Bupropion overdoseMANAGEMENT

TOXICOLOGIC PRESENTATIONS · 12 SECTIONS

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604 items

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01Approach to the Critical Patient/attcp35

Immediate stabilization priorities

›Attach continuous cardiac monitoring, pulse oximetry, and non-invasive blood pressure on arrival

›Establish two large-bore intravenous lines

›Point-of-care glucose in every patient with agitation, seizure, or depressed mental status

›Bedside 12-lead ECG within 10 minutes and repeated serially

›Characterize the ingestion before the patient deteriorates

›Formulation is the single most important history point: immediate-release versus sustained-release versus extended-release

›Sustained-release and extended-release ingestions produce delayed seizures up to 24 hours after ingestion

›Estimate total milligrams ingested and time since ingestion

›Contact the regional poison centre or medical toxicologist early

›Every deliberate ingestion and every symptomatic child warrants consultation

›Raise extracorporeal membrane oxygenation availability early when QRS widening or shock is present

›Anticipate a deceptively well-appearing early presentation

›A normal initial ECG and normal mental status do not exclude evolving cardiotoxicity or a delayed seizure

›Do not medically clear a sustained-release or extended-release ingestion on the basis of an early normal examination

Seizure as the sentinel event

›Treat the seizure and its triggers together

›Benzodiazepine first-line: lorazepam 0.1 mg/kg IV, maximum 4 mg per dose

›Point-of-care glucose, sodium, and core temperature with every seizure

›Protect the airway and give high-flow oxygen in the post-ictal phase

›Recognize progression to status epilepticus

›A seizure beyond 5 minutes, or repeated seizures without recovery between them

›Move to a second benzodiazepine dose then a second-line anticonvulsant without delay

›Expect delayed and recurrent seizures

›Sustained-release and extended-release ingestions can seize up to 24 hours after ingestion

›Keep the patient on a monitor and never discharge a modified-release ingestion early

Circulatory collapse and refractory shock

›Escalate cardiac support in a defined sequence

02History/hx32

Ingestion characterization

›Formulation taken

›Immediate-release, sustained-release, or extended-release preparation

›Combination product bupropion-naltrexone for weight loss contains 90 mg bupropion per tablet

›Branded smoking-cessation product versus antidepressant product, to gauge household pill availability

›Dose and timing

›Estimated total milligrams and number of tablets, cross-checked against the prescription and pharmacy fill

›Time of ingestion and whether it was a single acute ingestion or staggered

›Acute ingestion above 600 mg in an adult carries meaningful seizure risk

›Ingestion above 4.5 g predicts wide-complex dysrhythmia and shock

›Co-ingestants

›Alcohol, benzodiazepines, and antiepileptic drugs recently stopped, all of which lower the seizure threshold

›Serotonergic agents, tricyclics, stimulants, tramadol, and antipsychotics that compound cardiac and seizure toxicity

›Acetaminophen and salicylate as routine occult co-ingestants in deliberate overdose

›Intent and circumstances

›Deliberate self-harm versus therapeutic error versus recreational insufflation

›Prior overdoses, psychiatric diagnoses, and current stressors

›Witnessed seizure, syncope, or fall before arrival

Medication history and seizure-threshold risk factors

›Conditions that lower the seizure threshold

›Known epilepsy or a prior provoked seizure

›Anorexia nervosa or bulimia nervosa, in which bupropion is contraindicated

›Abrupt alcohol or sedative withdrawal

›Traumatic brain injury, central nervous system tumour, or prior stroke

›Cardiac history

›Known coronary disease, heart failure, or prior ventricular dysrhythmia

›Baseline QT prolongation or a family history of sudden death

›Current QT-prolonging medications

03Physical Exam/exam42

Vital signs and physiologic thresholds

›Heart rate and rhythm

›Sinus tachycardia above 100 in an adult is expected and is not by itself an indication for rate control

›Use age-based limits in children rather than the adult number

›An irregular or wide-complex rhythm signals evolving cardiotoxicity

›Blood pressure

›Early hypertension from catecholamine excess

›Systolic below 90 mmHg or mean arterial pressure below 65 mmHg defines hypotension and is an ominous late sign

›In chronic hypertension, dialysis, and the elderly, judge against the patient's usual pressure and weight relative drops more heavily

›Temperature

›Above 38.5 C is concerning after a seizure or with agitation

›Above 39.5 C mandates active cooling

›Interpret against ambient temperature and prehospital wrapping

›Respiratory rate and oxygenation

›Adult rate above 22 or below 8 is abnormal; infant above 60, 1 to 5 years above 40, 6 to 12 years above 30

›Lower absolute thresholds are tolerated in chronic lung disease

›SpO2 target 94 to 98 percent, or 88 to 92 percent in known chronic obstructive pulmonary disease or chronic hypercapnia

