Transcript The Poisoned Patient: A Medical Student Review

The Poisoned Patient:
A Medical Student Review
William Beaumont Hospital
Department of Emergency
Medicine
Introduction
• 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 Approach
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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
History
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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.
Pupils
• Dilated – anticholinergic or
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sympathomimetic
Constricted – Cholinergic
Pinpoint – Opiods
Nystagmus – horizontal – ethanol,
phenytoin, ketamine
Nystagmus – rotatory or vertical - PCP
Skin
Hyperpyrexia – anticholinergic,
sympathomimetic, salicylates
Hypothermic – Opiods, sedative-hypnotics
Dry skin – anticholinergics
Moist skin – cholinergics,
sympathomimetics
Color – cyanosis, pallor, erythema
Overall 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)
Laboratory studies
• Accucheck
• Chemistries (BUN, Cr, CO2)
• Urinalysis – Calcium oxalate crystals in
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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 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
GI 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
Orogastric Lavage
• Indications – life threatening ingestions who
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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 Charcoal
• Adsorbs toxin within the gut making it
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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 Charcoal
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MDAC
Large doses of toxin
Slow release toxins
Enterohepatic or enterenteric circulation
Toxins that form bezoars
“gastrointestinal dialysis”
Phenobarbital, theophylline,
carbamazepine, dapsone, quinine
Cathartics
• 70% Sorbitol 1g/kg, administered with
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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)
• 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
Hemodialysis
• 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
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Acetaminophen
Anticholinergic agent
Benzodiazepines
Beta blockers or calcium
channel blockers
• Carbon monoxide
• Cardiac glycosides
• Cyanide
Antidotes
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N-Acetylcysteine
Physostigmine
Flumazenil
Glucagon, calcium
• Oxygen
• Digoxin-specific Fab fragments
• Amyl nitrate, sodium nitrate,
sodium thiosulfate,
hydroxycobalamin
Toxin
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Ethylene glycol
Heparin
Hydrofluoric acid
Iron
Isoniazid
Lead
Antidote
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4-Methylpyrazole, ethanol
Protamine sulfate
Calcium gluconate
Desferoxamine
Pyridoxime (Vit B6)
BAL or DMSA, Calcium
disodium EDTA
• Mercury, arsenic, gold • BAL
• 4-Methylpyrazole, ethanol
• Methanol
• Nitrites (Methemoglobin) • Methylene blue
Toxins
• Opiates,
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propoxyphene, lomotil
Organophosphates
Sulfonylureas
Tricyclic
antidepressants
Antidote
• Naloxone (Narcan)
• Atropine, pralidoxime
• Glucose, octreotide
• Sodium bicarbonate,
benzodiazepines
Case 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?
The Toxidromes - Opioid
• Heroin, Morphine, fentanyl
• CNS depression, lethargy, confusion, coma,
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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 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
Toxidromes Sympathomimetics
• Management - primarily supportive - Benzo’s,
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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 - 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
The 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
The 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
Case 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?
Case 2
• Meds
– She has been using oral benadryl and topical
caladryl lotion for the poison ivy
What is her toxidrome?
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 - 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
The Toxidromes - Anticholinergic
• R/O psychiatric disorders, DTs,
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sympathomimetic toxicity
Dry skin and absent bowel sounds indicate likely
anticholinergic toxicity
Management
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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 - Salicylate
• Aspirin, oil of wintergreen, OTC remedies
• Altered mentation, tinnitus, diaphoresis, nausea
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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)
• 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)
• 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 Treatment
• Supportive care
• Single dose AC (ensure airway control)
• Benzodiazepines to treat discomfort, muscle
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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 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
Acetaminophen Poisoning
RummackMathew
nomogram
acetaminophen
levels vs time
Plot 4 hr level
Useful for single
acute ingestion
only
Acetaminophen Poisoning
• Management
– AC assume polypharmacy OD
– NAC - N-acetylcysteine (NAC) indicated if
• patient ingested over 140 mg/kg OR toxic
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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 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?
CASE 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?
Toxic Alcohols
• Typical Agents
– Ethanol
– Isopropanol
– Methanol
– Ethylene glycol (EG)
• All toxic alcohols cause an osmolar gap
• Methanol and EG cause an anion gap
acidosis
Useful Equations
• Anion Gap (mEq/L)
Na - (Cl + HCO3)
• Calculated Osmolarity (mosm/L)
2Na + BUN/2.8 + Glu/18 + ETOH/4.6
Toxic Alcohols - Isopropanol
• Rubbing alcohol > solvents, antifreeze,
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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 - Isopropanol
• Metabolized by alcohol dehydrogenase to
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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 - Methanol
• Typical agent is wood alcohol, used in
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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 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
Toxic Alcohols - Ethylene Glycol
• Typical agent is antifreeze
• Often seen in alcoholics, suicide attempts and
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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 Glycol
• Common Clinical Findings
– Three phases
• 1-12 hours - CNS Depression: inebriation,
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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 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
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
Treatment of EG and Methanol
• Supportive, especially airway
• Correct acidosis with IV bicarb,
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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 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)
Treatment 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
Tricyclics
• Agents
– Amitriptyline (Elevil), desipramine
(Norpramin), imipramine (Tofranil) and
nortriptyline (Pamelor)
– Narrow therapeutic index
– Have returned to popularity with nondepression indications such as chronic pain,
migraines, ADHD and OCD
Tricyclics
• 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
Tricyclics
• EKG during TCA toxicity and after treatment with
bicarb. Note wide QRS, prolonged QT and
terminal R’s > 3mm in AVR
Treatment 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
CO
• 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
CO
• 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
CO
• 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 treatment
• 100% O2 via NRB for 4 hrs minimum if
mild symptoms (nausea, heachache,
malaise)
CO
• 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
References
• Tintinalli, J., Kelen, G.D., Stapczynski, J.S., Emergency Medicine, A
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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