Toxicology

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Toxicology

• Kristopher R. Brickman, MD, FACEP
• UTMC Emergency Medicine

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(No Transcript)
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Objectives

• General approach to the poisoned patient
• Toxidromes
• Specific antidotes
• Decontamination and enhanced elimination

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General Approach

• ABCs
• History
• Physical examination
• Labs, imaging
• Diagnosis, antidotes
• Disposition

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ABCs
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Airway

• Airway obstruction can cause death after
  poisoning
• Flaccid tongue
• Aspiration
• Respiratory arrest
• Evaluate mental status and gag/cough reflex
• Airway interventions
• Sniffing position
• Jaw thrust
• Head-down, left-sided position
• Examine the oropharynx
• Clear secretions
• Airway devices nasal trumpet, oral airway
• Intubation?
• Consider naloxone first

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Breathing

• Determine if respirations are adequate
• Give supplemental oxygen
• Assist with bag-valve-mask
• Check oxygen saturation, ABG
• Auscultate lung fields
• Bronchospasm Albuterol nebulizer
• Bronchorrhea/rales Atropine
• Stridor Determine need for immediate intubation

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Circulation

• IV access
• Obtain blood work
• Measure blood pressure, pulse
• Hypotension treatment
• Normal saline fluid challenge, 20 mL/kg
• Vasopressors if still hypotensive
• PRBCs if bleeding or anemic
• Hypertension treatment
• Nitroprusside, beta blocker, or nitroglycerin
• Continuous ECG monitoring
• Assess for arrhythmias, treat accordingly

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Supportive Care

• Foley catheter
• Rectal temperature
• Accucheck, treat hypoglyemia
• Coma cocktail
• Thiamine 100 mg IV, before dextrose
• Dextrose 50 grams IV push
• Naloxone 0.01 mg/kg IV

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Supportive Care

• Treat Seizures
• Lorazepam 2 mg IV, may repeat as needed
• Dilantin 10 mg/kg IV
• Control agitation
• Haldol 5-10 mg IM
• Ativan 2-4 mg IM or IV
• Geodon 20 mg IM
• Think about trauma

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REASSESS . . . frequently
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History

• What, when, how much, why?
• Rx, OTC, herbals, supplements, vitamins
• Talk to family, friends, EMS
• Pill bottles, needles, beer cans, suicide note
• Call pharmacy
• Allergies, medical problems

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Physical examination

• Vital signs BP, HR, RR, T, O2 sat
• Mouth odors, mucous membranes
• Pupils
• Breath sounds
• Bowel sounds
• Skin
• Urination/defecation
• Neurologic exam

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Essential Laboratory Tests

• Electrolytes
• Glucose
• BUN and creatinine
• LFTs, CK
• Urinalysis, urine drug screen
• Etoh, alcohol screen
• Serum osmolality
• Acetaminophen, salicylates
• Specific drug levels
• Pregnancy test

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Anion Gap

• Na (HCO3 Cl)
• Normal 8-12 mEq/L
• Causes
• Methanol
• Uremia
• DKA
• Paraldehyde, phenformin
• Iron, isoniazid, ibuprofen
• Lithium, lactic acidosis
• Ethylene glycol
• Strychnine, starvation, salicylates

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Osmolar Gap

• Calculated osmolality measured osmolality
• 2(Na) glucose/18 BUN/2.8
• Normal 285-290 mOsm/L
• Gap gt 10 mOsm/L suggests the presence of extra
  solutes
• Ethanol, methanol
• Ethylene glycol, isopropyl alcohol
• Mannitol, glycerol
• Clinical Pearl Anion gap acidosis with an
  osmolar gap should suggest methanol or ethylene
  glycol poisoning

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Electrocardiogram

• Prolonged QRS
• TCAs
• Phenothiazines
• Calcium channel blockers
• Sinus bradycardia/AV block
• Beta-blockers, calcium channel blockers
• TCAs
• Digoxin
• organophosphates
• Ventricular tachycardia
• Cocaine, amphetamines
• Chloral hydrate
• Theophylline
• Digoxin
• TCAs

