2. Epidemiology
• 64 Poison Centers serving 295 million people
• 2.4 million exposures last year
– 39% are children younger than 3 years
– 52% in children younger than 6 years
• 106 deaths in age <19 for 2003
2003 Annual report of the American Association of Poison Control Centers Toxic Exporure
Surveillance System – Watson et. al
3. Epidemiology
• Most commonly fatal classes of poisoning
– Analgesics (375)
• 62 Tylenol only, 52 Tylenol + 1 other, 100 Tylenol
combination products (Lortab, etc.)
• 23 ASA – more than half did not have ASA levels >100mg/dl
– early and more aggressive dialysis recommended
– Street drugs (124)
– Antidepressants (112)
• Amitriptyline
4. Epidemiology
• Most common Pediatric Exposure
– Cosmetics and personal care products (13%)
– Cleaning substances (10%)
– Analgesics (7.8%)
– Foreign Bodies (7.4%)
– Topicals (7.4%)
– Cold and Cough Preparations (5.5%)
– Plants (4.6%)
– Pesticides (4.1%)
5. Epidemiology
• Unintentional (1-2 years)
– Exploratory
– Boys > girls
– Unable to discriminate safe from unsafe liquid
• Intentional (adolescent)
– Purposeful
– Girls > boys
6. Epidemiology
• Around meal time
• Grandparents home
• Kerosene or gasoline in a soda bottle
• Older sibling can pharmaceutically treat younger
sibling
7. Evaluation of Suspected
Poisoning
• ABC’s and routine ICU management
• Establishing the diagnosis
– Must consider poisoning, especially in “at risk” age
groups
• Less than 6 year old with acute decompensation (AMS,
arrhythmias, hypotension, metabolic acidosis, etc.)
8. Evaluation
• History of poisoning
• Physical Examination
• Laboratory studies
• Gastrointestinal decontamination
19. Muscarinic Effects of
Organophosphate Poisoning
• S alivation *D iaphoresis/diarrhea
• L acrimation *U rination
• U rination *M iosis
• D efecation *B radycardia/bronchospasm
• G I secrestion/upset*E mesis
• E mesis *L acrimation excess
*S alivation excess
20. Nicotinic Effects of
Organophosphate Poisoning
• Muscle fasciculation
• Cramping
• Weakness (extreme is diaphragmatic failure)
• Autonomic nicotinic effects include hypertension,
tachycardia, pupillary dilation, and pallor
29. Laboratory Testing
• What is in a “urine drug screen”?
– Amphetamines, Barbiturates, Cocaine, Benzodiazepine,
Opiates, THC, PCP
• What is in a “serum drug screen”?
– Acetaminophen, ETOH, Salicylate, TCA
• What is in a “comprehensive drug screen”?
– Barbiturates, Salicylates, Cannabinoids, PCP, TCA,
Sedatives, Benzodiazepines, Stimulants, Opium
alkaloid, Synthetic Narcotics, Tranquilizers, Cocaine
30. Laboratory Testing
• Grady unfortunately doesn’t do HPLC anymore
• Options for more “comprehensive” screen
– Quest lab – if needed in 24 hours or less
– ARUP – 2-4 days turn around
• SERUM: Acetaminophen, alcohols, barbiturates, benzodiazepines,
carbamazepine, carisoprodol, disopyramide, meprobamate, phenytoin,
primidone, salicylate, theophylline, tricyclic and other antidepressants
• URINE: acetaminophen, alcohols, barbiturates, benzodiazepines,
carbamazepines, carisoprodol, chlorpheniramine, cocaine &
metabolites, diphenhydramine,ethchlorvynol, ibuprefen, lidocaine,
meprobamate, narcotics & synthetics, phencyclidine, phenothiazines,
phenytoin, primidone & metabolites, pyrilamine, salicylate,
sympathomimetic amines, theophylline, tricyclic and other
antidepressants, trimethoprim
31. Laboratory Testing
• Additional testing is helpful if you have a specific substance that
you suspect
• Usually less helpful as a “fishing expedition” and won’t affect
management
• Am J Emerg Med. 1999 May:17(3):221-4. Belson MG, Simon HK
– Evaluate the clinical utility and cost-effectiveness of the limited component
vs the HPLC component of comprehensive toxicologic screens in children
– Retrospective from HSCH ED Jan 1994-July 1995
– The comprehensive test included a broad-spectrum HPLC component as
well as a limited component that examined serum for ethanol, aspirin, and
acetaminophen and urine for benzodiazepines, barbiturates, amphetamines,
