The Poisoned Patient: A Medical Student Review William Beaumont Hospital Department of Emergency Medicine William Beaumont Hospital Department of Emergency.

The Poisoned Patient:A Medical Student Review

The Poisoned Patient:A Medical Student Review

William Beaumont Hospital

Department of Emergency Medicine

William Beaumont Hospital

Department of Emergency Medicine

IntroductionIntroduction

• All chemicals, especially medicines, have the potential to be toxic

• 2006 TESS data– 2.7 million exposures– 19.8% were treated in a healthcare facility– 21.6% of those had more than minor

outcomes including death

• Over half of poisonings occur in children less than 5 years of age

• All chemicals, especially medicines, have the potential to be toxic

• 2006 TESS data– 2.7 million exposures– 19.8% were treated in a healthcare facility– 21.6% of those had more than minor

outcomes including death

• Over half of poisonings occur in children less than 5 years of age

The Initial ApproachThe Initial Approach

• Always consider poisoning in differential dx

• IV, O2, monitor

• Accucheck – in all pts with altered mental status

• D50 +/-Thiamine or Naloxone as indicated

• Decontamination, protect yourself

• Enhanced elimination

• Antidotal therapy

• Supportive care

• Always consider poisoning in differential dx

• IV, O2, monitor

• Accucheck – in all pts with altered mental status

• D50 +/-Thiamine or Naloxone as indicated

• Decontamination, protect yourself

• Enhanced elimination

• Antidotal therapy

• Supportive care

HistoryHistory

• Name, quantity, dose and route of ingestant(s)

• Time of ingestion

• Any co-ingestions

• Reason for ingestion – accidental, suicidal

• Other medical history and medications

• EMS – inquire what they saw at the scene, notes left, smells, unusual materials, pill bottles, etc.

• Name, quantity, dose and route of ingestant(s)

• Time of ingestion

• Any co-ingestions

• Reason for ingestion – accidental, suicidal

• Other medical history and medications

• EMS – inquire what they saw at the scene, notes left, smells, unusual materials, pill bottles, etc.

PupilsPupils

• Dilated – anticholinergic or sympathomimetic

• Constricted – Cholinergic

• Pinpoint – Opiods

• Nystagmus – horizontal – ethanol, phenytoin, ketamine

• Nystagmus – rotatory or vertical - PCP

• Dilated – anticholinergic or sympathomimetic

• Constricted – Cholinergic

• Pinpoint – Opiods

• Nystagmus – horizontal – ethanol, phenytoin, ketamine

• Nystagmus – rotatory or vertical - PCP

SkinSkin

Hyperpyrexia – anticholinergic, sympathomimetic, salicylates

Hypothermic – Opiods, sedative-hypnotics

Dry skin – anticholinergics

Moist skin – cholinergics, sympathomimetics

Color – cyanosis, pallor, erythema

Hyperpyrexia – anticholinergic, sympathomimetic, salicylates

Hypothermic – Opiods, sedative-hypnotics

Dry skin – anticholinergics

Moist skin – cholinergics, sympathomimetics

Color – cyanosis, pallor, erythema

Overall examOverall exam• Stimulants – everything is UP

– temp, HR, BP, RR, agitated– Sympathomimetics, anticholinergics,

hallucinogens

• Depressants – everything is DOWN – temp, HR, BP, RR, lethargy/coma– Cholinergics, opioids, sedative-hypnotics

• Mixed effects: Polysubstance overdose, metabolic poisons (hypoglycemic agents, salicylates, toxic alcohols)

• Stimulants – everything is UP – temp, HR, BP, RR, agitated– Sympathomimetics, anticholinergics,

hallucinogens

• Depressants – everything is DOWN – temp, HR, BP, RR, lethargy/coma– Cholinergics, opioids, sedative-hypnotics

• Mixed effects: Polysubstance overdose, metabolic poisons (hypoglycemic agents, salicylates, toxic alcohols)

Laboratory studiesLaboratory studies• Accucheck• Chemistries (BUN, Cr, CO2)• Urinalysis – Calcium oxalate crystals in

ehtylene glycol poisoning• Drugs of abuse and comprehensive drug

screen• Acetaminophen, aspirin and ethanol levels• Urine HCG if warranted• EKG • ABG, serum osmolality, Toxic Alcohol screen,

LFTS if warranted

• Accucheck• Chemistries (BUN, Cr, CO2)• Urinalysis – Calcium oxalate crystals in

ehtylene glycol poisoning• Drugs of abuse and comprehensive drug

screen• Acetaminophen, aspirin and ethanol levels• Urine HCG if warranted• EKG • ABG, serum osmolality, Toxic Alcohol screen,

LFTS if warranted

General DecontaminationGeneral Decontamination

• Remove all clothing, wash away any external toxic substances– If suspect transmittable contaminant,

perform in special decontamination area

• If ocular exposure – flush eyes copiously with at least 2 L NS using lid retractors, until pH 7 – 7.5

• Remove all clothing, wash away any external toxic substances– If suspect transmittable contaminant,

perform in special decontamination area

• If ocular exposure – flush eyes copiously with at least 2 L NS using lid retractors, until pH 7 – 7.5

GI DecontaminationGI Decontamination

• Three methods– Gastric emptying– Bind the toxin in the gut– Enhance elimination

• Always consider the patient’s mental status, risk of aspiration, airway security and GI motility before attempting any method

• Three methods– Gastric emptying– Bind the toxin in the gut– Enhance elimination