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Diagnosis

• May not identify ingested substance(s)
• Provide ABCs and supportive care
• Give antidote when appropriate
• Call regional poison control center
• Carolinas Poison Center, Charlotte
• 800-848-6946

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Disposition

• Case-based
• ICU admission
• Period of observation
• Psychiatric evaluation

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Toxidromes
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Cholinergic Toxidrome

• Diarrhea Salivation
• Urination Lacrimation
• Miosis Urination
• Bradycardia Defecation
• Bronchospasm GI upset
• Emesis Emesis
• Lacrimation
• Limp
• Salivation, sweating

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Cholinergics

• Organophosphates
• Irreversibly bind cholinesterases
• Carbamate
• Reversibly bind cholinesterases, poor CNS
  penetration
• Muscarinic and nicotinic effects
• Pesticides, nerve agents
• Military personnel
• Field workers, crop dusters
• Truckers
• Pest control, custodial workers
• Antidote
• Atropine for muscarinic effects
• Pralidoxime reverses phosphorylation of
  cholinesterase

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Anticholinergics

• Atropine
• Scopolamine
• Glycopyrrolate
• Benztropine
• Antispasmotics
• Dicyclomine
• Hyoscyamine
• Oxybutynin
• clidinium
• TCAs
• Mydriatics

• Antihistamines
• Chlorpheniramine
• Cyproheptadine
• Hydroxyzine
• Diphenhydramine
• Meclizine
• promethazine
• Antipsychotics
• Clozapine
• Olanzapine
• Thioridazine
• Jimson weed

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Anticholinergic Toxidrome

• Dry mucus membranes (Dry as a bone)
• Mental status changes (Mad as a hatter)
• Flushed skin (Red as a beet)
• Mydriasis (Blind as a bat)
• Fever (Hot as a hare)
• Tachycardia
• Hypertension
• Decreased bowel sounds
• Urinary retention
• Seizures
• Ataxia

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Toxidromes

• Opioids
• Respiratory depression
• Miosis
• Hypoactive bowel sounds
• Sympathomimetics
• Hypertension
• Tachycardia
• Hyperpyrexia
• Mydriasis
• Anxiety, delirium
• Clinical Pearl Sweating differentiates
  sympathomimetic
• and anticholinergic
  toxidromes

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Antidotes

• Acetaminophen N-acetylcysteine
• Organophosphates Atropine,
  pralidoxime
• Anticholinergic physostigmine
• Arsenic, mercury, gold dimercaprol
• Benzodiazepines flumazenil
• Beta blockers glucagon
• Calcium channel block calcium
• Carboxyhemoglobin 100 O2
• Cyanide nitrite, Na thiosulfate
• Digoxin digoxin antibodies
  

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Antidotes

• Ethylene glycol fomepizole, HD
• Heparin protamine
• Iron deferoxamine
• Isoniazid pyridoxime
• Methanol fomepizole, HD
• Methemoglobin methylene blue
• Opioids naloxone
• Salicylate alkalinization, HD
• TCAs sodium bicarbonate
• Warfarin FFP, vitamin K

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Decontamination
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Principles of Decontamination

• External
• Protect yourself and others
• Remove exposure
• Irrigate copiously with water or normal saline
• Dont forget your ABCs
• Internal
• Patient must be fully awake or intubated
• Most common complication is aspiration
• Very little evidence for their use

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Decontamination

• Skin
• Protect yourself and other HC workers
• Remove clothing
• Flush with water or normal saline
• Use soap and water if oily substance
• Chemical neutralization can potentiate injury
• Corrosive agents injure skin and can have
  systemic effects

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Decontamination

• Eyes
• remove contact lens
• Flush copiously with water or normal saline
• Use local anesthetic drops
• Continue irrigation until pH is normal
• Slit lamp and fluorescein exam

