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Monoamine Oxidase Inhibitor Poisoning, Emergency Medicine

Basics

Description

- MAO: Principal inactivator of neural bioactive amines: - MAO A: - Present in the gut and liver - Protects against dietary bioactive amines

- MAOI overdose: - Toxicopharmacology poorly understood - MAO inhibitors: Amphetamine-like in structure: - Early: Indirect sympathomimetic effect - Late: Sympatholytic response (hypotension)

- Serotonin syndrome (SS): - Commonly results from exposure to combinations of agents that affect serotonin metabolism or action - Increases serotonin synthesis: Tryptophan - Increase serotonin release: - Indirect- and mixed-acting sympathomimetic agents and dopamine receptor agonists

- Decrease serotonin reuptake: - Selective serotonin reuptake inhibitors - Tricyclic antidepressants - Newer antidepressants: Trazodone, nefazodone, venlafaxine - Phenylpiperidine opioids: Meperidine, dextromethorphan, tramadol, methadone, propoxyphene

- Direct serotonin receptor agonists: - Buspirone, sumatriptan, lysergic acid diethylamide

- Neuromuscular hyperactivity: - Myoclonus - Rigidity - Tremors - Hyperreflexia

- Autonomic hyperactivity: - Tachycardia or bradycardia - Fever - Diaphoresis

- Hyperthermia: - Benzodiazepines if agitated - Active cooling if temperature >40 °C: - Tepid water mist - Evaporate with fan

- Paralysis: - Indicated if muscle rigidity and hyperactivity contributing to persistent hyperthermia - Nondepolarizing agent (e.g., vecuronium) - Avoid succinylcholine - Intubation; mechanical ventilation

- Seizures: - Benzodiazepines - Barbiturates if benzodiazepines unsuccessful - Pyridoxine for refractory seizures

- DIC: - Fresh-frozen plasma - Platelets - Whole-blood transfusions

- Rhabdomyolysis: - IV isotonic crystalloid solution - Maintain hydration to ensure adequate urine output

  • Primarily for depression
  • Selegiline, a selective monoamine oxidase B inhibitor, is sometimes used to treat Parkinson disease, and also comes in a transdermal preparation.
  • Monoamine oxidase inhibitor (MAOI) pharmacologic actions:Disruption of equilibrium between endogenous monoamine synthesis and degradation, resulting in:Increased neural norepinephrine levelsDownregulation of several receptor typesInhibition of irreversible (noncompetitive) enzymeInhibition of other B6-containing enzymes
  • MAO: Principal inactivator of neural bioactive amines:MAO A:Present in the gut and liverProtects against dietary bioactive aminesMAO B:Present in neuron terminals and plateletsSympathomimetic amines: Types of bioactive amines

Etiology

  • MAOI overdose:Toxicopharmacology poorly understoodMAO inhibitors: Amphetamine-like in structure:Early: Indirect sympathomimetic effectLate: Sympatholytic response (hypotension)
  • MAOI hypertensive crisis syndrome:Results from impaired norepinephrine degradation and large norepinephrine release precipitated by an indirect- or mixed-acting sympathomimetic agentCommon precipitants: Tyramine, cocaine, amphetamines
  • Serotonin syndrome (SS):Commonly results from exposure to combinations of agents that affect serotonin metabolism or actionIncreases serotonin synthesis: TryptophanIncrease serotonin release:Indirect- and mixed-acting sympathomimetic agents and dopamine receptor agonistsDecrease serotonin reuptake:Selective serotonin reuptake inhibitorsTricyclic antidepressantsNewer antidepressants: Trazodone, nefazodone, venlafaxinePhenylpiperidine opioids: Meperidine, dextromethorphan, tramadol, methadone, propoxypheneDirect serotonin receptor agonists:Buspirone, sumatriptan, lysergic acid diethylamideDecrease serotonin breakdown:Increases nonspecific serotonin activity:

