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Intoxication
Viktória Bertalan M.D.
Diagnosis of poisoning
Diagnosis and treatment often must proceed rapidly!
Toxicology screens
How will the result of the test alter the
approach to treatment?
Can the result of the test be returned in
time to affect therapy positively?
Limitations:
• panels may look for only 40-100 drugs
– more than 10.000 possible drugs or toxins
– 6 million chemicals
• a negative result does not always rule out
poisoning, negative predictive value is about
70%, positive predictive value 90%
Common drug of abuse panel
History
• frequently unreliable or incomplete!
• early signs and symptoms
• drugs taken:
– (nonprescription drugs, herbal medicines, vitamins)
patient / family member / friend / paramedics
General findings: autonomic
syndromes
α-adrenergic:
1.
–
2.
hypertension with reflex bradycardia, usually with mydriasis (eg,
phenylephrin)
ß-adrenergic:
–
hypotension (ß2-mediated vazodilation) and tachycardia (eg,
caffeine, theophylline)
mixed α+ß adrenergic:
3.
–
4.
hypertension and tachycardia, with mydriasis, sweathening, dry
mucous membranes (eg, cocaine, amphetamines)
sympatholytic:
–
hypotension and bradycardia with miosis (pin point), decreased GI
peristalsis (eg, clonidine, opiates)
General findings: autonomic
syndromes
5. Nicotinic cholinergic:
–
–
both parasympathetic and sympathetic stimulation,
unpredictable symptoms: cxcessive stimulation
frequently causes depolarization blockage.
Thus
•
•
–
initial tachycardia, may be followed by bradycardia
muscle fasciculations may be followed py paralysis
eg, nicotin, succinylcholin
6. Muscarinic cholinergic:
–
bradycardia, miosis, sweathing, hyperperistalsis,
bronchorrea, wheezing, excessive salivation, urinary
incontinence (eg, bethanechol)
General findings: autonomic
syndromes
5.
Mixed cholinergic:
–
–
–
6.
both nicotinic and muscarinic receptors are stimulated: mixed effects
usually miotic (pin point) pupils, sweathy skin, increased peristalsis,
fasciculation to paralysis
eg, organophosphate, carbamate insecticides
Anticholinergic (antimuscarinic):
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Tachycardia, mild hypertension, myosis (widely dilated)
Skin: flushed, hot, dry
Decreased peristalsis, commonly urinary retention
Myoclonic jerking or choreoatetoid movements
Agitation, delirium
Hyperthermia
eg, atropin, antihistamines, antidepressants
Eye findings:
• Nystagmus:
– usually horizontal-gaze: eg, barbiturat, etanol,
carbamazepine, phenytoin, scorpion envenomation
– PCP (phencyclidine) may cause horizontal, vertical
and rotatory
Eye findings:
• Miosis:
– Sympatholythic agents:
eg, clonidine, opiates
– Cholinergic agents: eg,
carbamate insecticides,
nicotine*,
organophosphates
Eye findings
• Mydriasis
• Sympathomimetics:
– eg, amphetamines,
cocaine, LSD (lysergic
acid diethylamide),
monoamine oxidase
inhibitors
• Anticholinergics:
– antihistamines, atropine,
tricyclic antidepressants
Skin
• sweating or absence of
sweating:
– autonomic syndromes
• flushed red:
– carbon monoxide
• cherry red
– boric acid
– chemical burns
• corrosives or hydrocarbons
– anticholinergic agents
– vasodilatation
• eg, phenothiazines
Skin 2
• pale:
– with diaphoresis:
sympathomimetic agents
– localised: possible
arterial vasospasm (eg,
ergot, amphetamines)
• cyanosis:
– hypoxia
– sulf- or methemoglobinaemia
Skin
• blisters
– insect bites
– barbiturates
Abdominal findings: ileus
• paralythic: drugs
• mechanical factors
– perforation, peritonitis,
mechanical obstruction
• bowel infarction
– rare, but catastrophic
– prolonged hypotension
– vasospasm
(eg, amphetamines)
Abdominal findings: vomiting
• hematemesis: corrosive substance
Odors
•
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•
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•
acetone: acetone, izopropil alcohol
acrid, pearlike: paraldehyde, chloral hydrate
bitter almonds: cyanide
garlic: arsenic, organophosphates
mothballs: naphtalene
rotten eggs: hydrogen sulfide
carrot: water hemlock
Airway
Most common factor contributing to death!
