Term
Evaluate laboratory and clinical parameters specific
to the overdosed patient.
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Definition
For labs, you would want:
- Anion gap
- Osmolal gap
- Serum Tox screen
- Urine tox screen
- Quantitative analysis |
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Term
Describe the general management of the overdosed
patient.
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Definition
To diagnose....
Look at the patient and their skin
Listen to their heart and lungs
Smell their breath
Examine their abdomen and extremities, do neuro exam
Airway - Sx include dyspnea, dysphonia, air hunger, hoarseness, signs of stridor, retractions, Cyanosis
Breathing - Pt. needs oxygenation, pulse oximetry, treatment with 100% O2 facemask except in those with high PCO2 levels
Circulation - Check pulse, BP, need a peripheral line placed and given a fluid bolus.
Drug-Induced CNS depression - Give 50ml 50% dextrose IV, Thiamine 100mg IV, Naloxone 0.4-2mg in most, but lower doses if you suspect an opioid addiction |
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Term
List the options available for gastrointestinal
decontamination.
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Definition
Ipecac syrup is for exposures < 4-6 hours, limited data
- For children < 1 year, give 5-10ml
- For children 1-11 years, give 15ml
- For children >12 years, give 30ml
**For any age group, if no response, give 1 more dose in 20 minutes
Gastric Lavage (stomach pump?), varying efficacy
Charcoal has excellent efficacy, indications are for adsorbable agents. Give 1g/kg in infants up to a year, 25-50g in kids 1-12, and 25-100g in older pt's. Cathartics MIGHT be given also, but whole bowel irrigation with PEG-3350 is not uncommon b/c of potential obstruction |
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Term
Compare and contrast the roles of activated charcoal
and ipecac.
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Definition
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Term
Describe pharmacokinetic and pharmacodynamic
concepts inherent to clinical toxicology
(toxicokinetics).
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Definition
Toxicokinetics is the ADME of drugs at doses associated with clinical toxicology
According to the graphics, lithium tends to have concentrations in the plasma > RBC's > Brain |
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Term
Explain pathophysiologic states which may alter the
handling of substances in the poisoned patient.
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Definition
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Term
List the most common pharmaceuticals involved in
overdoses and fatalities.
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Definition
Analgesics 12.5%;
Sedatives/hypnotics/antipsychotics 6.2%; Cough
and cold preps 4.5%; Topical preparations 4.5%
Antidepressants 4%; Cardiovascular drugs 3.5%;
Alcohols 3.3%; Antihistamines 3.2%; Antimicrobials 2.7%; Vitamins 2.7%
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Term
Outline the risk factors, signs and symptoms consistent with acetaminophen overdose.
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Definition
Risk Factors - Alcoholism, starvation, AIDS, race, liver disease, pregnancy?
Drug induced alteration - anticonvulsants, isoniazid
Signs:
0-24h --> N/V, anorexia, diaphoresis, many will have no sx, known as the "silent toxin."
1-3 days --> Latent phase with decrease in sx, liver enzymes/bilirubin may increase, may have hepatic tenderness/abd. pain
3-6 days --> max increase in liver enzymes, Sx of hepatic injury, jaundice, encephalopathy, hypoglycemia, reduction in clotting factors, pancreatitis, carb intolerance, myocarditis, low phosphate levels
7-8 days --> hepatic damage leads to coma, hepatorenal syndrome, potentially death; remarkable healing ability may be seen so sx could resolve, but recovery could take up to 7 months |
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Term
Describe the mechanism of acetaminophen toxicity.
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Definition
- Normally, APAP metabolized to glucuronide and sulfate conjugates
- Small % of this is metabolized to NAPQI, which is toxic but normally detoxed by glutathione into cysteine and mercapturate conjugates
- If this pathway becomes saturated, and there is no more glutathione, then NAPQI becomes toxic to liver cells, and results in centrilobular necrosis
- NAPQI occurs with <30% glutathione stores gone
- 20% of pt's with toxic levels do not get toxicity, 1-2% of the population suffer from toxicity
**Toxicity could also bew caused by lipid peroxidation and oxidation of thiol groups on key hepatic enzymes** |
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Term
Manage a patient with acetaminophen overdose.
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Definition
< 4 hours
–
– Begin N-acetylcysteine
–
– Continue NAC if incr APAP level
– D/C NAC if low APAP level. Levels over 200 ug/ml appear to be considered toxic
- NAC is a sulfhydryl compound that replenishes glutathione stores by combining directly with reactive metabolites.
