Exam 2: Management of Poisoned Patient

Question 1

1) toxicokinetics

vs.

2) toxicodynamics

Answer 1

1) toxicokinetics denotes the absorption, distribution, excretion, and metabolism of toxins, toxic doses of therapeutic agents, and their metabolites
2) toxicodynamics denotes the injurious effects of these substances on body functions

Question 2

Understand the comprehensive approach to a poisoned patient

Answer 2

• “ABCDs”
  
  • Airway, Breathing, Circulation, Dextrose (every patient with altered mental status should receive a challenge with concentrated dextrose, unless a rapid bedside blood glucose test result is not hypoglycemic)
• Hx
• Physical Exam
• Labs
• Tox screen
  
  • The clinical examination of the patient and selected routine laboratory tests are usually sufficient to generate a tentative diagnosis and an appropriate treatment plan.
  • Although screening tests may be helpful in confirming a suspected intoxication or for ruling out intoxication as a cause of apparent brain death, they should not delay needed treatment.

Question 3

Dialysis Procedures

Answer 3

• Peritoneal dialysis
  
  • Although it is a relatively simple and available technique, peritoneal dialysis is inefficient in removing most drugs.
• Hemodialysis
  
  • Hemodialysis is more efficient than peritoneal dialysis
  • The efficiency of both peritoneal dialysis and hemodialysis is a function of the molecular weight, water solubility, protein binding, endogenous clearance, and distribution in the body of the specific toxin
  • Hemodialysis is especially useful in overdose cases in which the precipitating drug can be removed and fluid and electrolyte imbalances are present and can be corrected
• Forced Diuresis and Urinary pH Manipulation
  
  • Previously popular but of unproved value, forced diuresis may cause volume overload and electrolyte abnormalities and is not recommended.
  • Renal elimination of a few toxins can be enhanced by alteration of urinary pH.

Question 4

Management of the Poisoned Patient with poison(s):

Acetaminophen

Answer 4

Acetylcysteine (Acetadote, Mucomyst)

• Initially, the patient is asymptomatic or has mild gastrointestinal upset (nausea, vomiting).
• After 24–36 hours, evidence of liver injury appears, with elevated aminotransferase levels and hypoprothrombinemia.
• In severe cases, fulminant liver failure occurs, leading to hepatic encephalopathy and death. Renal failure may also occur.

Question 5

Management of the Poisoned Patient with poison(s):

1) Anticholinesterase intoxication: organophosphates, carbamates
2) Organophosphate (OP) cholinesterase inhibitors

Answer 5

1) Atropine

(effective competitive inhibitor at muscarinic sites but has no effect at nicotinic sites)

2) Pralidoxime (2-PAM)

(No proved benefit in carbamate poisoning; uncertain benefit in established OP poisoning.) (Pralidoxime given early enough may be capable of restoring the cholinesterase activity and is active at both muscarinic and nicotinic sites)

• The mnemonic DUMBELS (diarrhea, urination, miosis and muscle weakness, bronchospasm, excitation, lacrimation, and seizures, sweating, and salivation) helps recall the common findings.
• Stimulation of muscarinic receptors causes abdominal cramps, diarrhea, excessive salivation, sweating, urinary frequency, and increased bronchial secretions.
• Stimulation of nicotinic receptors causes generalized ganglionic activation, which can lead to hypertension and either tachycardia or bradycardia.
• Muscle twitching and fasciculations may progress to weakness and respiratory muscle paralysis.
• CNS effects include agitation, confusion, and seizures.
• Blood testing may be used to document depressed activity of red blood cell (acetylcholinesterase) and plasma (butyrylcholinesterase) enzymes, which provide an indirect estimate of synaptic cholinesterase activity.

