Catecholamine Levels in Tricyclic Antidepressant Self-Poisoning

Summary: In a consecutive series of 20, patients with tricyclic antidepressant self-poisoning, urinary catecholamine excretion was measured, and the catecholamine level compared with that in ten patients having taken an overdose of other drugs. In both patient groups the electrocardiograph was monitored continuously for a minimum of 48 hours to detect cardiac arrhythmias. Urinary nor-adrenaline excretion was elevated during the first 24 hours after tricyclic anti-depressant self-poisoning, to a level 2–3 times that found in the other overdose group, but was normal by the third day. Cardiac tachyarrhythmias developed in four of the patients with antidepressant overdosage. The findings support the concept that sympathetic nervous system overactivity underlies the cardiac tachyarrhythmias which commonly accompany self-poisoning with this class of drugs.     

Cardiac effects of acute poisoning with tricyclic antidepressants: systematic review of the literature. Part I]

Tricyclic antidepressant overdose is a frequent diagnosis in the emergency room. It is responsible for a significant percentage of hospital admissions for observation and treatment. This is due to its cardiac (as well as neurologic) toxicity, and the difficulty in predicting its clinical gravity. The authors present the paper with two objectives in mind: 1) information about a common and significant cardiological emergency; 2) presentation of the methodology concerning systematic reviews of the literature. In this first (of four) articles, the epidemiology tricyclic antidepressant overdose is presented. In the remaining three papers we will present its clinical presentation, diagnosis, treatment, prognosis and prevention. Note: this is the first of a series of four articles on the cardiac toxicity of tricyclic antidepressant overdose; the next three articles will be presented in the July, August and September issues of the RPC.     

Cardiac effects of acute poisoning with tricyclic antidepressants: systematic review of the literature -- Part IV]

Tricyclic antidepressant overdose is a frequent diagnosis in the emergency room. It is responsible for a significant percentage of hospital admissions for observation and treatment. This is due to its cardiac (as well as neurologic) toxicity, and the difficulty in predicting its clinical gravity. The authors present this paper with two objectives in mind: 1) information about a common and significant cardiological emergency; 2) presentation of the methodology concerning systematic reviews of the literature. In this fourth article (the last in a series), we present the prevention and management of tricyclic antidepressant overdose (in the three previous articles--published in previous issues of the Revista--we discussed the epidemiological aspects as well as the clinical presentation and the diagnosis, and the prognosis). Note: this is the fourth and last article on the cardiac toxicity of tricyclic antidepressant overdose.     

Cardiac effects of acute poisoning with tricyclic antidepressants: systematic review of the literature -- Part II]

Tricyclic antidepressant overdose is a frequent diagnosis in the emergency room. It is responsible for a significant percentage of hospital admissions for observation and treatment. This is due to its cardiac (as well as neurologic) toxicity, and the difficulty in predicting its clinical gravity. The authors present this paper with two objectives in mind: 1) information about a common and significant cardiological emergency; 2) presentation of the methodology concerning systematic reviews of the literature. In this second (of four) articles, the clinical presentation and diagnosis of tricyclic antidepressant overdose are presented (in the first article--published in the previous issue of the Journal--we discussed the epidemiological aspects). In the remaining two papers we will present its management, prognosis and prevention. NOTE: This is the second of a series of four articles on the cardiac toxicity of tricyclic antidepressant overdose; the next two articles will be presented in the September and October issues of the Revista.     

Cathartic-induced magnesium toxicity during overdose management

A 39-year-old women was admitted to the hospital following a large ingestion of a tricyclic antidepressant. The administration of magnesium citrate in repeated doses with activated charcoal resulted in a striking increase in serum magnesium levels followed by acute neuromuscular deterioration and respiratory depression. The patient required dialysis for control of hypermagnesemia. Her clinical condition improved slowly without further complication and she was discharged to a rehabilitation center.     

