WORKUP	Section 5 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Lab Studies:

• Studies have shown that serum cyclic antidepressant (CA) level does not correlate well with severity of CA toxicity and is a poor predictor of clinical outcome.

• Because multisubstance ingestion is common, routine screening for other potentially treatable toxins is recommended (eg, acetaminophen). Request for the other serum toxicologic levels should be guided based on the clinical picture (eg, acidosis: aspirin, ethylene glycol, methanol)

• Check electrolytes, BUN, creatinine, and anion gap.

• CBC

• Alcohol level

• ABG for evaluation of acidosis or hypoxia

Imaging Studies:

• A chest radiograph should be obtained in cases of suspected aspiration or when respiratory symptoms are noted, and it may be used to rule out other causes of fever, tachycardia, and altered mental status.

Other Tests:

• ECG - Sinus tachycardia is the most common ECG finding in CA toxicity.

• Measurement of limb-leads QRS duration can be used to assess severity of CA exposure. QRS interval of greater than 100 msec is the basis for treatment with bicarbonate (alkalinization).

• Patients with QRS less than 100 msec are unlikely to develop seizures and arrhythmias. Those with QRS greater than 100 msec have up to a 34% chance of developing seizures and up to a 14% chance of developing a life-threatening cardiac arrhythmia. With QRS complex greater than 160 msec, chances for ventricular arrhythmias increase to 50%.

• The amplitude of the R wave in lead aVR and the ratio of the R/S waves in aVR are greater in patients who developed seizures or dysrhythmias.

• According to Liebelt et al, when the R wave in aVR equals 3 mm or more, the sensitivity and specificity for subsequent development of seizures or arrhythmias are 81% and 73%, respectively.

• ECG changes that can be observed in CA toxicity include sinus tachycardia; prolongation of the PR, QRS, and QTc intervals; nonspecific ST-segment and T-wave changes; AV block; right-axis deviation of the terminal 40-msec vector of the QRS complex in the frontal plane; and the Brugada pattern (downsloping ST-segment elevation in leads V1-V3 in association with RBBB).

• Brugada pattern ECG was seen in 17% of patients with TCA toxicity in a retrospective study completed by Monteban-Kooistra et al. The ECG abnormalities resolved after administration of sodium bicarbonate.

• Early recognition of conduction disturbances is important for suspecting a CA poisoning case.

Procedures:

• GI decontamination may be helpful within the first several hours postingestion because CAs can slow gastric emptying through the anticholinergic activity.

• Gastric lavage may be helpful in recovering and identifying the cyclic antidepressant ingested. However, a study comparing the use of gastric lavage and activated charcoal versus charcoal alone shows no benefit in clinical outcome. Usually, lavage is recommended for patients who developed significant toxicity requiring endotracheal intubation and who presented after relatively recent ingestion (several hours).

• Activated charcoal reduces the absorption of CAs. It may also be beneficial in cases of multisubstance ingestion. It should be administered only in patients who are able to protect the airway.

• Endotracheal intubation is indicated if the patient cannot adequately maintain a safe airway.

	TREATMENT	Section 6 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Prehospital Care: Endotracheal intubation is necessary in a patient who is obtunded and unable to protect his or her airway. Intravenous access should be established as soon as possible. Administer intravenous fluid if the patient is hypotensive. Prompt transport of the patient to the nearest emergency department is implicit.

Emergency Department Care: The greatest risk of seizures and arrhythmias occurs within the first 6-8 hours of CA ingestion. The treatment of an asymptomatic patient with a history of CA ingestion is mainly supportive therapy. For all patients with possible cyclic antidepressant toxicity, airway protection, ventilation and oxygenation, intravenous fluids, cardiac monitoring, and obtaining ECGs are all essential measures.

Consider early gastric decontamination using charcoal if the patient presents within 2 hours of ingestion.

Once suicidal ideation is ruled out and the patient remains asymptomatic for 6-8 hours postingestion without any ECG changes, the patient may be discharged home. If suicidal ideation is present, evaluation for admission to a psychiatric facility is mandatory.

• Airway: Endotracheal intubation may be necessary in patients who present with seizures or who are in a comatose state for airway protection.