• Always consider the patient’s mental status, risk of aspiration, airway security and GI motility before attempting any method

Orogastric LavageOrogastric Lavage

• Indications – life threatening ingestions who present one hour within ingestion

• With the patient in the left lateral decub position, a 36 fr tube is passed oral - gastric to evacuate gastric contents and lavage with room temperature water until effluent is clear

• Studies show little benefit (may remove as little as 35% of the substance), the need of a secure airway and relatively high complication rate

• Indications – life threatening ingestions who present one hour within ingestion

• With the patient in the left lateral decub position, a 36 fr tube is passed oral - gastric to evacuate gastric contents and lavage with room temperature water until effluent is clear

• Studies show little benefit (may remove as little as 35% of the substance), the need of a secure airway and relatively high complication rate

Activated CharcoalActivated Charcoal

• Adsorbs toxin within the gut making it unavailable for absorption

• 1 g/kg PO or via NGT

• Contraindications: bowel obstruction or perforation, unprotected airway, caustics and most hydrocarbons, anticipated endoscopy

• Not effective for alcohols, metals (iron, lead), elements (magnesium, sodium, lithium)

• Adsorbs toxin within the gut making it unavailable for absorption

• 1 g/kg PO or via NGT

• Contraindications: bowel obstruction or perforation, unprotected airway, caustics and most hydrocarbons, anticipated endoscopy

• Not effective for alcohols, metals (iron, lead), elements (magnesium, sodium, lithium)

Multi-dose Activated CharcoalMulti-dose Activated Charcoal

• MDAC

• Large doses of toxin

• Slow release toxins

• Enterohepatic or enterenteric circulation

• Toxins that form bezoars

• “gastrointestinal dialysis”

• Phenobarbital, theophylline, carbamazepine, dapsone, quinine

• MDAC

• Large doses of toxin

• Slow release toxins

• Enterohepatic or enterenteric circulation

• Toxins that form bezoars

• “gastrointestinal dialysis”

• Phenobarbital, theophylline, carbamazepine, dapsone, quinine

CatharticsCathartics

• 70% Sorbitol 1g/kg, administered with charcoal

• Decreased transit time of both toxin and charcoal through the GI tract

• Typically only used with the first dose if MDAC

• Do not use in children under 5, caustic ingestions, or possible bowel obstruction

• 70% Sorbitol 1g/kg, administered with charcoal

• Decreased transit time of both toxin and charcoal through the GI tract

• Typically only used with the first dose if MDAC

• Do not use in children under 5, caustic ingestions, or possible bowel obstruction

Whole Bowel Irrigation (WBI)Whole Bowel Irrigation (WBI)

• Go-Lytely via PO or NGT at a rate of 2L/hr (500 ml/hr in peds)

• Typically used for those substances not bound by Activated Charcoal

• Do not use in patients with potential bowel obstruction

• Go-Lytely via PO or NGT at a rate of 2L/hr (500 ml/hr in peds)

• Typically used for those substances not bound by Activated Charcoal

• Do not use in patients with potential bowel obstruction

HemodialysisHemodialysis

• Useful for Salicylates, Methanol, Ethylene Glycol, Lithium, Amanita mushrooms, Isopropyl alcohol, Chloral hydrate

• Patients must be hemodynamically stable and without bleeding disturbances

• Charcoal hemoperfusion – essentially HD with a charcoal filter in the circuit– Barbituates, Carbamazepine, Phenytoin,

Methotrexate, Theophylline and Amanita poisonings

• Useful for Salicylates, Methanol, Ethylene Glycol, Lithium, Amanita mushrooms, Isopropyl alcohol, Chloral hydrate

• Patients must be hemodynamically stable and without bleeding disturbances

• Charcoal hemoperfusion – essentially HD with a charcoal filter in the circuit– Barbituates, Carbamazepine, Phenytoin,

Methotrexate, Theophylline and Amanita poisonings

Toxin AntidotesToxin Antidotes

• Acetaminophen• Anticholinergic agent• Benzodiazepines• Beta blockers or calcium

channel blockers• Carbon monoxide• Cardiac glycosides• Cyanide

• Acetaminophen• Anticholinergic agent• Benzodiazepines• Beta blockers or calcium

channel blockers• Carbon monoxide• Cardiac glycosides• Cyanide

• N-Acetylcysteine• Physostigmine• Flumazenil• Glucagon, calcium

• Oxygen• Digoxin-specific Fab fragments• Amyl nitrate, sodium nitrate,

sodium thiosulfate, hydroxycobalamin

• N-Acetylcysteine• Physostigmine• Flumazenil• Glucagon, calcium

• Oxygen• Digoxin-specific Fab fragments• Amyl nitrate, sodium nitrate,

sodium thiosulfate, hydroxycobalamin

Toxin AntidoteToxin Antidote

• Ethylene glycol• Heparin• Hydrofluoric acid• Iron• Isoniazid• Lead

• Mercury, arsenic, gold• Methanol• Nitrites (Methemoglobin)

• Ethylene glycol• Heparin• Hydrofluoric acid• Iron• Isoniazid• Lead

• Mercury, arsenic, gold• Methanol• Nitrites (Methemoglobin)

