Toxicology
National Review Course
Dr. Marco Sivilotti
Dr. Ian Ball
October 17, 2013
Acknowledgements
• Dr. Jason Lord, University of Calgary
Objectives
1. Clinical examination of the overdosed
patient
2. General treatment strategies
3. Common poisonings
4. Toxicological concepts applicable to the
ER
5. Examinable / Important Lists
History unreliable?
•
•
•
•
•
•
•
•
•
What was ingested? How much and when?
What was the patient doing when they became ill?
Past medical records or d/c summaries
Talk to family, friends, paramedics
Search belongings
All bottles and containers – pill count
Search scene ie/ home or garage
Track marks, packer and stuffer
Query pharmacy or provincial datasets
Physical Examination
•
•
•
•
•
Vital Signs including temp and glucose
ABC’s (Kussmaul, breath odour, Cspine)
D = mental status, seizures, tone
E = expose, skin findings
Autonomic nervous system
TOXIDROME
Odors in Toxicology
•
•
•
•
•
•
•
Almonds – CN
Mint – Methyl Salicylate
Fruity – Acetone, ETOH, Isopropyl Alcohol
Garlic – Organophosphates, Arsenic
Glue – Toluene, solvents
Rotten Eggs – Hydrogen Sulfide
Pears – Paraldehyde, Chloral Hydrate
Know Your Toxidromes
Mental Status
Vital Signs
Pupils
Skin
Secretions
Motor Activity
GI/GU
Toxidromes: Cholinergic
•
Muscarinic symptoms –
• Peripheral: DUMBELS (diarrhea/diaphoresis,
urination, miosis, bradycardia/bronchospasm,
emesis, lacrimation, salivation) or SLUDGE
• Central: seizures, dec LOC
• Nicotinic symptoms –
• Fasciculations, weakness, respiratory arrest
•
Organophosphates, carbamates, nerve agents
Anticholinergic = AntiMUSCARINIC
•
•
•
Mad as a hatter, Blind as a bat, Dry as a bone,
Hot as a hare, Red as a beet
(Anti-DUMBELS) - hot, flushed and dry
skin, tachycardia, hypertension, psychosis,
mydriasis
Cyclic antidepressants, atropine, benztropine,
antihistamines, antiemetics, Jimson weed
Toxidromes: Opioid
– Decreased LOC
– Respiratory depression
– Miosis
•
•
miosis may be absent with meperidine
microdose/titrated naloxone to reverse
respiratory depression
Toxidromes: Sedative/Hypnotics
•
CNS depression (respiratory depression late,
and only at very high doses)
•
•
hallmark is spared pupillary reactions and normal
VS
Barbiturates, Ethanol, Benzos, GHB
Toxidromes: Sympathomimetics
•
Psychosis, diaphoresis, mydriasis, agitated,
seizure, tremors, HTN (wide pulse pressure),
tachycardic, tachypneic
•
Amphetamines, cocaine
Cocaine:
Pharmacokinetics
• Variable onset (Body packers vs stuffers)
• Duration of effect short
• Direct Na channel blocker, interferes with
neurotransmitter uptake, vasoconstriction
• Sensitizes the myocardium to catecholamines and
decreases myocardial blood flow
• Increased platelet adhesion
• Combines with EtOH to form cocaethylene (more
potent, longer acting, inc CV injury)
Cocaine:
Clinical Features
•
•
•
Sympathomimetic Toxidrome
CNS: excitation, psychosis, bleeds, seizure,
washed out syndrome
CV – ischemia, AMI, HTN, platelet aggregation,
dysrhythmias, Ao dissection, sudden death
1.
2.
3.
4.
5.
Vasospasm
Thrombus
Increased O2 demand – ischemia
Dissection
Cardiomyopathy
Cocaine:
Clinical Features
• Resp – Asthma exacerbation, NCPE, PTX,
airway burns, pneumomediastinum,
pulmonary HTN
• MSK – Rhabdo and ARF
• Psych – cocaine bugs, excoriations, crack
dancing (choreoathetoid movements)
Cocaine:
Treatment
• AC if stuffer or WBI if packer
• Aggressively treat agitation with BENZOS
• Hyperthermia associated with death
– paralyze with nondepolarizing agents and pack in ice
• Refractory HTN - Alpha blockade with phentolamine 1-5
mg Q5min PRN or Nitroprusside infusion
• AVOID Beta blockers (unopposed alpha stimulation),
neuroleptics (lower seizure threshold)
What Tests Should You Order?