Diagnosis

Signs and Symptoms

  • MAOI overdose:Delayed onset (6 " 12 hr)Initial hypertension with headacheHyperadrenergic activity:TachycardiaHypertensionMydriasisAgitationNeuromuscular excitation:NystagmusHyperreflexiaTremorMyoclonusRigiditySeizuresHyperthermiaAssociated complications:RhabdomyolysisRenal failureDisseminated intravascular coagulation (DIC)Acute respiratory distress syndrome (ARDS)
  • MAOI hypertensive crisis syndrome (MAOI interaction with drug or food):HypertensionTachycardia or bradycardiaHyperthermiaHeadache, usually occipitalAltered mental statusIntracranial hemorrhageSeizures
  • SS:Increased neuromuscular activityIncreased deep tendon reflexes:Lower extremity may be greater than upperTremorMyoclonusRigidity (when severe)Autonomic nervous system hyperactivity:CNS:AgitationHallucinationsDeliriumComaDiarrheaSS vs. neuroleptic malignant syndrome (NMS):Both present along a spectrum of severity (mild to severe)Onset: Hours (SS) vs. days (NMS)Gastrointestinal symptoms: May be present (SS) vs. absent (NMS)Only drug/medication history may differentiate in many cases

History

  • Time of ingestion
  • Bottle available
  • Intentional or accidental
  • Coingestions

Physical Exam

  • Neuromuscular hyperactivity:MyoclonusRigidityTremorsHyperreflexia
  • Autonomic hyperactivity:Tachycardia or bradycardiaFeverDiaphoresis
  • Altered mental status:Agitation, confusion, or excitement

Essential Workup

  • History of ingested substances
  • Rectal temperature monitoring as indicated
  • Blood pressure/cardiac monitoring

Diagnosis Tests & Interpretation

Lab

  • Urinalysis:
  • Electrolytes, BUN/creatinine, glucose:Hypoglycemia may contribute to altered mental status.Acidosis may accompany severe toxicity.Rhabdomyolysis may cause renal failure.Hyperkalemia " life-threatening consequence of acute renal failure
  • Coagulation profile to monitor for potential DIC:INR, prothrombin time, partial thromboplastin time, platelets
  • Creatinine kinase:Markedly elevated in rhabdomyolysis
  • Urine toxicology screen:May be positive for amphetamines, given the structural similarities between some MAOIs and amphetamines
  • Aspirin and acetaminophen levels if suicide attempt a possibility
  • Arterial blood gas

Imaging

  • Chest radiograph:
  • Head CT if significant headache or altered mental status or focal neurologic signs:Subarachnoid hemorrhage, intracerebral bleed

Diagnostic Procedures/Surgery

Lumbar puncture for:

  • Suspected meningitis (headache, altered mental status, hyperpyrexia)
  • Suspected subarachnoid hemorrhage and CT normal

Differential Diagnosis

  • Hyperthermia:InfectionHyperthyroidismHeat strokeAnatomic thalamic dysfunctionNMSMalignant hyperthermiaMalignant catatoniaEthanol or drug withdrawalAnticholinergic toxicitySympathomimetic overdoseCocaine-associated delirium/rhabdomyolysisSalicylate toxicityTheophylline toxicityNicotine toxicity
  • Hypertension:HypoglycemiaCarcinoid syndromePheochromocytomaAccelerated renovascular hypertensionEthanol or drug withdrawalSympathomimetic toxicity

Treatment

Pre-Hospital

  • Patient may be uncooperative or violent.
  • Secure IV access.
  • Protect from self-induced trauma.

Initial Stabilization/Therapy

  • Airway, breathing, and circulation (ABCs)
  • IV access and fluid resuscitation if hypotensive
  • Oxygen
  • Cardiac monitor
  • Naloxone, thiamine, D50W (or Accu-Chek) if altered mental status

Ed Treatment/Procedures

  • Gastrointestinal decontamination:In potential life-threatening ingestions gastric lavage may be carefully considered if within 1 hr of ingestionAdminister activated charcoal
  • Hyperthermia:Benzodiazepines if agitatedActive cooling if temperature >40 °C:Tepid water mistEvaporate with fanParalysis:Indicated if muscle rigidity and hyperactivity contributing to persistent hyperthermiaNondepolarizing agent (e.g., vecuronium)Avoid succinylcholineIntubation; mechanical ventilationAdminister acetaminophen.Apply cooling blankets.
  • Severe, malignant hypertension:Nitroprusside (for MAOI overdose)Calcium-channel blocker or phentolamine (for MAOI + food interaction)Use short-acting IV agent that can be rapidly "turned off. "
  • Hypotension:Initially bolus with isotonic crystalloid solutionIf no response, administer norepinephrine.Dopamine may be ineffective
  • Dysrhythmias (premorbid sign in MAOI overdose):Treatment based on dysrhythmia
  • Seizures:BenzodiazepinesBarbiturates if benzodiazepines unsuccessfulPyridoxine for refractory seizures
  • Rigidity:BenzodiazepinesParalysis with vecuronium, endotracheal intubation, and mechanical ventilation
  • ARDS:OxygenIntubation and positive end-expiratory pressure as indicated
  • DIC:Fresh-frozen plasmaPlateletsWhole-blood transfusions
  • Rhabdomyolysis:IV isotonic crystalloid solutionMaintain hydration to ensure adequate urine output
  • Specific treatment for SS:Mainstay: Supportive care, discontinuation of offending agentsNonselective serotonin antagonist:

