Introduction to General Toxicology & Toxidromes

Approach to General Toxicology & Toxidromes

Introduction

An estimated 732 Canadians (.4% of total mortality) died from the use of illicit drugs in 1992. Of these, 42% were suicides, 14% were from opiate poisoning, 9% were cocaine poisonings and 8% were AIDS-related deaths in injection drug users. In addition, there were 7,100 hospitalizations – half of which were for drug psychosis, assaults and cocaine abuse.  In total, substance abuse cost Canadians more than $18.4 billion in 1992 ($649 per capita), which is 2.7% of the Gross Domestic Product. Direct health care costs due to illicit drugs are estimated at $88 million.  (Canadian Foundation for Drug Policy)

 

Toxicology (Wikipedia) is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms. It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people.

General Approach to Toxicology

A general rule of thumb to approaching all toxicology patients is to address the following issues:

1) Resuscitation & evaluation of ABCDs

Pearls:

- Evaluate ECG for conduction abnormalities ie QRS >100ms or increased QTc

- Don’t forget to include a finger prick glucose

- If seizures or agitation are present, benzodiazapines are usually the best intervention

2) Diagnosis of Poisoning

- Through historical information or identification of toxidromes

3) Decontamination

4) Increase Elimination

5) Antidote (if applicable)

 

5 Basic Toxidromes

1) Anticholinergic:

“Hot as a Hare, Mad as a Hatter, Red as a Beet, Dry as a Bone, Blind as a Bat”

Signs secondary to muscarinic receptor blockade:

Delirium w/ mumbling speech, tachy, dry flushed skin, dilated pupils, myoclonus, slightly elevated temperature, urinary retention, decreased bowl sounds. Seizures and dysrhythmias in severe cases.

Causes:

Antihistamines, antiparkinsonians, atropine, scopolamine, amantadine, antipsychotics, antidepressants, muscle relaxants, plants ie. Jimson weed

Mgmt:

- Supportive care: IV fluids to replace insensible losses from agitation & hyperthermia

- Benzodiazepines to stop agitation secondary to delerium

- Consider physostigmine

  • Induces cholinergic effects
  • Short acting
  • May help with uncontrollable delerium
  • Do NOT use if ingestion is unknown, as it is carries a risk of asystole in TCA ingestions

2) Sympathomimetics:

Signs due to stimulation of a, b, or dopaminergic receptors or indirect norepinephrine or epinephrine effects:

Delusions, paranoia, tachy (reflex brady w/ pure α- agonists), HTN, hyperpyrexia, diaphoresis, piloerection, mydriasis, hyperreflexia

Seizures, hypotension, and wide complex dysrhythmias in severe cases

Causes: Cocaine, amphetamines, methamphetamines, OTC decongestants

Differentiation from anticholinergics:

- Mental status: tend to be more coherent

- Diaphoretic

- Pt w/ anticholinergics tend to be in urinary retention

Mgmt:

- Supportive care: IV fluids for insensible losses & volume repletion, monitor airway, observe for intracranial hemorrhage or rhabdomyolysis

- Benzodiazepine titration

- Management of blood pressure if severe and symptoms of end organ dysfunction (but do NOT use B-blockers as there is a risk of unopposed a effect)

3) Cholinergic:

“SLUDGE”: Salivation, Lacrimation, Urination, Defecation, GI cramping, Emesis + “Killer B’s”: Bronchorrhea, Bradycardia, Bronchospasm

Signs due to binding and inhibition of plasma cholinesterase, and thus excess acetylcholine (ACh):

Confusion, CNS depression, weakness, salivation, lacrimation, urinary/fecal incontinence, GI cramping, emesis, diaphoresis, muscle fasiculations, pulmonary edema, miosis, brady/tachy, seizures

Causes:

Organophosphate and carbamate insecticides, physostigmine, edrophonium, some mushrooms, “nerve” agents ie sarin

Management:

- Atropine: antagonizes muscarinic actions of ACh

- 2-PAM: stops aging of enzyme blockade

- Diazepam: prevents and terminates seizures

- Supportive care

4) Opioid/Sedative/Ethanol agents:

