Management of Zolpidem Overdose
Zolpidem overdose is generally benign when taken alone and requires primarily supportive care with airway management, though co-ingestion with other CNS depressants significantly increases risk of respiratory compromise and ICU admission. 1, 2
Immediate Assessment and Stabilization
Clinical Presentation
- Isolated zolpidem overdose typically presents with somnolence to coma, with doses up to 600 mg (60 times therapeutic dose) causing only mild-to-moderate symptoms in most patients 2, 3
- Combined ingestions with alcohol, benzodiazepines, or other psychotropic medications can cause coma at doses as low as 100-150 mg and dramatically increase morbidity 4, 3
- Serious manifestations include impaired consciousness, cardiovascular compromise, respiratory depression, and pulmonary edema in severe cases 1, 5
- Rare cardiac complications such as atrial fibrillation may occur in patients with underlying cardiomyopathy 6
Initial Management Steps
- Monitor vital signs continuously: respiration, pulse, blood pressure, and oxygen saturation 1
- Secure airway and provide respiratory support as needed—this is the primary life-threatening concern 1
- Administer intravenous fluids as clinically indicated 1
- Perform gastric lavage when appropriate (if presentation is within 1-2 hours of ingestion) 1
Antidote Consideration: Flumazenil
Flumazenil is effective in reversing zolpidem-induced sedation but should be used selectively due to seizure risk. 1, 3
When to Use Flumazenil
- Flumazenil reduces zolpidem's sedative-hypnotic effects and can successfully reverse disturbances of consciousness in both mono- and combined intoxications 1, 3
- Dosing: 0.01-0.02 mg/kg IV (maximum 0.2 mg initially), repeat at 1-minute intervals to maximum cumulative dose of 0.05 mg/kg or 1 mg total 7
Critical Contraindications and Warnings
- Do NOT use flumazenil if tricyclic antidepressant co-ingestion is suspected—may precipitate seizures or arrhythmias 7
- Use extreme caution in patients with underlying seizure disorders or chronic benzodiazepine use—may precipitate withdrawal seizures 7, 1
- Flumazenil may contribute to neurological symptoms including convulsions 1
- Duration of flumazenil is shorter than zolpidem; observe continuously for at least 2 hours after last dose and be prepared for re-sedation 7
Disposition and Monitoring
Admission Criteria
- ICU admission is frequently required when zolpidem is co-ingested with over-the-counter medications (OR 3.33), other psychotropic drugs (OR 3.11), or alcohol (OR 2.12) 4
- In one series, 44% of ED patients required ICU admission, with only 17% discharged home 4
- Monitor for approximately 24 hours in combined intoxications, even if initial presentation appears mild 3
Expected Clinical Course
- Symptoms typically remit rapidly in 91% of isolated zolpidem overdoses 2
- Recovery is generally complete with supportive care alone 2, 3
Key Clinical Pitfalls to Avoid
- Do not assume benign course with co-ingestions: Even low zolpidem doses (100-150 mg) can cause coma when combined with other CNS depressants 3
- Do not withhold sedating drugs if excitation occurs following overdose—this paradoxical reaction requires careful management 1
- Do not rely on dialysis: Zolpidem is not dialyzable and hemodialysis is ineffective 1
- Always consider multiple drug ingestion and contact poison control for up-to-date management guidance 1
- Avoid co-prescribing opioids and zolpidem: This combination carries 3-10 fold increased mortality risk 7
Specific Monitoring Parameters
- Cardiovascular: Monitor for hypotension, arrhythmias (especially atrial fibrillation in patients with cardiomyopathy) 1, 6
- Respiratory: Watch for respiratory depression and pulmonary edema 1, 5
- Neurological: Assess level of consciousness, watch for seizures if flumazenil administered 1
- Duration: Symptoms in isolated overdose resolve quickly, but combined ingestions require extended observation 2, 3