The predictive value of heart rate in determining clinical course after a bupropion overdose.

INTRODUCTION: Bupropion is a popular antidepressant due to its favorable side effect profile and indications for smoking cessation and weight loss. Due to the possibility of delayed onset seizure and other adverse outcomes after bupropion overdose, patients are often observed for periods of 12-24 hours following suspected ingestion. Tachycardia is a clinical predictor that holds promise in differentiating cases at risk for seizures from low-risk cases that do not require prolonged observation. This study assessed whether heart rate within the first eight hours of presentation can identify cases that do not require extended observation. METHODS: This is a retrospective cohort study of all supra-therapeutic bupropion cases from two hospital systems between 2010 and 2022. RESULTS: Data from 216 charts were included. Seizures, hypotension, and dysrhythmias occurred in 19 percent (n = 41), 1.4 percent (n = 3), 0.9 percent (n = 2) respectively. One patient died. Delayed adverse effects were rare (n = 4); they occurred from 14 hours to 28 hours post-ingestion. Maximum heart rate in eight hours was associated with a risk of adverse outcomes. (odds ratio, 1.07; 95 percent confidence interval: 1.05 to 1.09; P < 0.001). An eight hour maximum heart rate threshold of 104 beats/minute had a negative predictive value of 100 percent (95 percent confidence interval: 96.7 percent to 100 percent) for the occurrence of delayed adverse effects. All patients with delayed effects had tachycardia within five hours of emergency department arrival. DISCUSSION: Delayed adverse outcomes of seizures, hypotension, dysrhythmia, and death were uncommon in this cohort. Heart rate during the first eight hours of observation performs reliably as a screening test to identify patients at low risk for delayed adverse outcomes. This study is limited by its retrospective nature, the inability to ascertain time of ingestion for most cases and the lack of confirmatory laboratory testing. CONCLUSION: This study supports the use of an eight hour observation period when there are no other clinical signs of toxicity to warrant admission and if no co-ingestion or administration of substances that mask tachycardia are present.

Planned complex suicide involving combined drug intoxication and femoral catheterization.

Complex planned suicide is characterized by the simultaneous use of two or more methods to ensure that death occurs even if one method fails. The authors present an original combination of two self-killing methods. A 42-year-old cardiologist, with a major depressive syndrome and several suicide attempts, as well as cocaine addiction, was found dead at his home with a femoral catheter inserted in the right femoral artery. The autopsy concluded that death was due to major hemorrhagic process in a context of suicide. Toxicological analyses, performed in peripheral blood by gas chromatography coupled to mass spectrometry and by liquid chromatography-diode array detection, revealed the presence of ethanol (0.13 g/L), cocaine, and metabolites (cocaine: 432 µg/L, benzoylecgonine: 3286 µg/L, ecgonine methyl ester: 1195 µg/L, cocaethylene: 41 µg/L), a potentially lethal concentration of citalopram (1.03 mg/L), toxic concentrations of hydroxyzine (0.11 mg/L), bromazepam (2.06 mg/L), and lidocaine (7.30 mg/L). At the end of these analyses, the death was reclassified as planned complex suicide combining drug intoxication and catheterization of the femoral artery. The authors discuss the main aspects of this case and stress the importance of meticulous analysis of all available evidence: witness reports, victim's medical history and occupation, findings of at-the-scene examination, autopsy, and toxicological analyses, in order to exclude homicide and to understand the sequence of events that led to death.

Acute Compartment Syndrome.

Acute compartment syndrome occurs most frequently in connection with injuries, terminal or chemical damage of tissues, ischemia, the activity of toxins or in patients with tissue ischemia or muscle necrosis. Clinical findings have found pronounced pain, followed by paresthesias, pallor, and paresis. Decreased pulsation of arteries has also been a frequent finding. In severe forms decompressive fasciotomy has been indicated within the first 12-24 hours after diagnosis. In the following paper, the authors present the case report of a 68-year woman who swallowed 1500 mg of trazodone as an attempt at suicide. After 12 hours her husband found her lying on the carpet with compression of the left arm under the trunk. The patient was treated conservatively and followed clinically, examined by ultrasonography, EMG and finally MRI.

Bupropion associated seizures following acute overdose: who develops late seizures.

