1. National Review Course
Toxicology
National Review Course
Dr. Marco Sivilotti
Dr. Ian Ball
October 17, 2013

2. Acknowledgements
Dr. Jason Lord, University of Calgary

3. Objectives Clinical examination of the overdosed patient
General treatment strategies
Common poisonings
Toxicological concepts applicable to the ER
Examinable / Important Lists

4. 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

5. 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

6. 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

7. Know Your Toxidromes Mental Status Vital Signs Pupils Skin Secretions
Motor Activity
GI/GU

10. 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

11. 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

13. Toxidromes: Opioid Decreased LOC Respiratory depression Miosis
miosis may be absent with meperidine
microdose/titrated naloxone to reverse respiratory depression

14. 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

15. Toxidromes: Sympathomimetics
Psychosis, diaphoresis, mydriasis, agitated, seizure, tremors, HTN (wide pulse pressure), tachycardic, tachypneic
Amphetamines, cocaine

16. 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)

17. Cocaine: Clinical Features
Sympathomimetic Toxidrome
CNS: excitation, psychosis, bleeds, seizure, washed out syndrome
CV – ischemia, AMI, HTN, platelet aggregation, dysrhythmias, Ao dissection, sudden death
Vasospasm
Thrombus
Increased O2 demand – ischemia
Dissection
Cardiomyopathy

18. 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)

19. 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)

21. 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

22. 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

23. 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

24. When is it Safe to Discharge My Patient?
If intentional ingestion for self-harm, 6 hrs of observation recommended, provided:
History does not suggest a dangerous substance or toxic time bomb
Asymptomatic
Routine labs are negative
Reliable observer at discharge
Psychiatric issues addressed

25. 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

26. When is it Safe to Discharge My Patient?
Now, if accidental and assuredly non-toxic ingestion:
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

27. 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

28. Where to Turn for Advice?
Poisindex (Micromedex)
Regional Poison Centre
Local Toxicologist
Textbooks
Internet:
UpToDate™
ToxBase™
ToxiNZ™

29. 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?

30. 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

31. 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

32. 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)

33. 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

34. 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

35. 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

36. HA A- + H+ HA HA H+ + A- A- + H+ H+ + A- HA Urine Blood: Blood Urine:
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.

37. 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

38. Enhanced Elimination: 3. Continuous Renal Replacement
NOT generally of benefit for removing toxins
peritoneal dialysis also NOT helpful

39. 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?

40. 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.”

41. 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

42. Acetaminophen Antidote: N-acetylcysteine
Ideally administer within 8 hrs of ingestion
Mechanism of action:
GSH precursor
GSH substitute
Substrate for sulfation
Non-specific free radical binder

43. 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

44. 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

45. 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

46. 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

47. “Patient-tailored Acetylcysteine”

48. Continue NAC until Stopping Criteria: OR transplant/death
[APAP] undetectable
AST or ALT < 100 IU/L (or have peaked), AND
INR < 1.5
OR transplant/death

49. “Patient-tailored Acetylcysteine”
Start NAC unless:
below Rumack-Matthew nomogram
“Stopping Criteria” are met at the outset

50. 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

51. 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

52. 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?

53. 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)

54. 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!

55. 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!

56. 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!

57. 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

58. Fastest way to kill an ASA overdose is to sedate for agitation!
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

59. Predominate (nonspecific)
Acute
Chronic
Age
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%

60. 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

61. 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

62. Salicylates: Alkalinization
Indications:
Symptoms of salicylism
Tinnitus
Metabolic derangements
Serum level > 2 mmol/L (or expected to get there!)

63. 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

64. 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!

65. 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

66. Tricyclic Antidepressants: Clinical Presentation
End organ effects
Cardiovascular :
hypotension, widened QRS and Qt, dysrythmias
CNS:
abrupt and unpredictable decreased LOC and seizure
Anticholinergic toxicity:
Tachycardia, confused, flushed

67. 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

68. Lead I
Lead aVR

69. 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

70. Tricyclic Antidepressants: Treatment
Indications for Alkalinization:
QRS >100 msec in limb leads
“VT” (Second Line = Lidocaine, Amiodarone)
Cardiac arrest in young adult

71. 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

72. 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

73. 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

74. 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)

75. 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.

