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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 death1. Vasospasm2. Thrombus3. Increased O2 demand – ischemia4. Dissection5. 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 Methadone• Anticoagulants MAOIs• Antimetabolites Hypoglycemics• Body Packers Sotalol• Enteric coated products (ASA) SR products• Heavy metals Thyroids meds• Iron Toxic alcohols• Lithium Valproic acid• Lomotil Tricyclics
When is it Safe to Discharge My Patient?
Now, if accidental and assuredly non-toxic ingestion:
1. Product identified with certainty
2. Single product involved
3. Reliable estimate of maximal possible exposure
4. Asymptomatic
5. Assuredly unintentional/no self-harm intent
6. Reliable patient/parent
7. 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?
Decontamination1. 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 RSIleft lateral decubitus position 200 cc aliquots warm tap water until clearFinish 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+ + A-
HA
A- + H+
Blood Urine
HA
H+ + A-
HA
A- + H+
Blood: lower pH
Urine: higher pH
Unionized molecules diffuse across renal tubular membranes from blood to renal filtrate but ionized ones cannot cross from one compartment into the other.
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. GSH precursor
2. GSH substitute
3. Substrate for sulfation
4. 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 ChronicAge Younger Older
Etiology Overdose Accidental
Dx Classic Subtle
Comorbidities Few Many
Suicide attempt Often Rarely
Clinical course Rapid Progression
Neurologic
Predominate (nonspecific)
Serum levels Mortality Uncommon ~ 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 effects1. 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 1993Hoegholm & 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.
DigoxinFAB 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)
DigoxinFAB 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
IronTreatment
• 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 AlcoholsDiagnosis 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:
• 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 > 10a. Etoh: Target serum Etoh level > 20 mmol/Lb. 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 2000Weaver et al., NEJM 2002Thom et al., Ann Emerg Med 1995Kao & Nanogas, Med Clin NA, 2005 - Review
“There is insufficient evidence to support the use of hyperbaric oxygen for treatment of patients with carbon monoxide poisoning”
Bottom line:
Toxins and Seizures
• Anticholinergics Methylxanthines
• Antidepressants Opiods
• ASA Propranolol
• Camphor Stimulants
• Carbamazapine TCA’s
• Tegretol Withdrawal
• INH
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 Theophylline
• Sulfonylureas Methyl salicylate
• Essential oils Quinine
• Chloroquine Phenothiazines
• Ca blockers TCA’s
• Beta blockers Lomotil
• Methadone
Nifty antidotes
• Octreotide
• Physostigmine
• High dose insulin
• Intralipid
• Hydroxocobalamin
Clinical Syndromes from Chemical Exposures
Syndrome EtiologyCholinergic 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, ColchicineMMWR 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 use, Rigid
Gradual, days Benzos, hydrate, cool, paralysis
? Bromocriptine or Dantrolene
Serotonin Syx Serotonin in CNS
Recent SSRI or DA agonist
DTR, clonus
Rapid with recent dose or drug change
Benzos, hydrate, cool
Cyproheptadine
Malignant Hyperthermia
Genetically unstable sarc. Retic. massive Ca release
Inhalational anesthetic or sux
Rigid
Immediate Hydrate, cool
Dantrolene
MAOI OD Inhibited monoamine oxidase
Adrenergic overdrive
Variable Hydrate, cool, paralysis