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Decontamination

• Inhalation
• Give supplemental humidified oxygen
• Observe for airway obstruction
• Intubate as necessary

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GI Decontamination

• Syrup of ipecac
• Within minutes of ingestion
• Aspiration, gastritis, Mallory-Weiss tear,
  drowsiness
• Rarely, if ever, given in ED
• Gastric lavage
• Does not reliably remove pills and pill fragments
• Used 30-60 minutes after ingestion
• Useful after caustic liquid ingestion prior to
  endoscopy
• Not used for sustained release/enteric coated
  ingestions
• Perforation, nosebleed, vomiting, aspiration
• Recent studies suggest that activated charcoal
  alone is just as effective as gut emptying
  followed by charcoal.

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GI Decontamination

• Activated charcoal
• Limits drug absorption in the GI tract
• Within 60 minutes of ingestion
• Patient must be awake or intubated
• Vomiting, aspiration, bezoar formation
• Contraindication bowel obstruction or ileus with
  distention
• 1 gram/kg PO or GT

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Activated Charcoal

• Not good for
• Lithium
• Iron
• Alcohols
• Lead
• Hydrocarbons
• Caustics

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GI Decontamination

• Cathartics
• Hasten passage of ingestions or AC
• Contraindications obstruction or ileus
• Severe fluid loss, hypernatremia, hyperosmolarity
• 10 magnesium citrate 3ml/kg or 70 sorbitol 1-2
  ./kg
• Whole bowel irrigation
• Large ingestions, SR or EC tablets, packers (ex.
  cocaine)
• Contraindications obstruction or ileus
• Aspiration, nausea, may decrease effectiveness of
  charcoal

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Enhanced Elimination

• Urinary manipulation
• Forced diuresis
• Alkalinization
• Repeat-dose activated charcoal
• Very large ingestions of toxic substance
• Sustained release and enteric coated preparations
• Carbamazepine, phenobarbital, phenytoin
• Salicylate, theophylline, digitoxin
• Hemodialysis, Hemoperfusion
• Peritoneal dialysis, Hemofiltration

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Enhanced Elimination

• Does the patient need it?
• Severe intoxication with a deteriorating
  condition despite maximal supportive care
• Usual route of elimination is impaired
• A known lethal dose or lethal blood level
• Underlying medical conditions that can increase
  complications

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Specific Toxins

• Acetominophen
• Salicylates
• Tricyclic Antidepressants (TCA)

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Acetominophen (apap)
Magic number to remember is 140

• Max dose
• 4g/day adults
• 90 mg/kg day kids
• Peak serum levels 4 hours after overdose
• What are the three methods of APAP metabolism?
• Glucuronidation (90 normal thru pathway)
• Sulfonation
• P450 mixed oxidase enzymes (5 nl thru pathway)

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Acetominophen (apap)

• Toxicity
• 140mg/kg acute ingestion
• Direct hepatocellular toxicity with centrolobular
  distribution (hepatic vein)
• Can also have renal damage and pancreatitis

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Stages of Tylenol Toxicity

• I (0-24hrs) n/v, but most asymptomatic
• II latent stage (24-48hrs) subclinical increase
  in ast/alt/bili
• III hepatic stage (3-4dys) liver failure, ruq
  pain, vomiting, jaundice, coagulopathy,
  hypoglycemia, renal failure, metabolic acidosis
• IV recovery stage (4dys-2wks) resolution of
  hepatic dysfUTMCtion

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Need 4 hour level andN-acetylcysteine (NAC)

• Dx 4 hour level compared to the Rumack and
  Matthews nomogram
• 150ug/ml at 4 hours
• Rx NAC 140mg/kg then 70mg/kg every 4 hours for
  17 doses
• We Have PO and IV dosing
• Only useful for one time ingestion (not chronic
  ingestions)

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Acetominophen (apap)