•
•
•
•
•
•
•
CBC, full lytes (anion gap)
If altered mental status: capillary glucose, EtOH
If deliberate self-harm: ASA, APAP, pregnancy test
If suspect toxic alcohol: volatiles (serum osm if cannot)
If sick: ABG or VBG, lactate
Specific levels: Dig, Fe, DPH, VAL, CBZ, Li, theo
12-lead ECG
What Test Should You NOT Order?
• Urine “drug screen”
– Tests for common drugs of abuse, at threshold appropriate to
screen employees for recent use
– Fun to guess results, but easier/faster to ask the patient
– Results rarely change ED management
Extra tests to consider
• CXR
– Caustics, Aspiration
• Abdominal XR
– Body packer
– CHIPES: Chloral hydrate, Heavy Metals, Iron,
Phenothiazines, EC tablets, Solvents
• Urinalysis
– FeCl2 (ASA), pH, ketones, myoglobin
When is it Safe to Discharge My
Patient?
If intentional ingestion for self-harm, 6 hrs of
observation recommended, provided:
1. History does not suggest a dangerous
substance or toxic time bomb
2. Asymptomatic
3. Routine labs are negative
4. Reliable observer at discharge
5. Psychiatric issues addressed
Toxic Time Bombs
•
•
•
•
•
•
•
•
•
Acetaminophen
Anticoagulants
Antimetabolites
Body Packers
Enteric coated products (ASA)
Heavy metals
Iron
Lithium
Lomotil
Methadone
MAOIs
Hypoglycemics
Sotalol
SR products
Thyroids meds
Toxic alcohols
Valproic acid
Tricyclics
When is it Safe to Discharge My
Patient?
Now, if accidental and assuredly non-toxic
ingestion:
1.
2.
3.
4.
5.
6.
7.
Product identified with certainty
Single product involved
Reliable estimate of maximal possible exposure
Asymptomatic
Assuredly unintentional/no self-harm intent
Reliable patient/parent
Poison-proofing advice given
Is the CPS a Useful Resource for
the Poisoned Patient?
• Compendium of Pharmaceuticals and
Specialties*
– 60% contain dangerous or misleading advice
– Only 21% are adequate to allow clinician to
manage overdose
Brubacher J, et al. Salty Broth for Salicylate poisoning? CMAJ 165(9). Oct 2002
Where to Turn for Advice?
•
•
•
•
•
Poisindex (Micromedex)
Regional Poison Centre
Local Toxicologist
Textbooks
Internet:
– UpToDate™
– ToxBase™
– ToxiNZ™
Whom Should I Decontaminate?*
• Step 1 – Determine risk of ingestion
– How much? How toxic? Reliable historian?
• Step 2 – Decide if substance can be removed
– Time of ingestion? Likelihood of recovery?
• Step 3 – Consider risk/benefit
– Any contraindications to procedure?
• Step 4 – Determine the most appropriate technique
– Lavage, Charcoal, WBI?