›Glucose and mental status

›Point-of-care glucose in every seizure or altered patient; treat if below 3.9 mmol/l, or below 2.6 mmol/l in a neonate

›Glasgow Coma Scale and a focused agitation score

Neurologic findings

›Seizure activity

›Generalized tonic-clonic seizure, typically brief and single but occasionally repetitive or status

›Post-ictal confusion and transient focal deficit

›A persistent focal deficit points to an alternative or additional diagnosis

›Sympathomimetic and serotonergic overlap

›Tremor, hyperreflexia, and inducible clonus

›Agitation, restlessness, and visual or tactile hallucinations

04Differential Diagnosis/ddx34

Other causes of drug-induced seizure

›Antidepressants and analgesics

›Tricyclic antidepressant overdose, with a broader anticholinergic toxidrome and more bicarbonate-responsive QRS widening

›Venlafaxine and other serotonin-norepinephrine reuptake inhibitors

›Tramadol, meperidine, and diphenhydramine

›Stimulants and withdrawal

›Cocaine, amphetamines, and synthetic cathinones

›Alcohol or benzodiazepine withdrawal

›Other toxins

›Isoniazid, treated with pyridoxine 1 g IV per gram ingested, or 5 g IV empirically if the amount is unknown

›Theophylline, camphor, lamotrigine, and organophosphates

›Water intoxication and drug-induced hyponatremia

Competing toxidromes

›Sympathomimetic toxidrome

›Shared features: tachycardia, hypertension, hyperthermia, agitation, mydriasis, diaphoresis

›Bupropion sits in this group because it is a norepinephrine-dopamine reuptake inhibitor and a substituted cathinone

›Anticholinergic toxidrome

›Distinguished by dry flushed skin, urinary retention, absent bowel sounds, and agitated delirium

›Bupropion generally spares these features, which aids the distinction

›Sodium channel blocker pattern

›Wide QRS, terminal R wave in aVR, and hypotension

›Also seen with tricyclics, class I antiarrhythmics, diphenhydramine, cocaine, and carbamazepine

›Serotonin syndrome and neuroleptic malignant syndrome

›Clonus, hyperreflexia, and onset over hours favour serotonin syndrome

›Lead-pipe rigidity, bradyreflexia, and onset over days favour neuroleptic malignant syndrome

Non-toxicologic mimics of bupropion toxicity

›Primary neurologic

›New epilepsy, intracranial hemorrhage, ischemic stroke, or central nervous system infection

05Laboratory Tests/lt39

Core metabolic and co-ingestant panel

›Immediate bedside tests

›Point-of-care glucose for every seizure or altered mental status

›Venous or arterial blood gas with lactate

›Electrolytes and renal function

›Sodium for hyponatremia as a seizure cause

›Potassium, magnesium, and calcium for arrhythmia risk and QT interpretation

›Urea and creatinine for clearance of bupropion and its metabolites

›Co-ingestant screen in deliberate overdose

›Acetaminophen concentration

›Salicylate concentration

›Ethanol concentration

›Reproductive and muscle markers

›Beta human chorionic gonadotropin in any patient of childbearing potential

›Creatine kinase for rhabdomyolysis after a seizure or agitation

›Tests that do not help acutely

›Serum bupropion concentrations are not available in a clinically useful timeframe

›Urine drug screen does not change bupropion management

Tests driven by specific findings

›Chest pain, shock, or a marked ECG change

›Troponin for myocardial injury

›Repeat troponin and echocardiography rather than proceeding to angiography for toxic changes alone

›Hypoxia or pulmonary findings

›Chest radiograph for aspiration pneumonitis or pulmonary edema

›Prolonged seizure or hyperthermia

›Coagulation panel and fibrinogen for disseminated intravascular coagulation

›Repeat creatine kinase and renal function to track rhabdomyolysis

›Persistent acidosis

06Diagnostic Tests/dt60

ECG

›Obtain and repeat systematically

›12-lead ECG within 10 minutes of arrival

›Repeat every 1 to 2 hours for at least 8 hours after an immediate-release ingestion

›Repeat for at least 24 hours after a sustained-release or extended-release ingestion

›Repeat immediately after any seizure or hemodynamic change

›Measurements that change management

›QRS duration above 100 ms is a warning marker for seizure and dysrhythmia

›QRS duration above 120 ms is the trigger for sodium bicarbonate therapy

›QTc above 500 ms marks meaningful torsades de pointes risk

›Terminal R wave above 3 mm in lead aVR suggests sodium channel blockade

›Patterns to actively seek

›Brugada-type coved ST elevation in the right precordial leads

›Right bundle branch block and first-degree atrioventricular block

›Sinus tachycardia is near universal and is not by itself an indication for rate control