Question 6

Management of the Poisoned Patient with poison(s):

Rapid-onset mushroom poisoning with predominant muscarinic
excess symptoms

Answer 6

Atropine

Question 7

Management of the Poisoned Patient with poison(s):

Membrane-depressant cardiotoxic drugs (tricyclic antidepressants,
quinidine, etc)

Answer 7

Bicarbonate, sodium

Do not use physostigmine! Although physostigmine does effectively reverse anticholinergic symptoms, it can aggravate depression of cardiac conduction and cause seizures.

• Tricyclic antidepressants are competitive antagonists at muscarinic cholinergic receptors, and anticholinergic findings (tachycardia, dilated pupils, dry mouth) are common even at moderate doses.
• Some tricyclics are also strong α blockers, which can lead to vasodilation.
• Centrally mediated agitation and seizures may be followed by depression and hypotension.
• Most important is the fact that tricyclics have quinidine-like depressant effects on the cardiac sodium channel that cause slowed conduction with a wide QRS interval and depressed cardiac contractility. This cardiac toxicity may result in serious arrhythmias, including ventricular conduction block and ventricular tachycardia.

Question 8

Management of the Poisoned Patient with poison(s):

Fluoride; calcium channel blockers

Answer 8

Calcium

• These channel blockers depress sinus node automaticity and slow AV node conduction.
• They also reduce cardiac output and blood pressure.
• Serious hypotension is mainly seen with nifedipine and related dihydropyridines, but in severe overdose all of the listed cardiovascular effects can occur with any of the calcium channel blockers.

Question 9

Management of the Poisoned Patient with poison(s):

Iron salts

Answer 9

Deferoxamine

Question 10

Management of the Poisoned Patient with poison(s):

Digoxin and related cardiac glycosides

Answer 10

Digoxin antibodies

• Vomiting is common in patients with digitalis overdose.
• Hyperkalemia may be caused by acute digitalis overdose or severe poisoning, whereas hypokalemia may be present in patients as a result of long-term diuretic treatment. (Digitalis does not cause hypokalemia.)
• A variety of cardiac rhythm disturbances may occur, including sinus bradycardia, AV block, atrial tachycardia with block, accelerated junctional rhythm, premature ventricular beats, bidirectional ventricular tachycardia, and other ventricular arrhythmias.

Question 11

Management of the Poisoned Patient with poison(s):

Theophylline, caffeine, metaproterenol

Answer 11

Esmolol

• In addition to sinus tachycardia and tremor, vomiting is common after overdose.
• Hypotension, tachycardia, hypokalemia, and hyperglycemia may occur, probably owing to β2-adrenergic activation.
• Cardiac arrhythmias include atrial tachycardias, premature ventricular contractions, and ventricular tachycardia.
• In severe poisoning (eg, acute overdose with serum level > 100 mg/L), seizures often occur and are usually resistant to common anticonvulsants.

Question 12

Management of the Poisoned Patient with poison(s):

Methanol, ethylene glycol

Answer 12

Ethanol

Fomepizole (More convenient than ethanol)

• Ethylene glycol and methanol are alcohols that are important toxins because of their metabolism to highly toxic organic acids.
• They are capable of causing CNS depression and a drunken state similar to ethanol overdose.
• In addition, their products of metabolism—formic acid (from methanol) or hippuric, oxalic, and glycolic acids (from ethylene glycol)
  
  • cause a severe metabolic acidosis
    
    • and can lead to coma and blindness (in the case of formic acid)
    • or renal failure (from oxalic acid and glycolic acid).
• Initially, the patient appears drunk,
  
  • but after a delay of up to several hours, a severe anion gap metabolic acidosis becomes apparent,
  • accompanied by hyperventilation and altered mental status.
• Patients with methanol poisoning may have visual disturbances ranging from blurred vision to blindness.

Question 13

Management of the Poisoned Patient with poison(s):

Benzodiazepines

Answer 13

Flumazenil

• Comatose patients often have depressed respiratory drive.
  
  • Depression of protective airway reflexes may result in pulmonary aspiration of gastric contents, leading to pneumonia.
• Hypothermia may be present because of environmental exposure and depressed shivering.

