Tricyclic Antidepressant Overdosage Research Articles

Fab Antibody Fragments

This review provides current information on the use of antigen-binding fragments (Fab) from cleaved antibodies to treat poisoning with digoxin and other potent, low formula mass poisons, such as colchicine and tricyclic antidepressants. Anti-digoxin Fab fragments have been used successfully for many years in the management of severe poisoning with digoxin, digitoxin, and a range of other structurally related compounds, including cardiotoxins from Nerium and Thevetia sp. (oleander) and Bufo sp. (toads). However, their main use remains treating digoxin poisoning. Equimolar doses of anti-digoxin Fab fragments completely bind digoxin in vivo. The approximate dose of Fab fragments (mg) is 80 times the digoxin body burden (mg). If neither the dose ingested nor the plasma digoxin/digitoxin concentration is known, in an adult 380 mg of anti-digoxin Fab fragments should be given. The dose for elderly patients or those with renal impairment should be similar to that for those with normal renal function. Fab fragments have a plasma half-life of 12-20 hours, but this can be prolonged in patients with renal impairment. Analysis of serum ultrafiltrate using an immunoassay shown not to have matrix bias remains the most accurate approach to measuring free digoxin in the presence of anti-digoxin Fab fragments. The antibody fragments are given intravenously over 15-30 minutes after dilution to at least 250 mL with plasma protein solution, 0.9% (w/v) sodium chloride, or deionised water, except in infants where the volume infused can be reduced. Factors limiting the efficacy of Fab fragments are the dose, the duration of the infusion and any delay in administration. Guidelines for Fab fragment administration in children include (i) dilution to a final Fab concentration of 10 g/L in either 5% (w/v) dextrose or 0.9% (w/v) sodium chloride; (ii) infusion through a 0.22 microm filter; (iii) administration of the total dose over a minimum of 30 minutes; and (iv) avoiding coadministration of other drugs and/or electrolyte solutions. Fab fragments are generally well tolerated. Adverse effects attributable to Fab treatment include hypokalaemia and exacerbation of congestive cardiac failure; renal function could be impaired in some patients. Fab fragment preparations for treating acute colchicine and tricyclic antidepressant poisoning have been developed, but are not available commercially. Colchicine poisoning is rare in Western countries, and pharmacological management together with supportive care is usually effective even in severe tricyclic antidepressant overdosage. Attempts have been made to produce anti-paraquat antibodies capable of enhancing paraquat elimination from the lung, but thus far all such attempts have proved unsuccessful.

QRS interval in tricyclic antidepressant overdosage: Inaccuracy as a toxicity indicator in emergency settings

Emergency department treatment and disposition of tricyclic antidepressant (TCA)-overdose patients remains a common and difficult problem. Various clinical findings have been proposed as toxicity indicators. To study the performance of QRS duration as a predictor of toxicity in our patient population, we retrospectively reviewed the cases of all patients presenting to our ED with TCA overdosage. The charts of 102 patients with quantitative or qualitative laboratory confirmation of TCA ingestion were reviewed for ED findings and hospital course with specific attention to the occurrence of ventricular arrhythmias (VAs) or seizures. The ED ECG revealed that 57 patients had a maximal 12-lead ECG QRS interval duration (QRS) of less than .10 seconds (Group 1). The remaining 45 patients had QRS greater than or equal to .10 seconds (Group 2). Three patients (5%) in Group 1 and three (6%) in Group 2 experienced VAs. Four patients (7%) in Group 1 and five (11%) in Group 2 experienced seizures. There was no significant difference in the rate of occurrence of VAs or seizures between the two groups. Of note was the fact that five of eight VAs and nine of 11 seizures occurred in the ED setting. We conclude that determination of QRS duration is not an accurate indicator of VA or seizure risk for all TCA-overdose populations. In particular, risk of toxic events during the emergency phase of TCA overdose does not appear to be indicated by evaluation of the QRS duration in the ED.