Phentolaminecontraindicated in MAOI overdose (results in unopposed ²-agonist)

Medication

  • Activated charcoal: 1 " 2 g/kg PO
  • Cyproheptadine: 4 " 8 mg PO/nasogastric tube q1 " 4h until therapeutic response; max. daily dose: 0.5 mg/kg (peds: 0.25 mg/kg/d; max. 12 mg/d; safety not established age <2 yr)
  • Dextrose: D50W 1 " 2 amp (50 " 100 mL or 25 " 50 g) (peds: D25W 2 " 4 mL/kg) IV push (IVP)
  • Diazepam: 5 " 10 mg (peds: 0.1 mg/kg slowly) increments IVP
  • Lorazepam: 1 " 2 mg increments IVP
  • Nitroprusside: 0.3 " 10 Ό/kg/min IV
  • Norepinephrine: 2-4 Ό/kg/min (peds: 0.05 " 0.1 Ό/kg/min) IV
  • Phentolamine: 5 mg (peds: 0.05 " 0.2 mg/kg/dose) increments IVP
  • Sodium bicarbonate: Bolus 1 " 2 mEq/kg IVP; adult infusion: 3 amp (50 mEq per amp) sodium bicarbonate in 1,000 mL D5W at 2 " 3 mL/kg/h IV
  • Vecuronium: 0.1 mg/kg IVP

Follow-Up

Disposition

MAOI toxicity can occur in delayed fashion necessitating an extended observation period

Admission Criteria

  • All MAOI overdose patients require admission to a monitored unit for 24 hr.
  • ICU admission for seriously ill patients

Discharge Criteria

  • Resolved mild hypertensive syndrome or resolved mild serotonin syndrome may be discharged after several hours of ED observation.

Issues for Referral

Intentional overdoses should receive a psychiatry consult for suicide attempt.

Followup Recommendations

Following significant MAOI toxicity, medications need to be reassessed to prevent future crises.

Pearls and Pitfalls

  • Delayed onset of 6 " 12 hr prior to symptoms
  • Linezolid and methylene blue are MAOIs.
  • Phentolamine is contraindicated in MAOI overdose secondary to unopposed ²-agonist.

Additional Reading

  • Boyer EW, Shannon M. The serotonin syndrome. New Engl J Med. 2005;352:1112 " 1120.
  • Brush DE, Bird SB, Boyer EW. Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances. J Toxicol Clin Toxicol. 2004;42:191 " 195.
  • Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth. 2005;95:434 " 441.
  • Oates JA, Sjoerdsma A. Neurologic effects of tryptophan in patients receiving a monoamine oxidase inhibitor. Neurology. 1960;10:1076 " 1078.
  • Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: Inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol. 2007;152:946 " 951.

See Also (Topic, Algorithm, Electronic Media Element)

Sympathomimetic Poisoning

Codes

ICD9

969.01 Poisoning by monoamine oxidase inhibitors

ICD10

  • T43.1X1A Poisoning by monoamine-oxidase-inhibitor antidepressants, accidental (unintentional), initial encounter
  • T43.1X2A Poisoning by monoamine-oxidase-inhibitor antidepressants, intentional self-harm, initial encounter
  • T43.1X4A Poisoning by MAO inhib antidepressants, undetermined, init

SNOMED

  • 9291000 Poisoning by monoamine oxidase inhibitor (disorder)
  • 295889000 Overdose of monoamine oxidase inhibitor antidepressant drug (disorder)
  • 216548005 Accidental poisoning by monoamine oxidase inhibitors (disorder)