TOXOCOLOGY

Abdullah AlOlayan, R4

• Summary of Pocket ICU for Toxicology

 DECONTAMINATION
1. Activated charcoal (AC)
• No trials prove benefits
• Use of AC does carry the risk of aspiration pneumonitis
• Limitations of AC – poor adsorption of alcohols, acids, bases, metals
• Recommendation: single dose AC if the ingestion occurred within an hour
• Multiple dose activated charcoal (MDAC) for drugs with enterohepatic or enteroenteric recirculation

2. Whole bowel irrigation (WBI)

• Method of propelling the intestinal contents rapidly through the gut
• Indications:
➢ Toxic ingestion of sustained-release preparations
➢ Ingestion of a large amount of a highly toxic substance not well adsorbed by AC
➢ Removal of drug packets from the intestine

3. Enhanced elimination
HD and CVVH
Exchange transfusion
Plasmapheresis
Manipulation of urinary pH
Ion exchange resins

Indications for all

• Low volume of distribution (Vd)
• MW < 500 daltons

o Plasmapheresis or exchange transfusion

Indications
1) Toxin molecular weight TOO GREAT for dialysis
2) Toxin highly PROTEIN BOUND

o Manipulation of urinary pH
Enhancing excretion of acidic substances in nephron
• Used in treatment of salicylate and uranium toxicity
• Goal urine pH > 7.5
• Arterial pH should not be allowed to exceed 7.55
 METABOLIC TOXINS

1. Salicylates
• Compounds including: ASPIRIN, Oil of wintergreen, Pepto-Bismol (bismuth subsalicylate)
o Toxic-therapeutic window is relatively narrow
o Presentation is a patient comes with Tachypnea, N&V, TINNITUS, Hyperthermia, AG METABOLIC
ACIDOSIS WITH RESPIRATORY ALKALOSIS, Pulmonary edema ( capillary permeability)
o Indications of hemodialysis: level >90mg/dl, Renal failure, Pulmonary edema, Seizure
o Concentration >30 mg/dl should prompt urine alkalization

2. Toxic Alcohols
• Most common agents: methanol (MeOH) and ethylene glycol (EG), Isopropanol
• Toxic alcohols are metabolized by: Alcohol dehydrogenase (ADH)
Aldehyde dehydrogenase (AlDH)
• Resulting in a metabolic acidosis and the formation of a toxin
• Majority of Methanol ➔ Formate ➔ Damage to the RETINA (Hallmark) & Ischemia or hemorrhage
in basal ganglia, QT prolongation, Coma or seizures
• Ethylene Glycol is more readily excreted by the kidney ➔ Calcium oxalate crystals (enveloped
shape) + ATN-Renal failure + Hypocalcemia
• Diagnosis: 1) All are AG metabolic Acidosis except (Isopropanol)
2) Serum osmolality is measured and an osmolar gap of 25 mOsm or more should
prompt diagnosis
3) Serum samples should be sent for gas chromatography/mass spectrometry analysis
for toxic alcohols,
• Treatment
1) with intravenous fluid and sodium bicarbonate.
2) All suspected or proven cases should receive antidotal therapy with FOMEPIZOLE
3) Hemodialysis removes the toxic alcohol, corrects acidosis, and removes the toxic metabolite.
4) In Methanol = FOLINIC ACID helps to metabolize formate
5) In Ethylene glycol = pyridoxine and thiamine should be given to help with metabolism of glyoxalic
acid to nontoxic substances.

4. Cyanide
• Sources ➔ Product of combustion of a number of synthetic textiles, silk, and wool
• Administration of sodium NITROPRUSSIDE at high rates can result in elevated cyanide levels,
• Mechanism ➔ a ‘cellular toxin’ as it inhibits mitochondrial cytochrome oxidase, disrupting aerobic
metabolism ➔ Lactic acid anion gap metabolic acidosis
• History is usually more important than the physical examination in making the diagnosis
• Laboratory testing should include simultaneous ABG and VBG, as the inability of the tissues to
extract oxygen results in similar pO2 measurements in both samples. A lactate of above 8 mmol/l
• Management of toxicity
➢ HD stable + normal parameter = Supportive care
➢ Severe = hydroxocobalamin
 NEUROTOXINS
Carbon Monoxide
• Sources: Incomplete combustion of hydrocarbon fuel, whether that is charcoal, wood, gasoline or
diesel, heating oil, natural gas, or propane
• Methylene chloride, a solvent It is metabolized in the liver ➔ CO
• Mechanism of Action:
a. Binds to hemoglobin more avidly than oxygen ➔ Impairs dissociation of oxygen from
hemoglobin.
b. Binding to iron-containing proteins and enzymes ➔ CELLULAR HYPOXIA.
c. Binding to endothelium and platelets releases nitric oxide ➔ VASODILATION
• Clinical presentation:
a) Mild = headache, weakness, or nausea
b) Severe measurable end-organ dysfunction, CNS, Acute or as a form of delayed
neurologic sequelae (DNS)
• Evaluation of the patient for CO toxicity ➔ABG or VBG with co-oximetry
• Treatment with Normobaric (NBO) or hyperbaric (HBO) oxygen
• Measurement of COHb yields the concentration however not significant to reflect tissue
compromise.
• Use of HBO over NBO is somewhat controversial but most toxicology texts recommend its use
(HBO is C/I in untreated pneumothorax)