- Most protective if started early
- Efficacy beyond 14-36 hours is controversial
- Some studies suggest that use up to 72 hours may decrease liver failure
Administration of NAC
- Give bolus of 140mg/kg dose. Supplied in 10% or 20% solution, must dilute to 5%, preferable with fresca. Vomitting is common, so nasogastric tube can be used
- 17 more doses after bolus must be given at intervals of 4h, at 70mg/kg each.
- Over 72 hours, total dose must be 1330mg/kg
- If patient vomits within an hour of taking a dose, the dose must be repeated
- IV can be used, very expensive, or prepared from oral solution. If latter is used, must use filter needle to prepare, better for those with N/V
IV administration
- 20% solution
- Do 150mg/kg in 200ml dex over 15 minutes THEN
- 50mg/kg in 500 ml dex over 4 hours THEN
- 100mg/kg in 1000ml dex over 16 hours
ADR's
- Unpleasant odor (straw could help)
- Sulfhemoglobinemia (cyanosis without respiratory distress) rare
*Methionine available in Europe
Take blood for APAP level>4 hours - < 8 hours after overdoseAdminister activated charcoal
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Term
Outline the signs and symptoms consistent with salicylate overdose.
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Definition
- Vomiting, hyperapnea, tinnitus, lethargy
- Mixed respiratory alkalosis and metabolic acidosis
- Severe intoxication can lead to coma, seizures, hypoglycemia, hyperthermia, and pulmonary edema
- Death is caused by CNS failure and CV collapse |
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Term
Describe the mechanism of salicylate toxicity.
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Definition
-Central stimulation of the respiratory center leads
to hyperventilation and a respiratory alkalosis.
This leads to dehydration and compensatory
metabolic acidosis
-Uncoupling of oxidative phosphorylation
- Interruption of glucose and fatty acid metabolism
which contributes to metabolic acidosis
- May alter capillary wall integrity leading to cerebral
- Vd is markedly increased in salicylate overdose, tablet concretions can act as reservoirs for drugs, mainly metabolized by liver but renal excretion more apparent in very large doses
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Term
Manage a patient with salicylate overdose.
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Definition
Acute Ingestion - Serum levels > 90-100mg/dL associated with severe toxicity, must have multiple determination to see if there is bezoar formation, nomogram available but not widely used
Chronic Ingestion - Sx correlate poorly with levels
Management:
- Use supportive measures
- Oral decontamination, charcoal is key, but Ipecac can be used for children at home is < 30 minutes of exposure
- No specific antidotes available
- Sodium Bicarb IV to treat acidemia and urinary clearance of salicylate
- Urinary alkalinization using 100meq of sodium bicarb to 1 liter of dex (D5W) + 0.25-0.5 normal saline at 200ml/hr
- Consider IV supplementation
- Consider Hemo in severe intoxications involving seizures and coma, metabolic acidosis esp. with concurrent renal failure, those at risk for non-cardiogenic pulmonary edema (older age, his. smoking, ASA intox, ineffective diuresis) |
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Term
Outline the signs and symptoms consistent with ethylene glycol and methanol overdose.
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Definition
Ethylene Glycol:
- Stage 1 (30 minutes to 12 hours) - Neurologic --> Inebriation, N/V, hyporeflexia, seizures, coma, opthalmoplegia, nystagmus, papilledema
- Stage 2 (12-24 hours) - Cardiopulmonary --> Tachycardia, HTN, pulmonary edema
- Stage 3 (>24 hours) - Renal --> Flank pain, oliguria progressing to anuria, renal failure
** The difference in methanol toxicity is that it can lead to blindness and Parkinsonism** |
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Term
Describe the mechanism of ethylene glycol and methanol toxicity.
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Definition
- Metabolized by alcohol dehydrogenase to toxic metabolites which include glycolic and oxalic acid
- These acids along with lactic acid create an anion gap metabolic acidosis
- Oxalate readily precipitates with calcium to form insoluble calcium oxalate crystals
- Tissue injury is caused by widespread deposition of Ca oxalate and toxic effects of noted metabolites
- Methanol is converted to formic acid |
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Term
Manage a patient with ethylene glycol overdose.
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Definition
- labs are extremely slow, so initiate therapy IMMEDIATELY
- Deadly poison that doesn't take much to cause fatality.
