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.

Charcoal hemoperfusion in bupropion overdose.

Bupropion is a relatively new and popular medication for depression, with seizures as its major side effect. In the literature, there are insufficient data about hemodialysis following bupropion overdose. A 23-year-old female patient was brought to our emergency department with acute change in mental status and seizure after deliberate self-poisoning with approximately 25-30 tablets of bupropion hydrochloride. Her Glasgow coma scale score was 8/15. The patient underwent hemodialysis about 4 hours later. After 4 hours of extracorporeal treatment, she became conscious and was extubated. We present a case of full recovery after charcoal hemoperfusion following a bupropion overdose.

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.

ABCB1 gene polymorphisms are associated with fatal intoxications involving venlafaxine but not citalopram.

P-glycoprotein (P-gp), encoded by the ABCB1/MDR1 gene, is a drug transporter at the blood-brain barrier. Several polymorphisms in the ABCB1 gene are known to affect the activity and/or expression of P-gp, thereby influencing the treatment response and toxicity of P-gp substrates like citalopram and venlafaxine. In this study, we aimed to investigate the frequency of ABCB1 genotypes in forensic autopsy cases involving these two antidepressants. Further, the distribution of ABCB1 genotypes in deaths related to intoxication was compared to cases not associated to drug intoxication. The study included 228 forensic autopsy cases with different causes and manners of deaths. The ABCB1 single nucleotide polymorphisms (SNPs) G1199A, C1236T, C3435T and G2677T/A for these individuals were determined. The SNPs C1236T and C3435T in venlafaxine-positive cases were significantly different between the intoxication cases and non-intoxications. This was not seen for cases involving citalopram, indicating that the effect of genetic variants might be substrate specific. This novel finding should, however, be confirmed in future studies with larger number of cases.

Fatal venlafaxine poisonings are associated with a high prevalence of drug interactions.

Venlafaxine (VEN) is an antidepressant found to possess a higher fatal toxicity index (FTI, i.e., deaths in proportion to consumption) than other newer antidepressants and selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to elucidate using post-mortem cases whether the apparent high toxicity of VEN is associated with adverse drug interactions, pharmacogenetic factors and/or the manner of death. Within a 2-year period, a comprehensive post-mortem database and death certificates were searched for cases with laboratory findings of VEN, findings of other drugs, associated background information and the cause and manner of death. In 123 cases, the concentrations of VEN and its two metabolites, O-desmethylvenlafaxine (O-VEN) and N-desmethylvenlafaxine (N-VEN), and the CYP2D6 genotype were determined in post-mortem blood. The median concentrations of VEN, O-VEN and N-VEN were 560, 420 and 49 µg/l, respectively. A prominent feature of the VEN-positive cases was the high abundance of interacting drugs (46%), being more common with higher VEN concentrations. Compared to other common antidepressants, VEN-positive cases showed the highest suicide frequency, but also the proportion of suicidal VEN poisonings of all suicides was substantially higher than that of mirtazapine or SSRIs. Relative CYP2D6 activity did not predispose to high VEN concentrations, and the frequency of the extreme phenotypes followed the general population. In conclusion, the high suicide potential of VEN in combination with the high prevalence of drugs causing adverse interactions could be the reason for the observed high FTI.

Refractory hypotension from massive bupropion overdose successfully treated with extracorporeal membrane oxygenation.

An 11-month-old male infant presented with history of bupropion ingestion (750 mg/kg). He developed seizures, respiratory failure, and severe hypotension with metabolic acidosis refractory to inotropic support. The patient received mechanical ventilation, intralipids, phenytoin, inotropic support (dopamine, norepinephrine, and epinephrine), and extracorporeal membrane oxygenation (ECMO). Inotropes were weaned upon initiation of ECMO and discontinued 66 hours after ingestion. Total ECMO duration was 71 hours. The patient was extubated on hospital day 8 and has not had any neurological sequelae upon 12-month follow-up examinations. We report for the first time successful use of ECMO after ingestion of a potentially fatal dose of bupropion.

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.

An autopsy case of poisoning with selective serotonin reuptake inhibitor, paroxetine.

A female in her twenties was found dead in her room. She had received medications for depression and panic disorder, and had attemped suicide several times. Many packets of prescribed drugs, including paroxetine, were found near the corpse. At autopsy, the lungs were edematous. The organs were slightly congested with putrefactive change. Autolytic rupture, considered as gastromalasia, was observed in the anterior cardiac portion of stomach wall. Toxicological examination revealed 0.78, 3.20 and 17.63 microg/ml of paroxetine in the heart blood, femoral blood and urine, respectively. Acetaminophen and phenobarbital were also identified within therapeutic or sub-lethal levels. Taking into consideration postmortem diffusion of drugs, we evaluated postmortem data and concluded that the death was mainly due to toxicity of paroxetine with serotonin syndrome.