• 4-Methylpyrazole, ethanol• Protamine sulfate• Calcium gluconate• Desferoxamine• Pyridoxime (Vit B6)• BAL or DMSA, Calcium

disodium EDTA• BAL• 4-Methylpyrazole, ethanol• Methylene blue

• 4-Methylpyrazole, ethanol• Protamine sulfate• Calcium gluconate• Desferoxamine• Pyridoxime (Vit B6)• BAL or DMSA, Calcium

disodium EDTA• BAL• 4-Methylpyrazole, ethanol• Methylene blue

Toxins AntidoteToxins Antidote

• Opiates, propoxyphene, lomotil

• Organophosphates

• Sulfonylureas

• Tricyclic antidepressants

• Opiates, propoxyphene, lomotil

• Organophosphates

• Sulfonylureas

• Tricyclic antidepressants

• Naloxone (Narcan)

• Atropine, pralidoxime

• Glucose, octreotide

• Sodium bicarbonate, benzodiazepines

• Naloxone (Narcan)

• Atropine, pralidoxime

• Glucose, octreotide

• Sodium bicarbonate, benzodiazepines

Case OneCase One

56 y/o male found unconscious in a basement. He has snoring respirations, frothing at the mouth, and rales on pulmonary exam. His pupils are pinpoint. He wakes up swearing and swinging at staff after a little narcan.

What could it be?

56 y/o male found unconscious in a basement. He has snoring respirations, frothing at the mouth, and rales on pulmonary exam. His pupils are pinpoint. He wakes up swearing and swinging at staff after a little narcan.

What could it be?

The Toxidromes - OpioidThe Toxidromes - Opioid

• Heroin, Morphine, fentanyl• CNS depression, lethargy, confusion, coma,

respiratory depression, miosis• Vital signs: temp, HR, RR, +/- BP• Pulmonary edema, aspiration, resp arrest• Check for track marks, rhabdomyolysis,

compartment syndrome• Tx: Naloxone 0.4 - 2 mg iv/im/sc slowly

• May result in severe agitation• Monitor closely and re-dose if necessary

• Heroin, Morphine, fentanyl• CNS depression, lethargy, confusion, coma,

respiratory depression, miosis• Vital signs: temp, HR, RR, +/- BP• Pulmonary edema, aspiration, resp arrest• Check for track marks, rhabdomyolysis,

compartment syndrome• Tx: Naloxone 0.4 - 2 mg iv/im/sc slowly

• May result in severe agitation• Monitor closely and re-dose if necessary

The Toxidromes - SympathomimeticThe Toxidromes - Sympathomimetic• Cocaine, amphetamines (speed, dex,

ritalin), Phencyclidine (PCP), methamphetamines (crank, meth, ice), MDMA (Ecstasy, X, E) – Stimulant: Meth > amphetamines > MDMA– Hallucinogen: MDMA > Meth > amphetamines

• Agitation, temp, HR, BP, mydriasis

• Seizures, paranoia, rhabdomyolysis, MI, arrythmias

• Cocaine, amphetamines (speed, dex, ritalin), Phencyclidine (PCP), methamphetamines (crank, meth, ice), MDMA (Ecstasy, X, E) – Stimulant: Meth > amphetamines > MDMA– Hallucinogen: MDMA > Meth > amphetamines

• Agitation, temp, HR, BP, mydriasis

• Seizures, paranoia, rhabdomyolysis, MI, arrythmias

Toxidromes - SympathomimeticsToxidromes - Sympathomimetics

• Management - primarily supportive - Benzo’s, IV hydration, cooling if hyperthermic

• Treat HTN with benzodiazepines, nitrates, phentolamine

• MI – avoid beta blockers• Bodystuffers (small amount, poorly

contained) – Asymptomatic - AC, monitor for toxicity– Symptomatic - AC, WBI, treat symptoms

• Bodypackers (lg amount, well contained)– Asymptomatic - WBI followed by imaging– Symptomatic - Immediate surgical consultation

• Management - primarily supportive - Benzo’s, IV hydration, cooling if hyperthermic

• Treat HTN with benzodiazepines, nitrates, phentolamine

• MI – avoid beta blockers• Bodystuffers (small amount, poorly

contained) – Asymptomatic - AC, monitor for toxicity– Symptomatic - AC, WBI, treat symptoms

• Bodypackers (lg amount, well contained)– Asymptomatic - WBI followed by imaging– Symptomatic - Immediate surgical consultation

The Toxidromes - CholinergicThe Toxidromes - Cholinergic• Organophosphates

– Insecticides, nerve gas (Sarin, Tabun, VX) – Irreversible binding to ACHe – “aging”

• Carbamates– Insecticides (Sevin)– Reversible binding to ACHe – short duration

• Physostigmine, Edrophonium, Nicotine

• All increase Ach at CNS, autonomic nervous system and neuromuscular jx

• Organophosphates – Insecticides, nerve gas (Sarin, Tabun, VX) – Irreversible binding to ACHe – “aging”

• Carbamates– Insecticides (Sevin)– Reversible binding to ACHe – short duration

• Physostigmine, Edrophonium, Nicotine

• All increase Ach at CNS, autonomic nervous system and neuromuscular jx

The Toxidromes - CholinergicThe Toxidromes - Cholinergic

• Common Clinical Findings– SLUDGE Syndrome

• Parasympathetic hyperstimulation• Salivation, Lacrimation, Urinary Incontinence,

Defecation, GI pain, Emesis

– Killer B’s• Bradycardia, Bronchorrhea, Bronchospasm

– Bronchorrhea and respiratory failure is often the cause of death

– Miosis, garlic odor, CNS ( MS, seizures, muscle fasciculations and weakness, resp depression, coma