76. Digoxin FAB Indications
Adults:
Ventricular dysrhythmia
Progressive/refractory hemodynamic instability or bradycardia
K > 5 mmol/L (acute)
Ingested Plant + dysrhythmia
Acute ingestion > 10 mg (adult) or 4 mg (peds)

77. Digoxin FAB Indications
Pediatrics:
Ingested dose > 0.1 mg/kg or serum level > 5 ng/ml with progressive symptoms or K > 5
Coingestion with other CV med or TCA
Ingested plant + other indication

78. Digoxin: FAB Dosing Empiric: Based on steady state Vd (~6 hrs):
Acute: adults and peds 5 vials
Chronic: adults 2-4 vials, peds 1 vial
Based on steady state Vd (~6 hrs):
(serum dig level x wt in kg) / 100 = # vials

79. 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

80. 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

81. Iron: Clinical Manifestations
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
Stage II: 6-12 hrs
Latent stage with apparent recovery
Never asymptomatic, just less violently ill

82. Iron: Clinical Manifestations
Stage III: hrs
Acidosis, CV collapse, GI bleed, lethargy and coma
Stage IV: 2-5 days
Hepatic failure / death
Stage V: delayed corrosive effects
GI scarring, strictures and obstruction

83. 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

84. 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…

85. 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

86. 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

87. 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

88. 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)

89. Ethylene Glycol: Clinical Presentation
Acute Neurologic Stage (30 min – 12 hrs)
Inebriation, seizure, N/V, coma, osmolar gap
Cardiopulmonary Stage (12-24 hrs)
HTN, tachycardia, tachypnea, AKI, metabolic acidosis +/- pulmonary edema or circulatory collapse
Hypocalcemia and dysrhythmias

90. Ethylene Glycol: Clinical Presentation
Renal Stage (24-72 hrs)
Crystalluria, hematuria, proteinuria, ATN and flank pain
Delayed Neurologic Stage (6-12 d)
Cranial nerve palsies, deafness, cognitive and motor abnormalities, personality changes

91. 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

92. 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 Etoh (N = -2 +/- 6 mOsm)
(Ethanol, Ethylene glycol, Methanol, Isopropyl alcohol, Mannitol, Glycerol)

93. “Gap Dynamics”…

94. Toxic Alcohols: Treatment
Correct acidosis with Bicarb
Prevents diffusion of toxic metabolites into target tissues

95. Toxic Alcohols: Treatment
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 > 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

96. Toxic Alcohols: Treatment
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

97. Toxic Alcohols: Treatment
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

98. 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 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*)

99. 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

100. So why is 50% carboxyhemoglobin fatal?

102. Carbon Monoxide 1/2 life carboxyhemoglobin on room air = 5-6 hrs
1/2 life 100% O2 = min
1/2 life HBO (3 atm) = 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, Review

103. Bottom line:
“There is insufficient evidence to support the use of hyperbaric oxygen for treatment of patients with carbon monoxide poisoning”

104. Toxins and Seizures Anticholinergics Methylxanthines
Antidepressants Opiods
ASA Propranolol
Camphor Stimulants
Carbamazapine TCA’s
Tegretol Withdrawal
INH

105. 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

106. 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

107. Single Tablet/Dose Toxins That Kill
Camphor Theophylline
Sulfonylureas Methyl salicylate
Essential oils Quinine
Chloroquine Phenothiazines
Ca blockers TCA’s
Beta blockers Lomotil
Methadone

108. Nifty antidotes Octreotide Physostigmine High dose insulin Intralipid
Hydroxocobalamin

109. Clinical Syndromes from Chemical Exposures
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

110. Hyperthermia, Altered Mental Status and Rigidity
Malignant hyperthermia
Serotonin Syndrome
Neuroleptic Malignant Syndrome
MAOI overdose

111. 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