Question 14

Management of the Poisoned Patient with poison(s):

β blockers

Answer 14

Glucagon

• Bradycardia and hypotension are the most common manifestations of toxicity.
• Agents with partial agonist activity (eg, pindolol) can cause tachycardia and hypertension.
• Seizures and cardiac conduction block (wide QRS complex) may be seen with propranolol overdose.

Question 15

Management of the Poisoned Patient with poison(s):

Cyanide

Answer 15

Hydroxocobalamin

• Cyanide binds readily to cytochrome oxidase, inhibiting oxygen utilization within the cell and leading to cellular hypoxia and lactic acidosis.
• Symptoms of cyanide poisoning include
  
  • shortness of breath, agitation, and tachycardia
  • followed by seizures, coma, hypotension, and death.
• Severe metabolic acidosis is characteristic.
• The venous oxygen content may be elevated because oxygen is not being taken up by cells.

Question 16

Management of the Poisoned Patient with poison(s):

Narcotic drugs, other opioid derivatives

Answer 16

Naloxone

Question 17

Management of the Poisoned Patient with poison(s):

Carbon monoxide

Answer 17

Oxygen

Question 18

Management of the Poisoned Patient with poison(s):

Suggested for delirium caused by anticholinergic agents

Answer 18

Physostigmine

• The classic anticholinergic (technically, “antimuscarinic”) syndrome is remembered as
  
  • “red as a beet” (skin flushed)
  • “hot as a hare” (hyperthermia)
  • “dry as a bone” (dry mucous membranes, no sweating)
  • “blind as a bat” (blurred vision, cycloplegia)
  • “mad as a hatter” (confusion, delirium).
• Patients usually have sinus tachycardia, and the pupils are usually dilated.
• Agitated delirium or coma may be present.
• Muscle twitching is common, but seizures are unusual unless the patient has ingested an antihistamine or a tricyclic antidepressant.
• Urinary retention is common, especially in older men.

Question 19

Management of the Poisoned Patient with poison(s):

Amphetamines & Other Stimulants

Answer 19

Treatment for stimulant toxicity includes general supportive measures as outlined earlier. There is no specific antidote.

• At the doses usually used by stimulant abusers
  
  • euphoria and wakefulness are accompanied by a sense of power and well-being.
• At higher doses
  
  • restlessness, agitation, and acute psychosis may occur, accompanied by hypertension and tachycardia.
• Prolonged muscular hyperactivity or seizures may contribute to hyperthermia and rhabdomyolysis.
• Body temperatures as high as 42°C (107.6°F) have been recorded.
  
  • Hyperthermia can cause brain damage, hypotension, coagulopathy, and renal failure.

Question 20

Management of the Poisoned Patient with poison(s):

Aspirin (Salicylate)

Answer 20

Supportive care, gastric lavage, activated charcoal, whole bowel irrigation.

For moderate intoxications, intravenous sodium bicarbonate

For severe poisoning (eg, patients with severe acidosis, coma, and serum salicylate level > 100 mg/dL), emergency hemodialysis is performed

• The first sign of salicylate toxicity is often hyperventilation and respiratory alkalosis due to medullary stimulation.
• Metabolic acidosis follows
  
  • an increased anion gap results from accumulation of lactate as well as excretion of bicarbonate by the kidney to compensate for respiratory alkalosis.
  • Arterial blood gas testing often reveals a mixed respiratory alkalosis and metabolic acidosis.
• Body temperature may be elevated owing to uncoupling of oxidative phosphorylation. Severe hyperthermia may occur in serious cases.
• Vomiting and hyperpnea as well as hyperthermia contribute to fluid loss and dehydration.
• With very severe poisoning, profound metabolic acidosis, seizures, coma, pulmonary edema, and cardiovascular collapse may occur.
• Absorption of salicylate and signs of toxicity may be delayed after very large overdoses or ingestion of enteric coated tablets.