• Common Clinical Findings– SLUDGE Syndrome

• Parasympathetic hyperstimulation• Salivation, Lacrimation, Urinary Incontinence,

Defecation, GI pain, Emesis

– Killer B’s• Bradycardia, Bronchorrhea, Bronchospasm

– Bronchorrhea and respiratory failure is often the cause of death

– Miosis, garlic odor, CNS ( MS, seizures, muscle fasciculations and weakness, resp depression, coma

The Toxidromes - CholinergicThe Toxidromes - Cholinergic

• Diagnose – RBC or plasma cholinesterase level

• Management– Decontamination – protect yourself– Supportive therapy– Atropine - competitive inhibition of ACH

• Large doses required - 2-5 mg q 5 minutes

• End point is the drying of secretions

– Pralidoxime (2-PAM) - breaks OP-ACHe bond• Start with 1-2 g IV over 30 minutes, give before “aging”

• Adjust dose based on response, ACHe level

• Diagnose – RBC or plasma cholinesterase level

• Management– Decontamination – protect yourself– Supportive therapy– Atropine - competitive inhibition of ACH

• Large doses required - 2-5 mg q 5 minutes

• End point is the drying of secretions

– Pralidoxime (2-PAM) - breaks OP-ACHe bond• Start with 1-2 g IV over 30 minutes, give before “aging”

• Adjust dose based on response, ACHe level

Case 2Case 2

22 y/o F presents with decreased urine output. She is febrile, confused, flushed and has dilated pupils on exam. You also notice a linear, vesicular rash on her lower legs.

What do you want to know?

22 y/o F presents with decreased urine output. She is febrile, confused, flushed and has dilated pupils on exam. You also notice a linear, vesicular rash on her lower legs.

What do you want to know?

Case 2Case 2

• Meds– She has been using oral benadryl and topical

caladryl lotion for the poison ivy

What is her toxidrome?

• Meds– She has been using oral benadryl and topical

caladryl lotion for the poison ivy

What is her toxidrome?

The Toxidromes - AnticholinergicThe Toxidromes - Anticholinergic

• Agents– Antihistamines: diphenhydramine, loratadine,

meclizine, prochlorperazine– Antipsychotics: chlorpromazine (Thorazine),

Thiroidazine (Mellaril),– Belladonna Alkaloids: Jimsonweed, deadly

nightshade, mandrake, atropine, scopolamine– Cyclic Antidepressants: amitriptyline (Elevil),

nortriptyline (Pamelor), fluoxetine (Prozac)– OTC’s: Excedrin PM, Actifed, Dristan, Sominex– Muscle Relaxants: Orphenadrine (Norflex),

cyclobenzaprine (Flexeril)– Amanita mushrooms The Toxidromes - Anticholinergic

• Agents– Antihistamines: diphenhydramine, loratadine,

meclizine, prochlorperazine– Antipsychotics: chlorpromazine (Thorazine),

Thiroidazine (Mellaril),– Belladonna Alkaloids: Jimsonweed, deadly

nightshade, mandrake, atropine, scopolamine– Cyclic Antidepressants: amitriptyline (Elevil),

nortriptyline (Pamelor), fluoxetine (Prozac)– OTC’s: Excedrin PM, Actifed, Dristan, Sominex– Muscle Relaxants: Orphenadrine (Norflex),

cyclobenzaprine (Flexeril)– Amanita mushrooms The Toxidromes - Anticholinergic

The Toxidromes - AnticholinergicThe Toxidromes - Anticholinergic

• Common Clinical Findings– Dry as a bone - lack of sweating, dry skin and

mucous membranes– Red as a beet - flushed, vasodilated– Hot as Hades - hyperthermia, may be agitation

induced– Blind as a bat - mydriasis– Mad as a hatter - anticholinergic delirium,

hallucinations– Stuffed as a pipe - hypoactive bowel sounds, ileus,

decreased GI motility, urinary retention– VS: temp, HR, BP

• Common Clinical Findings– Dry as a bone - lack of sweating, dry skin and

mucous membranes– Red as a beet - flushed, vasodilated– Hot as Hades - hyperthermia, may be agitation

induced– Blind as a bat - mydriasis– Mad as a hatter - anticholinergic delirium,

hallucinations– Stuffed as a pipe - hypoactive bowel sounds, ileus,

decreased GI motility, urinary retention– VS: temp, HR, BP

The Toxidromes - AnticholinergicThe Toxidromes - Anticholinergic

• R/O psychiatric disorders, DTs, sympathomimetic toxicity

• Dry skin and absent bowel sounds indicate likely anticholinergic toxicity

• Management– Sedation with high dose benzodiazepines– AC (esp if BS), temp control– Treat widened QRS and dysrhythmias with bicarb– Physostigmine

• far more effective but use only in clear cut cases• 0.5 to 2.0 mg IVP, every 30-60 minutes• Monitor for excess cholinergic response - SLUDGE

• R/O psychiatric disorders, DTs, sympathomimetic toxicity

• Dry skin and absent bowel sounds indicate likely anticholinergic toxicity

• Management– Sedation with high dose benzodiazepines– AC (esp if BS), temp control– Treat widened QRS and dysrhythmias with bicarb– Physostigmine

• far more effective but use only in clear cut cases• 0.5 to 2.0 mg IVP, every 30-60 minutes• Monitor for excess cholinergic response - SLUDGE