cocaine, phencyclidien, and opiates
– Comprehensive toxicology screens were performed in 463 cases during the
study period; 234 (51%0 were positive for exogenous toxin
32. Laboratory Testing
• In 227 of 234 positive screens (97%), toxins were either suspected
by history and/or physical, were present on the limited portion of
the toxicology screens, or were clinically insignificant
• The remaining 7 of the 234 positive screens (3%) were clinically
significant and detected solely by the broad-spectrum HPLC
portion of the comprehensive screen
• However, in none of these 7 cases was patient management
clinically altered as a result of the positive screen
• The total additional cost of the HPLC component was $16,205
($35x464), an average distributive charge of $2,315 per patient in
whom the HPLC portion provided additional clinical information
($16,205/7)
• Although adding significant charges to the evaluation of suspected
toxic exposures in children, the HPLC component of the
comprehensive drug screen was of no additional clinical benefit
compared with its limited component alone
33. Urine Drug Screens
• THC 1-3 weeks*
• Cocaine 2-4 days
• Amphetamine 2 days
• Barbiturates 1-2 days
• Opiates 1-2 days
• PCP 5-7 days
• LSD 1-2 days
• Steroids 3 days or longer
* Longer if prolonged exposure
48. Elimination of Poisons
• Surface decontamination
– Reduce any additional absorption
• Ipecac
– Not routinely recommended anymore
– Possible useful in an observed, in hospital poisoning
• Gastric Lavage
– Most effective 1-2 hours after ingestion
• Can be effective later in drugs that delay gastric emptying
49. Elimination of Poisons
• Activated charcoal
– Adsorbs many drugs, thus decreasing systemic absorption
• Doesn’t work well for lithium, iron, hydorcarbons, alcohols, solvents,
acid/alkali ingestions
– Role of charcoal in gastrointestinaldialysis
• Cathartics
– Not generally used
– Some charcoal has sorbitol in it
• Whole bowel irrigation
– Golytely infusions
– Initially done with success in iron ingestions
– Used mostly for drugs that charcoal doesn’t work well with
50. Elimination of Poisons
• Diuresis +/- alteration of urine pH
– Obviously, only useful for renally excreted drugs
– Altering pH example
• ASA – pkA3
– At a pH of 3, there is a 1:1 ratio of ionized/unionized
– At a pH of 7.4, the ratio is 25,000:1
– Ionized form can’t cross cell membranes – so when you dump
ASA into the tubule, if the pH is 4.5 you would have about
5,00:1 ratio, if you increase urine pH to 8.0, then essentially all
of it is in the ionized form, and can’t get reabsorbed
51. Elimination of Poisons
• Altering pH
– Alkalinize the urine – ASA, isoniazid, phenobarb
• Use bicarb in the fluids
• Don’t use acetazolamide (Diamox) in ASA poisoning
– Metabolic acidosis increases unionized form which can cross
into CNS, worsening poisoning
– Acidify the urine (usually not needed) – quinidine,
PCP, fenfluramine, amphetamine
52. Elimination of Poisons
• Dialysis
– What makes things “dialyzable”
• Low molecular weight
• Low volume of distribution
• Low protein binding
• Charge
– Methods
• Intermittent Hemodialysis
• CVVH/CVVHD/CVVHDF
– Albumin dialysis
53. Elimination of Poisons
• Charcoal hemoperfusion
– Clear chemicals by direct adsorbtion with charcoal in
an extracorporeal circuit
– Doesn’t depend of molecular size, protein binding
– Can be used for a variety of otherwise difficult to
manage poisonings
• Digoxin, ASA, barbiturates, TCA’s, theophylline
• Not used that much anymore
54. Elimination of Poisons
• Plasmapheresis
– Works very well with highly protein (albumin) bound
drugs
– Not a routine methodology, but has been used to
remove theophylline and digoxin/digibind complexes
• Exchange transfusion
– Use in smaller infants where vascular access for
extracorporeal techniques can’t be done
55. Tylenol Ingestion
• Clinical manifestations
– Stage 1
• First 12-24 hours
• Nausea, vomiting, anorexia