Signs:

Coma, respiratory depression, miosis, hypotension, bradycardia, hypothermia, pulmonary edema, decreased bowel sounds, hyporeflexia, needle marks

Causes:

Narcotics, barbiturates, BZDs, Ethanol, clonidine

Management of Narcotic overdoses:

- Naloxone: competitive opiod antagonist

            * Goal is return of spontaneous respirations  adequate to ventilate the patient

            * May require re-dosing as opiates may have a longer half-life than antagonist

5) Serotonin Syndrome:

“FARM”: Fever, Altered mental status, Rigidity, Myoclonus

Signs:

Altered mental status, fever, agitation, tremor, myoclonus, hyperreflexia, ataxia, poor co-ordination, diaphoresis, shivering

SSRI interaction or OD

Management:

- Supportive: IV fluids to replenish losses from agitation and hyperthermia, benzodiazepines

- Cyproheptadine

 

Diagnostic Investigations

CBC, electrolytes, glucose, creatinine, BUN, LFTs, Serum osmolality

Acetaminophen, salicylate, ethanol level

Urinalysis, urine pregnancy test (if female)

ECG

*Toxicology screens (urine or blood) may not identify the ingested agent

  • Labs do not routinely screen for many substances capable of causing critical illness and other substances may cross-react resulting in false positives
  • Urine Screen often performed soon after ingestion when drug concentrations are too low for a positive result ie. TCAs
  • Drugs found on screening may not be those responsible for initial symptoms and are often not quantified
  • Results of toxicology screens are often not available until many hours after treatment decisions need to be made
  • Toxicology screens are often very expensive (>$300) and routine use in most OD not warranted from the perspective of ED management
  • Useful in patients critically ill for unknown reason where identifying an unsuspected toxin may change mgmt

 

Consider AXR if radiopaque tablets (“CHIPES”: chloral hydrate, heavy metals, iron, phenothiazines, enteric coated, sustained release) or concern of “body packing/stuffing”

 

Calculating the Osmolar Gap

Calculated Osm= 2[Na] + glucose + BUN

OG= Serum Osm- Calc Osm

Normal: <12mmol/L

** Correction for Ethanol:  Add serum EtOH level x 1.25 to the calculated Osm

 

Causes of Elevated OG:

Acetone

Mannitol

Dimethyl sulfoxide

Metaldehyde

Ethanol

Methanol

Ethyl ether

Osmotic contrast dyes

Ethylene glycol

Propylene glycol

Isopropyl alcohol

Renal failure w/o dialysis

Magnesium

Severe alcoholic ketoacidosis, diabetic ketoacidosis, or lactic acidosis

 

Anion Gap Metabolic Acidosis

AG= [Na+] – [Cl-]- [HCO3-]

Normal: 8-12 mEq/L

Accounts for unmeasured anions (phosphate, sulfate, anionic proteins)

 

Causes of ↑ AG: “CAT MUDPILES”

Methanol                        Cyanide, Carbon monoxide

Uremia                        Alcoholic ketoacidosis

DKA                                    Toluene

Paraldehyde

Isoniazid, Iron

Lactic acid

Ethylene glycol

Salicylates

*** In any pt w/ ↑ OG + ↑ AG need to consider toxic alcohols ie. methanol, ethylene glycol & antidotal tx w/ fomepizole, EtOH, or hemodialysis

 

Decontamination

a) Surface Decontamination

Skin: remove corrosive agents, other toxins absorbed through skin

** Beware attempts to neutralize acids/bases can cause more harm by inducing an exothermic reaction

Inhalation: potential for acute irritation of the pulmonary system by gases/fumes or late onset non-cardiogenic pulmonary edema

b) GI Decontamination

Emesis induction, gastric lavage, activated charcoal, whole bowel irrigation

Little support in literature, especially after delay >60min

Indications for aggressive gut decontamination:

