toxicology national review course dr. marco sivilotti dr. ian ball october 17, 2013

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