
- Atrial fibrillation with rapid ventricular response
- If digoxin-specific antibody Fab fragments not immediately available initiate the following:
- Lidocaine:
- For ventricular dysrhythmias without AV block
- Not harmful but not very effective
- For bradydysrhythmias:
- Pacing for symptomatic bradydysrhythmia
- MgSO
4
for ventricular dysrhythmias with torsades de pointes
- Quinidine, procainamide contraindicated
- Cardioversion is last resort for severe, life-threatening tachydysrhythmia:
- Start at low energy 10–50 J, then increase to high levels if ineffective.
- Safe if digoxin level <2 ng/mL
MEDICATION
- Activated charcoal slurry:
- Digoxin-specific antibody Fab fragments:
- 40-mg vial neutralizes 0.5 mg of digoxin.
- If amount ingested known:
- Number of vials needed to treat equals [amount ingested (mg)/0.5 (mg/vial)]
- If steady serum level known:
- Number of vials needed equals [SDC (ng/mL) × weight (kg)]/100
- If neither amount ingested nor serum level known:
- Acute toxicity: 5–10 vials adults or children
- Chronic toxicity: 1--2 vials in adults or children
- Bolus digoxin-specific antibody Fab fragments for cardiac arrest
- Additional doses as needed
- Standard treatment for hyperkalemia and bradycardia (calcium only if necessary)
Geriatric Considerations
- Dosage is based on weight and serum concentration. There is no change in the setting of renal or hepatic dysfunction.
- Recrudescence of toxicity has been reported in patients with concomitant renal failure. Redosing of digoxin-specific antibody Fab fragments should be used again when indicated.
Pediatric Considerations
- Weight-based dosing for children is the same as it is for adults.
- On some occasions, accidental dose ingested by a child is known and the number of vials is indicated by the amount of digoxin bound by each vial. See dosing.
Pregnancy Considerations
Digoxin-specific Fab fragments are pregnancy class C.
FOLLOW-UP
DISPOSITION
Admission Criteria
- ICU:
- Unstable cardiovascular status in acute or chronic toxicity
- Telemetry:
- Asymptomatic or mildly symptomatic dysrhythmia
- High risk for developing toxicity
Discharge Criteria
Acute/chronic ingestion:
- Digoxin level <2 ng/mL
- Asymptomatic for 6 hr and no ECG abnormalities
FOLLOW-UP RECOMMENDATIONS
Psychiatric referral for stable patients who are suicidal
PEARLS AND PITFALLS
When it is known that the patient is on digoxin and presents with cardiovascular instability, and/or hyperkalemia, treatment should begin with the antidote: Digoxin-specific Fab fragments.
ADDITIONAL READING
- Erickson CP, Olson KR. Case files of the medical toxicology fellowship of the California poison control system-San Francisco: calcium plus digoxin-more taboo than toxic?
J Med Toxicol
. 2008;4(1):33–39.
- Levine M, Nikkanen H, Pallin DJ. The effects of intravenous calcium in patients with digoxin toxicity.
J Emerg Med.
2011;40(1):41–46.
CODES
ICD9
972.1 Poisoning by cardiotonic glycosides and drugs of similar action
ICD10
- T46.0X1A Poisoning by cardi-stim glycos/drug simlar act, acc, init
- T46.0X4A Poisoning by cardi-stim glycos/drug simlar act, undet, init
DIPLOPIA
Jonathan A. Edlow
BASICS
DESCRIPTION
- Double vision
- Simultaneous perception of 2 images
- Can be oriented horizontally, vertically, or diagonally from one another.
- Diplopia is usually due to abnormal movement of the extraocular muscles (EOMs), which are innervated by 3 cranial nerves (CNs):
- CN 3 – superior, inferior, and medial rectus and inferior oblique muscles
- CN 4 – superior oblique muscle
- CN 6 – lateral rectus muscle
- Brainstem lesions can damage CN nuclei or their connections (medial longitudinal fasciculus, MLF), causing an internuclear ophthalmoplegia (INO)
- CN dysfunction
- Compression as they traverse the subarachnoid space and venous sinuses
- Inflammation
- Elevation (or reduction) of CSF pressure can cause CN 6 palsy
- Disease affecting the orbits and the bony skull can cause restriction of motion of one or both eyes or EOMs