Objectives: Bupropion is an antidepressant that is commonly known to cause seizures in overdose. Because of concern for delayed onset of seizures, patients are frequently observed for prolonged periods after overdose. The primary objective is to evaluate the incidence and clinical parameters associated with late seizures following bupropion overdose.Methods: This retrospective study of acute bupropion overdose who presented to 26 different hospitals in California and Arizona during an 8 year time period.Results: 437 patients were identified. Tachycardia and altered mental status were common. A total of 122 (27.9%) patients had seizures following their overdose. Only eight patients (1.8%) had a seizure more than 8 h after hospital arrival. None of these patients were asymptomatic on arrival. Among patients with tachycardia on arrival, the odds of having a seizure was 6.7 (95% CI 3.7-10.9); the odds of a seizure more than 8 h after arrival was 5.24 (95% CI 1.2-23.5). Similarly, altered mental status on arrival was significantly associated with the risk of a seizure; OR 3.93 (95% CI 2.21-7.0).Conclusion: Seizures are relatively common, and are associated with antecedent tachycardia or altered mental status.

Seizure in venlafaxine overdose: a 10-year retrospective review of the California poison control system.

Background: The optimal observation time period with respect to seizures after venlafaxine overdose is unclear. We conducted a 10-year retrospective review of calls to the California Poison Control System to describe the time of onset of seizures in adult and pediatric overdose of venlafaxine.Methods: Inclusion criteria included adult and pediatric patients with exposure to venlafaxine, who were admitted to a health care facility and who had at least one seizure. We did not exclude cases in which co-ingestions of other drugs were reported. Data extraction of a priori defined variables was recorded. Descriptive statistics were used to characterize the cohort of patients, including means, medians, and interquartile ranges.Results: The total number of cases included in the data analysis was 123 (12.9% of all venlafaxine ingestions). The longest time to last seizure was 24 h. Twenty-five percent of participants had a seizure from hour 7 to 24 h. This did not differ significantly between IR and XR formulations.Conclusions: Optimal observation time with respect to seizures after overdose of immediate-release formulation of venlafaxine is 18 h (24 h if ingested with other medications), and 21 h for patients who are poisoned with the sustained-release formulation.

Pediatric Toxidrome Simulation Curriculum: Bupropion Overdose.

Introduction: Bupropion is a commonly used antidepressant, and overdose can lead to both neurologic and cardiovascular toxicity, including agitation, seizure, tachycardia, QT and QRS prolongation, and rhythm disturbances. Methods: We developed this simulation case for attendings, fellows, nurse practitioners, and nurses in the pediatric emergency department (ED). The scenario involved a 13-year-old male presenting to the ED with altered mental status and a generalized tonic-clonic seizure shortly after arrival. The team needed to quickly perform primary and secondary surveys, manage his airway and breathing, and initiate treatment for seizure. The team had to obtain an abbreviated history and include ingestion in the differential. The patient then developed pulseless ventricular tachycardia, and the team needed to respond with high-quality CPR, defibrillation, and advanced airway management. Preparatory materials, a debriefing guide, and scenario evaluation forms assisted with facilitation. Results: Twenty-eight physicians, 56 nurses, 10 nurse practitioners, four pharmacists, two students, and one respiratory therapist completed this simulation in 13 sessions. On a 5-point Likert scale, participants agreed with the stated objective of ability to manage a patient with a bupropion overdose (M = 4.09; range, 2-5). The scenario was rated as highly relevant (M = 4.93) and the debriefing as very effective (M = 4.85). Discussion: This scenario is a complete educational resource for setting up, implementing, and debriefing in an interprofessional setting. It was well received by learners from diverse professional backgrounds working together in actual care teams in the pediatric ED.

Suicidal bupropion ingestions in adolescents: increased morbidity compared with other antidepressants.