Lithium
• Kinetics: rapidly and completely absorbed in the small intestine
• Bimodal distribution, peaks within hours but reach tissue within week.
Presentation ➔ Tremor, ataxia, dysarthria, nystagmus, renal impairment, confusion, and convulsions.
• Chronic lithium toxicity can cause significant renal dysfunction, including nephrogenic diabetes
insipidus
• Laboratory testing ➔ Serum electrolytes, electrocardiogram, and urine analysis
• Optimally sample collected >6hrs to accurately measures serum level.
• lithium concentrations often do not correlate with clinical signs of toxicity
Treatment: 1) Fluid resuscitation to maintain normal urine output
2) Benzodiazepines or barbiturates for agitation or seizure
3) Dialysis ➔ Severe symptoms, Renal failure, Lithium concentration >3.5 mEq/l

INH (Isoniazid)
• Metabolized by N-acetyltransferase (NAT)
• Inhibits pyridoxine phosphokinase ➔ converts pyridoxine to its active form + binds to it ➔ The
resultant decrease in pyridoxine activity + decrease in (GABA) concentration ➔ Unresponsive
seizure
• Clinical picture ➔ Status epilepticus, LOC, Metabolic acidosis, rhabdomyolysis and Coma
• Hepatotoxicity and Peripheral neuropathy are in Chronic toxicity
• Ingestion of as little as 2 g of INH in an adult can cause toxicity
• 10 g is considered a lethal dose without treatment
• GI symptoms predominate in the early stages
• Treatment ➔ Pyridoxine is 1 g IV for every gram of INH ingested (Dose equivalent) ➔ Refractory
metabolic acidosis or renal failure ➔ Hemodialysis
Organophosphate Poisoning
• presents with manifestations of cholinergic EXCESS. ➔ classically bradycardia, miosis, lacrimation,
salivation, bronchorrhea, bronchospasm, urination, emesis, and diarrhea
• 40% of organophosphorus poisoned patients develop a distinct neurologic within 2 days of exposure.
➔ neck flexion weakness decreased deep tendon reflexes, cranial nerve abnormalities, proximal
muscle weakness, and respiratory insufficiency.
• Diagnosis clinically
• Treatment:
1) LOC or Respiratory compromise ➔ Intubation
2) Assure good volume status
3) Atropine + Pralidoxime (Antidote)

CARDIOVASCULAR TOXINS

Calcium channel blockers (CCBs)

• Bioavailability is 90% or greater
• There is first-pass metabolism,
• Mechanism of action ➔ In overdose, receptor selectivity is lost, and even peripheral tissue calcium
channels are affected
• Clinical picture➔ Cardiac output decreases, SVR decreases, and bradycardia with AV block can be
seen, Pulmonary edema may be due to reduced cardiac output.
• The degree of hyperglycemia used to predict the degree of toxicity (blockage of L-Calcium channels
in Pancreas)
• EKG = COMPLETE AVB, Laboratory = HYPERGLYCEMIA, LACTIC ACIDOSIS
• Treatment = Supportive care (Vasopressors), Atropine/Pacing for bradycardia, High dose Calcium
chloride q2-3 mins until response is seen
• Amrinone and Glucagon are useful by increasing cyclic AMP,
• Insulin infusion shows results.
• Cardiac bypass or intra-aortic balloon pump can be used in very severe refractory cases

Digoxin
• It is therefore NOT amenable to dialysis
• It is renally excreted, with a half-life of over 24 hrs.
• Mechanism of action ➔ the sodium–potassium ATPase pump in cell membranes becomes
dysfunctional ➔ intracellular calcium and serum potassium
• Clinical picture ➔ cardiac manifestations of digitalis toxicity can include virtually any type of
arrhythmia with the exception of rapidly conducted atrial arrhythmias.
• Nausea and vomiting and Abdominal pain.
• Altered mental status or visual changes (yellowing of vision)
• Laboratory analysis ➔ serum potassium is of use in correlates with the severity of poisoning and
serum Digoxin level does not correlates with severity.
• Mortality 100% in patients with potassium above 6.4 mEq/l

ECG:
• Occurs even with normal level digoxin
• MOST COMMON is PVC’s
 • Treatment
1) Atropine or pacing for bradycardia
2) But the definitive is FAB ➔ Indications: Evidence of end-organ damage, Arrythmia,
Hyperkalemia

HEPATIC AND GI TOXINS

Acetaminophen (APAP)
• The majority of APAP is conjugated and excreted renally.
• Mechanism of action In cases of overdose, glutathione is depleted and toxicity results
• hepatic injury occurs in a centrilobular pattern
• The clinical course of APAP poisoning has been artificially divided into four phases

• Treatment dependent on timing of presentation

➢ activated charcoal, 1 g/kg within 4 hours of ingestion
➢ N-acetylcysteine (NAC) for ALL PATIENTS with acetaminophen poisoning at significant risk
for hepatotoxicity, NAC most effective 8 hours of APAP ingestion ➔ Routine measurement
of LFTs is crucial for response
➢ Dialysis can also be used to remove APAP in cases where the concentration is severely
elevated (over 1,000 mcg/dl)
• Criteria for liver transplantation are presented in the table below. Patients should be evaluated for
transplant as soon as a concern develops

Caustics
Alkaline and acidic substances
• Drain cleaners, oven cleaners, automatic dishwasher detergents, brake dust removers.
• Cause significant injury to the skin and mucosa
• Alkalis cause a so-called ‘liquefaction’ necrosis ➔ Perforation
• Acids, on the other hand, cause a coagulation ➔ Perforation
• Burns to the GI tract are classified into 3 grades, and the progression of injury into 4 stages
• Treatment = No AC or gastric lavage ➔ NO BEINIFTS
• Perforation, which can be seen on chest radiograph or CT scan ➔ Surgical intervention
• Steroid therapy ➔ prospective trial failed to demonstrate benefit in preventing stricture.