All poisoned patients should be suspected of
having potentially compromised airway!
Airway: assessment
• Awake:
– likely intact reflexes
– should be monitored (potentially rapid loss of
airway!)
• Lethargic or obtunded:
– assess: gag or cough reflex
– consider endotracheal intubation
Airway: treatment
Optimize the airway position!
B. sniffing position
C. jaw thrust
D. head down, left sided
position
Do not perform neck manipulation
if you suspect neck injury!
Airway: clean it!
Remove any obstruction or secretions!
• Magill forceps
Airway: secure it!
• artificial oropharyngeal or nasopharyngeal
devices
• endotracheal intubation:
– Nasotracheal:
• disadvantages: stimulation of vomiting, spontaneous
breath required
– Orotracheal
Breathing:
1. Ventillatory failure
2. Hypoxia
3. Bronchospasm
Breathing: ventillatory failure
1. muscle paralysis:
–
eg, botulism, nicotine, organophosphates,
strychnine, neuromuscular blockers
2. CNS depression:
–
eg, antihistamines, barbiturates, ethanol, opiates,
triciclic antidepressants (TCA)
Breathing: hypoxia
1. Insufficient oxygen in ambient air
–
inert gases: carbon monoxide, methane, propane,
nitrogen
2. Disruption of oxygen absorption by the lung
1. pneumonia or noncardiogenic pulmonary edema:
eg. aspiration of gastric contents or hydrocarbons,
chlorine, mercury vapor, opiates, paraquat, salicylates,
smoke, sedative-hypnotic drugs
2. cardiogenic pulmonary edema:
eg. ß-blockers, procainamid, TCA, verapamil
Breathing: hypoxia
3. Cellular hypoxia:
1. limited oxygen binding:
•
•
carbon monoxide, methemoglobinemia
dissolved oxygen unchanged (pO2), oxygen content
deteriorated
2. cellular oxygen utilization disturbances:
•
•
cyanide, hydrogen sulfide
high venous oxygen saturation (decreased cellular
oxygen uptake)
Breathing: bronchospasm
1. direct irritant agents:
–
smoke, chlorine, hydrocarbon aspiration
2. pharmacologic effect:
–
organophosphate, insecticides, ß-blockers
3. hypersensitivity or allergy
Circulation
1.
2.
3.
4.
5.
6.
Bradycardia and AV block
QRS interval prolongation
Tachycardia
Ventricular arrythmias
Hypotension
Hypertension
Circulation: bradycardia and AV block
• cholinergic vagotonic agents:
– digitalis, organophosphates, neostigmine
• membrane-depressant drugs:
– ß-blockers, flecainide, quinidine, procainamid, TCA
• sympatholytic agents:
– ß-blockers, clonidine, opiates
• other:
– calcium antagonists, carbamazepine, lythium, α-agonists
Do NOT treat unless the patient is symptomatic!
Both may be a protective reflex in life-threatening
hypertension!
Circulation: bradycardia and AV block
• Differential diagnosis
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hypothermia
myocardial ischaemia
electrolyte abnormality (eg, hyperkalaemia)
metabolic disturbance (eg, hypothyroidism)
Cushing-reflex (severe intracranial hypertension)
physiologic athletes, or vaso-vagal reaction
Circulation: bradycardia and AV block
• Rewarm hypothermic patients!
– 40-50/min sinus bradycardia is normal when core
temperature is 32-35 °C
• Administer atropine
– 0.01-0.03 mg/kg iv.
• Use transcutaneous or transvenous PM!
• Use specific antidotes!
