Intoxication Viktória Bertalan M.D.. Diagnosis of poisoning Diagnosis and treatment often must...

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

1. α-adrenergic:– hypertension with reflex bradycardia, usually with mydriasis (eg,

phenylephrin)

2. ß-adrenergic: – hypotension (ß2-mediated vazodilation) and tachycardia (eg,

caffeine, theophylline)

3. mixed α+ß adrenergic:– hypertension and tachycardia, with mydriasis, sweathening, dry

mucous membranes (eg, cocaine, amphetamines)

4. 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, succinylcholin6. Muscarinic cholinergic:

– bradycardia, miosis, sweathing, hyperperistalsis, bronchorrea, wheezing, excessive salivation, urinary incontinence (eg, bethanechol)

General findings: autonomic syndromes

5. Mixed cholinergic: – 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

6. Anticholinergic (antimuscarinic):– 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

• 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 lung1. 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. Bradycardia and AV block

2. QRS interval prolongation

3. Tachycardia

4. Ventricular arrythmias

5. Hypotension

6. 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 – 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,

theophylline2. agents causing cellular hypoxia

– carbon monoxide, cyanide, hydrogen sulfide, oxidizing agents (methemoglobinaemia)

3. anticholinergic agents– Amanita muscaria mushrooms, antihistamies, atropin,

phenothiazines, TCA4. 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:– 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, sedative-

hypnotic 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

• 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

• 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. Coma or stupor

2. Seizures

3. Confusion or delirium

4. 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:– 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: – 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:– 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

A B C

Airway:Cough and gag reflexesPatient positionClear airway

Disability/altered mental statusHypoglycaemia?Body tempreture (core)Organic causes?Anticonvulsive therapyAdequate sedation

Breathing:Arterial blood gassesAssist with bag/mask deviceGive oxygen

Coma or stupor?Hypothermia?Hyperthermia?SeizuresAgitation?

CirculationBP and pulseECG monitoringstart 1-2 iv. linesRoutine bloodwork

Endotracheal intubation

Respiratory failure?Hypoxia?Bronchospasm?

Bradycardia /AV blockProlonged QTTachycardiaVentricular arrythmiasHypotensionSevere hypertension

Other complications:Urine myoglobinObtain allergy history

Enhanced removalHemodialysisHemoperfusionRepeat dose charcoral

Clinical diagnosisPhysical findingsEssential labtests

Hazardous material?

DecontaminationSkin and eyesEmesis or gastric lavageCharcoral or cathartic

Dystonia or rigidity?Rhabdomyolysis?Allergy or anaphylaxis?

Osmolar gapAnion gap acidosisHyper/hypoglycaemiaHypo/hypernatremiaHypo/hyperkalemiaRenal failureLiver failureToxicology screeningAbdominal X-ray

DispositionToxicology consultationPsychosocial evaluation

Regional poison center consulatation