OBJECTIVE: Bupropion is often categorized as a newer generation antidepressant and assessed with serotonin reuptake inhibitors as a lower risk than older tricyclic antidepressants (TCAs). The objective of this study was to compare outcomes in adolescent suicide from ingestions between bupropion and TCA medications. STUDY DESIGN: An analysis of the National Poison Data System for exposures coded "suspected suicide" in adolescents (age: 13-19) was undertaken for the years 2013-2016 and included TCAs or bupropion. We compared clinical effects, therapies and medical outcomes. RESULTS: Over the four-year period there were 2253 bupropion and 1496 TCA adolescent suspected suicide calls. There was a significant linear increase in bupropion ingestions over the four years. Across all years, there were on average 189.2 (95% CI: 58.1-320.4; p = .01) more ingestions of bupropion than TCA. When comparing bupropion to a TCA, ingestions of bupropion were significantly more likely to be accompanied by seizure (30.7% vs 3.9%; p < .01), to be admitted (74.8% vs 61.6%; p < .01) and medical outcomes to be coded as a major outcome (19.3% vs 10.0%; p < .01). The number of cases with death or major clinical outcome for both increased over the four-year period. Ingestions of bupropion were less likely to have hypotension (2.7% vs 8.0%; p < .01) and less likely to be intubated (5.6% vs 16.4%; p < .01) as compared to ingestions of TCA. CONCLUSIONS: Adolescents who overdose on a single medication in a suicide attempt with bupropion have a statistically significant higher incidence of major outcomes and seizures. The risks of bupropion as a potential means of suicidal gesture by overdose must be considered, and weighed against its benefits and side effect profile when choosing an appropriate agent for the treatment of depression in adolescents.

Bupropion Overdose Resulted in a Pharmacobezoar in a Fatal Bupropion (Wellbutrin® ) Sustained-release Overdose: Postmortem Distribution of Bupropion and its Major Metabolites.

Bupropion (BUP) overdose commonly causes generalized seizures and central nervous system depression. The case of a 28-year-old woman who died from a massive lethal overdose with sustained-release bupropion (Wellbutrin® 300 mg) is herein presented. The autopsy revealed the presence of a pharmacobezoar consisting of at least 40 tablets in the stomach. Determination of bupropion and its active metabolites (hydroxybupropion, threobupropion, erythrobupropion) was achieved by a liquid chromatographic mass spectrometry (LC-MS/MS) method. Postmortem concentrations for bupropion, hydroxybupropion, threobupropion, and erythrobupropion were obtained in intracranial blood, urine, bile, liver, kidney, and vitreous humor. In this case, intracranial blood level of the parent drug was 1.9 mg/L. Threobupropion was the most abundant metabolite in both blood and urine, 59.3 and 890.6 mg/L. Tissue distribution showed the highest concentration in the liver, 12.3 mg/kg. The 0.8 bupropion concentration ratio vitreous/blood suggested that vitreous could be a valuable specimen for toxicological analysis should postmortem blood be unavailable.

Seizure due to multiple drugs intoxication: a case report / Convulsão por causa de intoxicação por múltiplas drogas: relato de caso

Abstract The mechanism of the antidepressant effect of bupropion is not fully understood. Besides, using it in the treatment of depression, it is found to be effective in reducing withdrawal symptoms due to smoking cessation. A 28-year-old female patient with a history of depression was admitted to emergency department an hour after ingestion of bupropion, quetiapine, and levothyroxine in high doses to commit suicide. While accepting her into the Intensive Care Unit, she was awake, alert, disoriented and agitated. After 2 h, the patient had a generalized tonic-clonic seizure. The necessary treatment was given and 9 h later with hemodynamic improvement, the patients’ mental status improved. Bupropion may cause unusual behaviors such as delusions, paranoia, hallucinations, or confusion. The risk of seizure is strongly dose-dependent. We want to emphasize the importance of early gastric lavage and administration of activated charcoal.

Resumo O mecanismo do efeito antidepressivo de bupropiona ainda não está bem esclarecido. Contudo, seu uso no tratamento de depressão revelou ser eficaz para reduzir os sintomas de abstinência relacionados à cessação do tabagismo. Uma paciente do sexo feminino, 28 anos, com história de depressão, deu entrada no setor de emergência uma hora após a ingestão de bupropiona, quetiapina e levotiroxina em doses elevadas para cometer suicídio. Ao ser internada em unidade de terapia intensiva, estava acordada, alerta, desorientada e agitada. Após duas horas, apresentou uma crise tônico-clônica generalizada. O tratamento necessário foi administrado e nove horas mais tarde, com a estabilização hemodinâmica, o estado mental da paciente melhorou. Bupropiona pode causar comportamentos incomuns, incluindo delírios, paranoia, alucinações ou confusão mental. O risco de convulsão é altamente dependente da dose. Queremos enfatizar a importância da lavagem gástrica precoce e da administração de carvão ativado.