Decontamination
1. Syrup of Ipecac
• Rarely indicated:
– no improved mortality/potential for harm
– complicates care, including other GID
– contraindicated when potential for seizures or
dec LOC, as well as hydrocarbons, caustics
– should be considered obsolete
Decontamination:
2. Gastric Lavage
• Life threatening ingestion despite maximal
supportive care/antidote/elim going forward
• Drug in stomach (cf < 1 hr since ingestion)
• 10-30% reduction in absorption
– ASA, colchicine, TCA
• 40 Fr Ewald (15-28 in peds) after RSI
left lateral decubitus position
200 cc aliquots warm tap water until clear
Finish off with AC and remove tube
Decontamination:
3. Activated Charcoal
•
•
•
•
Recent, likely toxic ingestion (“soft hour”)
Not useful – alcohols, metals, hydrocarbons
C/I = caustics, aspiration, ileus, perforation
1 g/kg plain or with sorbitol OR
10:1 rule (for every ingested 1g toxin, give
10 g charcoal)
– e.g. ASA, theophylline (10+g ingestions)
Decontamination:
4. Multidose Activated Charcoal
• Severe ingestions that are well adsorbed
– EC or SR drugs, toxins that slow GI motility,
enterohepatic recirculation, anticonvulsants
– 0.25 to 0.5 g/kg q2-4h PLAIN AC (no sorbitol)
– Probably effective: phenobarb, CBZ, quinine,
theophylline
– Possibly effective: digoxin, VAL, sotalol
Decontamination:
5. Whole Bowel Irrigation
• Life-threatening ingestion in which MD-AC
or GL of limited utility
– Iron, body packers, heavy metals like Pb
– sustained release CCBs
• Isotonic PEG solution
– Not absorbed, no fluid shifts
– 2L/hr via ng until effluent clear (c. 6 hrs)
– 500 ml/hr in children
Enhanced Elimination:
1. Urinary Alkalinization
• Promotes ionization of the excreted drug which
prevents tubular reabsorption
– Useful for ingestions of weak acids
• ASA, phenobarb, chlorpropamide
– Target urine pH >7
– Often difficult to achieve your target pH
• Replenish Na and K, Foley catheter and hourly pH
• ASA, lytes q2h
– Do not use acetazolamide b/c of concomitant metabolic
acidosis and inc toxicity
– Not forced diuresis
HA
H+ + ABlood
HA
HA
A- + H+ H+ + AUrine
Unionized molecules diffuse across renal tubular
membranes from blood to renal filtrate but ionized ones
cannot cross from one compartment into the other.
Blood:
lower pH
HA
A- + H+
Urine:
higher pH
When urine is alkalinized, weak acids like salicylates will
dissociate into ions, become “trapped” and excreted in the
urine. Unionized parent molecules then diffuse down their
concentration gradient from blood into the urine.
Enhanced Elimination:
2. Hemodialysis
• Small Vd, low protein binding, small size,
water soluble, low endogenous clearance
– methanol, ethylene glycol, ASA, Li,
Theophylline
– Less commonly severe acetaminophen, VAL,
atenolol, sotalol
Enhanced Elimination:
3. Continuous Renal Replacement
• NOT generally of benefit for removing
toxins
• peritoneal dialysis also NOT helpful
Case
A 24 year female presents to the emergency
following a mixed drug ingestion. The
paramedics find empty containers of
acetaminophen, ASA and diazepam. The
ingestion was witnessed approximately 45
min ago. She is now obtunded.
What form of GI decontamination, if any,
should be performed?
One good answer
“Following RSI for airway protection, I will
give her 50g of activated charcoal with
sorbitol after the position of the ng tube has
been confirmed radiographically. The need
for subsequent doses of charcoal could be
predicated upon the serial serum salicylate
concentrations.”
Thou Shalt Know the Big Ones
•
•
•
•
•
•
•
•
APAP
ASA
(Toxic) Alcohols
CCBs
Dig
Cocaine
Methamphetamine
Opioids
• OP/nerve agents
• CO
• Cyanide
• Iron in a toddler
• TCAs
• Caustics
• Antidotes
and maybe a few more
Acetaminophen Antidote:
N-acetylcysteine
•
•
Ideally administer within 8 hrs of
ingestion
Mechanism of action:
1.
2.
3.
4.
GSH precursor
GSH substitute
Substrate for sulfation
Non-specific free radical binder
Acetaminophen:
1. Single Ingestion < 8 Hours
• Toxic dose >150 mg/kg
• Rumack-Matthew Nomogram at 4+ hrs (use
the lower line of 1000 M or 150 g/mL)
• Pre-4 hour level helpful?