Brugada electrocardiographic pattern due to tricyclic antidepressant overdose

The Brugada syndrome is an arrhythmogenic disease with characteristic coved ST-segment elevation 2 mm or greater in the right precordial leads (type 1 Brugada electrocardiogram [ECG] pattern or “Brugada sign”] and is estimated to be responsible for at least 20% of sudden deaths in patients with structurally normal hearts [Circulation 2005;111(5):659-70]. The Brugada sign has been described in asymptomatic patients after exposure to various drugs. As published reports of the drug-induced Brugada sign have become increasingly prevalent, there is growing interest in the mechanisms responsible for this acquired ECG pattern and its clinical significance.We report a case of a patient who developed the type 1 Brugada ECG pattern after intentional overdose of a tricyclic antidepressant agent, review the literature concerning tricyclic antidepressant agent-induced Brugada sign, discuss potential mechanisms, and evaluate the clinical significance of this ECG abnormality.     

Seizures due to maprotiline overdose

Maprotiline, a new tetracyclic antidepressant, has a pattern of toxicity that is different from that of tricyclics. Maprotiline overdosage appears more likely to cause seizures but less likely to cause the peripheral autonomic and cardiac manifestations seen with tricyclics. Two cases of maprotiline overdose resulting in seizures without significant anticholinergic or cardiotoxic effects are presented. Both patients were treated acutely with gastric emptying and were observed to have no further seizures during subsequent drug-free hospital and outpatient follow up. Physostigmine salicylate has been used as an antidote for the anticholinergic syndrome of tricyclic overdose, but probably offers less in maprotiline overdose. Careful observation for seizures appears to be warranted.     

Pulmonary complications after tricyclic antidepressant overdose

We studied 82 consecutive patients admitted to the ICU with predominant tricyclic antidepressant overdose (mean plasma tricyclic level, 1,025 ng/ml) to determine the nature and incidence of respiratory complications. The majority of patients (80.4 percent) had a decreased arterial to alveolar oxygen tension ratio (PaO2/PAO2) on initial emergency room arterial blood gas analysis (mean, 0.56). Mechanical ventilation was required in 76.8 percent of the patients for a mean duration of 46.2 h. Chest radiograph abnormalities developed during the first 48 h in 32/82 patients (39 percent). The group with radiographic abnormalities had higher mean drug levels than the group without (p less than 0.05). Of 82 patients, nine (11 percent) developed radiographic evidence of bilateral alveolar infiltrates suggestive of acute lung injury. This group had significantly higher mean drug levels than the groups with other types of radiographic abnormalities (p less than 0.001). Charcoal was recovered from the airway of 18/72 patients who received activated charcoal slurry by nasogastric tube in the emergency room after endotracheal intubation. The group who aspirated did not show statistically significant difference in the incidence of chest radiograph abnormalities, gas exchange, or survival compared with the group that did not aspirate.     

Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal

Activated charcoal usually provides effective and safe treatment for drug overdose. We describe a patient who developed bronchiolitis obliterans and respiratory failure following aspiration of activated charcoal. This patient had a markedly reduced vital capacity with roentgenographic evidence of airtrapping. Chest roentgenograms did not demonstrate the large amount of charcoal identified at postmortem examination.     

Cross hepatotoxicity between tricyclic antidepressants.

Cross hepatotoxicity between drugs in very uncommon. We report the case of a patient in whom acute hepatitis was induced by a tricyclic antidepressant, amineptine, and recurred early after administration of another tricyclic antidepressant, clomipramine. This observation suggests that the tricyclic ring is involved in the mechanism of the deleterious effect of both drugs to the liver.     

Amoxapine cardiotoxicity

Prolongation of the QRS interval, cardiopulmonary arrest, and death in a 31-year-old woman following an overdose of 2 g amoxapine, a tricyclic antidepressant, is reported. The patient's QRS interval prolonged to beyond 100 ms throughout hospitalization. Thirty-three hours after admission she suffered a bradycardiac-hypotensive event, followed by electromechanical dissociation and subsequent death. Cardiotoxicity has not been directly related to amoxapine; a 2-g acute ingestion is the lowest reported lethal dose.     

Level of consciousness as a predictor of complications following tricyclic overdose

In order to determine whether patients at low risk for complications following tricyclic antidepressant (TCA) overdose can be identified, we analyzed the records of all admissions for TCA overdose from 1975 to 1985. Of the 92 patients reviewed, 37 had serious complications including hypoventilation, loss of protective airway reflexes, seizures, hypotension, hemodynamically significant arrhythmias, or death. Patients with complications had increased heart rate, depressed level of consciousness, depressed Glasgow Coma Scale, and prolonged QRS interval, as compared to patients without complications. All 37 patients with serious complications required intubation in the emergency department. A Glasgow Coma Scale of less than 8 was the most sensitive predictor of serious complications (sensitivity = .86; specificity = .89). This was significantly better than the QRS interval (QRS greater than or equal to 100 msec; sensitivity = 59; specificity = .76). We conclude that level of consciousness is a better predictor of risk of complications and need for ICU admission than the QRS interval. Patients who are responsive to verbal stimuli on leaving the ED are at very low risk of developing complications.     

