From the Guidelines
Diazepam overdose is a medical emergency that requires immediate attention, and treatment should prioritize supportive care over the administration of flumazenil due to its potential risks, as evidenced by recent guidelines 1. The effects of a diazepam overdose can be severe and life-threatening, particularly when combined with other central nervous system depressants like alcohol or opioids. Symptoms of overdose include extreme drowsiness, confusion, impaired coordination, slowed breathing, slurred speech, and potentially coma.
Treatment Approach
The treatment approach for diazepam overdose should focus on supportive care, including:
- Establishing an open airway and providing bag-mask ventilation, followed by endotracheal intubation when appropriate 1.
- Monitoring vital signs and providing respiratory support if needed.
- Administering activated charcoal if the overdose was recent.
- Considering the administration of naloxone if opioid overdose is suspected, given the presence of opioid-adulterated illicit drugs 1.
Use of Flumazenil
Flumazenil, a benzodiazepine antagonist, should be used cautiously due to its potential to precipitate seizures, dysrhythmias, and other adverse effects, especially in patients with benzodiazepine tolerance or co-ingestion of other substances 1. Its use is generally not recommended in patients with undifferentiated coma or unknown medical history, substance use history, and potential poison(s) involved 1. However, it may be considered in specific cases where the benefits outweigh the risks, such as in pediatric exploratory ingestions or iatrogenic overdoses during procedural sedation, and when high-risk conditions can be reliably excluded 1.
Prevention and Recovery
Prevention of diazepam overdose includes taking medication exactly as prescribed, keeping track of doses, and storing medications securely away from children and others. Recovery from overdose depends on the amount ingested, time elapsed before treatment, and whether other substances were involved. Given the potential severity of diazepam overdose and the risks associated with flumazenil administration, it is crucial to prioritize supportive care and cautious use of antidotes, as recommended by the most recent guidelines 1.
From the FDA Drug Label
OVERDOSAGE Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma The effects of an overdose of Diazepam include:
- Central nervous system depression ranging from drowsiness to coma
- Mild to moderate symptoms:
- Drowsiness
- Confusion
- Dysarthria
- Lethargy
- Hypnotic state
- Diminished reflexes
- Ataxia
- Hypotonia
- Rare paradoxical or disinhibitory reactions:
- Agitation
- Irritability
- Impulsivity
- Violent behavior
- Confusion
- Restlessness
- Excitement
- Talkativeness
- Severe overdosage: respiratory depression and coma 2
From the Research
Effects of Diazepam Overdose
- The effects of a diazepam overdose can be complex and result in a variety of physiological effects, including coma 3.
- High concentrations of diazepam and its metabolites can be present in the body after an overdose, but rapid clinical recovery is not attributable to rapid elimination of these compounds, but rather to adaptation or tolerance to their depressant effects 4.
- Serum diazepam concentrations in overdose cases have been correlated with clinical manifestations, and concentrations of total benzodiazepine have ranged from 1 to 22 microgram/ml 5.
- Patients who have ingested only diazepam are often awake or in grade 0 coma, even when drug concentrations are ten-fold greater than the accepted upper limit of the therapeutic range, and may not require hospitalization 5.
Treatment of Diazepam Overdose
- Treatment of diazepam overdose often involves supportive therapy only, and invasive procedures such as gastric lavage and whole-bowel irrigation are not appropriate for the majority of overdose situations 3.
- The use of oral activated charcoal may also be of limited value in treating diazepam overdose 3.
- Flumazenil, a specific benzodiazepine antagonist, can be used to attenuate or reverse the CNS-depressant effects of benzodiazepines, including diazepam, in cases of overdose 6.
- In severe cases of polypharmacy overdose, including diazepam, multimodality extracorporeal life support, such as percutaneous venoarterial extracorporeal membrane oxygenation (ECMO) and plasmapheresis, may be necessary 7.