As part of the Medication Monday and Antidote Series posts, we last talked about Narcan and its reversal effect on opiates, but what about a class of medications that is not only heavily abused in this county, but is often taken WITH opiates? In fact, it’s estimated that over 30% of overdoses that involve opiates also involve... that’s right, Benzodiazepines.
Benzodiazepines, or ‘Benzos’ are often prescribed for medical conditions such as anxiety, insomnia, seizure disorders, agitation, severe muscle spasms, alcohol withdrawal/DT prevention, and commonly in the hospital setting, sedation. Benzos are actually relatively safe and work by increasing the efficiency of the brain chemical, GABA, which in turn decreases the excitability of neurons. Valium, Versed, Xanax, Klonopin, and Librium are some of the most common benzos in this country.
Benzos are actually considered relatively safe, and even an overdose of benzos alone rarely results in death. Unfortunately, issues tend to arise when benzos are mixed with other CNS depressants such as sleep aids, alcohol, or opiates.
So, onto the purpose of this article! There is a reversal agent available, and it’s called Flumazenil (Romazicon). Flumazenil is a competitive benzo receptor antagonist, and when it was first released in the 1980s, it was touted as an antidote comparable to Narcan. Soon though, unlike Narcan its use became controversial due to its numerous contraindications.
Flumazenil should not be used on those who are on long-term benzos (it can cause instant withdrawl leading to seizure), those prone to seizures or on drugs that lower the seizure threshold, or in patients who are tachycardic or have a widened QRS. In fact, in most cases the risk of cardiac arrest or death outweighs the potential benefits of giving the reversal agent, and obtaining a maintained airway is far preferred as treatment.
Because of these risks, Flumazenil is not used as a diagnostic tool or as part of the ‘coma cocktail’ like Narcan can be. Classically, the ‘Coma Cocktail’ was made up of Thiamine 100mg IV, 1 amp D50W IV, Narcan 2mg IV and Flumazenil 0.2mg IV but has lost popularity as glucometers have become common with pre-hospital EMS crews and Flumazenil garners further criticism.
Flumazenil is also rarely used in the emergency setting, either pre-hospital or in the ER. It is most commonly used in controlled environments, such as PACU to reverse anesthesia if needed as the patient is likely still intubated and monitored.
There are however studies with promising results of low dose-slow infusions of Flumazenil in the treatment of both dependence and tolerance. Of course, with any controversial drug, debates of its role in overdose reversal and its risks are still ongoing.
Dosing for use in anesthesia reversal or overdose begins with 0.2mg (1ml) IV push over 15 seconds and can be increased by 0.2mg every minute until desired effect to a maximum dose of 1mg (10ml). Pediatric dosing is 0.01mg/kg up to 0.2mg, with a similar procedure as described above for repeat.
If the patient becomes resedated (the benzo is outlasting the antidote), doses can be repeated at 20-minute intervals PRN. During repeat dosing no more than 1mg (given as 0.2mg/min) should be pushed. Max is 3mg per hour.