Tricyclic antidepressant overdose: Emergency department findings as predictors of clinical course

There is controversy regarding the appropriate utilization of health care resources in the management of tricyclic antidepressant overdosage. Antidepressant overdose patients presenting to the emergency department (ED) are routinely admitted to intensive care units, but only a small proportion develop cardiac arrhythmias or other complications requiring such an environment. The authors reviewed the findings in 165 patients presenting to an ED with antidepressant overdose. They found that major manifestations of toxicity on ED evaluation (altered mental status, seizures, arrhythmias, and conduction defects) were commonly associated with a complicated hospital course. Patients with the isolated findings of sinus tachycardia or QTc prolongation had no complications. No patient experienced a serious toxic event without major evidence of toxicity on ED evaluation and continued evidence of toxicity during the hospital course. These data support the concept that proper ED evaluation can identify a large body of patients with trivial ingestions who may not require hospital observation.

Clinical presentation and treatment of tricyclic antidepressant overdosage

Clinical presentation and treatment of tricyclic antidepressant overdosage

Poisoning Due to Tricyclic Antidepressant Overdosage

Tricyclic antidepressants are among the commonest causes of both non-fatal and fatal drug poisoning in the world. Their toxicity is due to effects on the brain, the heart, the respiratory system and the parasympathetic nervous system. Symptoms usually appear within 4 hours of an overdose and all but the most seriously poisoned patients recover within 24 hours. The most common clinical features are dry mouth, blurred vision, dilated pupils, sinus tachycardia, pyramidal neurological signs, and drowsiness. In severe poisoning, there may be coma, convulsions, respiratory depression, hypotension and a wide range of electrocardiographic (ECG) abnormalities. The most frequent findings on the ECG are prolongation of the PR and QT intervals; the tracing may resemble bundle branch block or supraventricular or ventricular tachycardias. Treatment of poisoning due to the tricyclic antidepressants is essentially supportive, there being insufficient evidence at present to recommend the use of methods to increase elimination of the drug from the body. Gastric aspiration and lavage should be performed if more than 750 mg of drug have been taken. There must be regular monitoring for hypoxia, acidosis and hypokalaemia and these complications should be corrected enthusiastically. Convulsions should be treated with diazepam or chlormethiazole. Muscular paralysis and artificial ventilation should be employed if anticonvulsants are ineffective. Hypotension should be treated firstly by fluid replacement and then with sympathomimetic agents (dopamine or dobutamine). Antiarrhythmic drugs should only be employed if there is evidence of circulatory failure which fails to respond to correction of hypotension. Sodium bicarbonate infusions should be given to cardiotoxic patients who are acidotic and are worth trying even if the patient is not acidotic. Although physostigmine salicylate will reverse most of the features of tricyclic antidepressant poisoning, its effects are short-lived in serious toxicity and it can produce dangerous side effects; physostigmine should therefore be reserved for those patients who have complications of coma or who have resistant cardiotoxicity or convulsions. Drug screening and quantitative determination of tricyclic antidepressant serum concentrations are useful in a minority of patients who have severe, unusual or prolonged symptoms.

Prevention of Cardiovascular and Renal Complications in Tricyclic-Drug Overdose

To the Editor. —I. read with interest the article entitled "Amoxapine-Associated Acute Renal Failure" by Jennings et al, 1 published in the August 1983Archives. These authors described a patient who had acute renal failure, a brief seizure, and mild rhabdomyolysis that developed after an overdose with the tricyclic antidepressant (TCA) amoxapine. Although the authors were unable to define clearly the cause of the acute renal failure in their patient, they commented that rapid hydration with a physiologic saline solution might prevent acute renal failure in patients with amoxapine overdosage. It is this point that I wish to address. The major clinical manifestations in TCA overdosage, requiring the attention of the clinician, include severe cardiovascular disturbances (eg, hypotension and dysrhythmia), CNS depression, respiratory failure, seizures, 2 and acute renal failure. 1 After initial strategies to obtain and maintain an airway and to support respiratory and cardiovascular function, beginning treatment of

Tricyclic antidepressant overdosage: experimental studies on the management of circulatory complications.

Tricyclic antidepressant overdosage may be complicated by cardiac arrhythmias, which were sometimes difficult to treat prior to the use of sodium bicarbonate. Experiments have been done with several antiarrhythmics in an attempt to define the optimum treatment. Sodium bicarbonate proved the most effective experimentally and this supports our clinical experience. Physostigmine is a useful second drug, having beneficial effects against arrhythmias and central nervous system manifestations of toxicity. Practolol, although reversing the arrhythmias, tends to cause hypotension. Other drugs tried were less effective.