Theophylline toxicity: clinical features of 116 consecutive cases

PURPOSE: To examine the predisposing factors, clinical and laboratory characteristics, management, course, and outcome of consecutive cases of theophylline toxicity in an outpatient setting. PATIENTS AND METHODS: Toxicology records and hospital charts of consecutive patients with a serum theophylline concentration (STC) greater than 30 mg/L (167 mumol/L) identified in the emergency departments (EDS) of a University Medical Center and a Veterans Administration Medical Center were reviewed. RESULTS: Ten percent and 2.8% of 5,557 consecutive STCs measured in the EDs over 2 years were greater than 20 mg/L (111 mumol/L) and greater than 30 mg/L (167 mumol/L), respectively. One hundred sixteen cases with STC greater than 30 mg/L were identified. Fourteen (12%) and 102 (88%) were due to acute overdose and chronic overmedication, respectively. Principal predisposing factors included patient and/or physician dosing errors and conditions or medications that reduce theophylline clearance. One or more toxic manifestations were present in 109 (94%) cases. Fifty percent of patients had mild toxicity, 38% had moderate toxicity, and 7% had severe or life-threatening toxicity. Seven (6%) patients died when STC was still in the toxic range and/or as a result of toxicity. Acute overdose was associated with higher peak STC (p less than 0.001), younger age (p less than 0.01), and greater mortality (p less than 0.05) than chronic overmedication. Peak STC correlated significantly with the severity of toxicity for patients with acute overdose (p less than 0.01) but not for patients with chronic overmedication. All three patients with acute overdose and fatal toxicity had peak STCs greater than 100 mg/L (555 mumol/L) and fulminant toxicity, whereas the four patients with chronic overmedication who died during toxicity had peak STCs in the 40 to 60 mg/L (222 to 333 mumol/L) range and most died of respiratory failure rather than directly from toxicity. Patients with acute overdose who had the delayed onset of severe or life-threatening toxicity and/or died from toxicity were accurately identified using previously published criteria for prophylactic charcoal hemoperfusion. In contrast, the predictive value of the criteria applied to patients with chronic overmedication was poor. Two patients with acute overdose underwent charcoal hemoperfusion, but died. No patient with chronic overmedication received charcoal hemoperfusion. CONCLUSION: Toxic-range STCs are relatively common in the ED population, occur primarily as a result of patient and physician dosing errors, and cause a broad range of toxic manifestations of varying severity. Peak STC correlates with the severity of toxicity and outcome for acute overdose but not chronic overmedication intoxication. Previously published criteria for prophylactic charcoal hemoperfusion accurately identify patients with acute overdose but not patients with chronic overmedication at risk for serious complications and death.     

Pharmacotherapy of depression in old age

This review addresses the pharmacotherapy of antidepressants in the elderly. We performed a search based on Medline and the Cochrane Library. In addition to a meta-analysis of 17 randomised controlled studies, 36 randomised controlled trials of patients over the age of 60 published between 1980 and 2005 in English met the selection criteria and were included. Existing evidence suggests that no one class of antidepressant drugs has been found to be more effective than another in the treatment of depression in the elderly. Although newer antidepressants are not more effective than older ones, they are better tolerated and are safe especially in overdose. The adverse effect data suggest modest superiority of selective serotonin reuptake inhibitors over tricyclic antidepressants. The evidence available indicates that antidepressant treatment of four weeks has a beneficial effect compared to placebo. As to prevention of relapse and recurrence, antidepressants should be continued for at least six months after good initial response. In patients with high risk of relapse, treatment should be continued for at least two years. Long-term efficacy has been shown for dosulepin, nortriptyline and citalopram. In patients with dementia with persistent and significant symptoms antidepressant treatment may be indicated. At present, clomipramine, citalopram and sertraline have been reported as being superior to placebo. There is a paucity of data on the use of antidepressants in very elderly individuals, patients with significant comorbidity and patients with dementia. More data on the effect of antidepressants in the elderly, especially in the over 80-age group are needed.     

