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Toxicity, Antidysrhythmic: Treatment & Medication
Updated: Jul 9, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
An advanced life support (ALS) unit is recommended for transport and establishment of ABCs.
Emergency Department Care
Airway, breathing, circulatory support, IV access, and ECG monitoring are of paramount importance. Torsade de pointes is the most common proarrhythmia encountered. (See Torsade de pointes treatment following the individual discussion of the drugs.)
- Treatment based on grouping is as follows (for more details on each respective agent, refer to each individual section):
- GI decontamination - Disopyramide, quinidine, flecainide, propafenone, ajmaline/cibenzoline/detajmium, amiodarone, and N -acetyl procainamide
- Hemodialysis - Disopyramide, procainamide, mexiletine/tocainide, and bretylium (limited experience)
- Pacemaker or intra-aortic balloon pump (IABP) - Procainamide, quinidine, propafenone, ajmaline/cibenzoline/detajmium, and amiodarone
- Pressors - Quinidine, amiodarone, and propafenone
- Seizure control - Quinidine, lidocaine, flecainide, and propafenone
- All dysrhythmias resulting from sodium channel poisons may respond to sodium bicarbonate or cautious hypertonic saline therapy.
- Disopyramide - Class IA GI decontamination is warranted to decrease GI disopyramide absorption because of its anticholinergic effects. Hemodialysis is effective in decreasing the serum half-life and may be useful when supportive care is not effective. Unfortunately, no significant clinical experience is available to guide therapy. Calcium chloride doses of 0.5 g every 5 minutes (up to maximum of 3 g) in combination with ACLS therapy may be required.
- Procainamide - Class IA Implement supportive. GI decontamination and activated charcoal are indicated following an oral overdose. If renal failure is present, consider hemodialysis even though its role has not yet been defined. Avoid quinidine and disopyramide. Consider early pacemaker with increasing atrioventricular block. VF/VT in the setting of Brugada syndrome is best managed with isoproterenol as opposed to amiodarone.
- Quinidine - Class IA After IV, oxygen, and cardiac monitoring are initiated, seizures may be responsive to diazepam or any other benzodiazepine of choice; check electrolyte levels, especially calcium, and glucose if seizures are not responsive. GI lavage and/or activated charcoal, with repeated doses, may be indicated. Treat hypotension with fluids and then pressors. Isoproterenol and norepinephrine have been used successfully. Use IABP as a last resort. Use class IB agents for treating dysrhythmias; avoid class IA drugs. Correct electrolyte imbalances (eg, potassium, calcium) and glucose. Dialysis is not helpful. Experience with charcoal hemoperfusion is limited. Glucagon has been proven useful in animal models but such data are lacking in humans.
- Lidocaine - Class IB Supportive measures are sufficient because of the short half-life (2.7-3.8 h). Consider extracorporeal pump for massive overdose, which have been useful in reducing mortality.Adequate ventilation and perfusion is imperative because hypoxia and hypercarbia increases penetration of basic drug lidocaine into brain. Use diazepam for seizures. Avoid phenytoin because of its synergistic cardiac effects.
- Mexiletine and tocainide - Class IB, lidocaine analogs No antidotes are available for either drug. GI decontamination based on emesis is contraindicated because of very rapid development of seizures. Theoretically, hemodialysis could decrease the serum level of these agents and alkalinization of urine would increase serum level.
- Encainide - Class IC Transport as quickly as possible to ED. Do not be fooled by the "they-look-good" syndrome because individuals with encainide toxicity can decompensate quickly. GI decontamination is relatively contraindicated because encainide is quickly absorbed. Treating overdose with hypertonic sodium bicarbonate and hypertonic saline reportedly has been successful.Always monitor glucose in patients with insulin-dependent diabetes mellitus (IDDM) and non–insulin-dependent diabetes mellitus (NIDDM) because encainide may exacerbate hyperglycemia by unknown mechanism.
- Flecainide - Class IC After ABCs are stabilized, early (within 1 h) gastric emptying is recommended. Secure airway before this step because seizures can occur within 2 hours of ingestion or overdose.Hemodialysis and hemoperfusion have not been effective in overdose therapy. Intravenous sodium bicarb, 100 mEq over 5 minutes, followed by continuous infusion to maintain a serum pH of 7.5-7.55 reversed hypotension and resulted in narrowing of the QRS complex in isolated case reports.
- Propafenone - Class IC Once the airway is secured via an endotracheal tube (ETT), gastric emptying may be done to reduce amount absorbed. Activated charcoal may be used, although no evidence suggests that this actually helps to decrease toxicity.Supportive measures are the only therapy because hemodialysis and hemoperfusion are not useful and no antidote is available.Sodium lactate has been used to theoretically load sodium channels, thus improving the widening of the QRS interval. Diazepam is the drug of choice for seizures. Pressors and pacers are indicated for cardiac support.
- Ajmaline, cibenzoline, detajmium - Class IC Establishment of ABCs is priority, including installation of a temporary transvenous pacemaker before gastric decontamination because vagal stimulation can worsen existing bradyarrhythmias.Supportive measures are the only therapy because hemodialysis and hemoperfusion are not useful and no antidote is available.