›Interpretation cautions

›ST-segment changes and a modest troponin rise can mimic acute coronary syndrome

›A normal early ECG does not exclude delayed cardiotoxicity from a sustained-release formulation

›Do not activate the catheterization laboratory for toxic wide-complex changes without independent ischemic evidence

Scoring Systems

›No bupropion-specific validated severity score exists

›Risk stratification is driven by formulation, dose, QRS duration, and seizure occurrence

›Do not use the absence of a score to justify early discharge of a sustained-release ingestion

›Generic tools that inform disposition

›Glasgow Coma Scale below 8 supports intubation for airway protection

›Poison Severity Score is used for research and registry comparison, not bedside decisions

›Richmond Agitation-Sedation Scale to titrate benzodiazepine sedation

›Status epilepticus is defined by time, not a score

›A generalized convulsive seizure lasting 5 minutes, or two seizures without recovery between them

›Escalate on the clock rather than waiting for a scoring threshold

›Non-contrast head CT indications

›First-ever seizure with a focal neurologic deficit or failure to return to baseline

›Head trauma from a witnessed fall during a seizure

›Anticoagulant or antiplatelet use, advanced age, or immunosuppression

›Persistent altered mental status out of proportion to the ingestion

›When head CT can be deferred

›Single self-limited generalized seizure with full neurologic recovery and a clear ingestion history

›Normal mental status, a non-focal neurologic examination, and no head trauma

›Other CT considerations

›CT pulmonary angiography only if pulmonary embolism is independently suspected as a shock cause

›CT of the abdomen is not used to quantify tablet burden and adds little to management

›Do not transport an unstable patient to CT before airway and circulation are secured

MRI

›Not part of the routine bupropion overdose evaluation

›Acute structural imaging needs are usually met by non-contrast CT

›Defer MRI until the patient is hemodynamically and neurologically stable

›Brain MRI indications after stabilization

›Persistent unexplained coma once seizures and metabolic derangement are corrected

›Suspected hypoxic-ischemic injury after prolonged status epilepticus or cardiac arrest

›Posterior reversible encephalopathy syndrome on the differential with refractory hypertension and visual symptoms

›Practical cautions

›Prolonged scanner time is unsafe in a patient at risk of recurrent seizure or arrhythmia

›Confirm the MRI-conditional status of any temporary pacing or infusion equipment

Ultrasound

›Focused cardiac ultrasound in hypotension or a wide-complex rhythm

›Left ventricular systolic function to distinguish toxic myocardial depression from distributive shock

›Serial studies to track response to sodium bicarbonate, lipid emulsion, and inotropes

›Global hypokinesis with a rising vasopressor requirement supports early extracorporeal membrane oxygenation referral

›Volume assessment

›Inferior vena cava diameter and collapsibility to guide cautious fluid resuscitation

›Avoid over-resuscitation when the primary lesion is myocardial rather than hypovolemic

›Pulmonary and gastric views

›Lung ultrasound for B-lines of pulmonary edema or consolidation from aspiration during a seizure

›Gastric ultrasound may show a retained tablet mass or pharmacobezoar after a massive sustained-release ingestion

07Disposition/dispo30

Observation windows by formulation

›Immediate-release ingestion

›Minimum 8 hours of continuous cardiac monitoring from the time of ingestion

›Medically clear only if asymptomatic with normal serial ECGs and no seizure

›Sustained-release and extended-release ingestion

›Minimum 24 hours of continuous cardiac monitoring because seizures can be delayed up to 24 hours

›Do not shorten this window based on an early normal examination

›Clock resets

›Any seizure, tachycardia, QRS above 100 ms, QTc above 500 ms, or hypotension restarts the observation period

›Recurrent vomiting that prevents charcoal or delays absorption extends monitoring

Admission and intensive care criteria

›Intensive care admission

›Any seizure, status epilepticus, or recurrent seizures

›QRS above 100 ms, QTc above 500 ms, or any ventricular dysrhythmia

›Hypotension, cardiogenic shock, or a vasopressor requirement

›Depressed mental status or a need for airway protection

›Monitored ward admission

›Large sustained-release or extended-release ingestion still within the 24-hour window

›Persistent sinus tachycardia or mild agitation not needing sedation

›A significant co-ingestant requiring its own monitoring

›Suitable for discharge

›Immediate-release ingestion, asymptomatic at 8 hours, normal serial ECGs, and psychiatrically cleared

Transfer, psychiatric hold, and poison centre

›Poison centre and toxicology

›Consult the regional poison centre or a medical toxicologist for every deliberate ingestion and every symptomatic child

