Pharmacology & Poisoning
This was previously featured in an exam
This was previously featured in an exam
Question 55 of 300
A 23 year old woman is brought to the Emergency Department by paramedics. She had been in a house fire and was removed from the property by the fire service. She has no signs of burns. She is drowsy and responsive only to pain. An arterial blood gas is taken:
- pH: 7.15
- PaO2: 17 kPa
- PaCO2: 4.8 kPa
- HCO3-: 11 mmol/L
- Cl-: 100 mmol/L
- K+: 4.5 mmol/L
- Na+: 135 mmol/L
- Lactate: 21 mmol/L
What is the single most likely diagnosis?
Answer:
- Carbon monoxide and cyanide are highly lethal toxic compounds that can cause significant morbidity and mortality. Smoke inhalation victims present a unique challenge because they can be exposed to both substances. Carbon monoxide poisoning can be identified with detection of carboxyhemoglobin levels in blood or bedside co-oximetry. For cyanide poisoning, there is no quick bedside or laboratory confirmatory test, and it remains a clinical diagnosis. Fire victims with soot in their mouth, altered mental status, and metabolic acidosis with extremely high lactate levels suggest cyanide poisoning.
- In the absence of a cyanide concentration the following features suggest cyanide poisoning:
- Lactate more than 7 mmol/L (< 10 mmol/L = mild poisoning, 10 - 15 mmol/L = moderate poisoning, > 15 mmol/L = severe poisoning)
- Severe metabolic acidosis with an increased anion gap
- Reduced venous-arterial PO2 gradient
Cyanide Poisoning
Pharmacology & Poisoning
Last Updated: 12th February 2021
Causes
Cyanide poisoning may result from a broad range of exposures:
- Fire
- In industrialised countries, the most common cause of cyanide poisoning is domestic fires. Cyanide can be liberated during the combustion of products containing both carbon and nitrogen. These products include wool, silk, polyurethane (insulation/upholstery), polyacrylonitriles (plastics), melamine resins (household goods), and synthetic rubber.
- Industrial
- Occupational exposures account for a significant number of cyanide poisonings. Metal extraction in mining, electroplating in jewelry production, photography, plastics and rubber manufacturing, hair removal from hides, and rodent pesticide and fumigants have all been implicated in cyanide poisonings.
- Medical
- Cyanide exposures can result from alternative and standard medical treatments, including:
- Laetrile/amygdalin
- Sodium nitroprusside
- Cyanide exposures can result from alternative and standard medical treatments, including:
- Diet
- The family Rosaceae, which includes the bitter almond, cherry laurel, apricot, plum, peach, pear, and apple, is responsible for many reported cyanide poisonings. These foods all contain cyanogenic glycosides, such as amygdalin, in their pits and seeds. Other foods containing possible cyanogens include cassava root, bamboo shoots, and soy.
- Other
- Ingestion of cyanide salts, such as potassium cyanide (KCN) and sodium cyanide (NaCN), continues to be a method of both suicide and homicidal/terrorist acts. Miscellaneous exposure to cyanide may occur during illicit synthesis of phencyclidine, ingestion of acetonitrile (artificial nail polish remover), and cigarette smoking.
Pathophysiology
- Cyanide binds to and inhibits mitochondrial cytochrome oxidase preventing oxidative phosphorylation and thus aerobic respiration. The cell must then switch to anaerobic metabolism of glucose to generate ATP
- Anaerobic respiration leads to the formation of lactic acid and the development of metabolic acidosis. Hydrogen ions produced by ATP hydrolysis are no longer consumed in aerobic ATP production, exacerbating this acidosis. Serum bicarbonate decreases as it buffers excess acid, leading to an increased anion gap.
- Despite an ample oxygen supply, cells cannot utilise oxygen because of their poisoned electron transport chain. This functional (or "histotoxic”) hypoxia is particularly deleterious to the cardiovascular and central nervous systems (especially the basal ganglia).
Clinical features
- Early features include headache, nausea, dizziness, anxiety and a metallic taste, followed by confusion, drowsiness, tachycardia, palpitations, hypertension and tachypnoea.
- In cases of moderate toxicity there may be brief episodes of loss of consciousness, seizures, vomiting, bradycardia and hypotension. Classically there is a smell of bitter almonds on the breath and skin may be flushed with 'cherry red' colour.