– If undetectable, excludes APAP overdose
Acetaminophen:
2. Single Ingestion Between 8-24 hrs
• Start NAC if likely toxic/symptomatic
• Send serum acetaminophen level, AST, INR
• Continue NAC based on level plotted on
nomogram, until Stopping Criteria met
• Efficacy of NAC decreases with time if
administered post 8 hours
– Only rare fatalities if initiated within 24 hours
Acetaminophen:
3. Staggered, Unknown or
Ingestion > 24 hrs
• Empirically start NAC if concerning history and
symptomatic
• Draw serum acetaminophen, AST and INR
– If any are abnormal (ie detectable APAP, AST > 100,
OR INR > 1.5) – treat until Stopping Criteria met
– If all normal (undetectable APAP, AST < 100, AND
INR < 1.5) – D/C NAC
• Some countries use creatinine as well
Acetaminophen:
4. Slow Release Formulations
• Draw serum acetaminophen at 4 hrs
– If above toxic threshold on nomogram = NAC
– Subtoxic level – repeat serum level at 8 hrs, and
treat if above threshold
“Patient-tailored Acetylcysteine”
Continue NAC until
• Stopping Criteria:
– [APAP] undetectable
– AST or ALT < 100 IU/L (or have peaked),
AND
– INR < 1.5
• OR transplant/death
“Patient-tailored Acetylcysteine”
• Start NAC unless:
– below Rumack-Matthew nomogram
– “Stopping Criteria” are met at the outset
N-acetylcysteine
• IV protocol used in Canada
–
–
–
–
150 mg/kg over 60 minutes
12.5 mg/kg/hr for 4 hours
6.25 mg/kg/hr until Stopping Criteria met:
? double the 6.25 to 12.5 in high risk pt??
• Do not write for finite duration
• APAP, AST, ALT, INR, lytes q12h
Anaphylactoid reactions to N-AC
• Stop the infusion
• diphenhydramine, fluids, rarely more
• Verify need for N-AC, and resume at
slower rate if still indicated
• No need to withhold in future
Case
A 75 year old alcoholic male fell and broke
several ribs a few days ago. He has been
taking 2 extra strength Tylenol every few
hours for 3 days. He presents with
abdominal pain and nausea.
How would you manage this patient?
Case
Start NAC empirically (?orally), draw
Acetaminophen level, AST and INR in
addition to other bloodwork, and treat until
normalize
(if AST abnormal at baseline, treat until
returns to prior baseline, or peaks and falls
by >50% of peak)
Salicylates:
Pharmacokinetics
• Rapidly absorbed in therapeutic doses
– NOT after overdose!
• Rapidly eliminated in therapeutic doses
– NOT after overdose! (zero order kinetics)
• No antidote!
• Toxicity = rate of absorption > rate of elimination
• Serum level cannot be interpreted in isolation,
without knowing serum pH!
• Serum levels most helpful in hindsight!
Salicylates
• Done Nomogram NOT clinically useful
– Modeled after single, acute ingestion of NON- EC
ASA, in peds!
– Nontoxic levels drawn before 6 hrs not useful
– Patients may become rapidly toxic prior to 6 hr
– Not useful for staggered or chronic ingestions
– Does not correlate with serum pH or clinical status
• TREAT THE PATIENT, NOT THE LEVEL!
Salicylates:
Toxicity
•
•
•
Every organ system affected, but…
…Brain toxicity kills patient
Beware methyl salicylate (7.5 g ASA in 5cc);
most toddler exposures die en route to pediatric
hemodialysis centre!
Salicylates:
Clinical Presentation
• Early = N/V, tinnitus, diaphoresis,
confusion, deafness, tachypnea, vertigo,
respiratory alkalosis (direct stimulation)
• Late = anion gap metabolic acidosis, 
LOC, NCPE, hypoglycemia, hepatic and
renal dysfunction, death
Increased tissue and CNS penetration with
acidosis is a very important concept!
Fastest way to kill an ASA overdose is to
sedate for agitation!
