Comparative resuscitation measures for the treatment of desipramine overdose.

A toxic dose of desipramine (tricyclic antidepressant) causes cardiac arrhythmias and ultimately asystole. Resuscitation is difficult and almost always unsuccessful. Anecdotal evidence suggests that an infusion of lipid emulsion may be an effective treatment. The purpose of this study was to determine the optimal combination of lipid rescue and traditional Advanced Cardiac Life Support therapy for the treatment of desipramine overdose. We use a prospective, experimental, between subjects design with a swine model investigating the effectiveness of the drugs and drug combinations administered with cardiopulmonary resuscitation. Subjects were randomly assigned to 1 of 8 cardiopulmonary resuscitation/drug combination interventions, and the results from each group were compared using an analysis of variance and post hoc Tukey where appropriate. The groups that received vasopressin were more likely to survive than those that did not receive vasopressin, and the groups that received lipid emulsion were more likely to survive than those that did not receive lipid emulsion. Vasopressin alone was shown to be the most effective treatment in the management of desipramine overdose. The results of this study may warrant changes in treatment protocols for desipramine overdose.

Clinical psychopharmacology and medical malpractice: the four Ds.

The four Ds of medical malpractice are duty, dereliction (negligence or deviation from the standard of care), damages, and direct cause. Each of these four elements must be proved to have been present, based on a preponderance of the evidence, for malpractice to be found. The principles of psychopharmacology and the information in the package insert for a drug often play a central role in deciding whether dereliction and direct cause for damages were or were not applicable in a particular case. The author uses data from two cases in which patients were inadvertently fatally poisoned by medication to illustrate two ways in which such information can affect the outcome. In one case, the clinician should have known that he was giving a toxic dose to the patient, whereas that was not true in the other case.

Simultaneous ST-segment elevation in inferior and precordial leads following ingestion of a lethal dose of desipramine: a novel Brugada-like EKG pattern.

The typical Brugada electrocardiographic (EKG) pattern includes ST-segment elevation in the right precordial leads (V1-V3) associated with right bundle branch block (rSR') like morphology. Recently, a Brugada-like EKG pattern with ST-segment elevation in inferior leads called the "Brugada variant" has been reported. We report a case of simultaneous typical and variant Brugada EKG patterns with ST-segment elevation in the inferior as well as the precordial leads following ingestion of a lethal dose of desipramine.

Tricyclic antidepressant toxicity treated with massive sodium bicarbonate.

Tricyclic antidepressant (TCA) morbitity is primarily due to cardiac arrhythmias and hypotension, which become more refractory to treatment as acidosis progresses (Ann Emerg Med. 1985;14:1-9; Clin Toxicol. 2007;45:203-233; Flomenbaum N, Goldfrank L, Hoffman R, et al. Goldfrank's toxicologic emergencies. 8th ed. McGraw-Hill Companies, Inc, 2006). Early recognition and aggressive treatment are necessary for patient survival.

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.

Excess fatality from desipramine and dosage recommendations.

Higher case fatality rates (CFR) were previously reported from desipramine than for 3 other tricyclic antidepressants (TCAs): amitriptyline, nortriptyline, and imipramine. The database of the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) for the 20 years 1983-2002 was used to evaluate the CFR of desipramine and the other TCAs. The CFR of desipramine was 2.25-, 2.31-, and 2.62-fold the CFR for amitriptyline, nortriptyline, and imipramine, respectively (P < 0.001). Mechanisms of desipramine toxicity and its dosage recommendations are discussed. Desipramine and nortriptyline have higher distribution volumes and erythrocyte/plasma ratios than their parent compounds imipramine and amitriptyline. This implies lower therapeutic plasma levels and reduced doses for desipramine and nortriptyline compared with their parent compounds. Such adjustments have been done for nortriptyline, but not for desipramine. The authors suggest that the high CFR of desipramine might be reduced by lowering its dose, therapeutic plasma level, and maximal pill content.

The study of tricyclic antidepressants in formalin-fixed human liver and formalin solutions.

The stability of amitriptyline, nortriptyline, desipramine and imipramine in formalin-fixed human liver tissue and formalin solutions was investigated. The levels of the tricyclic and its primary demethylated metabolite in the frozen liver were determined and compared with levels obtained in the formalin-fixed liver and formalin solutions in which the liver was stored. It was obvious that some methylation of the secondary amine, nortriptyline, to the corresponding tertiary amine, amitriptyline, and of desipramine to imipramine took place in the formalin environment. Nortriptyline was not detected in most cases, suggesting that it may degrade more rapidly than desipramine. There was no consistent ratio between the concentration of the drug in the frozen liver tissue versus formalin-preserved tissue or versus formalin solution. The methylation rates of the secondary amines could not be quantitated. Storage of the liver tissue in formalin at room temperature resulted in leaching of the drugs into the formalin solution. The drugs tested may be detected for up to 22 months in the formalin-fixed liver and in the formalin medium.

Pulmonary complications following tricyclic antidepressant overdose in an adolescent.

OBJECTIVE: To report a case of pulmonary edema following a tricyclic antidepressant (TCA) overdose in an adolescent. CASE SUMMARY: A 14-year-old girl with a history of prior suicide attempts ingested 54 50-mg desipramine hydrochloride tablets (45 mg/kg ingestion). The patient developed a cardiac dysrhythmia and hypotension, which were successfully treated. She subsequently developed pulmonary edema and a clinical picture suggestive of adult respiratory distress syndrome (ARDS). She was successfully managed with fluid restriction, tracheal intubation, application of positive end-expiratory pressure (PEEP), and vasopressors. The patient was discharged without any clinical sequelae. DISCUSSION: Pulmonary complications secondary to TCA overdose have rarely been reported in children. We reviewed literature pertaining to the etiology, epidemiology, pathophysiology, and management of TCA-induced lung injury, as well as other case reports. We discuss the potential relationship between sequelae resulting from TCA ingestion (e.g., cardiac disturbances, hypotension, acidosis, gastric aspiration, pneumonia) and the development of ARDS and pulmonary edema, and relate this association to our patient. CONCLUSIONS: Pulmonary edema and a clinical picture suggestive of ARDS was noted in an adolescent girl who ingested a large quantity of desipramine. Her lung injury may have been the result of a variety of factors including hypotension, metabolic acidosis, possible aspiration, or a direct action on the lung parenchyma by desipramine. We attribute her favorable clinical outcome to early intervention consisting of tracheal intubation, PEEP, fluid restriction, and vasopressor therapy.

Calcium metabolism in acute renal failure due to rhabdomyolysis.

We report a patient with drug and hyperthermia induced rhabdomyolysis who developed acute renal failure. During the oliguric phase of 22 days, there was profound hypocalcemia (lowest ionized calcium of 0.34 mmol/l), associated with appropriately elevated intact PTH levels and high normal 1,25(OH)2D levels. Massive calcification in necrotic muscle occurred during this time. In the recovery phase, hypercalcemia was present lasting 33 days (maximum ionized calcium of 1.99 mmol/L), associated with suppression of PTH secretion, low 1,25(OH)2D3 levels, decreased bone resorption and mobilization of the muscle calcium deposits. This case report illustrates that the changes in serum calcium in rhabdomyolysis-associated acute renal failure are explicable by the deposition or removal of mineral into or from necrotic muscle with the parathyroid and vitamin D changes occurring secondarily.