- Amiodarone - Class III GI decontamination is useful because of slow oral absorption; activated charcoal decreases amiodarone absorption. Patients should be responsive to supportive measures as described with other drugs. If bradycardia occurs, use a pacemaker or beta-adrenergic agonist.Consider cholestyramine to decrease the enterohepatic recirculation of amiodarone. Corticosteroids have been used to increase recovery after pulmonary toxicity.
- Bretylium - Class III Treatment is supportive and symptomatic. Bretylium is dialyzable, but limited experience with this method of treatment exists in literature.
- N -acetyl procainamide - Class III Airway, circulatory support, IV access, and ECG monitoring are of paramount importance. Implement supportive measures.GI decontamination and activated charcoal within 3-4 hours are indicated following an oral overdose.Intoxication may be responsive to hemodialysis, or inline hemodialysis/hemoperfusion may decrease levels more rapidly.
- Sotalol - Class III Treatment is supportive and symptomatic. See Torsade de pointes treatment below for therapy. Bradycardia of hypotension not responding to atropine or pacing may respond to glucagon.
- Ibutilide and dofetilide - Class III Treatment still is under investigation; however, suggestions for management include correction of hypokalemia and hypomagnesemia. Cardioversion or pacing may be helpful for arrhythmias.
- Adenosine Treatment is supportive and symptomatic. Have external pacing available while using adenosine. Be prepared for transient AVB.One report states that theophylline may alleviate chest pain induced by adenosine in patients with ischemic heart disease.
- Torsade de pointes treatmentTorsade de pointes is a common proarrhythmia, aggravation, or provocation of arrhythmias provoked by antidysrhythmic agents. Risk factors for this include toxic blood levels (due to advanced age or renal, hepatic, or heart disease), severe ventricular dysfunction (ejection fraction [EF] <35%), serious presenting arrhythmia, concomitant digoxin therapy, hypokalemia or hypomagnesemia, and certain drug combinations (eg, class IA + class IA, class IA + class III, or class IA + TCAs).Torsade de pointes generally occurs immediately after precipitating drug therapy has begun; therefore, discontinuing drug therapy is very important. Intravenous magnesium and temporary atrial or ventricular overdrive pacing suppresses the ventricular tachycardia; ventricular tachycardia usually does not recur after terminating the pacer. Isoproterenol can be used to increase heart rate cautiously until pacer is placed. Magnesium is an effective and safe for treatment of torsade de pointes. A study by Tzivoni et al (1984-1988) demonstrated the termination of torsade de pointes within 5 minutes after administering magnesium using the following dosages:16
- Step 1: Administer 2 g bolus of magnesium sulfate over 3-5 minutes.
- Step 2: Repeat 2 g bolus of magnesium if partial response is observed within 10-15 minutes.
- Step 3: Infuse 2-10 mg/min if no torsade de pointes is present but premature ventricular contractions (PVCs) continue.
- Step 4: Treat with overdrive pacing or isoproterenol if torsade de pointes continues.
Consultations
- Consult with a medical toxicologist and/or a regional poison control center for acute toxicity.
- Consult with a cardiologist for long-term plans to continue intensive monitoring in cardiac unit.
Medication
Discontinuation of the precipitating drug is of paramount importance.
GI decontaminants
Empirically used to minimize systemic absorption of the toxin.
Activated charcoal (Liqui-Char)
Prevents absorption by adsorbing drug in intestine. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. Theoretically, by constantly bathing the GI tract with charcoal, the intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into intestine. Supply as an aqueous mixture or in combination with a cathartic (usually sorbitol 70%).
Adult
1 g/kg PO; may repeat in 2-4 h at one-half original dose
Pediatric
1 g/kg PO (typical 12.5-25 g)
<2 years: Use aqueous charcoal without cathartic
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases adsorptive properties)
Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies; unprotected airway; absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administering; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black; protect airway in patients with depressed level of consciousness; if using multiple dose charcoal, monitor for presence of bowel sounds to minimize risk of charcoal ileus and vomiting with subsequent pulmonary aspiration
Cardiovascular agents
Alter the electrophysiologic mechanisms responsible for arrhythmia.
Calcium chloride
Moderates nerve and muscle-performance by regulating action potential excitation threshold.
Adult
0.5 g q5min, up to 3 g in combination with ACLS therapy
Pediatric
Not established
Coadministration with digoxin may cause arrhythmias; with thiazides, may induce hypercalcemia; may antagonize effects of calcium channel blockers, atenolol, and sodium polystyrene sulfonate
Ventricular fibrillation not associated with hyperkalemia; digitalis toxicity; hypercalcemia; renal insufficiency; cardiac disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Administer slowly (not to exceed 0.5-1 mL/min) to avoid extravasation; hypercalcemia may occur in renal failure
Magnesium sulfate
Acts as antiarrhythmic agent and diminishes frequency of PVCs, particularly when secondary to acute ischemia.