Decreasing serum levels may reflect:
•
Increased ASA excretion, OR
•
Increased tissue penetration and toxicity
Acute
Chronic
Age
Etiology
Dx
Comorbidities
Suicide attempt
Clinical course
Younger
Overdose
Classic
Few
Often
Rapid
Progression
Serum levels
Mortality

Uncommon
Older
Accidental
Subtle
Many
Rarely
Neurologic
Predominate
(nonspecific)

~ 25%
The Anion Gap
• Sodium – (Chloride + Bicarb)
– N = 7 +/- 4 meq/L
– MUDPILES CAT
– Serum lactate (Elevated level does not rule out
a toxic ingestion)
– Serial measurements are very important
– Venous gas can be substituted for ABG
Salicylates:
Treatment
•
•
•
•
•
Volume resuscitate!
GL, MDAC and WBI all recommended
Urinary alkalinization
Empiric dextrose (low CNS Glc)
Use pH and mental status to guide Rx
Salicylates:
Alkalinization
• Indications:
– Symptoms of salicylism
• Tinnitus
• Metabolic derangements
– Serum level > 2 mmol/L (or expected to get
there!)
Salicylates:
Alkalinization
• Target Urine pH >7
• Keep serum pH < 7.55
• Avoid hypokalemia (K+/H+ exchange in
distal tubule)
• No role for forced diuresis
• q2h testing of ‘lytes and salicylate levels
Salicylates:
Hemodialysis
• Indications:
–
–
–
–
–
Worsening clinical status
End organ toxicity – AKI, NCPE, CNS
Severe acid base disturbance
Volume overload
Serum level > 7 mmol/L (acute) or > 4 mmol/L
(chronic)… or expected to get there despite
urine alkalinization and GID!
Tricyclic Antidepressants:
Pharmacokinetics
• Rapidly absorbed, large Vd, variable protein
binding, lipophilic
• Mechanism of action:
– Inhibits voltage gated Na channels (prolongs phase 0
depolarization) and blocks K efflux
– Negative cardiac inotrope
– Blocks H1, H2 and D2 receptors
– Blocks muscarinic receptors
– Alpha blockade
– Inhibits DA, serotonin & Norepinephrine reuptake &
interacts with GABA receptors
Tricyclic Antidepressants:
Clinical Presentation
•
End organ effects
1. Cardiovascular :
•
hypotension, widened QRS and Qt, dysrythmias
2. CNS:
•
abrupt and unpredictable decreased LOC and seizure
3. Anticholinergic toxicity:
•
Tachycardia, confused, flushed
Tricyclic Antidepressants:
Diagnosis
• Drug levels do NOT correlate with toxicity
• EKG diagnostic of Na channel blockade:*
– limb QRS >100 msec = 30% risk seizure
– >160 msec = 50% risk arrhythmias
– R axis deviation in terminal 40 msec QRS of
aVR (tall slurred R wave > 3mm)
– Sinus tachycardia with prolonged QT interval
Boehnert & Lovejoy, NEJM, 1985
Lead I
Lead aVR
Tricyclic Antidepressants:
Treatment
• Consider gastric lavage and AC
• Beware rapid LOC and seizures
• Avoid acidosis at all costs (seizures, BP, CO2)
• Sodium bicarbonate boluses for wide QRS
Tricyclic Antidepressants:
Treatment
• Indications for Alkalinization:
– QRS >100 msec in limb leads
– “VT” (Second Line = Lidocaine, Amiodarone)
– Cardiac arrest in young adult
Tricyclic Antidepressants:
Treatment
• Hypertonic Saline (when serum pH > 7.55)
• Benzos for sedation or seizure, propofol if
refractory
• Fluids and -agonists for hypotension
• Physostigmine can be considered if survive
cardiac toxicity
Hoffman, Votey et al., Am J Emerg Med 1993
Hoegholm & Clementsen, J Toxicol Clin Toxicol 1991
Digitalis:
Pharmacokinetics
• Binds to the Na-K ATPase (inhibits active
transport of Na and K)
– Increased intracellular Ca
• Enhanced automaticity with decreased
conduction + Vagolytic
– ECG: Slow A. Fib, Nonparoxsymal junctional
tachycardia, Atrial tachycardia with block,
Bidirectional V. Tach
Digitalis:
Clinical Presentation
• Acute hyperkalemia
• G/I = sine qua non: N/V, anorexia,
abdominal pain
• CNS – confusion, dec LOC, headache,
seizures
• Visual – blurred, scotoma, altered color
vision, halos
Digitalis:
Treatment
•
•
•
•
•
•
MDAC
Correct serum electrolytes
Atropine for bradycardia (may not be effective)
Avoid 1A, 1C antidysrhythmics
Avoid Calcium if concomitant AKI
Digoxin specific FAB fragments (Digibind)
Digoxin:
Digibind
•
•
•
Binds free drug and promotes transport of
bound digoxin from tissue to serum
Bound drug excreted renally
Onset ~ 15 min (complete by 90 min)
•
Downside – cost.