The Toxidromes - SalicylateThe Toxidromes - Salicylate

• Aspirin, oil of wintergreen, OTC remedies

• Altered mentation, tinnitus, diaphoresis, nausea and vomiting, tachycardia

• Metabolic acidosis and respiratory alkalosis

• Dx: + anion gap, salicylate level > 30mg/dl

• Treatment– Multidose AC– Alkalinize urine – HD if levels > 100 mg/dl, altered MS, renal failure,

pulmonary edema, severe acidosis or hypotension

• Aspirin, oil of wintergreen, OTC remedies

• Altered mentation, tinnitus, diaphoresis, nausea and vomiting, tachycardia

• Metabolic acidosis and respiratory alkalosis

• Dx: + anion gap, salicylate level > 30mg/dl

• Treatment– Multidose AC– Alkalinize urine – HD if levels > 100 mg/dl, altered MS, renal failure,

pulmonary edema, severe acidosis or hypotension

The Toxidromes - Serotonin Syndrome (SS)The Toxidromes - Serotonin Syndrome (SS)

• SSRI’s: fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro)

• MAOI’s, meperidine, tricyclics, trazadone, mertazapine, dextromethorphan, LSD, lithium, buproprion, tramadol

• SS may be caused by any of the above, but usually occurs with a combination of agents, even if in therapeutic doses

• SSRI’s: fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro)

• MAOI’s, meperidine, tricyclics, trazadone, mertazapine, dextromethorphan, LSD, lithium, buproprion, tramadol

• SS may be caused by any of the above, but usually occurs with a combination of agents, even if in therapeutic doses

The Toxidromes - Serotonin Syndrome (SS)The Toxidromes - Serotonin Syndrome (SS)

• altered MS, mydriasis, myoclonus, hyperreflexia, tremor, rigidity (especially lower extremities), seizures, hyperthermia, tachycardia, hypo or hypertension

• Citalopram and escitalopram - prolonged QT and QRS

• No confirmatory tests – diagnosis is based on clinical suspicion

• altered MS, mydriasis, myoclonus, hyperreflexia, tremor, rigidity (especially lower extremities), seizures, hyperthermia, tachycardia, hypo or hypertension

• Citalopram and escitalopram - prolonged QT and QRS

• No confirmatory tests – diagnosis is based on clinical suspicion

The Toxidromes - Serotonin Syndrome TreatmentThe Toxidromes - Serotonin Syndrome Treatment

• Supportive care• Single dose AC (ensure airway control)• Benzodiazepines to treat discomfort, muscle

contractions or seizures) and cooling measures• Treat prolonged QT with magnesium• Treat widened QRS with Bicarb• Cyproheptadine (antiserotonin agent) - 4 to 8 mg

PO. Dose may be repeated in 2 hrs. If positive response, give 4 mg PO q 6 hrs for 48 hrs.

• Supportive care• Single dose AC (ensure airway control)• Benzodiazepines to treat discomfort, muscle

contractions or seizures) and cooling measures• Treat prolonged QT with magnesium• Treat widened QRS with Bicarb• Cyproheptadine (antiserotonin agent) - 4 to 8 mg

PO. Dose may be repeated in 2 hrs. If positive response, give 4 mg PO q 6 hrs for 48 hrs.

Acetaminophen PoisoningAcetaminophen Poisoning

• Common Clinical Findings– Stage I 0-24 hrs, nausea, vomiting, anorexia– Stage II 24-72 hrs, RUQ pain, elevation of AST

and ALT, also elevation of bilirubin and PT if severe poisoning

– Stage III 72-96 hrs, peak of AST, ALT, bilirubin and PT, possible renal failure and pancreatitis

– Stage IV > 5 days, resolution of hepatotoxicity or progression to multisystem organ failure

• Common Clinical Findings– Stage I 0-24 hrs, nausea, vomiting, anorexia– Stage II 24-72 hrs, RUQ pain, elevation of AST

and ALT, also elevation of bilirubin and PT if severe poisoning

– Stage III 72-96 hrs, peak of AST, ALT, bilirubin and PT, possible renal failure and pancreatitis

– Stage IV > 5 days, resolution of hepatotoxicity or progression to multisystem organ failure

Acetaminophen PoisoningAcetaminophen Poisoning

Rummack-Mathew nomogram

acetaminophen levels vs time

Plot 4 hr level

Useful for single acute ingestion only

Rummack-Mathew nomogram

acetaminophen levels vs time

Plot 4 hr level

Useful for single acute ingestion only

Acetaminophen PoisoningAcetaminophen Poisoning

• Management– AC assume polypharmacy OD– NAC - N-acetylcysteine (NAC) indicated if

• patient ingested over 140 mg/kg OR toxic level on nomogram

• IV dose: 150mg/kg IV load, 50 mg/kg over 4 hrs, then 100mg/kg over 16 hrs

• PO dose: 140 mg/kg load, then 70 mg/kg q 4 hrs x 17

– Draw baseline LFTs and PT

• Management– AC assume polypharmacy OD– NAC - N-acetylcysteine (NAC) indicated if

• patient ingested over 140 mg/kg OR toxic level on nomogram

• IV dose: 150mg/kg IV load, 50 mg/kg over 4 hrs, then 100mg/kg over 16 hrs

• PO dose: 140 mg/kg load, then 70 mg/kg q 4 hrs x 17

– Draw baseline LFTs and PT

CASE: UNKNOWN LIQUIDCASE: UNKNOWN LIQUID

17 y/o M brought in by family for acting “drunk.” He is lethargic, confused, disoriented. Vitals: 130, 90/60, 16, 37 C.