- Must impair metabolism of ethylene glycol
- Administer booze
- Given orally or IV
- Give 1000mg/kg/hr IV over 1-2 hours, then 100mg/kg/hr constant infusion
- Give more in known alcoholics
- Dose must be inc. in dialysis
- Administer fomepizole with bolus of 15mg/kg over 30 min. then 10mg/kg q12h x 4 doses
- Treatment should continue until E.G levels are less than 20 mg/dL and no detectable osmolal gap
- For methanol, the magic number is 50 mg/dL |
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Term
Describe lithium toxicity as it pertains to signs and symptoms
related to lithium level in an acute on chronic exposure.
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Definition
Acute Intoxication - intentionally or accidentally ingests lithium but is lithium naive. Mild N/V but systemic signs are delayed by hours due to half-life. Levels do NOT correlate with severity of toxicity.
Acute on Chronic intoxication - Intentional or accidental ingestion but is NOT lithium naive. Severe sx which could include slurred speech, ataxia, rigidity, EPS, delirium, coma, seizures, progressive dementia. In this case, levels correlate with toxicity.
0.4-1.3 is therapeutic
> 1.5 (V+D, mild tremor, ataxia, visual disturbances)
> 2.5 (possibly life-threatening, seizures, dysrrhythmias)
> 3.5 dialysis
Chronic Intoxication:
- Patient taking lithium but doesn't have acute ingestion, increase may be due to other factors
- Factors: Dose increase, drug intx (NSAIDS, Diuretics), renal failure, Volume depletion (increases Na and Li levels)
- Even though levels may be "therapeutic," patients may exhibit signs of toxicity |
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Term
Identify valid and inappropriate management strategies for lithium intoxication
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Definition
- Supportive measures, particularly replacing
fluid losses aggressively
- Charcoal IS NOT effective (however may be
used of co-ingestion of another substance is
suspected)
- Ipecac may be considered if within minutes of
exposure (esp. children)
- Whole bowel irrigation may enhance gut
- Hemodialysis
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an Acute on Chronic or Chronic exposure OR in
those with severe symptomatology.
Threshold for most is a lithium level of 2.5 mEq/L in
- Due to slow redistribution from tissues to blood,
rebound in the lithium level is expected after a
procedure.
– Prolonged dialysis may be necessary
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an Acute on Chronic or Chronic exposure OR in
those with severe symptomatology.
–
rebound in the lithium level is expected after a
procedure.
– Prolonged dialysis may be necessary
Due to slow redistribution from tissues to blood, Threshold for most is a lithium level of 2.5 mEq/L in
–
an Acute on Chronic or Chronic exposure OR in
those with severe symptomatology.
–
rebound in the lithium level is expected after a
procedure.
– Prolonged dialysis may be necessary
Due to slow redistribution from tissues to blood, Threshold for most is a lithium level of 2.5 mEq/L in
–
an Acute on Chronic or Chronic exposure OR in
those with severe symptomatology.
–
rebound in the lithium level is expected after a
procedure.
– Prolonged dialysis may be necessary
Due to slow redistribution from tissues to blood, Threshold for most is a lithium level of 2.5 mEq/L in
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Term
| How do we enhance elimination in GI decontamination? |
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Definition
Diuretics - Forced diuresis, alkalinization
Multiple-dose activated charcoal
Extracorpeal removal - Hemodialysis, Hemoperfusion, Peritoneal dialysis |
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Term
| Name some of the most often toxic agents with their common antidotes |
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Definition
Benzos - Flumazenil
Ethylene Glycol - Ethyl alcohol/fomepizole
Methanol - Ethyl alcohol/fomepizole
Opiods - Naloxone
Organophosphates - Pralidoxime
Warfarin - Vitamin K |
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Term
| What would the lab values look like for: an alcoholic with APAP toxicity, a suicide attempt with APAP, alcoholic hepatitis. |
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Definition
Alcoholics with APAP toxicity:
AST - increased
ALT - increased, < AST
AST/ALT - 2+
Prothrombin - Increased to marked
Apap level - Normal or slight increase
Suicide ingestion with APAP:
AST - Normal then increased
ALT - noraml to increase
AST/ALT - <2
Prothrombin - Normal to increase
APAP level - Increased
Alcoholic Hepatitis:
AST - <300
ALT - slight increase/normal
AST/ALT - 2+
Prothrombin - Increase, <20 seconds
APAP level - Normal |
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