›Document the recommended observation duration and monitoring plan

›Interfacility transfer

›Transfer to an extracorporeal membrane oxygenation-capable centre at the first sign of cardiotoxicity, before decompensation

08Treatment/t194

Airway, ventilation, and first-line seizure control

›First-line: benzodiazepine at the first seizure

›Lorazepam

›Lorazepam 0.1 mg/kg IV, maximum 4 mg per dose

›Repeat once after 5 to 10 minutes if the seizure continues

›Watch for respiratory depression and prepare airway equipment

›Diazepam when no lorazepam is available

›Diazepam 0.15 to 0.2 mg/kg IV, maximum 10 mg per dose

›Repeat once after 5 minutes if needed

›Midazolam when there is no intravenous access

›Midazolam 10 mg IM (0.2 mg/kg, maximum 10 mg)

›Intranasal or buccal route is acceptable at the same dose

›Pediatric benzodiazepine dosing

›Lorazepam 0.1 mg/kg IV (maximum 4 mg), or midazolam 0.2 mg/kg IM (maximum 10 mg)

›Verify against current pediatric guideline before use

›Correct reversible seizure triggers immediately

›Point-of-care glucose; treat if below 3.9 mmol/l

›Serum sodium for hyponatremia, plus ionized calcium and magnesium

›Core temperature; begin cooling if above 39.5 C

›Airway management

›Position, suction, and high-flow oxygen for the post-ictal patient

›Intubate for Glasgow Coma Scale below 8, recurrent seizures, refractory hyperthermia, or aspiration

›Induction with ketamine 1.5 to 2 mg/kg IV or propofol 1.5 to 2.5 mg/kg IV

›Propofol is preferred when seizures are ongoing because it raises the seizure threshold

›Rocuronium 1.2 mg/kg IV or succinylcholine 1.5 mg/kg IV for paralysis

›Prefer the non-depolarizing agent so paralysis does not mask an ongoing seizure without EEG

›Avoid succinylcholine if seizure-related rhabdomyolysis or hyperkalemia is suspected

›Ventilate to PaCO2 35 to 45 mmHg; avoid hypoventilation that worsens acidosis and sodium channel blockade

›Pediatric induction ketamine 1.5 to 2 mg/kg IV and rocuronium 1 mg/kg IV

›Verify against current pediatric guideline before use

Status epilepticus and refractory seizures

›Define and escalate on the clock

›A seizure lasting 5 minutes, or repeated seizures without recovery, is status epilepticus

›Give the full first benzodiazepine dose and a second dose before moving on

›Second-line antiseizure medication

›Levetiracetam

›Levetiracetam 60 mg/kg IV, maximum 4500 mg

›Reduce the dose in significant renal impairment

›Phenobarbital as an alternative second-line agent

›Phenobarbital 15 to 20 mg/kg IV at 50 to 100 mg/min

›Anticipate hypotension and respiratory depression; have airway and vasopressors ready

›Valproate where locally preferred

›Valproate 40 mg/kg IV, maximum 3000 mg

›Avoid in known hepatic dysfunction, suspected metabolic disease, and pregnancy

›Avoid phenytoin and fosphenytoin

›Ineffective for most toxin-induced seizures

›Its own sodium channel blockade can worsen bupropion cardiotoxicity and precipitate asystole

›Refractory status epilepticus

›Intubate and start a continuous infusion

›Midazolam infusion 0.1 to 0.3 mg/kg/hr after a 0.2 mg/kg bolus

›Propofol infusion 20 to 200 mcg/kg/min after a 1 to 2 mg/kg load

›Limit dose and duration to reduce propofol infusion syndrome risk, especially in children

›Titrate to seizure suppression on continuous EEG

›Continuous EEG is mandatory once a paralytic is used

›Reassess for hyponatremia, hypoglycemia, hyperthermia, a co-ingestant, and a structural lesion when seizures persist despite adequate therapy

›Pediatric anticonvulsant dosing mirrors adult weight-based dosing

›Levetiracetam 60 mg/kg IV (maximum 4500 mg) or phenobarbital 15 to 20 mg/kg IV

›Verify against current pediatric guideline before use

›Midazolam infusion 0.06 to 0.12 mg/kg/hr titrated on EEG

›Verify against current pediatric guideline before use

Gastrointestinal decontamination

›Activated charcoal

›Single-dose activated charcoal 1 g/kg PO or via nasogastric tube, maximum 50 g

›Greatest value within 1 to 2 hours, but reasonable later after a sustained-release or extended-release ingestion

›Only if the airway is intact or protected

›Withhold if a seizure appears imminent, mental status is declining, or the patient is vomiting

