Benzodiazepine Toxicity

Objectives

To guide the management of patients with benzodiazepine overdose in the deployed environment.

Scope

This guideline describes the management of patients with suspected benzodiazepine toxicity in a forward medical context or deployed Emergency Department. It should not be used in the Firm Base or when access is available to TOXBASE® is available.

Audience

This guideline is intended for the use of registered healthcare professionals fulfilling a general role in a forward medical location or in an Emergency Department on deployed operations.

Initial Assessment & Management

Toxicity (overdose) from benzodiazepines may result from medical administration (iatrogenic) or from illicit drug use. Check the toxicity of the dose ingested using the table in accordion content.

Patients who are symptomatic will require further assessment and management. 

Asymptomatic patients who have ingested a potentially toxic dose should be observed for a least 4 hours after exposure. Patients who remain asymptomatic after this time can be considered for discharge. Asymptomatic adult patients who have accidentally ingested a sub-toxic dose do not require further assessment. 

This does not apply to patients who have been exposed as a result of self-harm and who will require a mental health assessment irrespective of symptoms, nor to children who should be assessed and observed for a minimum of 4 hours, regardless of symptoms or exposed dose. 

If there is uncertainty as to the specific drug or the source of the drug is unclear the patient should be assessed and observed.

Consider prompt treatment with activated charcoal if available (50 g for adults; 1 g/kg for children) if the patient presents within 1 hour of ingestion of a toxic dose.

 

Symptoms and signs

Key features: reduced consciousness, respiratory depression, hypotension, bradycardia.

Airway:

  • Progressive loss of protective reflexes
  • Airway obstruction

Breathing:

  • Reduced respiratory rate
  • Hypercapnia
  • Hypoxia

Circulation:

  • Hypotension
  • Bradycardia

Disability:

  • Reduced consciousness
  • Coma
  • Nystagmus

Ataxia

Exposure:

  • Hypothermia
     

Co-ingestion of alcohol and other central nervous system depressants potentiates the effects of benzodiazepines and can increase toxicity. 

 

Management 

Monitor vital signs and cardiac rhythm. 

Maintain airway and provide ventilatory support with bag valve mask if required.

Given supplemental oxygen to maintain saturations >92%. 

Treat hypotension by administering IV fluids. 

If bradycardia is noted, following standard protocols as per Bradycardia CGO (link to follow).

Flumazenil should NOT be routinely used to treat benzodiazepine overdose due to the risk of precipitating seizures. See below for detail.

Advanced Assessment & Management

Supportive care will follow the same principles outlined above, noting that intubation and mechanical ventilation may be required.

In patients who have ingested a potentially toxic dose or who experience features of toxicity:

Monitor for ECG changes. Transient first and second degree heart blocks may occur; if QT prolongation is seen then ensure hypoxia and acidosis are being treated, check and correct potassium, calcium, and administer magnesium (2g IV over 10-15 minutes).

Check bloods - including FBC, U&Es and LFTs. Seek expert advice via reach back if results are deranged. Additionally monitor CK in patients with prolonged loss of consciousness.

Prolonged Casualty Care

Casualties requiring supportive care following benzodiazepine overdose are likely to require evacuation to a facility equipped to provide critical care if needed. If this is impossible then continue supportive care in situ.

Paediatric Considerations

Although asymptomatic adult patients who have accidentally ingested a sub-toxic dose do not require further assessment, all children should be assessed and observed regardless of symptoms or exposed dose. 

Benzodiazepine Toxic Doses

Drug Potentially Toxic Dose
Alprazolam 0.05 mg/kg
Bromazepam 0.7 mg/kg
Chlordiazepoxide 2 mg/kg
Clobazam 1.5 mg/kg
Clonazepam 0.6 mg/kg
Clorazepate dipotassium 1 mg/kg
Diazepam 0.7 mg/kg
Estazolam 0.2 mg/kg
Etizolam 0.1 mg/kg
Flunitrazepam 0.05 mg/kg
Flurazepam 2 mg/kg
Imepitoin 30 mg/kg
Ketazolam 2 mg/kg
Loprazolam 0.07 mg/kg
Lorazepam 0.2 mg/kg
Lormetazepam 0.07 mg/kg
Medazepam 1.5 mg/kg
Midazolam 0.4 mg/kg
Nitrazepam 0.4 mg/kg
Oxazepam 3.5 mg/kg
Prazepam 2 mg/kg
Temazepam 1.5 mg/kg
Triazolam 0.02 mg/kg

 

Flumazenil

Flumazenil should not be routinely used to treat benzodiazepine overdose due to the risk of precipitating seizures.

Flumazenil should only be used in cases of inadvertent medicinal overdose of benzodiazepines. It should never be used to manage patients with suspected or confirmed mixed overdose.

Do not use flumazenil where there is a risk of seizures, including when benzodiazepines have been used to treat status epilepticus.

If used to treat inadvertent medicinal overdose of benzodiazepines, flumazenil should only be used at the lowest dose required to reverse ventilatory impairment. Full reversal of CNS depression should not be targeted. 

Flumazenil has a much shorter duration of action (approximately 1-2 hours) than many benzodiazepines and so respiratory impairment may re-occur. Patients must be continuously monitored following flumazenil administration and kept under observation for at least 4 hours. 

If respiratory depression reoccurs after 3 or more bolus doses consider an IV infusion. 

 

Adult and children > 50 kg 

Flumazenil - initial doses: 

  • Initial bolus (administered over 15 seconds): 200 micrograms 
  • Then 100 micrograms every 1 minute if required to a maximum of 2 mg. 

Flumazenil - infusion:

  • Initial rate 100 micrograms / hour, adjusted to response (see below).
  • Dilute 5 mg flumazenil (50 mL of ampoules containing 100 micrograms/mL) in glucose 5% or sodium chloride 0.9% to a total volume of 500 mL (final concentration 10 micrograms/mL). 

 

Children and adults < 50 kg

Flumazenil - initial dose: 

  • 10 micrograms/kg (maximum 200 micrograms), administered over 15 seconds. 
  • Repeat every 1 minute if required to a maximum 40 micrograms/kg (2 mg)

Flumazenil - infusion

  • Initial rate 20 micrograms/kg/hour, adjusted to response (see below).
  • Dilute 2 mg flumazenil (20 mL of ampoules containing 100 micrograms/mL) in glucose 5% or sodium chloride 0.9% to a total volume of 200 mL (final concentration of 10 micrograms/mL).

 

Adjusting flumazenil infusion rate: 

If respiratory depression recurs, further IV boluses of flumazenil (adults: 100-200 micrograms; children: 1-2 micrograms/kg) should be given every 60 seconds until respiratory function is adequate. The infusion rate per hour can then be increased by 60% of the total bolus dose of flumazenil that was required.

If the flumazenil infusion dose/rate is changed, more frequent monitoring should recommence with observations every 15 minutes for the first hour and every 30 minutes thereafter.

For patients with stable respiratory function, continue the infusion at the same rate for at least 4 hours before titrating it down by 25% of the maximum infusion rate every hour until it is stopped. A flumazenil infusion should not generally be stopped at night (midnight to 0600) unless the patient is experiencing adverse effects because recurrence of acute toxicity may be more difficult to routinely detect overnight if the patient is sleeping.

Stop the infusion if the patient shows adverse effects (agitation, arrhythmias or convulsions) and consider the need for ventilation if airway/breathing problems recur. 

Last reviewed: 19/03/2026

Next review date: 19/03/2027