Medication Summary
The mainstay of specific treatment of significant TCA-related toxicity is NaHCO3 administered in conjunction with supportive care, including aggressive airway support, antiseizure, vasopressor, and dysrhythmic medications. Indications for NaHCO3 administration include QRS widening, hypotension, dysrhythmias, and seizures that are associated with QRS widening. NaHCO3 replaces lidocaine as the drug of choice for ventricular tachycardia following TCA overdose in a variation of the usual ACLS guidelines. Hypotension with evidence of shock not responsive to judicious fluid therapy and sodium bicarbonate are indications for pressors. Norepinephrine has been reported to reverse refractory hypotension. A few recent reports also support a trial of vasopressin for refractory hypotension. Narcan or thiamine and immediate measurement of serum glucose concentration are indicated for any patients with altered mental status, such as that which occurs with TCA toxicity.
Contraindicated medications include flumazenil, beta-blockers, calcium channel blockers, and class IA (procainamide, quinidine, disopyramide, moricizine), class IC (flecainide, propafenone), and possibly class III (bretylium, amiodarone, sotalol) antidysrhythmics.
GI decontaminant
Class Summary
Activated charcoal is indicated for all TCA ingestions unless bowel obstruction, ileus, or perforation is suspected, even when a patient presents late following ingestion. Since the anticholinergic effects of TCAs delay gastric emptying and slow GI motility, this may allow efficacy for charcoal when administered relatively late postingestion. In cases of altered mental status, the benefits of charcoal need to be weighed against the risk of aspiration. Therefore, prior to charcoal administration, the airway needs to be secured in patients with an altered mental status.
Activated charcoal (Liqui-Char)
Binds TCAs, limiting absorption and speeding elimination. Clinical benefit of multiple doses has not been demonstrated clearly and is not recommended.
Cardiovascular agents
Class Summary
Serum alkalinization with NaHCO3 is the first-line and most effective therapy for arrhythmias. Vasopressors can be useful in correcting hypotension. Lidocaine is the second-line agent behind alkalinization for arrhythmias. Class IA and IC antiarrhythmic agents (eg, procainamide, disopyramide, quinidine, flecainide, encainide) are contraindicated, as are beta-blockers and calcium channel blockers. Animal studies show that TCA Fab effectively reduces hypotension, shortens QRS duration, and improves survival in TCA-poisoned animals, and one study by Heard et al in humans involving 7 patients showed that the use of TCA Fab was associated with a fall in serum free TCA levels with none of the patients in the study developing worsening signs of TCA toxicity.[6] Further studies are still needed to evaluate the routine use of TCA Fab in humans.
Sodium bicarbonate (Neut)
First-line drug for cardiovascular morbidity in TCA poisoning. Provides exogenous sodium to overcome the competitive fast sodium channel blockade produced by TCA, and produces an alkalemia (or reverses acidemia) that mitigates the fast sodium channel blockade by TCA.
Indicated for QRS widening, dysrhythmias, hypotension, and seizures that are associated with QRS widening. Patient can be monitored and given boluses of bicarbonate prn if QRS widening and block resolves with initial treatment. Following bolus administration, an IV drip may be prepared with 3 ampules of bicarbonate in 1 L of D5W, run at 150-250 mL/h (monitor pH = 7.45-7.55). Maintain serum potassium levels (see Precautions below). Resolution of QRS widening is a reasonable endpoint for NaHCO3 administration. However, since it may recur, patients who have had QRS widening need to be on a cardiac monitor that is being continuously monitored.
Norepinephrine (Levophed)
Norepinephrine is the drug of choice. Other vasopressors may also be used, but norepinephrine has been reported to reverse hypotension that was refractory to other agents. This is thought to be because severe TCA toxicity causes depletion of synaptic norepinephrine that can then only be reversed with exogenous norepinephrine administration. Norepinephrine's vasopressive effect is from its alpha alpha-adrenergic agonist properties. Vasopressors are indicated for persistent hypotension not responsive to judicious fluid loading and sodium bicarbonate.
Epinephrine (Adrenaline)
Has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypertension, and vascular permeability. Beta-agonist effects of epinephrine include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Phenylephrine (Neo-Synephrine)
Strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body. Increases peripheral venous return. Generally not used as a first-line agent. Correct volume deficits before administration.
Lidocaine (Xylocaine)
Secondary to NaHCO3 for dysrhythmias due to TCA toxicity. Class IB antiarrhythmic that increases electrical stimulation threshold of the ventricle, suppressing automaticity of conduction through the tissue. Second-line agent for treatment of ventricular dysrhythmias.
Anticonvulsants
Class Summary
Most seizures are short, self-limited, and may resolve before treatment can be administered; however, if prolonged greater than several minutes or repetitive, treatment is indicated. Controversy exists about the indications for sodium bicarbonate with seizures. A trial of NaHCO3 is recommended for seizures that are associated with QRS widening, after benzodiazepine treatment. If seizures are refractory to all treatment, paralysis is indicated to stop motor activity and resultant metabolic acidosis. Benzodiazepines may calm a patient presenting with agitation secondary to the anticholinergic effects. However, their use may exacerbate CNS depression from TCA overdose, so their use for this indication must be accompanied by aggressive monitoring and management of the airway. Flumazenil is contraindicated in treatment of TCA toxicity.
Lorazepam (Ativan)
Increasing the action of GABA, a major inhibitory neurotransmitter, may depress all levels of CNS, including limbic and reticular formation. DOC because of more prolonged anticonvulsant effects than diazepam or midazolam (4-6 h vs 1-3 h). Has an excellent safety profile.
Diazepam (Valium)
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA.
Phenobarbital (Barbita, Luminal)
Not used often because of the preferable safety profile of benzodiazepines but an effective antiseizure medication.
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