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Questions Answered: 300

Final Score 76%

229
71

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Pharmacology & Poisoning

Question 249 of 300

A 19 year old man is brought to the Emergency Department following an overdose of diazepam. He was seen to ingest twenty 5 mg tablets by his partner, there is no history to suggest a mixed overdose. He has no past medical history. His GCS is recorded as 10/15. Which of the following can be used in benzodiazepine overdose?

Answer:

Although flumazenil, a benzodiazepine antagonist, is not advised as a routine diagnostic test in patients with a reduced level of consciousness, it is appropriate treatment in patients poisoned only with a benzodiazepine who develop reduced ventilation and coma and who otherwise would require mechanical ventilation.

Benzodiazepine Toxicity

Pharmacology & Poisoning

Last Updated: 21st February 2023

The primary toxicity of benzodiazepines is CNS depression; the effects are potentially more severe when co-ingested with alcohol and other CNS depressants.

Clinical features

Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Coma, hypotension, bradycardia and respiratory depression occasionally occur but are seldom serious if these drugs are taken alone. Coma usually lasts only a few hours but may be prolonged in elderly patients.

Benzodiazepine respiratory depressant effects are more serious in patients with chronic obstructive airways disease. Severe effects in overdose also include rhabdomyolysis and hypothermia.

ECG abnormalities include transient first degree and second degree block and QT prolongation. Abnormal LFTs may also occur.

Management

  • Maintain a clear airway and ensure adequate ventilation.
  • The benefit of gastric decontamination is uncertain. Consider activated charcoal (charcoal dose: 50 g for adults; 1 g/kg for children) if the patient presents within 1 hour of ingestion of a toxic dose or more, provided the airway can be protected.
  • Monitor vital signs and cardiac rhythm; check the capillary blood sugar. Check and record pupil size.
  • Perform a 12-lead ECG in all patients who require assessment. Check cardiac rhythm, QRS duration and QT interval. Consider repeating the ECG in ANY OF the following circumstances:
    • The initial ECG is abnormal
    • The patient is symptomatic
    • The recommended observation period (see below) is not yet complete
  • In all patients who require assessment check FBC, U&Es and LFTs. Check CK in patients with prolonged loss of consciousness.
  • All patients who require assessment should be observed for at least 4 hours after exposure. Asymptomatic patients can then be considered for discharge with advice to return if symptoms develop.
  • Consider arterial/venous blood gas analysis in patients who have a reduced level of consciousness, reduced oxygen saturation on pulse oximetry or metabolic disturbance.
  • Flumazenil:
    • Flumazenil, a GABA A receptor antagonist, may be used to avoid mechanical ventilation in patients who develop reduced ventilation and coma due to GABA A agonists. However, its use has been associated with convulsions; generally after very high doses (e.g. 10 mg IV bolus) and in the presence of proconvulsant drugs.
    • Flumazenil SHOULD NOT be used:
      • As a diagnostic test for benzodiazepine poisoning
      • At more than the minimum dose required to reverse ventilatory impairment; full reversal of CNS depression is neither necessary, nor desirable
      • When the risk of convulsions is high, e.g.:
        • Known poisoning with a drug that causes convulsions (e.g. a tricyclic antidepressant)
        • Features indicate sodium channel blocker or stimulant poisoning (wide QRS interval, tachycardia with large pupils), even if no such agent has been disclosed.
    • Flumazenil has a short half-life (about an hour) and an infusion may therefore be required.
  • Hypotension:
    • Ensure adequate fluid resuscitation.
    • Consider early referral to critical care for patients with fluid-resistant hypotension, as these patients can deteriorate extremely rapidly.
    • Invasive vascular monitoring and echocardiography may help determine the likely relative benefits of inotropes and vasopressors because reduced cardiac output and vasodilation often co-exist in severe or mixed poisoning.

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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
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