›Withhold if ileus or bowel obstruction is present

›Multiple-dose activated charcoal is not routinely recommended for bupropion

›Whole bowel irrigation for large modified-release ingestions

›Polyethylene glycol electrolyte solution

›Adults 1500 to 2000 mL/hr by nasogastric tube

›Children 6 to 12 years 1000 mL/hr; children 9 months to 6 years 500 mL/hr

›Continue until the rectal effluent is clear

›Stop for ileus, obstruction, hemodynamic instability, or an unprotected airway

›Best reserved for early presentation after a large extended-release ingestion

›Gastric lavage and induced emesis

›Not indicated; the risk of aspiration and seizure-related complications outweighs any benefit

›Enhanced elimination

›Hemodialysis does not meaningfully remove bupropion because of its large volume of distribution near 20 to 47 L/kg and protein binding near 84 percent

›Reserve hemodialysis for a dialyzable co-ingestant or for renal failure

Sodium channel blockade, QRS widening, and dysrhythmia

›Sodium bicarbonate for QRS above 120 ms or ventricular dysrhythmia

›Sodium bicarbonate 8.4 percent

›1 to 2 mmol/kg IV bolus

›Repeat 1 to 2 mmol/kg every 3 to 5 minutes while QRS remains above 120 ms or the rhythm is unstable

›Stop escalating boluses once arterial pH reaches 7.55

›Follow boluses with an infusion of 150 mmol in 1 litre of 5 percent dextrose at 1.5 to 2 times maintenance

›Target arterial pH 7.45 to 7.55 and serum sodium below 155 mmol/l

›Recheck arterial blood gas and potassium every 1 to 2 hours and replace potassium to 4.0 to 4.5 mmol/l, since alkalinization drives hypokalemia and further QT prolongation

›Response is less reliable than in tricyclic antidepressant poisoning because bupropion sodium channel blockade is only partly reversed by alkalinization and sodium loading

›Pediatric sodium bicarbonate 1 to 2 mmol/kg IV bolus

›Verify against current pediatric guideline before use

›QT prolongation and torsades de pointes

›Magnesium sulfate 2 g IV over 15 minutes for QTc above 500 ms with ectopy, or for torsades

›Repeat once for recurrent torsades and keep serum magnesium above 1.0 mmol/l

›Pediatric magnesium sulfate 25 to 50 mg/kg IV, maximum 2 g

›Verify against current pediatric guideline before use

›Keep serum potassium 4.0 to 4.5 mmol/l

›Overdrive pacing or isoproterenol 2 to 10 mcg/min for recurrent pause-dependent torsades

›Refractory wide-complex ventricular dysrhythmia

›Lidocaine 1 to 1.5 mg/kg IV bolus then 1 to 4 mg/min infusion

›Lidocaine is a class Ib antiarrhythmic with fast sodium channel off-kinetics, so it displaces bupropion from the channel without prolonging repolarization

›Avoid class Ia and class Ic antiarrhythmics (procainamide, flecainide, propafenone) because they deepen sodium channel blockade

›Avoid amiodarone when the QT is already prolonged because it adds further QT prolongation and hypotension

›Unstable ventricular tachycardia or fibrillation

›Synchronized cardioversion 120 to 200 J biphasic for unstable ventricular tachycardia with a pulse

›Defibrillation 200 J biphasic for ventricular fibrillation or pulseless ventricular tachycardia

›Prolonged resuscitation and early extracorporeal support are justified given the reversible, delayed nature of the toxicity

›Pediatric synchronized cardioversion 0.5 to 1 J/kg escalating to 2 J/kg; defibrillation 2 J/kg then 4 J/kg

›Verify against current pediatric guideline before use

Hypotension, cardiogenic shock, agitation, and hyperthermia

›Hypotension initial approach

›Isotonic crystalloid 10 to 20 mL/kg (1 to 2 litres in an adult), reassessed after each bolus

›Stop fluids and obtain echocardiography if the lungs become wet or filling pressures rise without a blood pressure response

›Pediatric crystalloid bolus 10 to 20 mL/kg

›Verify against current pediatric guideline before use

›Add sodium bicarbonate if hypotension coexists with QRS above 120 ms

›Vasopressors and inotropes

›Norepinephrine

›Norepinephrine 0.05 to 0.5 mcg/kg/min IV, titrated every 5 to 10 minutes to a mean arterial pressure of at least 65 mmHg

›Use a higher mean arterial pressure target in chronic hypertension and a lower acceptable target in young, previously healthy patients

›Around 1 mcg/kg/min, add a second agent rather than escalating further

›Add vasopressin 0.03 units/min or epinephrine 0.02 to 0.2 mcg/kg/min for refractory shock

›For echo-confirmed myocardial depression, add dobutamine 2.5 to 10 mcg/kg/min or epinephrine