Labs: Etoh 0, CO2 12

What else do you want to know?

17 y/o M brought in by family for acting “drunk.” He is lethargic, confused, disoriented. Vitals: 130, 90/60, 16, 37 C.

Labs: Etoh 0, CO2 12

What else do you want to know?

CASE UNKNOWN LIQUIDCASE UNKNOWN LIQUID

Accucheck: 102

Serum Osmolality 330

Na 140, K 4.0, Cl 100, CO2 12, glucose 90

BUN 28, Cr 2.0

UDS, APAP, ASA are all negative

U/A has calcium oxalate crystals

What are we hinting at?

Accucheck: 102

Serum Osmolality 330

Na 140, K 4.0, Cl 100, CO2 12, glucose 90

BUN 28, Cr 2.0

UDS, APAP, ASA are all negative

U/A has calcium oxalate crystals

What are we hinting at?

Toxic AlcoholsToxic Alcohols

• Typical Agents– Ethanol– Isopropanol– Methanol– Ethylene glycol (EG)

• All toxic alcohols cause an osmolar gap• Methanol and EG cause an anion gap

acidosis

• Typical Agents– Ethanol– Isopropanol– Methanol– Ethylene glycol (EG)

• All toxic alcohols cause an osmolar gap• Methanol and EG cause an anion gap

acidosis

Useful EquationsUseful Equations

• Anion Gap (mEq/L)Na - (Cl + HCO3)

• Calculated Osmolarity (mosm/L)2Na + BUN/2.8 + Glu/18 + ETOH/4.6

• Anion Gap (mEq/L)Na - (Cl + HCO3)

• Calculated Osmolarity (mosm/L)2Na + BUN/2.8 + Glu/18 + ETOH/4.6

Toxic Alcohols - IsopropanolToxic Alcohols - Isopropanol

• Rubbing alcohol > solvents, antifreeze, disinfectants

• It is the second most commonly ingested alcohol

• Isopropyl alcohol has twice the CNS depressing potency and up to 4 times the duration as ethanol

• Toxic dose of 70% isopropanol is 1ml/kg

• Lethal dose is as little as 2ml/kg

• Rubbing alcohol > solvents, antifreeze, disinfectants

• It is the second most commonly ingested alcohol

• Isopropyl alcohol has twice the CNS depressing potency and up to 4 times the duration as ethanol

• Toxic dose of 70% isopropanol is 1ml/kg

• Lethal dose is as little as 2ml/kg

Toxic Alcohols - IsopropanolToxic Alcohols - Isopropanol

• Metabolized by alcohol dehydrogenase to acetone

• Fruity breath, ketonuria, + osmolar gap, no acidosis

• Clinically may appear similar to ethanol intoxication with greater CNS depression

• Hypotension, respiratory depression, coma• Nausea, vomiting, abdominal pain and upper GI

bleeding secondary to hemorrhagic gastritis

• Metabolized by alcohol dehydrogenase to acetone

• Fruity breath, ketonuria, + osmolar gap, no acidosis

• Clinically may appear similar to ethanol intoxication with greater CNS depression

• Hypotension, respiratory depression, coma• Nausea, vomiting, abdominal pain and upper GI

bleeding secondary to hemorrhagic gastritis

Toxic Alcohols - MethanolToxic Alcohols - Methanol

• Typical agent is wood alcohol, used in solvents, paint removers, antifreeze and windshield washer fluid. Also may be found in bootleg liquor.

• Is rapidly metabolized to toxic formaldehyde and formic acid

• Can cause permanent retinal injury and blindness as well as parkinsonian syndrome if not treated promptly

• May have a long latent period (12 to 18 hours), especially if co-ingested with ethanol

• Typical agent is wood alcohol, used in solvents, paint removers, antifreeze and windshield washer fluid. Also may be found in bootleg liquor.

• Is rapidly metabolized to toxic formaldehyde and formic acid

• Can cause permanent retinal injury and blindness as well as parkinsonian syndrome if not treated promptly

• May have a long latent period (12 to 18 hours), especially if co-ingested with ethanol

Methanol diagnosisMethanol diagnosis

• Common Clinical Findings – Lethargy, nausea, vomiting, abd pain– Visual symptoms seen in 50% - blurring,

tunnel vision, color blindness– HR, RR, BP (poor prognosis if present)– CNS - head ache, seizures or coma

• Wide anion-gap metabolic acidosis with osmolar gap

• Toxic alcohol screen to confirm

• Common Clinical Findings – Lethargy, nausea, vomiting, abd pain– Visual symptoms seen in 50% - blurring,

tunnel vision, color blindness– HR, RR, BP (poor prognosis if present)– CNS - head ache, seizures or coma

• Wide anion-gap metabolic acidosis with osmolar gap

• Toxic alcohol screen to confirm

Toxic Alcohols - Ethylene GlycolToxic Alcohols - Ethylene Glycol

• Typical agent is antifreeze• Often seen in alcoholics, suicide attempts and

children• Colorless, odorless and sweet• Metabolism and treatment similar to methanol• Is rapidly absorbed and converted to toxic acids

responsible for clinical signs and symptoms• Lethal dose is as low as 2 ml/kg

• Typical agent is antifreeze• Often seen in alcoholics, suicide attempts and

children• Colorless, odorless and sweet• Metabolism and treatment similar to methanol• Is rapidly absorbed and converted to toxic acids

responsible for clinical signs and symptoms• Lethal dose is as low as 2 ml/kg

Toxic Alcohols - Ethylene GlycolToxic Alcohols - Ethylene Glycol

• Common Clinical Findings– Three phases

• 1-12 hours - CNS Depression: inebriation, vomiting, seizures, coma, tetany (hypocalcemia)