• Hyperventilation: The use of hyperventilation is controversial. It has been recommended traditionally for the resultant alkaline state hyperventilation achieves. Alkalinization is thought to increase protein binding of CA, promote CA excretion, and thereby decrease cardiotoxicity. However, a randomized controlled animal study shows that hyperventilation has little effect on reversing CA toxicity.

• Hypotension

• Normal saline intravenous fluids are indicated for CA-induced hypotension.

• For hypotension refractory to intravenous saline, vasopressors, such as Neo-Synephrine or norepinephrine, with alpha-agonist effect, may be used.

• GI decontamination: Once the patient is stabilized, activated charcoal can be considered.

• Intravenous sodium bicarbonate

• Serum alkalinization with intravenous sodium bicarbonate has been the mainstay of therapy in CA-induced cardiovascular toxicity. Prolonged QRS is most often the indication for serum alkalinization in CA toxicity. Not all physicians agree upon what the duration of QRS should be in order for them to institute intravenous sodium bicarbonate therapy. However, about 88% of the poison control directors in the United States use a QRS of 100 msec or greater as the cut off for intravenous sodium bicarbonate. Evidence exists demonstrating the reversal of toxic effects of CA such as QRS prolongation and myocardial depression following serum alkalization and sodium loading with sodium bicarbonate.

• Animal studies have shown hypertonic saline to be effective in reversing CA toxicity. However, no study adequately compared efficacy of hypertonic saline versus sodium bicarbonate. Sodium loading may be the most important factor in the reversal of the symptoms of cyclic antidepressant toxicity.

• Benzodiazepines: The seizures in CA toxicity are usually self-limited. The treatment of choice for prolonged or recurrent seizures in cyclic antidepressant toxicity is a benzodiazepine. Most CA-induced seizures are usually brief and resolve prior to the administration of anticonvulsants. General anesthesia should be reserved for patients in status epilepticus who are unresponsive to the standard treatment regimen (eg, benzodiazepines, barbiturates, propofol). This may prevent hyperthermia and rhabdomyolysis.

• Hemodialysis or hemoperfusion: Because of the large volume of distribution and high protein binding characteristics of CAs, hemodialysis has not been shown to be effective in the treatment of CA overdose.

• Physostigmine is a short-acting cholinesterase inhibitor used for the reversal of anticholinergic symptoms. It should not be used in treating CA toxicity because of the reported cases of physostigmine-induced seizures and asystole.

Consultations:

• Poison control center/toxicologist.

• Cardiologist when indicated, possibly for pacemaker placement and arrhythmia management

• ICU admission for patients with cardiovascular and/or neurologic manifestations of CA toxicity

	MEDICATION	Section 7 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Treatment of CA toxicity focuses on airway management, dysrhythmias, seizures, and hypotension. Sodium bicarbonate, benzodiazepines, and norepinephrine are DOCs for these complications.

	MISCELLANEOUS	Section 9 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical/Legal Pitfalls:

• Use of physostigmine in CA poisoning has been associated with complete heart block, asystole, and hypotension.

• Ipecac syrup is not recommended as the procedure in GI decontamination because of the possibility that patients experience sudden neurologic deterioration (eg, lethargy, seizures) and aspirate.

• Use of type IA and IC antidysrhythmics or other sodium channel blockade agents may exacerbate toxic effects of CAs on the myocardium.

• Use of flumazenil for reversal of benzodiazepines overdose with concomitant CAs exposure can precipitate seizures

Special Concerns:

• ECG is a highly sensitive tool and can be used to rule out CA toxicity. However, it is not specific enough to be used alone to diagnose CA overdose. Widening of QRS complex can be used as a rough guide in determining the prognosis of TCA poisoning (eg, seizures, dysrhythmias). However, characteristic ECG changes in addition to clinical presentation (anticholinergic toxidrome, seizures, hypotension, tachycardia) seen with CAs can be an adjunction in diagnosing CA toxicity.

• Lidocaine, when used to treat ventricular arrhythmia, should be administered with caution to avoid precipitating seizures.

• Ventricular bradyarrhythmias, due to depressed AV conduction and automaticity, can be treated by placement of a temporary pacemaker, or consider the use of a chronotropic agent.

• CA exposure in children is common. The potentially lethal dose (with desipramine, imipramine, or amitriptyline) is as low as 15 mg/kg. Toddlers can exceed this threshold with only 1 or 2 pills, and they should be evaluated in the emergency department.