›High-dose insulin euglycemia as a myocardial support adjunct

›Regular insulin 1 unit/kg IV bolus, then an infusion 0.5 to 1 unit/kg/hr titrated up to 10 units/kg/hr for refractory cardiogenic shock

›Dextrose infusion to keep glucose 5.5 to 11 mmol/l and potassium above 2.8 mmol/l

›Evidence in bupropion poisoning is limited to case reports; reserve for echo-confirmed myocardial depression refractory to standard care

›Agitation and sympathomimetic features

›Benzodiazepines are first-line: diazepam 5 to 10 mg IV or lorazepam 2 to 4 mg IV, repeated and titrated to calm

›Avoid antipsychotics as the primary sedative because they lower the seizure threshold and prolong the QT

›Dexmedetomidine 0.2 to 1.4 mcg/kg/hr is a reasonable adjunct once seizure risk is controlled

›Hyperthermia

›Active external cooling for a core temperature above 39.5 C

›Sedation, paralysis, and intubation for temperature above 41 C with rigidity

›Antipyretics are ineffective because the mechanism is increased muscle heat production, not a raised hypothalamic set point

Intravenous lipid emulsion

›Indication

›Cardiovascular collapse or refractory ventricular dysrhythmia not responding to sodium bicarbonate, vasopressors, and lidocaine

›Consider earlier if deterioration is rapid while extracorporeal support is being mobilized

›Dosing

›Lipid emulsion 20 percent

›1.5 mL/kg IV bolus over 2 to 3 minutes

›Repeat the bolus once or twice for persistent asystole or profound hypotension

›Follow with an infusion of 0.25 mL/kg/min for 30 to 60 minutes

›Increase to 0.5 mL/kg/min if blood pressure remains low

›The recommended ceiling is approximately 10 mL/kg in the first 30 minutes

›Pediatric lipid emulsion 20 percent 1.5 mL/kg IV bolus then 0.25 mL/kg/min

›Verify against current pediatric guideline before use

›Monitoring and adverse effects

›Check serum triglycerides, lipase, and a repeat ECG after administration

›Lipemia can interfere with many laboratory assays; draw a pre-infusion panel when feasible

›Watch for pancreatitis, acute respiratory distress syndrome, and fat overload syndrome

›Lipid emulsion can reduce the efficacy of other lipophilic drugs given at the same time

Extracorporeal membrane oxygenation and mechanical circulatory support

›Rationale

›Bupropion cardiotoxicity is often delayed, profound, and reversible, which makes it a favourable indication for venoarterial extracorporeal membrane oxygenation

›The parent and active metabolite half-lives near 20 hours mean bridging for 24 to 72 hours is often required

›Triggers to activate the extracorporeal team early

›Widening QRS with an escalating vasopressor requirement

›Cardiogenic shock with left ventricular global hypokinesis on echocardiography

›Refractory ventricular dysrhythmia, or cardiac arrest with a witnessed, monitored downtime

›Modality selection

›Venoarterial extracorporeal membrane oxygenation is the preferred mode for toxic cardiogenic shock and refractory arrest

›An intra-aortic balloon pump provides little benefit when the lesion is diffuse myocardial depression rather than ischemia

›A percutaneous ventricular assist device is an alternative where extracorporeal membrane oxygenation is unavailable

›Logistics

›Identify the nearest extracorporeal membrane oxygenation centre at first recognition of cardiotoxicity and transfer before decompensation

›Continue sodium bicarbonate, magnesium and potassium repletion, and lipid emulsion during transfer

Therapies that are ineffective or harmful

›Flumazenil

›Flumazenil 0.2 mg IV is the tempting diagnostic dose; it is contraindicated here

›It reverses the protective effect of benzodiazepines and precipitates seizures or status epilepticus

›Phenytoin and fosphenytoin

›Phenytoin 15 to 20 mg/kg IV is standard for epileptic status but is the wrong drug here

›Ineffective for toxin-induced seizures, and its sodium channel blockade can worsen cardiotoxicity

›Physostigmine

›Physostigmine 0.5 to 2 mg IV slow is used for anticholinergic delirium; bupropion is not anticholinergic and physostigmine may worsen seizures and conduction

›Class Ia and Ic antiarrhythmics

›Procainamide 15 to 17 mg/kg IV load deepens sodium channel blockade and is contraindicated

›Flecainide and propafenone are likewise contraindicated

›Amiodarone in the QT-prolonged patient

›Amiodarone 150 mg IV over 10 minutes adds QT prolongation and hypotension; avoid when QTc exceeds 500 ms

›High-dose epinephrine as the first-choice pressor

›As the initial pressor it increases myocardial oxygen demand and ectopy; prefer norepinephrine 0.05 to 0.5 mcg/kg/min