Digoxin
FAB Indications
A. Adults:
1. Ventricular dysrhythmia
2. Progressive/refractory hemodynamic
instability or bradycardia
3. K > 5 mmol/L (acute)
4. Ingested Plant + dysrhythmia
5. Acute ingestion > 10 mg (adult) or 4 mg
(peds)
Digoxin
FAB Indications
B. Pediatrics:
1. Ingested dose > 0.1 mg/kg or serum level > 5
ng/ml with progressive symptoms or K > 5
2. Coingestion with other CV med or TCA
3. Ingested plant + other indication
Digoxin:
FAB Dosing
1. Empiric:
Acute: adults and peds 5 vials
Chronic: adults 2-4 vials, peds 1 vial
2. Based on steady state Vd (~6 hrs):
(serum dig level x wt in kg) / 100 = # vials
Pitfalls of Using the Serum
Digoxin Level
• Interpreted with other electrolytes
• Pre-redistribution levels high (within 6 hr of
ingestion)
• False positives can occur
• Assays vary after FAB treatment; may be
very high if measure total dig
• Other cardiac steroids variably detected
Iron:
Pharmacokinetics
• Prescribed as Ferrous gluconate, sulfate and
fumarate with differing elemental Fe
concentrations; other forumulations available
–
–
–
–
< 20 mg/kg elemental Fe – likely asymptomatic
> 20 mg/kg – self limiting GI symptoms
> 40 mg/kg – potentially serious
> 60 mg/kg – may be lethal (~ 5 tabs for a toddler)
• Toxicity:
– Direct caustic injury to GI mucosa
– Impaired intracellular metabolism – liver, CNS and
CV collapse
Iron:
Clinical Manifestations
1. Stage I: 0-6 hrs
•
•
•
Acute corrosive effects on GI tract
N/V, diarrhea, abd pain and hypovolemia
If asymptomatic at 6 hours – no sig OD
2. Stage II: 6-12 hrs
•
•
Latent stage with apparent recovery
Never asymptomatic, just less violently ill
Iron:
Clinical Manifestations
3. Stage III: 12-48 hrs
•
Acidosis, CV collapse, GI bleed, lethargy and
coma
4. Stage IV: 2-5 days
•
Hepatic failure / death
5. Stage V: delayed corrosive effects
•
GI scarring, strictures and obstruction
Iron:
Diagnosis
• AXR if suspicious, does not rule out
• Serum Fe level 4 hours post ingestion
– <55 umol/L – Do not treat
– 55-90 umol/L – Treat if s/s
– >90 umol/L – Treat all
• Repeat level at 8 hours with SR or EC preps
Iron
Treatment
•
•
•
•
Fluid resuscitation
WBI
No role for AC
Deferoxamine IV x 24 hrs
–
–
–
–
chelates Fe  renally excreted
Resp toxicity (ARDS) with prolonged infusion
Slow infusion if hypotension develops
Yersinia sepsis…
Iron:
Causes of Metabolic Acidosis
•
•
•
•
Conversion of Fe2+ to Fe3+  liberates H+
Vasodilation and  BP – lactic acidosis
Direct neg inotrope =  Cardiac output
Disrupts oxidative metabolism
Toxic Alcohols
• Ethylene Glycol, Methanol, Isopropanol
• Same kinetics as ethanol:
–
–
–
–
peak serum levels by 1 hour
rapidly distribute into body water
small Vd, not protein bound
easily dialyzable
• Toxic acid metabolites of EG and MeOH
Ethylene Glycol
• Present in antifreezes and coolants
• Metabolized by alcohol dehydrogenase 
glycoaldehyde, glycolic acid and oxalic acid
• Inhibit oxidative phosphorylation and are
directly toxic to lungs, kidney and CNS
• Calcium oxalate crystals
Methanol
• Present in window cleaning solutions,
solvents, some antifreezes
• Metabolized by alcohol dehydrogenase 