• If time of ingestion unknown, draw level
  immediately and again at 2-4 hours.
• Labs LFTs, coags, lytes, aspirin, ETOH, tox
  screen

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NAC indications

• Ingestions with potential toxicity
• Late presentations with potential or ongoing
  toxicity
• Chronic overdose with evidence of hepatic damage

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Tylenol Overdose Disposition

• Admit if..
• Known toxicity / potential toxic levels
• Lab evidence of hepatic damage
• Unknown time of ingestion and sx consistent with
  toxicity
• Unknown ingestion time with measurable
  acetaminophen levels.

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Salicylates (asa)

• Weak acid, rapidly absorbed
• Enteric coated has delayed absorption
• Toxic dose 160 mg/kg
• Lethal dose 480 mg/kg
• Mixed respiratory alkalosis-metabolic acidosis
• Stimulates respiratory drive causing
  hyperventilation, but limits ATP production?
  metabolic acidosis
• Oil of wintergreen, 1ml 1400mg

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Salicylates Symptoms

• Tachypnea, tachycardia, hyperthermia
• Resp alkalosis-metabolic acidosis
• Altered serum glucose
• AG metabolic acidosis (MUDPILES)
• Dehydration (vomiting, tachypnea, sweating)

• Abd pain/n/v
• Tinnitus, hearing loss
• lethargy, seizures, altered mental status
• Noncardiogenic pulmonary edema

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Evaluation of ASA Overdose

• Lytes, ABG, LFTs, CBC, preg.test, urine PH
• Serum salicylate levels (toxicity at 25mg/dl)
• Toxicity correlates POORLY with levels
• Evaluation with DONE nomegram based on single
  ingestion of regular ASA at levels drawn 6 hrs
  after ingestion
• Underestimates toxicity in cases of severe
  acidemia or chronic ingestion

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Therapy for ASA Overdose

• ABCs
• Activated charcoal
• Urinary alkalinization (start if serum level is
  greater than 35mg/dl)
• 3 amps bicarbinate in 1 L D5W at 150 ml/hr
• By increasing urinary pH to greater than 8, ASA
  gets trapped in tubes and cannot be reabsorbed
• Dialysis for severe acidemia, volume overload,
  pulmonary edema, cardiac or renal failure,
  seizures, coma, levels gt 100mg/dl in acute
  ingestion, or gt 60-80 mg/dl in chronic ingestion

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Disposion for ASA Overdose

• Pt gets charcoal and remain asymptomatic after
  6-8 hours Possible D/C
• Sustained release requires longer observation
  period
• Pts with toxic levels, symptomatic, or develop
  symptoms Admission

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TCA (Tricyclic Antidepressants)

• Leading cause of death by intentional overdose
• Blocks sodium channels
• Death by cardiovascular dysrhythymias and
  cardiovascular collapse
• Most TCAs have anticholinergic effects
• Dry skin, blurry vision, hot
• Severe OD hypotension, seizures, respiratory
  depression
• In severe cases ARDS, rhabdomyolisis, DIC

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GET AN EKG

• What do you see?

Prolonged QRS, sinus tachycardia, tall R in R
tall R wave in lead aVR
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Treatment of TCA Overdose

• Sodium Bicarbinate
• Initial bolus of 2 amps
• Drip 3 amps in 1 L D5W at 150 ml/hr
• Titrate for serum pH of 7.45-7.5
• IV fluids
• Lidocaine for perisistent arrhythymias
• AVOID Class Ia drugs (procainimide quinidine)

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Thank You!

• Any Questions?

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References

• Poisoning Drug Overdose, California Poison
  Control System. KR Olson, 3rd edition, Appleton
  Lange, 1999.
• Emergency Medicine Board Review Series. L Stead,
  Lippincott Williams Wilkins, 2000.
• Emergency Medicine, A comprehensive study guide.
  Tintinalli, 6th edition, McGraw Hill, 2004.