Monoamine Oxidase Inhibitor Poisoning, Emergency Medicine

Basics

Description

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 levels
  - Downregulation of several receptor types
- Inhibition of irreversible (noncompetitive) enzyme
- Inhibition of other B6-containing enzymes
MAO: Principal inactivator of neural bioactive amines:
- MAO A:
  - Present in the gut and liver
  - Protects against dietary bioactive amines
- MAO B:
  - Present in neuron terminals and platelets
  - Sympathomimetic amines: Types of bioactive amines

Etiology

MAOI overdose:
- Toxicopharmacology poorly understood
- MAO inhibitors: Amphetamine-like in structure:
  - Early: Indirect sympathomimetic effect
  - Late: Sympatholytic response (hypotension)
MAOI hypertensive crisis syndrome:
- Results from impaired norepinephrine degradation and large norepinephrine release precipitated by an indirect- or mixed-acting sympathomimetic agent
- Common precipitants: Tyramine, cocaine, amphetamines
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
- Decrease serotonin breakdown:
  - MAOIs
- Increases nonspecific serotonin activity:
  - Lithium

Diagnosis

Signs and Symptoms

MAOI overdose:
- Delayed onset (6 " 12 hr)
- Initial hypertension with headache
- Hyperadrenergic activity:
  - Tachycardia
  - Hypertension
  - Mydriasis
  - Agitation
- Neuromuscular excitation:
  - Nystagmus
  - Hyperreflexia
  - Tremor
  - Myoclonus
  - Rigidity
  - Seizures
- Hyperthermia
- Associated complications:
  - Rhabdomyolysis
  - Renal failure
  - Disseminated intravascular coagulation (DIC)
  - Acute respiratory distress syndrome (ARDS)
MAOI hypertensive crisis syndrome (MAOI interaction with drug or food):
- Hypertension
- Tachycardia or bradycardia
- Hyperthermia
- Headache, usually occipital
- Altered mental status
- Intracranial hemorrhage
- Seizures
SS:
- Increased neuromuscular activity
- Increased deep tendon reflexes:
  - Lower extremity may be greater than upper
- Tremor
- Myoclonus
- Rigidity (when severe)
- Autonomic nervous system hyperactivity:
  - Hyperthermia
- CNS:
  - Agitation
  - Hallucinations
  - Delirium
  - Coma
- Diarrhea
- SS 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:
- Myoclonus
- Rigidity
- Tremors
- Hyperreflexia
Autonomic hyperactivity:
- Tachycardia or bradycardia
- Fever
- Diaphoresis
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:
- Blood
- Myoglobin
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:
- ARDS
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:
- Infection
- Hyperthyroidism
- Heat stroke
- Anatomic thalamic dysfunction
- NMS
- Malignant hyperthermia
- Malignant catatonia
- Ethanol or drug withdrawal
- Anticholinergic toxicity
- Sympathomimetic overdose
- Cocaine-associated delirium/rhabdomyolysis
- Salicylate toxicity
- Theophylline toxicity
- Nicotine toxicity
Hypertension:
- Hypoglycemia
- Carcinoid syndrome
- Pheochromocytoma
- Accelerated renovascular hypertension
- Ethanol or drug withdrawal
- Sympathomimetic 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 ingestion
- Administer activated charcoal
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
- Administer 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 solution
- If no response, administer norepinephrine.
- Dopamine may be ineffective
Dysrhythmias (premorbid sign in MAOI overdose):
- Treatment based on dysrhythmia
Seizures:
- Benzodiazepines
- Barbiturates if benzodiazepines unsuccessful
- Pyridoxine for refractory seizures
Rigidity:
- Benzodiazepines
- Paralysis with vecuronium, endotracheal intubation, and mechanical ventilation
ARDS:
- Oxygen
- Intubation and positive end-expiratory pressure as indicated
DIC:
- Fresh-frozen plasma
- Platelets
- Whole-blood transfusions
Rhabdomyolysis:
- IV isotonic crystalloid solution
- Maintain hydration to ensure adequate urine output
Specific treatment for SS:
- Mainstay: Supportive care, discontinuation of offending agents
- Nonselective serotonin antagonist:
  - Cyproheptadine

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.

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)

Home

Erectile Dysfunction

Doctor123.org