1) Ingestion of highly toxic drugs ie CCB

2) Ingestion of drugs not adsorbed to charcoal

3) Ingestion of massive amounts of a drug

4) Ingestion of sustained release, enteric coated meds, or drugs w/ anticholinergic properties

i) Emesis:

Syrup of ipecac no longer tx of choice for any ingestions

Employed rarely if medical care delayed >60min and if given within few min of ingestion

Not used in ED because persistent emesis likely to delay administration of AC

ii) Gastric Lavage:

-Used only occasionally in EDs

-Slightly more effective than ipecac for recently ingested liquid substances

-Does not reliably remove undissolved pills/pill fragments

-Most effective if within 30-60min of ingestion

Indications:

Removal of toxins in massive OD or highly toxic ingestions

Dilute/remove corrosive liquids and to empty stomach in preparation for EGD

iii) Activated Charcoal (AC)

Highly adsorbent powder made from distillation of wood pulp

Large surface area

Adsorbs most toxins when given in a ratio of 10:1 (AC: toxin)

Studies have demonstrated AC alone w/o prior gastric emptying is as or more effective than emesis/lavage in reducing drug adsorption

Dose: 1g/kg po/NG, may give multidose q1-2h

Indicated if risk of poisoning justifies risk of AC and administration within 60min of ingestion

Adverse Effects:

Constipation, intestinal impaction, bezoar

Gastric distention w/ risk of aspiration

If mixed w/ sorbitol can cause vomitting, and if repeateddoses can cause fluid shifts and hypernatremia

Contraindications:

Multiple doses if ileus w/o distention, 1 dose OK

Drowsy patients unless airway adequately protected

Toxins/Drugs Poorly Adsorbed by AC

Alkali

Inorganic salts

Ethanol/Alcohols

Iron

Ethylene glycol

Lithium

Fluoride

Mineral acids

Heavy Metals

Potassium

 

iv) Whole Bowel Irrigation:

PEG Lyte given at high flow rates (2L/h) to force intestinal contents out by sheer volume until rectal effluent is clear

Indications:

Large ingestions of Fe, Li, other drugs poorly adsorbed to AC

Large ingestions of SR or EC tablets of valproic acid, theophylline, ASA, verapamil, diltiazem, or other dangerous drugs

Ingestion of FB or drug filled packets in body stuffers/packers

Contraindications:

Ileus or intestinal obstruction

Obtunded, comatose, or convulsing patient unless airway is protected

Adverse Effects:

Nausea & bloating

Regurgitation and aspiration

AC may not be as effective when given w/ WBI

 

Enhanced Elimination

While desirable, frequently not practical or may be unsafe

  • Need to assess 3 issues:
  • Does the patient need enhanced removal?
    • Deteriorating condition despite maximal supportive care
    • Normal route of elimination impaired
    • Ingestion of a known lethal dose or has a lethal blood level
  • Is the drug/toxin accessible to removal procedures?
    • Asses volume of distribution, protein binding
  • Will the method of elimination work?
    • Assess “clearance” of substance, T1/2

 

Methods Available:

Forced diuresis, Urine alkalinization

Hemodialysis

Peritoneal Dialysis

Continuous renal replacement therapy

Repeat dose AC

*Only if need for rapid removal of toxin less urgent

Interrupts enterohepatic or eneteroenteric recirculation of the drug/toxin

Demonstrated to shorten T1/2 of phenobarbital, theophylline, nadolol, salicylate, phenytoin, caffine, etc

Not shown in clinical trials to alter patient outcome

 

 

Antidotes

Toxin

Antidote

Anticholinergics

Physostigmine 0.5-1mg

- Reversible cholinersterase inhibitor

- DO NOT use in TCA OD, can cause asystole

BZD

Flumazenil (w/ caution)

Opiods

Narcan

Cholinergics

Atropine 1-2mg IV +

Pralidoxime

Serotonin Syndrome

Mild: BZD

Severe: Cyproheptadine (5-HT antag)

Toxic Alcohols

EtOH or Fomepizole

Acetaminophen

N-acetylcysteine

B-blockers

Glucagon

CCB

CaCl +

Glucagon

 

 

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