[Acute lethal poisoning with venlafaxine]. / Ostre, smiertelne zatrucie wenlafaksyna.

The case of acute venlafaxine poisoning with fatal outcome is shown. The 52-year-old woman with depression disorder ingested 56 pills of Symfaxin ER 150 venlafaxine as a suicidal attempt. Initially she was observed in the Neurology Department because of seizures, but after her husband found empty packages of medicine she was sent to the Toxicology Department being suspected of venlafaxine poisoning. The qualitative toxicological test confirmed the presence of venlafaxine in urine. In the course of poisoning rhabdomiolysis, hypotension and consecutive acute renal failure were observed. Finally, severe ventricular tachyarrhythmia occurred leading do cardiac arrest. Despite intensive symptomatic and supportive treatment the patient died.

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.

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.

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.

Fatal fluoxetine intoxication with markedly elevated central blood, vitreous, and liver concentrations.

Since being introduced into clinical practice 20 years ago, fluoxetine, a serotonin-reuptake inhibitor, has remained one of the most popular antidepressants prescribed in the United States. Upon reviewing the literature, the highest reported postmortem central blood fluoxetine and norfluoxetine concentrations are 22 and 6.8 mg/L, respectively, and reported liver fluoxetine and norfluoxetine concentrations are 29-128 and 17 mg/kg, respectively. A 31-year-old female with convulsive activity was found at home by her husband. Emergency services was contacted, and responders found the patient unresponsive with agonal respirations, a pulse of 20 bpm, and no measurable blood pressure. Despite all resuscitative efforts, the patient expired. Postmortem analyses revealed concentrations of 33 mg/L fluoxetine and 12 mg/L norfluoxetine in central blood and 400 mg/kg fluoxetine and 460 mg/kg norfluoxetine in liver. Vitreous fluoxetine and norfluoxetine concentrations were 5.2 and 2.2 mg/L, respectively. Utilizing a sensitive and specific analytical procedure, we report the highest recorded central blood and liver fluoxetine and norfluoxetine concentrations.

[Poisoning with antidepressants]. / Intoxikationen mit Antidepressiva.

Intoxications with medications are among the most frequent diagnoses in patients admitted to medical emergency departments and intensive care units. Due to their particular toxicity tricyclic antidepressants play an important role despite a decreasing incidence. Tricyclic antidepressant toxicity includes an inhibition of myocardial excitability, central (sedation, seizures) and peripheral anticholinergic signs, and arterial hypotension. Cardiac arrhythmia including ventricular tachycardia and fibrillation, sustained seizures and severe central anticholinergic symptoms such as agitation, delirium, and hyperthermia, are life threatening. Important treatment options include gastrointestinal decontamination with oral single-dose activated charcoal within 1-2 hours post ingestion, and antidotal therapy with boluses of sodium bicarbonate for cardiotoxicity. The selective serotonin reuptake inhibitors (SSRI) and the atypical antidepressants are far less toxic than tricyclics. They may lead to serotonin toxicity (serotonin syndrome).

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.

Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine.

Animal studies show efficacy of intravenous lipid emulsion in the treatment of severe cardiotoxicity associated with local anesthetics, clomipramine, and verapamil, possibly by trapping such lipophilic drugs in an expanded plasma lipid compartment ("lipid sink"). Recent case reports describe lipid infusion for the successful treatment of refractory cardiac arrest caused by parenteral administration of local anesthetics, but clinical evidence has been lacking for lipid's antidotal efficacy on toxicity caused by ingested medications. A 17-year-old girl developed seizure activity and cardiovascular collapse after intentional ingestion of up to 7.95 g of bupropion and 4 g of lamotrigine. Standard cardiopulmonary resuscitation for 70 minutes was unsuccessful in restoring sustained circulation. A 100-mL intravenous bolus of 20% lipid emulsion was then administered, and after 1 minute an effective sustained pulse was observed. The patient subsequently manifested significant acute lung injury but had rapid improvement in cardiovascular status and recovered, with near-normal neurologic function. Serum bupropion levels before and after lipid infusion paralleled triglyceride levels. This patient developed cardiovascular collapse because of intentional, oral overdose of bupropion and lamotrigine that was initially refractory to standard resuscitation measures. An infusion of lipid emulsion was followed rapidly by restoration of effective circulation. Toxicologic studies are consistent with the lipid sink theory of antidotal efficacy.