The Poisoned Patient: A Medical Student Review

1
The Poisoned PatientA Medical Student Review

• William Beaumont Hospital
• Department of Emergency Medicine

2
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

3
The 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

4
History

• 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.

5
Pupils

• Dilated anticholinergic or sympathomimetic
• Constricted Cholinergic
• Pinpoint Opiods
• Nystagmus horizontal ethanol, phenytoin,
  ketamine
• Nystagmus rotatory or vertical - PCP

6
Skin

• Hyperpyrexia anticholinergic, sympathomimetic,
  salicylates
• Hypothermic Opiods, sedative-hypnotics
• Dry skin anticholinergics
• Moist skin cholinergics, sympathomimetics
• Color cyanosis, pallor, erythema

7
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)

8
Laboratory 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

9
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

10
GI Decontamination

• Three methods
• Gastric emptying
• Bind the toxin in the gut
• Enhance elimination
• Always consider the patients mental status, risk
  of aspiration, airway security and GI motility
  before attempting any method

11
Orogastric 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

12
Activated 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)

13
Multi-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

14
Cathartics

• 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

15
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

16
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

17
Toxin Antidotes

• 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

18
Toxin Antidote

• 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

19
Toxins Antidote

• Opiates, propoxyphene, lomotil
• Organophosphates
• Sulfonylureas
• Tricyclic antidepressants

• Naloxone (Narcan)
• Atropine, pralidoxime
• Glucose, octreotide
• Sodium bicarbonate, benzodiazepines

20
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?

21
The 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

22
The Toxidromes - Sympathomimetic

• Cocaine, amphetamines (speed, dex, ritalin),
  Phencyclidine (PCP), methamphetamines (crank,
  meth, ice), MDMA (Ecstasy, X, E)
• Stimulant Meth gt amphetamines gt MDMA
• Hallucinogen MDMA gt Meth gt amphetamines
• Agitation, ? temp, HR, BP, mydriasis
• Seizures, paranoia, rhabdomyolysis, MI, arrythmias

23
Toxidromes - Sympathomimetics

• Management - primarily supportive - Benzos, 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

24
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

25
The Toxidromes - Cholinergic

• Common Clinical Findings
• SLUDGE Syndrome
• Parasympathetic hyperstimulation
• Salivation, Lacrimation, Urinary Incontinence,
  Defecation, GI pain, Emesis
• Killer Bs
• 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

26
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

27
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?

28
Case 2

• Meds
• She has been using oral benadryl and topical
  caladryl lotion for the poison ivy
• What is her toxidrome?

29
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)
• OTCs Excedrin PM, Actifed, Dristan, Sominex
• Muscle Relaxants Orphenadrine (Norflex),
  cyclobenzaprine (Flexeril)
• Amanita mushrooms The Toxidromes - Anticholinergic

30
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

31
The 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

32
The 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 gt 30mg/dl
• Treatment
• Multidose AC
• Alkalinize urine
• HD if levels gt 100 mg/dl, altered MS, renal
  failure, pulmonary edema, severe acidosis or
  hypotension

33
The Toxidromes - Serotonin Syndrome (SS)

• SSRIs fluoxetine (Prozac), sertraline (Zoloft),
  paroxetine (Paxil), fluvoxamine (Luvox),
  citalopram (Celexa), escitalopram (Lexapro)
• MAOIs, 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

34
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

35
The 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.

36
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 gt 5 days, resolution of hepatotoxicity
  or progression to multisystem organ failure

37
Acetaminophen Poisoning

• Rummack-Mathew nomogram
• acetaminophen levels vs time
• Plot 4 hr level
• Useful for single acute ingestion only

38
Acetaminophen 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

39
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?

40
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?

41
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

42
Useful Equations

• Anion Gap (mEq/L)
• Na - (Cl HCO3)
• Calculated Osmolarity (mosm/L)
• 2Na BUN/2.8 Glu/18 ETOH/4.6

43
Toxic Alcohols - Isopropanol

• Rubbing alcohol gt 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

44
Toxic 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

45
Toxic 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

46
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

47
Toxic 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

48
Toxic 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

49
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
  Ts (hyperkalemia)
• Myalgias, secondary to acidosis and elevated CPK

50
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

51
Treatment of EG and Methanol

• Supportive, especially airway
• Correct acidosis with IV bicarb, 1meq/kg IV
• Benzos 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

52
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 gt 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)

53
Treatment of EG and Methanol

• Hemodialysis indicated if
• Serum level gt 50 mg/dl
• Signs of nephrotoxicity (EC) or CNS or visual
  disturbances (Methanol)
• Severe metabolic acidosis

54
Tricyclics

• 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

55
Tricyclics

• Common Clinical Findings
• CNS - decreased LOC
• Confusion, hallucinations, delirium, seizures
• Cardiovascular - arrhythmias and hypotension
• QRS gt 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

56
Tricyclics

• EKG during TCA toxicity and after treatment with
  bicarb. Note wide QRS, prolonged QT and terminal
  Rs gt 3mm in AVR

57
Treatment of tricyclic overdose

• AC
• Na Bicarb to treat QRS prolongation gt 100 msec
  and hypotension refractory to IV fluids
• Benzos to treat seizures and hyperthermia (avoid
  physostigmine)
• Magnesium and Lidocaine for Ventricular
  arrythmias refractory to Bicarb
• Magnesium for QT prolongation or Torsades

58
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 its ability to
  transport oxygen

59
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

60
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

61
CO treatment

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

62
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 gt 15
• Arrythmias
• /- COHb gt 25-40
• Only absolute contraindication to hyperbaric
  chamber is pneumothorax

63
References

• 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.,
  Goldfranks 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