• 12-24 hours - Cardiopulmonary Phase: hypotension, tachydysrhythmias, tachypnea and ARDS

• 24-72 hours - Nephrotoxic Phase: Oliguric renal failure, ATN, flank pain, calcium oxylate crystalluria

• Common Clinical Findings– Three phases

• 1-12 hours - CNS Depression: inebriation, vomiting, seizures, coma, tetany (hypocalcemia)

• 12-24 hours - Cardiopulmonary Phase: hypotension, tachydysrhythmias, tachypnea and ARDS

• 24-72 hours - Nephrotoxic Phase: Oliguric renal failure, ATN, flank pain, calcium oxylate crystalluria

Toxic Alcohols - Ethylene GlycolToxic Alcohols - Ethylene Glycol

• Additional findings– Hypocalcemia secondary to precipitation

with oxylate, excreted as urinary calcium oxylate crystals

– Urine may also fluoresce secondary to fluorescence dye in antifreeze

– EKG: QT prolongation (hypocalcemia) and peaked T’s (hyperkalemia)

– Myalgias, secondary to acidosis and elevated CPK

• Additional findings– Hypocalcemia secondary to precipitation

with oxylate, excreted as urinary calcium oxylate crystals

– Urine may also fluoresce secondary to fluorescence dye in antifreeze

– EKG: QT prolongation (hypocalcemia) and peaked T’s (hyperkalemia)

– Myalgias, secondary to acidosis and elevated CPK

Diagnose Ethylene Glycol (EG)Diagnose Ethylene Glycol (EG)

Always consider EG in an inebriated patient without alcohol breath, an anion-gap metabolic acidosis, osmolar gap and calcium oxylate crystalluria

Always consider EG in an inebriated patient without alcohol breath, an anion-gap metabolic acidosis, osmolar gap and calcium oxylate crystalluria

Treatment of EG and MethanolTreatment of EG and Methanol

• Supportive, especially airway• Correct acidosis with IV bicarb,

1meq/kg IV• Benzo’s if seizures develop• Folic acid 50mg IV q 4 hrs for both• Pyridoxine 100 mg IV q 6 hrs, Thiamine

100mg IV q 6 hrs, Magnesium for EG• Ca gluconate 10 ml of 10% IV – to

correct hypocalcemia – EG only

• Supportive, especially airway• Correct acidosis with IV bicarb,

1meq/kg IV• Benzo’s if seizures develop• Folic acid 50mg IV q 4 hrs for both• Pyridoxine 100 mg IV q 6 hrs, Thiamine

100mg IV q 6 hrs, Magnesium for EG• Ca gluconate 10 ml of 10% IV – to

correct hypocalcemia – EG only

Treatment of EG and MethanolTreatment of EG and Methanol

• Block production of toxic metabolites– Ethanol infusion or oral administration

• Load 10% in D5W at 10 ml/kg over 30 min• Infuse 10% in D5W at 1.5 ml/kg to maintain

ETOH level at > 100 mg/dl

– Fomepizole - preferred method• 15 mg/kg over 30 minutes, then 10 mg/kg q

12 hrs x 4• Has 8000 times the affinity for ADH as ETOH

without CNS depression and hypoglycemia• Or 4-MP (4-methylpyrazole)

• Block production of toxic metabolites– Ethanol infusion or oral administration

• Load 10% in D5W at 10 ml/kg over 30 min• Infuse 10% in D5W at 1.5 ml/kg to maintain

ETOH level at > 100 mg/dl

– Fomepizole - preferred method• 15 mg/kg over 30 minutes, then 10 mg/kg q

12 hrs x 4• Has 8000 times the affinity for ADH as ETOH

without CNS depression and hypoglycemia• Or 4-MP (4-methylpyrazole)

Treatment of EG and MethanolTreatment of EG and Methanol

• Hemodialysis indicated if– Serum level > 50 mg/dl– Signs of nephrotoxicity (EC) or CNS or visual

disturbances (Methanol)– Severe metabolic acidosis

• Hemodialysis indicated if– Serum level > 50 mg/dl– Signs of nephrotoxicity (EC) or CNS or visual

disturbances (Methanol)– Severe metabolic acidosis

TricyclicsTricyclics

• Agents– Amitriptyline (Elevil), desipramine

(Norpramin), imipramine (Tofranil) and nortriptyline (Pamelor)

– Narrow therapeutic index– Have returned to popularity with non-

depression indications such as chronic pain, migraines, ADHD and OCD

• Agents– Amitriptyline (Elevil), desipramine

(Norpramin), imipramine (Tofranil) and nortriptyline (Pamelor)

– Narrow therapeutic index– Have returned to popularity with non-

depression indications such as chronic pain, migraines, ADHD and OCD

TricyclicsTricyclics• Common Clinical Findings

– CNS - decreased LOC

• Confusion, hallucinations, delirium, seizures– Cardiovascular - arrhythmias and hypotension

• QRS > 100 msec, conduction delays

• Arrhythmias such as V-tach & Torsades may develop as QRS widens and QT prolongs

– Anticholinergic Toxidrome

• Tachycardia, mydriasis, hyperthermia, anhydrosis, urinary retention, decreased bowel sounds