– ß-blockers – glucagon
– digitalis – Fab fragments
– triciclic antidepressant or membrane-depressant drugs –
sodium bicarbonate
– calcium antagonist – calcium
Circulation: QRS interval prolongation
• QRS interval
prolongation
– > 0.12 s in limb leads
– eg, ß-blockers,
chloroquin, digitalis,
flecainid, hyperkalemia,
phenotiazines, quinidine,
procainamide, TCA
• Ventricular escape
rhythm
– complete heart block
– digitalis, calcium
antagonists
Circulation: QRS interval prolongation
• differential diagnosis:
– intrinsic conduction system
disease
• check an old ECG if available
– hyperkalaemia:
• sine wave pattern, with wide QRS,
peaked T waves
– hypothermia
• <32 °C
• extra terminal QRS deflection
(J or Osborne wave)
Circulation: QRS interval prolongation
• Treatment:
– treat hyperkalemia and hypothermia
– treat AV block with atropin or PM
– for TCA or other sodium channel-blockers give
sodium bicarbonate 1-2 mEq/kg iv bolus, repeat as
needed
– antidotes:
• digoxin – Fab antibodies
• ß-blockers – glucagon
• calcium antagonist – calcium
Circulation: tachycardia
1. sympathomimetic agents
– amphetamines, caffeine, cocaine, ephedrine, PCP,
theophylline
2. agents causing cellular hypoxia
– carbon monoxide, cyanide, hydrogen sulfide, oxidizing
agents (methemoglobinaemia)
3. anticholinergic agents
– Amanita muscaria mushrooms, antihistamies, atropin,
phenothiazines, TCA
4. other
– ethanol or sedative-hypnotic drug withdrawal,
vasodilators (reflex tachycardia) tyroid hormone
Circulation: tachycardia
• sinus or supraventricular tachycardia:
– may also be a reflex response to hypotension
• sinus tachycardia + QRS interval
prolongation
– may have the appearance of VT
Circulation: tachycardia
• Differential diagnosis:
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–
–
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occult blood loss
fluid loss
hypoxia
fever and infection
AMI
anxiety
intrinsic conduction system disease (eg, WPW)
Circulation: tachycardia
• Treatment:
– hypotension, chest pain
– for sympathomimetic-induced: propranolol
– for anticholinergic-induced: neostigmin,
physostigmine
In TCA overdose additive depression of conduction
may result in asystole!
Circulation: ventricular arrythmias
• VT or VF
– amphetamin or other sympathomimetics, aromatic
hydrocarbons, caffeine, cocaine, digitalis, theophylline,
TCA
• QT prolongation or torsades des pointes
– amiodarone, arsenic, fluorid, TCA, moxifloxacin,
levofloxacin, erythromycin, organophosphates
Circulation: ventricular arrythmias
• treatment:
– CPR
– for TCA or other sodium channel-blocking drug:
• administer sodium bicarbonate 1-2 mEq/kg iv in
repeated boluses until the QRS interval narrows or the
pH exceeds 7.7
– for torsade de pointes:
• overdrive pacing
• administer iv. magnesium sulfate 1-2 g in adults over
20-30 minutes
Circulation: hypotension
hypotension with relative bradycardia
• Sympatholythic agents
– β-blockers, clonidine, hypothermia, opiates
• Membrane-depressant drugs
– β-blockers (propranolol), procainamid, TCA
• Others:
– barbiturates, calcium antagonists, fluoride,
organophosphates and carbamates
Circulation: hypotension
hypotension with tachycardia
• fluid loss or third spancing
– amatoxin containing mushroom, arsenic, sedativehypnotic agents
• Peripheral venous or arterial dilation
– α-agonists, β2-stimulants, caffeine, calcium
antagonists
Hypotension: therapy
• fluid challenge: 10-20 ml/kg
• vasopressor therapy
– dopamine, norepinephrine
• TCA, reserpine, norepinephrine more effective
(depleted neuronal CA stores)
Antidotes
•
•
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•
sodium bicarbonate – TCA
glucagon – beta blocker
calcium – calcium antagonist
propranolol – theophylline, caffeine, β-agonist
overdose.