Deficiency in this electrolyte is associated with sudden cardiac death and can precipitate refractory VF. Magnesium supplementation is used for treatment of torsade de pointes, known or suspected hypomagnesemia, or severe refractory VF.
Adult
Step 1: Bolus 2 g over 3-5 min
Step 2: Repeat 2 g bolus if partial response within 10-15 min
Step 3: Infusion of 2-10 mg/min if no torsade de pointes but PVCs continue
Step 4: Overdrive pacing or isoproterenol if torsade de pointes continue
Pediatric
0.2-0.4 mEq/kg (25-50 mg/kg) slow IV
Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade observed with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants and betamethasone; may increase cardiotoxicity of ritodrine
Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis; hypermagnesemia; renal failure
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
May alter cardiac conduction leading to heart block in digitalized patients; monitor respiratory rate, deep tendon reflex, and renal function when electrolyte is administered parenterally; caution when administering magnesium dose because may produce significant hypertension or asystole; in overdose, calcium gluconate (10-20 mL IV of 10% solution) can be administered as antidote for clinically significant hypermagnesemia
Norepinephrine (Levophed)
DOC. Vasopressors are indicated for persistent hypotension not responsive to judicious fluid loading and sodium bicarbonate.
Adult
0.05-0.15 mcg/kg/min IV infusion; titrate to effect
Pediatric
0.1-1 mcg/kg/min IV infusion; titrate to effect
Chlorpromazine enhances the pressor response of norepinephrine by blocking the reflex bradycardia caused by norepinephrine
Documented hypersensitivity; peripheral or mesenteric vascular thrombosis because ischemia may be increased and the area of the infarct extended; uncorrected hypovolemia
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Correct blood volume depletion, if possible, before therapy; administer into a large vein because extravasation may cause severe tissue necrosis; caution in occlusive vascular disease; consider risk vs benefit if hypercapnia is present
Benzodiazepines
By increasing action of GABA, a major inhibitory neurotransmitter, may depress all levels of CNS, including limbic and reticular formation.
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Third-line agent for agitation or seizures because of shorter duration of anticonvulsive effects and accumulation of active metabolites that may prolong sedation.
Adult
5-10 mg IV q10-15min until symptoms resolve; not to exceed 30 mg
Pediatric
30 days to 5 years: 0.2-0.5 mg IV (slowly) q2-5min until symptoms resolve; not to exceed 5 mg
>5 years: 1 mg IV (slowly) q2-5min until symptoms resolve; not to exceed 10 mg
Increases toxicity in CNS with coadministration of phenothiazines, H1 blockers, barbiturates, alcohols, and MAOIs
Documented hypersensitivity; hypotension; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with other CNS depressants, low albumin levels, or renal and hepatic disease (may increase toxicity); monitor for respiratory depression with high or repeated doses
Lorazepam (Ativan)
DOC for treatment of status epilepticus because persists in the CNS longer than diazepam. Rate of injection should not exceed 2 mg/min. May administer IM if unable to obtain vascular access.
Adult
0.044 mg/kg (2-4 mg) IV, titrate to desired effect
Status epilepticus: 4 mg IV over 2-5 min; may repeat second dose in 10-15 min, if needed; not to exceed 8 mg
Pediatric
Children: 0.05 mg/kg IV (range 0.02-0.1 mg/kg)
Adolescents: Administer as in adults
Status epilepticus:
Neonates: 0.05 mg/kg IV over 2-5 min; may repeat in 10-15 min, if needed
Infants and children: 0.1 mg/kg IV over 2-5 min; second dose of 0.05 mg/kg IV in 10-15 min, if needed; not to exceed 4 mg
Adolescents: 0.7 mg/kg IV; not to exceed 4 mg, given slowly over 2-5 min; second dose in 10-15 min, if needed
Alcohol, phenothiazines, barbiturates, and MAOIs increase CNS toxicity
Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor for respiratory depression with high or repeated doses; contains benzyl alcohol, which may be toxic to infants in high doses; caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, Parkinson disease, or patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Midazolam (Versed)
Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access.
Adult
0.01-0.05 mg/kg (usually 0.5-4 mg, up to 10 mg) IV given slowly over several min; may repeat q10-15min until adequate response achieved
Pediatric
<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg followed by continuous infusion of 1 mcg/kg/min, titrating dose upward q5min until seizures controlled
Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when using together
Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages in patients with organic brain syndrome and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
More on Toxicity, Antidysrhythmic |
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| Differential Diagnoses & Workup: Toxicity, Antidysrhythmic |
 Treatment & Medication: Toxicity, Antidysrhythmic |
| Follow-up: Toxicity, Antidysrhythmic |
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References
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Further Reading
Keywords
antidysrhythmic drug toxicity, antidysrhythmic drug poisoning, antidysrhythmic drug exposure, class I drugs, sodium channel blockers, class II drugs, beta-adrenergic blockers, class III drugs, potassium channel blockers, class IV drugs, calcium channel blockers, antiarrhythmic exposures
