Toxidromes

Today's case was of a young man with a history of depression who presented with an ingestion.  He had taken an SSRI and a neurolepticin an intentional suicide attempt.  Medical history was otherwise unremarkable and he denied any coingestions.  He was admitted for monitoring with telemetry and placed on a form 1.

We talked about a number of learning points:

-When patients present to medical attention with a known or suspected overdose (or even if they just have a decreased level of consciousness) it’s important to think about toxidromes.  These are syndromes describe the physiologic consequences of taking the medication or type of medication in question.  They are important because they will likely clue you into the overdose/ingestion long before laboratory tests are available.  We discussed some of them below:

Toxidrome	Mentation	HR	RR	Temp	Skin	Entities	Treatment
Anticholinergic	Agitated	high	-	high	Dry	TCA, antihistamines	Supportive, ?cholinergics
Cholinergic	Depressed	low	-	-	Wet	Organophosphate	Atropine, pralidoxime
Sympathomimetic	Agitated	high	high	high	Wet	Cocaine, MDMA	Benzodiazepine
Opioid	Depressed	low	low	-	Normal	Morphine	Naloxone, supportive

In addition to these classic toxidromes (which can typically be ascertained just by looking at the patient) we talked about a few others:

·      Serotonin syndrome – This occurs as a result of increased serotonergic activity from medications like TCA’s, SSRI’s, and even antibiotics like linezolid.  The triad is altered mentation, neuromuscular abnormalities, and autonomic abnormalities.  Classically these patients have hyperreflexia and even spontaneous clonus.

·      Neuroleptic malignant syndrome – This occurs as a result of dopamine blockade (absolute or relative).  That means that it can occur because of an antidopaminergic medication like haloperidol, or withdrawal of Parkinsonian medications.  Contrary to popular belief, domperidone which is thought not to cross the blood-brain-barrier can cause this condition. The mnemonic for the syndrome is FARM – fever, autonomic instability, rigidity (classically lead pipe rigidity) and mental status changes.  They typically have an elevated CK from rhabdomyolysis, leukocytosis, and for whatever reason, a low serum iron level.  The treatment is withdrawal of the offending agent, and either dopamine agonists like bromocriptine, or muscle relaxants like dantrolene.

·      Alcohol withdrawal syndromes – These occur as a result of habitual alcohol use.  It should be noted that while most withdrawal syndromes are a nuisance, alcohol withdrawal can be life-threatening.  Symptoms involve autonomic changes from sympathetic surges, mental status changes (alcoholic hallucinosis, typically with tacticle hallucinations like skin-crawling), and seizures (which are always GTC’s and rarely progress to status epilepticus).

-We talked about the approach to the overdose: ensure that the airway is patent, the patient is breathing, and the blood pressure and circulatory system is functioning normally.  If this is not the case, those abnormalities need to be dealt with.  In addition to the “ABC’s” we add “D” for decontamination with things like activated charcoal, whole-bowel irrigation, and the like.  “E” gets added for elimination.  This means using medications to enhance the natural hepatic/renal metabolism of certain drugs or dialysis to remove it from the bloodstream.  Also, things like antidotes need to be considered – some drugs like acetaminophen have an antidote that prevents toxic effects.  Others, like ethanol for methanol intoxication, rely on pharmacokinetics to reduce conversion of a relatively less toxic compound to the more toxic one through competitive inhibition.

-Poison centre should generally be called for any overdose like this.  They have toxicologists on call 24 hours/day and can help you by providing rare and exceptional consequences, suggestions for supportive care, monitoring frequency, and antidotes.  Further to that, they have an important role in documentation so they should always be called even if you know what you’re doing.

Further Reading:

Boyer, E. W., & Shannon, M. (2005). The serotonin syndrome. New England Journal of Medicine, 352(11), 1112-1120.

Perry, P. J., & Wilborn, C. A. (2012). Serotonin syndrome vs neuroleptic malignant syndrome: a contrast of causes, diagnoses, and management. Ann Clin Psychiatry, 24(2), 155-62.

Mégarbane, B. (2014). Toxidrome-based approach to common poisonings. Asia Pacific Journal of Medical Toxicology, 3(1), 2-12.

Turner, R. C., Lichstein, P. R., Peden Jr, J. G., Busher, J. T., & Waivers, L. E. (1989). Alcohol withdrawal syndromes. Journal of general internal medicine, 4(5), 432-444.