• Common Clinical Findings– CNS - decreased LOC

• Confusion, hallucinations, delirium, seizures– Cardiovascular - arrhythmias and hypotension

• QRS > 100 msec, conduction delays

• Arrhythmias such as V-tach & Torsades may develop as QRS widens and QT prolongs

– Anticholinergic Toxidrome

• Tachycardia, mydriasis, hyperthermia, anhydrosis, urinary retention, decreased bowel sounds

TricyclicsTricyclics

• EKG during TCA toxicity and after treatment with bicarb. Note wide QRS, prolonged QT and terminal R’s > 3mm in AVR

• EKG during TCA toxicity and after treatment with bicarb. Note wide QRS, prolonged QT and terminal R’s > 3mm in AVR

Treatment of tricyclic overdoseTreatment of tricyclic overdose

• AC • Na Bicarb – to treat QRS prolongation > 100

msec and hypotension refractory to IV fluids• Benzo’s to treat seizures and hyperthermia

(avoid physostigmine)• Magnesium and Lidocaine for Ventricular

arrythmias refractory to Bicarb• Magnesium for QT prolongation or Torsades

• AC • Na Bicarb – to treat QRS prolongation > 100

msec and hypotension refractory to IV fluids• Benzo’s to treat seizures and hyperthermia

(avoid physostigmine)• Magnesium and Lidocaine for Ventricular

arrythmias refractory to Bicarb• Magnesium for QT prolongation or Torsades

COCO

• Sources– Fossil fuel combustion (car exhaust), smoke,

kerosene or coal heaters, steel foundries– Methylene chloride vapor

• Found in bubble Christmas tree lights and in paint strippers

• CO binds to hemoglobin with 230 times the affinity to oxygen, decreasing it’s ability to transport oxygen

• Sources– Fossil fuel combustion (car exhaust), smoke,

kerosene or coal heaters, steel foundries– Methylene chloride vapor

• Found in bubble Christmas tree lights and in paint strippers

• CO binds to hemoglobin with 230 times the affinity to oxygen, decreasing it’s ability to transport oxygen

COCO

• Common Clinical Findings– Organs with high O2 demand become

dysfunctional– Nausea, malaise, headache, decreased

mental status, dizziness, paresthesias, weakness, syncope

– May progress to vomiting, lethargy, coma, seizures, CVA , MI or respiratory arrest

– Need a high index of suspicion – multiple family members with flu like symptoms without fever, winter months

• Common Clinical Findings– Organs with high O2 demand become

dysfunctional– Nausea, malaise, headache, decreased

mental status, dizziness, paresthesias, weakness, syncope

– May progress to vomiting, lethargy, coma, seizures, CVA , MI or respiratory arrest

– Need a high index of suspicion – multiple family members with flu like symptoms without fever, winter months

COCO

• COHb level may not represent the severity of the poisoning

• Pulse oximetry also may be misleading

• Half-life of COHb– 4 hours on room air– 60 minutes breathing 100% normobaric O2 (NBO)– 15 to 23 minutes breathing 100% hyperbaric O2

(HBO) at 2.5 atmospheres

• COHb level may not represent the severity of the poisoning

• Pulse oximetry also may be misleading

• Half-life of COHb– 4 hours on room air– 60 minutes breathing 100% normobaric O2 (NBO)– 15 to 23 minutes breathing 100% hyperbaric O2

(HBO) at 2.5 atmospheres

CO treatmentCO treatment

• 100% O2 via NRB for 4 hrs minimum if mild symptoms (nausea, heachache, malaise)

• 100% O2 via NRB for 4 hrs minimum if mild symptoms (nausea, heachache, malaise)

COCO

• 100% O2 and transfer to a hyperbaric center if any of the following

• Altered mental status or coma• History of LOC or near syncope• History of seizure• Hypotension during or after exposure• MI• Pregnant with COHb > 15%• Arrythmias• +/- COHb > 25-40%

• Only absolute contraindication to hyperbaric chamber is pneumothorax

• 100% O2 and transfer to a hyperbaric center if any of the following

• Altered mental status or coma• History of LOC or near syncope• History of seizure• Hypotension during or after exposure• MI• Pregnant with COHb > 15%• Arrythmias• +/- COHb > 25-40%

• Only absolute contraindication to hyperbaric chamber is pneumothorax

ReferencesReferences

• Tintinalli, J., Kelen, G.D., Stapczynski, J.S., Emergency Medicine, A Comprehensive Study Guide, Sixth Edition 2004, McGraw-Hill, New York, pp 1015-1172

• Flomenbaum, N., Goldfrank, L., et al., Goldfrank’s Toxicologic Emergencies, Eighth Edition 2006, McGraw-Hill, New York, pp 37-140, 523-614, 1070-1098, 1118-1162, 1447-1468, 1497-1512

• Ziad, N.K., Roberge, R.J., A Toxicology Handbook, American Academy of Emergency Medicine

• Tintinalli, J., Kelen, G.D., Stapczynski, J.S., Emergency Medicine, A Comprehensive Study Guide, Sixth Edition 2004, McGraw-Hill, New York, pp 1015-1172

• Flomenbaum, N., Goldfrank, L., et al., Goldfrank’s Toxicologic Emergencies, Eighth Edition 2006, McGraw-Hill, New York, pp 37-140, 523-614, 1070-1098, 1118-1162, 1447-1468, 1497-1512

• Ziad, N.K., Roberge, R.J., A Toxicology Handbook, American Academy of Emergency Medicine