formaldehyde and formic acid
• Inhibit cellular respiration and directly
toxic to CNS (including retina)
Ethylene Glycol:
Clinical Presentation
1. Acute Neurologic Stage (30 min – 12 hrs)
•
Inebriation, seizure, N/V, coma, osmolar gap
2. Cardiopulmonary Stage (12-24 hrs)
•
•
HTN, tachycardia, tachypnea, AKI, metabolic
acidosis +/- pulmonary edema or circulatory
collapse
Hypocalcemia and dysrhythmias
Ethylene Glycol:
Clinical Presentation
3. Renal Stage (24-72 hrs)
•
Crystalluria, hematuria, proteinuria, ATN and
flank pain
4. Delayed Neurologic Stage (6-12 d)
•
Cranial nerve palsies, deafness, cognitive and
motor abnormalities, personality changes
Methanol:
Clinical Presentation
• Early – inebriation, gastritis, altered LOC,
ataxia
• Late – Visual changes “snowstorm
blindness”, altered LOC, metabolic
acidosis, seizures
– Optic disc hyperemia, papilledema, sluggish
pupils
Toxic Alcohols
Diagnosis and the Gaps
• Forget the Wood’s lamp and crystals!
• Increased Anion Gap metabolic acidosis
• Increased Osmolar Gap
= Calculated Osmolality – Measured Osmolality
• 2 Na + Glucose + BUN + 1.25 Etoh (N = -2 +/- 6 mOsm)
– (Ethanol, Ethylene glycol, Methanol, Isopropyl
alcohol, Mannitol, Glycerol)
“Gap Dynamics”…
Toxic Alcohols:
Treatment
1. Correct acidosis with Bicarb
–
Prevents diffusion of toxic metabolites into
target tissues
Toxic Alcohols:
Treatment
2. Inhibit alcohol dehydrogenase
–
Suspected ingestion and 2 of:
•
•
•
•
–
–
a.
b.
Osmolar gap > 10
pH < 7.3
Bicarb < 20
Urinary oxalate crystals
Serum EG > 3mmol/l or Meoh level > 6 mmol/L
Documented ingestion and Osm Gap > 10
Etoh: Target serum Etoh level > 20 mmol/L
Fomepizole (4MP) – easier administration,
predictable, more potent inhibitor of ADH, safer,
avoids labs, longer half-life, no altered LOC
Toxic Alcohols:
Treatment
3. Enhanced metabolite elimination with
Hemodialysis
–
–
–
–
–
Serum EG > 8 mmol/L or Meoh > 15 mmol/L
Metabolic acidosis
Renal impairment
Electrolyte abnormalities
Unstable VS
–
END ORGAN DYSFUNCTION
Toxic Alcohols:
Treatment
4. Adjunctive Treatments
•
•
•
•
Folic/Folinic Acid 50 mg IV q6h for
methanol (very important)
Thiamine 100 mg IV and Pyridoxine for
ethylene glycol (not so important)
Calcium replacement for EG
Serial monitoring of acidosis and electrolytes
Toxic Alcohols: Triage Tools
• Fixed and dilated pupils very poor prognostic sign
following methanol ingestion
• ABG allows you to make immediate decisions
regarding fomepizole and hemodialysis
• A loading dose of fomepizole buys you 12-24
hours of time in non-acidotic patient
• Serial testing without ADH blockade following
accidental sip—if pH remains normal after 6 hours
can discharge (*unless EtOH or fomepizole on
board*)
Carbon Monoxide
• Most common cause of death by poisoning in the
US (20% accidental)
• Mild (5-10%) - mild headache, mild dyspnea
• Mod (10-30%) - headache, weakness, dizzyness,
dyspnea, irritability, N/V
• Severe (>30%) - coma, seizures, MSOF, death
• Delayed neuropsychiatric sequelae in 10-30% of
survivors (levels not predictive)
• Pulse oximeter falsely normal
So why is 50% carboxyhemoglobin fatal?
