Post on 28-Dec-2015
transcript
Toxicology:A Practical Approach
Lou Hampers, MDPediatric Emergency Medicine
The Children’s Hospital
Denver, CO
Thanks to:
Carl Baum MDToxikonCook County Hosp.Chicago, IL
Toxicology: the ABCs
• Airway
• Breathing
• Circulation
• Diagnosis
• Decontamination
• Enhanced removal
Diagnosis
• What?– Containers– PoisIndex and Pill ID– Avoid PDR
• How much?– Assume largest amount
• When?
Diagnosis
Pupils
• Constricted• sympatholytics• cholinergics• barbiturates• opiates• PCP• ethanol / sedative-hypnotics• other: heatstroke; pontine or subarachnoid
hemorrhage
Diagnosis
Pupils
• Dilated• sympathomimetics• anticholinergics
Diagnosis
Toxidromes: anticholinergic• Mad as a hatter
• Red as a beet
• Hot as a hare
• Blind as a bat
• Dry as a bone
Diagnosis
Toxidromes: cholinergic• muscarinic
• Salivation• Lacrimation• Urination• Defecation• GI motility
• nicotinic• tachycardia, hypertension• fasciculations, paralysis
Diagnosis
Odors
• arsenic, organophosphates, thallium: garlic• chloral hydrate, paraldehyde: pear• chloroform, isopropyl alcohol: acetone• cyanide (only 50% can detect): almond• methylsalicylate: oil of wintergreen• naphthalene, paradichlorbenzene: mothball• water hemlock: carrot
Diagnosis
Elevated anion gap
• Are organic acids present?
gap = Na - Cl - CO2
(normal = 8 - 12 meq/L)
Diagnosis
Elevated anion gap• Alcohol (but not isopropyl!)• Tolulene• Methanol• Uremia• Diabetes mellitus• Paraldehyde• Iron, Isoniazid• Lactic acidosis• Ethylene glycol• Salicylates, Strychnine
Diagnosis
Elevated osmolal gap
• What is the difference between what is measured and
what is calculated?
2 (Na) + glucose/18 + BUN/2.8 [calculated osm]
+ Methanol/2.8
+ Ethanol/4.3
+ Ethylene Glycol/5.0
+ Isopropanol/5.9
Diagnosis
“Tox screen”
• Plasma/Serum • good for levels of selected substances
– Acetaminophen, ASA, CO, CBZ, Dig, DPH, EtOH, Fe, Li, Phenobarb, Theo
• avoid comprehensive (send-out)
• Urine• good for drugs of abuse screen (in-house)
– amphetamines, barbs, benzodiazepines, cocaine, cannabinoids, opiates, pcp
Diagnosis
Abdominal xrays
“Bet-a-chip”Barium
Enteric coated tablets
Tricyclics
Antihistamines
Chloral hydrate, Cocaine, Condoms
Heavy metals
Iodides
Potassium, Phenothiazines
Decontamination
Universal Antidote
• Burned toast
• Milk of magnesia
• Strong tea
Decontamination
Emesis (ipecac)
• Indications (not many!)• home-management of Fe, Li, K
• Contra-indications• obtunded/comatose/convulsing• likelihood of rapid progression
– TCA, camphor, cocaine, INH• corrosives• petroleum distillates
Decontamination
Gastric lavage
• Indications• removal of ingested material• administration of charcoal/cathartics
• Contra-indications• obtunded/comatose/convulsing• corrosives (?)
Decontamination
Activated charcoal
• Indications• numerous poisons, except some which are not well
adsorbed:• alcohols, alkalis, acids• CN, Fe, K, Li, Pb
• Contra-indications• ileus/obstruction• corrosives (endoscopy)
Decontamination
• Repeat-dose charcoal• some anti-convulsants• salicylates• theophylline
• Cathartics• magnesium citrate (4 ml/kg)• use with caution in children < 2 years
• Whole Bowel Irrigation
Enhanced Elimination
Methods
• Urinary
• Hemodialysis
• Hemoperfusion
• Peritoneal dialysis
• Multi-dose charcoal
• Whole bowel irrigation
Enhanced Elimination
Specific “Antidotes”• Acetaminophen N-acetylcysteine• COHb oxygen, HBO• Digoxin Fab• Ethylene Glycol EtOH, dialysis• Iron deferoxamine• Lithium fluids, dialysis• Methanol EtOH, dialysis• Salicylate alkalinization, dialysis• Theophylline repeat AC, hemoperfusion
Acetaminophen
History• When? Acute or chronic? • How much?
– dosage? 80, 160, 325, 500, 650?– toxic: >150 mg/kg
Physical• Nausea, emesis
Acetaminophen
• AcetaminophenSulfate, Glucuronide (major)
NAPQI (minor)
• NAPQI is hepatotoxic
• Glutathione detoxifies NAPQI
Acetaminophen
Laboratory
• Acetaminophen (draw after 4 h)
• AST, ALT, PT may increase, but after 24 h
• Bili, Ammonia may also increase
Acetaminophen
Rumack-Matthew Nomogram
200
150
mcg/ml
4 h
Acetaminophen
Treatment
• Glutathione substitute
• Precursor for sulfate
• Antioxidant
Acetaminophen
N-acetylcysteine (NAC, Mucomyst®)
• Dilute to 5%, cover, on the rocks!• Load: 140 mg/kg po• Maint: 70 mg/kg po q 4 h x 17 doses• Premedicate with antiemetics prn• Follow LFTs, PT
Alcohols and Glycols
Methanol, Ethylene Glycol
alcohol dehydrogenase
Organic Acids
Alcohols and Glycols
History
• Lethargy, ataxia
Physical
• Hypothermia
• Respiratory depression
• CNS depression (“intoxication”)
Alcohols and Glycols
Laboratory
• Check d-stick
• Check anion and osm gap
• Send out methanol or ethylene glycol level
Alcohols and Glycols
Treatment
• Provide supportive care
• Block formation of toxic metabolites
• Dialysis
Alcohols and Glycols
Treatment
• Ethanol block– level (osm gap) > 20 mg/dl
• Dialysis– level (osm gap) > 50 mg/dl
Alcohols and Glycols
4-methylpyrazole (fomepizole, Antizol™)
Hydrocarbons
• Aromatics: systemic toxicity– benzene, toluene, xylene
• Aliphatics: aspiration hazard– gasoline, kerosene, lamp oil– Hx or PE significant for cough, dyspnea,
fever, cyanosis, rales
Hydrocarbons
• Aromatics– remove via NG if > 1 ml/kg
• Aliphatics– do not remove unless > 5 ml/kg– clinical/radiographic signs of pneumonitis
may be delayed– antibiotics, steroids not helpful
Iron
How much?