Seizure due to multiple drugs intoxication: a case report.

The mechanism of the antidepressant effect of bupropion is not fully understood. Besides, using it in the treatment of depression, it is found to be effective in reducing withdrawal symptoms due to smoking cessation. A 28-year-old female patient with a history of depression was admitted to emergency department an hour after ingestion of bupropion, quetiapine, and levothyroxine in high doses to commit suicide. While accepting her into the Intensive Care Unit, she was awake, alert, disoriented and agitated. After 2h, the patient had a generalized tonic-clonic seizure. The necessary treatment was given and 9h later with hemodynamic improvement, the patients' mental status improved. Bupropion may cause unusual behaviors such as delusions, paranoia, hallucinations, or confusion. The risk of seizure is strongly dose-dependent. We want to emphasize the importance of early gastric lavage and administration of activated charcoal.

Low-dose intravenous lipid emulsion for the treatment of severe quetiapine and citalopram poisoning.

The treatment of quetiapine and/or citalopram poisoning is mainly supportive and involves gastric lavage, activated charcoal, intubation, and mechanical ventilation. Recently, however, there were reports of successful treatment with intravenous lipid emulsion. Here we report a case of a 19-year-old Caucasian girl who ingested approximately 6000 mg of quetiapine, 400 mg of citalopram, and 45 mg of bromazepam in a suicide attempt. The patient developed ventricular tachycardia and epileptic seizures 12 h after admission to the hospital. As the patient's condition deteriorated, we combined standard therapy (intubation, mechanical ventilation, and vasopressors) with low-dose intravenous lipid emulsion (ILE) (a total of 300 mL of 20 % lipid emulsion) and normalised her heart rhythm and stopped the seizures. She was discharged to the psychiatric ward after 48 h and home after a prolonged (2-month) psychiatric rehabilitation. Intravenous lipid emulsion turned out to be effective even in the lower dose range than previously reported for quetiapine poisoning in patients presenting with seizure and ventricular arrhythmia. To our knowledge, there are no case reports describing the use of ILE in treating citalopram poisoning.

Two Cases of Refractory Cardiogenic Shock Secondary to Bupropion Successfully Treated with Veno-Arterial Extracorporeal Membrane Oxygenation.

Bupropion inhibits the uptake of dopamine and norepinephrine. Clinical effects in overdose include seizure, status epilepticus, tachycardia, arrhythmias, and cardiogenic shock. We report two cases of severe bupropion toxicity resulting in refractory cardiogenic shock, cardiac arrest, and repeated seizures treated successfully. Patients with cardiovascular failure related to poisoning may particularly benefit from extracorporeal membrane oxygenation (ECMO). These are the first cases of bupropion toxicity treated with veno-arterial EMCO (VA-ECMO) in which bupropion toxicity is supported by confirmatory testing. Both cases demonstrate the effectiveness of VA-ECMO in poisoned patients with severe cardiogenic shock or cardiopulmonary failure.

Wide complex tachycardia after bupropion overdose.

Here we describe a wide complex tachycardia after bupropion overdose that was responsive to sodium bicarbonate. This rhythm was likely secondary to bupropion-induced sodium channel blockade and corrected QT interval (QTc) prolongation. It is critical for the emergency medicine physician to recognize that a wide complex rhythm in a patient with bupropion overdose may be secondary to sodium channel toxicity and prolonged QTc as this rhythm may be responsive to sodium bicarbonate. Identifying this rhythm as purely ventricular tachycardia can lead to the administration of medications such as amiodarone that may further prolong QTc and contribute to sodium channel blockade, exacerbating bupropion-induced cardiotoxicity.

[A fatal overdose of venlafaxine]. / Dødelig venlafaxinforgiftning.

An 18-year-old woman ingested 22 g of venlafaxine with suicidal attempt. At admittance two hours after ingestion she had serotonine syndrome, repeated seizures and hypotension. After eight hours malignant arrythmias culminated in cardiac arrest, which was successfully resuscitated. Progressive liver and cardiac failure lead to fatal outcome after 48 hours. It is discussed whether early lipid infusion should be given in case of ingestion of high doses of venlafaxine, before myoclonia, seizures, hypotension, rhabdomyolysis and liver failure developed, since these can only be treated symptomatically.