›Large-volume fluid resuscitation

›Aggressive crystalloid loading precipitates pulmonary edema when the primary lesion is myocardial depression; give small boluses guided by echocardiography

›Fibrinolysis for wide-complex changes

›Alteplase (weight-based, about 100 mg over 90 minutes for pulmonary embolism) or tenecteplase (weight-based single bolus 30 to 50 mg) is not indicated; toxic QRS widening, ST changes, and a troponin rise are not thrombotic, and fibrinolysis adds hemorrhage risk after a seizure

›Anticoagulation

›Not required for the poisoning itself

›Systemic heparin is needed for an extracorporeal membrane oxygenation circuit; weigh it against post-ictal intracranial hemorrhage and obtain head CT first when feasible

›Tramadol and other proconvulsant analgesics

›Tramadol 50 to 100 mg lowers the seizure threshold and is contraindicated; use acetaminophen 1000 mg IV or PO, or a short-acting opioid with airway precautions, for pain

›Empiric antipsychotics for agitation

›Haloperidol 5 mg IM or droperidol 2.5 mg IV lower the seizure threshold and prolong the QT; use benzodiazepines instead

›Supplemental oxygen beyond target

›Titrate to SpO2 94 to 98 percent, or 88 to 92 percent in chronic hypercapnia; routine hyperoxia offers no benefit

›Hemodialysis for drug removal

›Ineffective because of the large volume of distribution and high protein binding; use only for a dialyzable co-ingestant or renal failure

›Routine multiple-dose activated charcoal

›Not supported for bupropion and adds aspiration and obstruction risk

09Special Populations/sp41

Pregnancy

›Maternal stabilization takes priority

›Untreated maternal seizure and hypoxia are the main fetal threats; treat exactly as in the non-pregnant patient

›Do not withhold benzodiazepines, levetiracetam, sodium bicarbonate, magnesium, lipid emulsion, or extracorporeal membrane oxygenation

›Left lateral decubitus positioning or manual uterine displacement after 20 weeks gestation

›Fetal monitoring

›Continuous cardiotocography for at least 4 hours once the mother is stabilized, if the fetus is potentially viable at 23 to 24 weeks or beyond

›Obstetric involvement for any hemodynamic instability or recurrent seizure

›Perimortem cesarean delivery within 4 to 5 minutes of maternal arrest not responding to resuscitation, if beyond about 20 weeks

›Agent-specific notes

›Valproate is avoided in pregnancy; use levetiracetam 60 mg/kg IV (maximum 4500 mg) as the second-line anticonvulsant

›Bupropion has no strong human teratogen signal, so the acute danger is the overdose physiology, not the drug itself

›Magnesium sulfate 2 g IV over 15 minutes is the antidysrhythmic dose and is already familiar in obstetrics

Geriatric

›Altered pharmacology

›Reduced hepatic and renal clearance prolongs elimination of bupropion and hydroxybupropion

›A lower baseline seizure threshold and higher arrhythmia risk at any given dose

›Comorbidity interactions

›Pre-existing coronary disease and heart failure worsen tolerance of toxic myocardial depression

›Co-prescribed QT-prolonging drugs and CYP2D6 substrates such as metoprolol, flecainide, and tricyclics compound toxicity

›Anticoagulant use raises the stakes of a seizure-related fall and head injury

›Disposition threshold

›Admit and monitor for 24 hours regardless of formulation when age and comorbidity are significant

›Use the patient's usual blood pressure, not a fixed systolic of 90 mmHg, to define hypotension

Pediatrics

›Exposure patterns

›Exploratory ingestion of one or two adult tablets can be toxic in a toddler

›Seizures have been reported in children after ingestions of roughly 9 mg/kg or more

10Background/b47

Epidemiology

›Prescribing and exposures

›Bupropion is among the five most prescribed antidepressants in the United States

›Antidepressants account for well over 100000 exposures reported to United States poison centres each year

›Unintentional exploratory ingestion in children under 6 years is a substantial minority of bupropion exposures

›Outcome burden

›Bupropion causes a disproportionate share of antidepressant-associated seizures, on the order of a quarter of them despite a smaller prescription share

›Seizures occur in roughly 10 to 30 percent of symptomatic bupropion overdoses

›Life-threatening cardiovascular events occur in a few percent of significant ingestions and rise sharply above 4.5 g

›Overall case fatality is under 1 percent but exceeds that of selective serotonin reuptake inhibitor overdose

›Trends

›Extended-release formulations and the bupropion-naltrexone weight-loss product (naltrexone 8 mg with bupropion 90 mg per tablet) have widened the exposed population

›Recreational insufflation for a stimulant-like effect is a recognized but uncommon pattern