Late death in tricyclic antidepressant overdose revisited

We report a late death following the ingestion of amitriptyline. A 46-year-old woman presented to the emergency department with coma, hypotension, tachycardia, and a prolonged QRS interval after the ingestion of a large quantity of Elavil. She was managed with aggressive supportive care, multiple doses of oral charcoal, and charcoal hemoperfusion. The patient's ECG and hemodynamic status returned to normal within 24 hours. Despite an apparent total recovery, she suddenly sustained a cardiorespiratory arrest and died 33 hours after ECG normalization (at 57 hours after admission). This case brings into question the feasibility of ceasing ECG monitoring in tricyclic antidepressant overdoses once the ECG has stabilized, especially in patients with a history of chronic usage. A possible explanation for late sequelae is the myocardial cell binding and depressant effect of preexisting therapeutic TCA medication.     

Failure of gastric emptying and charcoal administration in fatal sustained-release theophylline overdose: pharmacobezoar formation.

We report the case of a fatal theophylline overdose from a sustained-release preparation in a 54-year-old woman. Initial serum theophylline concentration was 31.3 mg/L. Manifestations of mild toxicity cleared in the emergency department after treatment with gastric lavage, charcoal, and a cathartic. A life-threatening overdose was not suspected, and the patient arrested eight hours after discharge from the ED. At autopsy, her serum theophylline concentration was 190.1 mg/L. A white, waxy mass weighing 318.8 g and containing 29 g theophylline, representing the residue of many sustained-release tablets, was found in her stomach. This case reinforces the importance of obtaining repeat serum theophylline levels in patients with sustained-release theophylline overdose. Gastric pharmacobezoar formation should be considered in cases of sustained-release theophylline overdose with rising theophylline levels and patient deterioration, despite adequate gut decontamination.     

Iatrogenic pleuropulmonary charcoal instillation in a teenager

Activated charcoal given through a nasogastric tube is a standard intervention for many types of toxic ingestions in the emergency department. This case study describes a teenage girl whose multidrug overdose was complicated by accidental charcoal instillation into her left lung and pleural space through a misplaced nasogastric tube. The ensuing empyema did not respond to antibiotic therapy alone, probably due to the inherent properties of charcoal, and required a chest tube placement with continuous irrigation. Unlike previously reported cases, this patient did well clinically, without long-term morbidity.     

Epidemiology of fatal tricyclic antidepressant ingestion: implications for management

Although there is a large body of literature documenting the lethal cardiotoxic complications of tricyclic antidepressant (TCA) overdose, the absence of reliable predictive signs has led to a policy of admitting even trivial-appearing overdoses for inpatient observation. A study of 18 fatal cases revealed that with the exception of two that received clearly inadequate medical care, all fatal ingestions developed major signs of toxicity mandating admission within two hours of arrival at the hospital, and the mean time from arrival to death was only 5.43 hours. All patients who died of direct TCA toxicity did so within 24 hours of arrival. In addition, half the fatal cases presented with only trivial signs of poisoning, but deteriorated catastrophically within one hour. These data lead to an algorithm to guide admission of serious cases.     

Expanded role of charcoal therapy in the poisoned and overdosed patient

Activated charcoal is widely used as an adsorbent for the management of patients with drug overdoses and poisonings. Activated charcoal can be used orally to prevent drug and poison absorption in cases of overdose and poisoning. Multiple oral doses of charcoal increase the elimination of several, but not all, drugs and poisons. The effectiveness of multiple oral doses of charcoal in accelerating drug clearance is dependent primarily on the endogenous clearance of the drug or poison and its volume of distribution. Multiple doses of charcoal are used to shorten the period of supportive care in certain patients or to more rapidly remove drugs or poisons that may cause tissue damage, eg, theophylline. Charcoal is a safe, effective, and inexpensive alternative to more invasive treatments for some cases of drug overdose and poisoning.     

Charcoal-containing empyema complicating treatment for overdose

A 25-year-old man was treated with gastric lavage and activated charcoal for alcohol and drug overdose; immediately following the initial treatment he developed tension pneumothorax successfully managed with a chest tube. The patient presented four weeks later with a charcoal-containing empyema, an unreported condition heretofore.