Circulation: hypertension
with tachycardia:
– generalized sympathomimetic agents
• amphetamines, cocaine, ephedrine, levodopa, LSD,
marihuana, MAO inhibitors
– anticholinergic agents
• antihistamines, atropine, TCA
– other:
• ethanol and sedative hypnotic drug withdrawal, nicotine
(early stage), organophosphates (early stage)
Circulation hypertension
with bradycardia or atrioventricular block
– clonidine, ergot derivates, methoxamine,
norepinephrine
Hypertension: complications
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intracranial hemorrhage
myocardial infarction
congestive heart failure
aortic dissection
Hypertension: therapy
• Rapid lowering is desirable: diastolic 100
mmHg (hypertensive) or 80 mmHg
• do not use propranolol or esmolol alone, beta
blockers may paradoxically worsen
hypertension if it is caused primarily by alpha
adrenergic stimulation
Altered mental status
1.
2.
3.
4.
Coma or stupor
Seizures
Confusion or delirium
Agitation or psychosis
Altered mental status:
coma or stupor
• Generalized CNS depressants
– anticholinergics, antihistamines, barbiturates,
benzodiazepines, ethanol, sedative-hypnotic agents, TCA
• Sympatholytic agents
– clonidine, methyldopa, opiates
• Cellular hypoxia:
– carbon monoxide, cyanide, hydrogen sulfide,
methemoglobinemia, sedium azide
• Other (unknown mechanism)
– bromide, disulfiram, lithium, PCP, salicylates
Altered mental status:
seizures
• adrenergic sympathomimetic agents
– amphetamines, caffeine, cocaine, ephedrine, PCP
• antidepressants and antipsychotics
– haloperidol, TCA, SSRI
• others:
– antihistamines, β-blockers, ethylene glycol, lead,
methanol, salicylates, strychnine
Altered mental status
• confusion or delirium:
– amantadine, anticholinergic agents, antihistamines,
bromde, carbon monoxide, H2 blockers, lead,
levodopa, lidocaine, lithium, salicylates,
withdrawal from ethanol or sedative-hypnotic
drugs
• agitation or psychosis:
– amphetamines, caffeine, cocaine, LSD, marihuana,
PCP, procaine, SSRI, steroids, theophylline
Coma
• antidotes:
– naloxone: opiates
– flumazenil: (BZD)
• can precipitate seizures in pts addicted to BZD or have
co-ingested a convulsant drug or poison
Altered mental status: diff. dg
• head trauma other causes of intracranial
bleeding
• abnormal levels of blood glucose, sodium...
• hypoxia
• liver or renal failure
• hypothermia / hyperthermia
• infections (encephalitis, meningitis)
Anion gap metabolic acidosis
• normal anion gap: 8-12 mEq/L
• unmeasured anions
– eg. phosphate, sulphate and anionic proteins
Anion gap metabolic acidosis:
• elevated anion gap:
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–
–
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hyperlipidaemia
hemodialysis (low-molecular-weight solutes)
lactic acid
unmeasured acid anions
• formate ( mehtanol poisoning)
• oxalate (ethylene glycol poisoning)
• narrow anion gap
– elevated serum chloride concentration:
• bromide, nitrate overdose
– lowered serum sodium concentration
• lithium, calcium, magnesium
Serum osmolality and osmolar gap
• normally 290 mosm/l
• calculated osmolarity 2[Na] + 2[K] + [urea]+
[glc]
• osmolar gap:
– measured – calculated: 0±5 mOsm/l
• causes:
– low molecular substances: eg, ethanol, glycol
Osmolar gap + anion gap =
methanol / ethylene glycol poisoning
(or severe diabetic ketoacidosis!)
Serum glucose level
• altered by nutritional state, endogenous insulin levels,
endocrine and liver function
• Hyperglycemia:
– usually mild and transient.