Pathophysiology

›Drug class and receptor actions

›Aminoketone and substituted cathinone that inhibits neuronal reuptake of norepinephrine and dopamine

›Catecholamine excess produces tachycardia, hypertension, tremor, agitation, and hyperthermia

›It markedly lowers the seizure threshold, the lowest of the commonly used antidepressants

›Cardiac mechanisms

›Fast sodium channel blockade widens the QRS and can produce a Brugada pattern and a terminal R wave in aVR

›Delayed rectifier potassium channel blockade prolongs the QT

›Myocardial gap junction and conduction effects can produce profound, sometimes delayed, cardiogenic shock

›Pharmacokinetics that shape management

›Time to peak is about 2 hours for immediate-release and about 5 hours for extended-release, and is later still in overdose

›Parent bupropion half-life is roughly 21 hours; the active metabolite hydroxybupropion half-life is roughly 20 hours

›Volume of distribution is large at about 20 to 47 L/kg and protein binding is about 84 percent, so hemodialysis does not remove it

›Sustained-release and extended-release tablets can form a pharmacobezoar that delays the peak effect and delays seizures

›Consequences for the clinician

11Patient Discharge Instructions/pdi31

Predischarge psychiatric and safety requirements

›Medical clearance conditions

›Applies only to immediate-release ingestions observed at least 8 hours with normal serial ECGs and no seizure

›Sustained-release and extended-release ingestions are not discharged from the emergency department within 24 hours

›Psychiatric safety

›Complete a formal psychiatric assessment for every intentional ingestion before discharge

›Arrange means restriction at home and confirm a support person

›Provide crisis line information and a specific outpatient follow-up appointment

›Medication safety

›Reconcile the remaining supply of bupropion and any other psychotropics

›Discuss with the prescriber whether bupropion should be continued, changed, or dispensed in limited quantities

copy discharge instructions

›Why you were seen

›You took more bupropion than prescribed. Brand names include Wellbutrin, Zyban, Forfivo, and Contrave.

›The main dangers are seizures and effects on the heart rhythm, and with long-acting tablets these can start up to 24 hours later.

›How long you must be watched

›If you took a regular (immediate-release) tablet, you are watched for at least 8 hours.

›If you took a sustained-release or extended-release tablet, you must stay for at least 24 hours of heart monitoring. Do not leave early.

›Call 911 or return to the emergency department immediately for

›Any seizure, jerking movements, or a blackout

›Fainting, chest pain, a pounding or racing heartbeat, or a fast pulse that will not settle

›Severe agitation, confusion, or a temperature above 40 C

›Repeated vomiting so that you cannot keep fluids down

›Medicines and substances

›Do not take any more bupropion. Bring all of your pill bottles to your follow-up visit.

›Do not drink alcohol or use recreational drugs for at least 72 hours; both make a seizure more likely.

›For aches or a low-grade fever you may use acetaminophen 1000 mg by mouth every 6 hours, up to 3000 mg in 24 hours; use no more than 2000 mg in 24 hours if you have liver disease or drink alcohol regularly.

›Do not use tramadol, or diphenhydramine for sleep, in the next few days; they also lower the seizure threshold.

12References/r19

Decontamination and poison centre references

›American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists

›Position Paper Update: Single-Dose Activated Charcoal. Clinical Toxicology, 2005

›Position Paper: Whole Bowel Irrigation and Gastrointestinal Decontamination, updated 2015. Clinical Toxicology

›American Association of Poison Control Centers

›Annual Report of the National Poison Data System (Gummin DD and colleagues), published annually in Clinical Toxicology

›National Poison Data System coding of antidepressant single-agent exposures and outcomes

Seizure and status epilepticus references

›American Epilepsy Society

›Glauser T and colleagues. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults. Epilepsy Currents, 2016

›Neurocritical Care Society

›Guidelines for the Evaluation and Management of Status Epilepticus. Neurocritical Care, 2012

Cardiotoxicity and extracorporeal therapy references

›American Academy of Clinical Toxicology Lipid Emulsion Workgroup

›Gosselin S and colleagues. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clinical Toxicology, 2016

›Journal of Medical Toxicology

›Bruccoleri RE and Burns MM. A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening. 2016

›Toxicology Investigators Consortium registry analyses of bupropion overdose, seizure, and extracorporeal membrane oxygenation use

›Extracorporeal Life Support Organization

›ELSO General Guidelines for Adult Cardiac Failure and Extracorporeal Cardiopulmonary Resuscitation

›Canadian Medical Association Journal

›Stall N, Godwin J, and Juurlink D. Bupropion abuse and overdose. CMAJ, 2014

Evidence & Review

Reviewed by SymptomDx Medical Team · Last reviewed September 13, 2026

SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.