Carbon Monoxide
• 1/2 life carboxyhemoglobin on room air = 5-6 hrs
• 1/2 life 100% O2 = 45-90 min
• 1/2 life HBO (3 atm) = 15-30 min*
– Indications controversial (dec LOC, severe symptoms
or levels, met acidosis, age >50 or preg - d/w
toxicologist)
– Reduced delayed sequelae if dived within 24hrs
(maybe…)
Juurlink et al., Cochrane Database Sys Rev 2000
Weaver et al., NEJM 2002
Thom et al., Ann Emerg Med 1995
Kao & Nanogas, Med Clin NA, 2005 - Review
Bottom line:
“There is insufficient evidence to support the use of
hyperbaric oxygen for treatment of patients with
carbon monoxide poisoning”
Toxins and Seizures
•
•
•
•
•
•
•
Anticholinergics
Antidepressants
ASA
Camphor
Carbamazapine
Tegretol
INH
Methylxanthines
Opiods
Propranolol
Stimulants
TCA’s
Withdrawal
Intractable Seizures
• ABC’s, glucose, benzos benzos benzos
• Propofol, Phenobarbital, Pyridoxine
• Preeclampsia / hyponatremia (MDMA) /
INH
• INH overdose
– Inhibits the formation of an important substrate
required for GABA
– Pyridoxine replaces this substrate
Tox – ACLS
• Sodium bicarbonate first line agent for wide
complex tachycardias (Cocaine, TCA) or tox
arrest
• Avoid procainamide
• Direct pressor (norepi) for refractory hypotension
• Prolonged resuscitative efforts not always futile
• Extracorporeal circulatory assistance in extremis
Single Tablet/Dose Toxins That
Kill
•
•
•
•
•
•
•
Camphor
Sulfonylureas
Essential oils
Chloroquine
Ca blockers
Beta blockers
Methadone
Theophylline
Methyl salicylate
Quinine
Phenothiazines
TCA’s
Lomotil
Nifty antidotes
•
•
•
•
•
Octreotide
Physostigmine
High dose insulin
Intralipid
Hydroxocobalamin
Clinical Syndromes from
Chemical Exposures
Syndrome
Etiology
Cholinergic
Organophosphates, nicotine,
carbamates
Muscle Rigidity or seizures
Strychnine
Oropharyngeal pain and ulcers
Paraquat, diquat, caustics,
inorganic mercuric salts, mustards
Cellular hypoxia
Cyanide, CO, methemoglobin
causing agents
Peripheral neuropathies or
neurocognitive
Organic mercurics, Lead, Arsenic
Severe GI distress
Ricin, Arsenic, Colchicine
MMWR 52(39) Oct 3, 2003
Hyperthermia, Altered Mental
Status and Rigidity
•
•
•
•
Malignant hyperthermia
Serotonin Syndrome
Neuroleptic Malignant Syndrome
MAOI overdose
Disease
Mechanism
Clinical
Onset
Treatment
NMS
 Central DA
activity in
thalamus
Neuroleptic Gradual, days Benzos, hydrate,
use, Rigid
cool, paralysis
? Bromocriptine or
Dantrolene
Serotonin Syx
 Serotonin in
CNS
Recent
SSRI or DA
agonist
 DTR,
clonus
Malignant
Hyperthermia
Genetically
unstable sarc.
Retic. 
massive Ca
release
Inhalational Immediate
anesthetic
or sux
Rigid
Hydrate, cool
Dantrolene
MAOI OD
Inhibited
monoamine
oxidase
Adrenergic
overdrive
Hydrate, cool,
paralysis
Rapid with
recent dose
or drug
change
Variable
Benzos, hydrate,
cool
Cyproheptadine