- In severe poisoning, deep coma, fixed unreactive pupils, cardiovascular collapse, respiratory depression, myocardial ischaemia, cardiac arrhythmias and pulmonary oedema may develop. Cyanosis is often a late sign and may not occur, even in patients with cardiovascular collapse.
- While toxicity from inhalational exposure begins within seconds, toxicity from ingestion or dermal exposure is delayed from minutes to hours, depending on the extent of exposure. Ingestion of cyanide salts results in gastric irritation, frequently causing vomiting and abdominal pain.
- Survivors of severe cyanide poisoning may develop delayed-onset Parkinsonism or other neurologic sequelae. The basal ganglia are particularly sensitive to cyanide toxicity.
Diagnosis
- Cyanide poisoning is an uncommon entity. Therefore, making the diagnosis requires that the clinician maintain a high index of suspicion based on history and clinical presentation. Patients who are victims of fires or reported ingestions, are exposed at work, or have recently been treated with sodium nitroprusside should all be considered potentially cyanide poisoned.
- When a clear history is unavailable, clinicians should consider any patient with altered mental status and a metabolic acidosis of unknown aetiology a possible victim of cyanide poisoning. Blood cyanide concentrations may not correlate with toxicity, and results are rarely available in time to guide the clinical management of acutely poisoned patients.
- In the absence of a cyanide concentration the following features suggest cyanide poisoning:
- Lactate more than 7 mmol/L (< 10 mmol/L = mild poisoning, 10 - 15 mmol/L = moderate poisoning, > 15 mmol/L = severe poisoning)
- Severe metabolic acidosis with an increased anion gap
- Reduced venous-arterial PO2 gradient
- Carboxyhaemoglobin and methaemoglobin levels (measured by co-oximetry) should be performed, particularly if there is any concern for concomitant carbon monoxide exposure (e.g. house or vehicle fire) or exposure to drugs that produce methaemoglobinaemia.
Management
- Untreated, cyanide poisoning is rapidly lethal. If clinical history and examination are suggestive of cyanide poisoning, antidotal therapy must be given immediately, barring any contraindications.
- General treatment
- Secure airway, breathing and circulation.
- Intubation is usually required.
- Administer high-flow oxygen by non-rebreather face mask regardless of pulse oximetry reading.
- Do NOT perform mouth to mouth resuscitation in cases of suspected cyanide toxicity.
- Patients with dermal exposure must be decontaminated using proper precautions.
- Give a single dose of activated charcoal if the airway is adequately protected (50 g in adults; 1 g/kg in children with maximum dose of 50 g).
- Treat hypotension with rapid IV boluses of isotonic fluid and vasopressors as needed.
- Treat seizures with a benzodiazepine.
- Obtain assistance from medical toxicologist or poison control center.
- Secure airway, breathing and circulation.
- Antidotal treatment
- Administer cyanide antidote when cyanide poisoning is clinically suspected.
- If hydroxocobalamin is available, give the following:
- Hydroxocobalamin 70 mg/kg up to 5 g IV (5 g is standard adult dose) AND
- Sodium thiosulfate (25 percent): 1.65 mL/kg up to 50 mL IV; may repeat once (maximum dose 12.5 g)
- If hydroxocobalamin is not available, cyanide toxicity is known or strongly suspected, and there are no contraindications to nitrites, give the following Cyanide Antidote Kit:
- Amyl nitrite inhaled by the patient (held under the patient's nose or via the endotracheal tube) for 30 seconds of each minute, for three minutes AND
- Sodium nitrite (3 percent) 10 mg/kg - up to 300 mg - by slow IV infusion; may repeat once AND
- Sodium thiosulfate (25 percent) 1.65 mL/kg up to 50 mL IV; may repeat once
- If hydroxocobalamin is not available and cyanide toxicity is possible but not certain, or the patient has contraindications to nitrites, give the following:
- Sodium thiosulfate (25 percent) 1.65 mL/kg up to 50 mL IV; may repeat once
- If hydroxocobalamin nor the Cyanide Antidote Kit is available, cyanide toxicity is known or strongly suspected, and there are no contraindications, give the following:
- 4-DMAP (5 percent) 5 mL IV over one minute OR
- Dicobalt edetate (1.5 percent) 20 mL IV over one minute
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