• No CNS involvement – of you see it, think of polysubstance
ingestion
– Stage 2
• Resolution of GI symptoms
• 36 hours after ingestion see biochemical evidence of liver
dysfunction – AST/ALT, bilirubin, PT
56. Tylenol Ingestion
• Clinical manifestation
– Stage 3
• Liver dysfunction reaches a peak on day 3-4
• Start GI symptoms again
• High transaminases (>10,000) do not necessarily predict liver
failure
• Fulminant liver failure can occur
– Stage 4
• Recovery stage – lasts 7-8 days
• Chronic hepatitis does not occur – LFT’s/biopsy return to
normal
57. Tylenol Ingestion
• Prediction of toxicity
– Rumack nomogram for single ingestion
– Rough guide for potential toxicity
• Children – 150 mg/kg
• Adults – 7.5 gm
– Uncommon 150mg/kg
– 50% with 250 mg/kg
– 100% with 350mg/kg
58. Tylenol Ingestion
• Therapy
– N-acetylcysteine (Mucomyst)
• Oral – 140 mg/kg load, followed by 70mg/kg q4 hours for 17
doses
– Repeat dose if vomits within 1 hour
– Can mix with carbonated drinks or grapefruit juice
• Intravenous – 150 mg/kg load over 15 minutes, then 50mg/kg
over 4 hours, then 100mg/kg over 16 hours
59. Volatile Alcohols
• Diagnosis
– High index of suspision
– Elevated osmolar gap
– Volatile alcohol screen + separate test for ethylen
glycol
– Methanol and ethylene glycol – no ketones
– Isopropyl alcohol – marked acetone
– Ethanol – acetoacetate and B-hydroxybutyrate
60. Volatile Alcohols
• Isopropyl Alcohol
– Toxic dose is 1 ml/kg of 70% solution
• More than one swallow in children should be presumed toxic
– About 20% is broken down by liver ADH to acetone
– Symptoms are like ethanol ingestion
• Nystagmus is common
• More CNS depressant than ETOH, because acetone is a CNS
depressant as well
– Management
• Supportive (without hypotension essentially 0% mortality)
• Levels don’t mean much prognostically
• Dialysis will remove it
– Coma + hypotension – 30% mortality
– Level over 400 (implied severe ingestion)
61. Volatile Alcohols
• Methanol
– No safe dose. 5ml is lethal in toddler age and can cause
blindness in adults. 1ml/kg is lethal in adults
– Metabolism
• 30% excreted by lungs
• 5% kidneys
• Rest to liver to make toxic metabolites
62. Volatile Alcohols
• Methanol
– Clinical symptoms – Biphasic
• Initial – CNS depression secondary to direct action of
methanol on CNS
• Delayed
– Visual disturbances
» Photophobia, “snowflakes”, blurred vision
» CAN HAVE FIXED DILATED PUPILS
– Metabolic acidosis
– Laboratory
• Elevated anion gap is due to formic acid and lactate
• Retinal damage is due to locally produced formic acid
64. Volatile Alcohols
• Ethylene Glycol
– Minimum lethal dose is 1.4-1.6 ml/kg
– Clinical symptoms
• Severe neurotoxicity, metabolic acidosis, renal failure, cardiovascular
collapse
• 1st
phase – 30 min –12 hours – CNS symptoms, N/V
– If LP – pleocytosis and elevated protein
• 2nd
phase – cardiorespiratory failure with pulmonary edema
• 3rd
phase – renal failure
– Metabolism
• 25% excreted unchanged by kidneys
• Remainder rapidly metabolized by liver and kidneys to toxic
metabolites
65. Volatile Alcohols
• Ethylene Glycol
– Lactic acidosis develops secondary to altered
NADH/NAD ratio
– Oxalic acid chelates calcium
• Tetany and myocardial dysfunction
– Renal failure is likely due to glycoaldehyde, glycolic
acid, glyoxylic acid
• Most recover – can be prolonged up to 2 months
• Can see calcium oxalate crystals in urine
67. Cyanide Poisoning
• Exposures
– Mostly from fires in children
– Acetonitrile in some cosmetics reported lethal
– “Vitamin B17” – cyanogenic glycosides – sold in
health food stores – from pits of apricots and bitter
almonds
– Laetrile – only when given orally or rectally
– Nipride – use sodium thiosulfate to reduce incidence –
1 gram per 100mg of Nipride
68. Cyanide Poisoning
• Pathophysiology
– Reversible binding to a-a3 cytochrome
– Halts aerobic metabolism and ATP formation
• Pushes to anaerobic metabolism and resultant lactic acidosis
– Inability to use oxygen at the cellular level