Tricyclic antidepressant overdose: clinical presentation and plasma levels.

Fifteen patients were studied at 8- to 12-hr intervals during the first 24 hr after overdosing with tricyclic antidepressants, and subsequently followed daily for up to 144 hr. The severity of the overdose was determined by measuring the plasma tricyclic antidepressant level using gas chromatography-mass fragmentography. No correlation was found between total, tertiary, or desmethyl tricyclic antidepressant plasma levels and maximum heart rate, lowest blood pressure, degree of unconsciousness, or EKG changes involving the P-R interval or ST-T wave changes. There was a weak correlation between drug plasma level and maximum pupil size (r = 0.46; p less than 0.05) and a strong correlation between the duration of the QRS complex and tricyclic antidepressant plasma levels (r = 0.75; p less than 0.01). All patients with a total tricyclic antidepressant plasma level greater than or equal to 1,000 ng/ml had a QRS interval greater than or equal to 100 msec. As the total plasma tricyclic level fell, the duration of the QRS interval returned to normal. Thus, the duration of the QRS complex on the electrocardiogram appears to be the most reliable clinical sign for evaluating the seriousness of tricyclic antidepressant overdosage.

Physostigmine salicylate in the treatment of tricyclic antidepressant overdosage

Physostigmine salicylate in the treatment of tricyclic antidepressant overdosage

Physostigmine Salicylate in the Treatment of Tricyclic Antidepressant Overdosage

Following intravenous administration of physostigmine salicylate for tricyclic antidepressant poisoning in 21 patients, convulsions occurred in two patients, and severe cholinergic manifestations occurred in two others. Because of these untoward effects and the very short duration of its beneficial action, it is very doubtful that physostigmine has any place in the routine management of tricyclic antidepressant poisoning.

Amitriptyline Cardiotoxicity

Tricyclic antidepressant overdosage has been reported to cause varions electrocardiographic abnormalities. This is a report of a patient in whom amitriptyline overdosage was associated with transient prolongation of the PR interval, complete right bundle branch block and marked right axis deviation (possible trifascicular block). The need for constant electrocardiographic monitoring and the availability of temporary pacing equipment is stressed. Tricyclic antidepressant overdosage has been reported to cause varions electrocardiographic abnormalities. This is a report of a patient in whom amitriptyline overdosage was associated with transient prolongation of the PR interval, complete right bundle branch block and marked right axis deviation (possible trifascicular block). The need for constant electrocardiographic monitoring and the availability of temporary pacing equipment is stressed.

Treatment of Tricyclic Antidepressant Overdosage Arrhythmias

The comments on treatment of tricyclic antidepressant intoxications in your May 1973 issue were interesting, but I feel prompted to stress the importance of sodium bicarbonate or alkalinization in the management of these arrhythmias. We have treated over 150 children with tricyclic antidepressant overdosage in our intensive care unit, and of these 50 have had serious manifestations of overdosage—arrhythmias, convulsions, unconsciousness or a combination of these. Initially we experienced the frustration of being unable to control the arrhythmias satisfactorily, but since the value of sodium bicarbonate (given as a bolus of 1-3 mEq/kg intravenously) has been recognized, we have only had one out of 20 patients who did not revert rapidly to sinus rhythm with sodium bicarbonate and even that patient reverted half an hour after diphenylhydantoin and sodium bicarbonate had been given.

Cardiovascular complications of tricyclic antidepressant overdosage.

Cardiovascular complications of tricyclic antidepressant overdosage.

The use of sodium bicarbonate in the treatment of tricyclic antidepressant-induced arrhythmias.

Sodium bicarbonate has been successfully used clinically to treat arrhythmias induced by tricyclic antidepressant drugs (imipramine, amitriptyline, nortriptyline, dibenzepin). Experiments conducted on puppies showed that arrhythmias caused by amitriptyline disappear when acidosis is adequately treated. Plasma protein binding of amitriptyline increases as pH rises, reducing the unbound fraction of drug. This mechanism is an important factor in the antiarrhythmic action of sodium bicarbonate in tricyclic antidepressant overdosage.