• Vitamins + Fe rarely a problem
• Prenatal iron can be lethal
• Ipecac: home-management of
> 20 mg/kg
Iron
History
• Within 2 h: GI symptoms
• 6-24 h: fever, metabolic acidosis, hepatic impairment, seizures, shock and coma
Iron
Laboratory
• Serum Fe level at 2 h – 6 h to r/o delayed absorption
• CBC, electrolytes if symptomatic
• Consider KUB to r/o radio-opaque tablets or bezoar
Iron
Treatment
• Consider whole bowel irrigation– 25 ml/kg/h
• Deferoxamine if serum Fe > 500 mg/dl– 15 mg/kg/h
Salicylates
History• Various forms of salicylates
Physical• Hyperthermia• Deep, rapid respirations• Emesis, dehydration• Coma, seizures
Salicylates
Laboratory
• Initial respiratory alkalosis
• Later metabolic acidosis
• Platelet, coag dysfunction
• Hyper- or hypoglycemia
Salicylates
Laboratory
• Peak serum levels @ 2 to 6 hours
• Symptomatic > 50 mg/dl
• Potentially fatal > 100 mg/dl
• Nomogram not helpful
Salicylates
Treatment
• Lower temperature (sponging)• Correct fluid losses, hypoglycemia• Correct prolonged PT with Vitamin K• Urine alkalinization (> pH 7.5)
– shortens half-life via ion trapping– may need potassium
Salicylates
Laboratory
• Consider multi-dose charcoal
• Consider dialysis for levels > 100 mg/dl
Tricyclic Antidepressants
Mechanisms
Therapeutic
• anticholinergic effects
• inhibition of neurotransmitter reuptake
• stabilization of membranes
Tricyclic Antidepressants
Mechanisms
Overdose
• therapeutic mechanisms are seen
• inhibition of fast Na channels– membrane-depressant effects– cardiac toxicity
Tricyclic Antidepressants
Physical
• Abrupt decompensation
• Tachycardia, dysrhythmias
• Sedation, seizures
Tricyclic Antidepressants
Laboratory
• ECG may reveal QRS > 100 msec– predicts toxicity– other ECG abnormalities seen
• TCA levels not clinically useful
Tricyclic Antidepressants
Treatment
• Anticipate dysrhythmias, respiratory failure and ARDS
• Ipecac: NO!
• Give charcoal (via NG prn)
Tricyclic Antidepressants
Treatment
If QRS prolongation or refractory hypotension:
• serum alkalinization
(pH 7.45-7.55)
Tricyclic Antidepressants
Serum Alkalinization
bolus Na bicarb 1-2 mEq/kg
• increase extracellular Na may reverse membrane depression
• alkaline pH may stabilize ion channels
• hyperventilation not as effective
Fun with Mnemonics
Hyperthermia
NASA• NMS, Nicotine• Antihistamines• Salicylates,
Sympathomimet.• Anticholinergics,
Antidepressants
Hypothermia
COOLS• CO• Opiates• Oral hypogly.
(insulin)• Liquor• Sed-hypnotics
Fun with Mnemonics
Tachycardia
FAST• Free base• Anticholinergics,
Amphetamines• Sympathomim.,
Solvent• Theophylline
Bradycardia
PACED• Propranolol• Anticholin’ase• Clonidine, CCBs• Ethanol• Digoxin
Fun with Mnemonics
Rapid Respirations
PANT• PCP, Paraquat,
Pneumonitis• ASA• Noncardio. PE• Toxin-induced
metabolic acid.
Slow Respirations
SLOW• Sed-hypnotics• Liquor• Opiates• Weed (marijuana)
Fun with Mnemonics
Hypertension
CT SCAN• Cocaine• Thyroid, Theoph.• Sympathomim.• Caffeine• Anticholinergics• Nicotine
Hypotension
CRASH• Clonidine, CCBs• Reserpine• Antidepressants• Sed-hypnotics• Heroin
Fun with MnemonicsSeizures
OTIS CAMPBELL
• Organophosphates• Tricyclics• INH, Insulin• Sympathomim.• Camphor, Cocaine• Amphetamines
• Methylxanthines• PCP• Benzo withdrawl• Ethanol withdrawl• Lithium, Lidocaine• Lead, Lindane
Non-toxic Ingestions
• Antibiotics• Baby oil• Bleach• Cigarettes• Cologne• Contraceptive pills• Cosmetics• Detergent
• Glue• Hydrogen peroxide• Laxatives• Paint• Rat poison• Shampoo• Thermometers• Vitamins