– eg, caffein, teophylline
– if severe:
• dehydration, electrolit imbalance (osmotic effect in the urine)
• shifting of water from brain into plasma: hyperosmolar coma
• Hypoglycaemia
– seizures, coma or altered mental status
– eg, insulin, ethanol, oral sulfonylurea agents, salicylate,
valproic acid
Renal failure
• Direct nephrotoxicity:
– acetaminophen, Amanita phalloides mushrooms, ibuprofen,
bromates, chlorates, ethylene glycol (oxalate, glycolate),
heavy metals
• Hemolysis:
– arsine, naphthalene
• Rhabdomyolysis:
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amphetamine, cocaine, PCP, strychnine
coma with prolonged immobility
hyperthermia
status epilepticus
• Hypoperfusion
Liver failure
• direct toxicity:
– amanita phalloides mushrooms
• hepatotoxic intermediate metabolits:
– acetaminophen
• hepatic vein thrombosis
– pyrrolizidine alkaloids
Decontamination
Emesis
• Early prehospital management of selected potentially
seious oral poisonings, particularly in the home
immediate after ingestion
• contraindications:
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obunded, comatose or consulsive
risk of CNS depression or seizures
corrosives
aliphatic hydrocarbones (pneumonitis)
• adverse effects:
– delayed administration of activated charcoral or oral
antidotes
– hemorrhagic gastritis or Mallory weiss tear
Gastric lavage
• more invasive
• occasionally used in ED, little evidence
• indications: massive overdose, or a particularly
toxic substance
• within 30-60 minutes of ingestion (after
several hours delayed gastric emptying eg,
salicylates or anticholinergic drugs)
• preparation for endoscopy
Gastric lavage: contraindications
• altered mental status, cunvulsion
– endotracheal intubation
• enteric coated pills
– too large to eliminate
• corrosive substance
– controversial
Gastric lavage: complications
•
•
•
•
perforation of the esophagus or stomach
bleeding
inadverent tracheal intubation
aspiration
Activated charcoral
• highly adsorbent, made from a distillation of
wood pulp
• poorly adsorbed toxins:
– alkali, cyanide, ethylene glycol, fluoride, inorganic
salts, iron, lithium, potassium
• dosage: 1g/kg
Whole bowel irrigation
• surgical bowel-cleansing solution (nonabsorbable
polyethylene glycol in a balanced electrolyte
solution)
• 2L/h until rectal effluent is clear
• indications:
– large ingestions of drugs poorly adsorbed to activated
charcoral
– large ingestion of enteric coated tablets containing
dangerous drugs (eg. verapamil)
– ingestion of foreign bodies (body stuffers)
Enhanced elimination
Does the patient need enhanced removal?
Is the drug or toxin accessible
to the removal procedure?
Urinary manipulation
• the renal route is the significant contributor to
total clearance
• Forced diuresis:
– may increase GFR risk of volume overload
• Alkalization and ion trapping:
– urinary pH manipulation may enhance elimination
of polar drugs eg, salicylates
Renal replacement or other eliminative
therapies
• Haemodialysis
• Hemoperfusion
• Plasm exchange
ABC
Airway:
Cough and gag reflexes
Patient position
Clear airway
Endotracheal intubation
Breathing:
Arterial blood gasses
Assist with bag/mask device
Give oxygen
Respiratory failure?
Hypoxia?
Bronchospasm?
Circulation
BP and pulse
ECG monitoring
start 1-2 iv. lines
Routine bloodwork
Bradycardia /AV block
Prolonged QT
Tachycardia
Ventricular arrythmias
Hypotension
Severe hypertension
Disability/altered mental status
Hypoglycaemia?
Body tempreture (core)
Organic causes?
Anticonvulsive therapy
Adequate sedation
Coma or stupor?
Hypothermia?
Hyperthermia?
Seizures
Agitation?
Other complications:
Urine myoglobin
Obtain allergy history
Clinical diagnosis
Physical findings
Essential labtests
Decontamination
Skin and eyes
Emesis or gastric lavage
Charcoral or cathartic
Dystonia or rigidity?
Rhabdomyolysis?
Allergy or anaphylaxis?
Osmolar gap
Anion gap acidosis
Hyper/hypoglycaemia
Hypo/hypernatremia
Hypo/hyperkalemia
Renal failure
Liver failure
Toxicology screening
Abdominal X-ray
Enhanced removal
Hemodialysis
Hemoperfusion
Repeat dose charcoral
Hazardous material?
Disposition
Toxicology consultation
Psychosocial evaluation
Regional poison center consulatation