• Normal oxygen content and oxygen delivery
69. Cyanide Poisoning
• Treatment
– 100% oxygen always
– Eli Lilly Cyanide Antidote Kit No M-76
• Amyl nitrate pearls – inhale for 15-30 secs
– Produces about 5% methemoglobinemia
• IV sodium nitrite
• IV sodium thiosulfate
– Aiming for methemoglobin of 30%
70. Hydrocarbon Ingestion
• Unintentional vs intentional
• Clinical presentation
– Respiratory distress
• Hydrocarbons dissolve the lipid layer in the lung
– Surfactant inactivation, distal airway closure, hypoxemia, V/Q
mismatch
• Can progress to ARDS
– CNS abnormalities
• Mostly due to hypoxia
– GI abnormalities
71. Hydrocarbons Ingestion
• Clinical presentation
– Fever and leukocytosis common in first 24-48 hours
• Treatment
– Supportive
– Treat the hypoxia
– No induction of vomiting
72. Iron Intoxication
• Relatively common ingestion
• About 5-10% require hospitalization
• Can be lethal
– <20 mg/kg elemental Fe – insignificant
– 20-60 mg/kg mild toxicity
– >60 mg/kg moderate to severe toxicity
– >200 mg/kg rapidly lethal if not treated
73. Iron Intoxication
• Pathophysiology
– Huge uptake of iron from small bowel
– Overwhelm transferrin’s ability to bind and thus get
free iron circulating in blood
• Disruption of CMS, GI, CV systems
• Major oxidant stress – possibly shunts electrons away from
cytochromes in the mitochondria
• Interferes with activation of thrombin and clot formation,
leading to coagulopathy
– Direct gut toxicity with hemorrhagic gastritis and
bowel perforation
74. Iron Intoxication
• Clinical manifestation
– 1st
phase – GI symptoms (N/V/D, hemorrhagic gastritis,
GI bleed) – direct effect
– 2nd
phase – temporary recovery – 6-12 hours from
ingestion – can last several days
– 3rd
phase – return of GIU symptoms and MSOF
• Metabolic acidosis, shock, CNS depression, liver dysfunction,
renal failure, coagulopathy, etc.
• Die or get better
– 4th
phase – 4-6 weeks out – pyloric, gastric, or intestinal
obstruction – due to healing of initial damage
75. Iron Intoxication
• Prognosis
– Ingestion size
– Serum iron levels
• Peak 2-6 hours after ingestion
– <100 – unlikely toxicity
– 100-300 minimal
– 300-500 moderate
– 500-1,000 severe
– >1,000 potentially lethal
• After 6 hours even in large ingestion, level may be normal
76. Iron Intoxication
• Therapy
– Role of gastric lavage
– Desferoxamine – iron chelator
• Binds iron to form ferrioxamine which can be safely excreted
renally
– Red (“vin rose”) color to urine
• Also has a protective effect of increasing intracellular binding
of iron, reducing toxicity
– Not dialysable
77. Beta Blockers
• Widely prescribed and available
• Phamacology
– Lipophilicity
– Membrane stabilizing effect
• Selective vs non-selective agents
• Propranolol is most common and most dangerous
78. Beta Blockers
• Toxic dose
– 2-3 times therapeutic dose
• Signs and symptoms
– Bradyarrhythmia
– Hypotension
– Decrease LOC
– Respiratory depression
– Seizure
– Ventricular arrhythmia
80. Beta Blockers
• Prehospital management
– Glucagon 5mg IV bolus
• Peds 0.2 mg/kg IV bolus
– Fluid resuscitation – peds 20 ml/kg
– Pressors
• Dopamine 5-10 mcg/kg/min
• Epinephrine drips
– Titrate to response. May need bigger than normal dose
81. Beta Blockers
• Other management issues
– Treat dysrhytmia
– Pediatric patient
• Hypoglycemia more common
• Seizures more likely than adult
– Consider heroic measures - ECMO
82. Calcium Channel Blocker
• Pharmacology
– Negative inotrope
• Blocks flow of calcium ions through slow channels
• Decreased amount of calcium from sarcoplasmic reticulum
– Negative chronotrope
• Decrease automaticity in SA node and AV junction
– Reduction in PVR
87. Calcium Channel Blocker
• Other management issues
– Pressors prn
• Dopamine 5 mcg/kg/min
• Epinephrine drip 2 mcg/kg/min
– Titrate to response, may need bigger dose than normal
– Treat dysrhythmias
– Pediatric patient
• Small dose can be lethal
• Seizures are more likely than adult
– Consider heroic measures - ECMO
