Becoming Well-Versed with Benzos

Whether it’s the undifferentiated agitated patient getting violent with staff or the subdued but anxious shoulder dislocation, many of our patients will require some sedation in the Emergency Department.

For the 17-year-old football player with that shoulder that just won’t go back in or the 35-year-old with new onset atrial fibrillation that needs cardioversion, we have time to ask them about their history, allergies, and get a pre-procedural ECG (QT interval, anyone?). In these situations, we generally aren’t on as tight of a timeline which allows us to consider many different agents for sedation (most of which won’t be discussed in detail here).

But for that patient who is acutely psychotic or agitated and is a danger to themselves or to staff (think spitting on nurses, screaming at other patients, smacking their head against the wall, etc.) you need something that is fast-acting (with few contraindications), readily available in your Pyxis/Omnicell as well as on the formulary (R.I.P droperidol), and most importantly, available IM (sorry diazepam/Valium). For many emergency departments this has always been a “5 & 2,” which consists of 5 mg of haloperidol (Haldol) and 2 mg of lorazepam (Ativan) coupled in the same syringe and given intramuscularly.

Why do we give both of these medications at the same time and how quick is “quick?”

Classic teaching is that the benzodiazepine (lorazepam) is given in combination with the antipsychotic (haloperidol) in order to more quickly calm/sedate the patient while the antipsychotic starts to take effect. But, if we actually look at the pharmacology of these meds, lorazepam and haloperidol both (20-25 min) have relatively slow onsets of action when administered IM*. When a patient keeps 4 nurses and a physician occupied along with the security team, 20-25 minutes is very resource intensive and may not be best for the patient or the staff.

*although a few studies have shown that the onset is faster when administered in combination than for either alone.

So, do we have any medications we can give that will work faster and help us with this agitated patient?

In fact, we do! The fastest acting IM benzodiazepine is midazolam (Versed) with an onset of action between 5-15 minutes.

Knowing this information, why do we keep administering lorazepam?

One potential reason is that the duration of action of lorazepam is longer (~4 vs ~1 hour) which can often be desirable, but generally our need for sedation isn’t that long. We just to get the patient to a controlled environment and provide them with the antipsychotics (onset of action around 30 minutes) or the protective restraints needed to prevent them from hurting themselves and others.

And now, for some fun facts about benzodiazepines:

All benzos are metabolized in the liver, just by varying degrees of CYP interaction. Lorazepam is the benzo which utilizes the CYP system the least and has no active metabolites. This makes it an ideal medication for patients with a tendency toward the Devil’s nectar. However, lorazepam is notorious for its long time to peak effect, so if additional sedation is needed, patients can end up with total body stores of lorazepam that exceed optimal dosing (and can keep the patient sedated much longer than necessary and lead to potential respiratory compromise).

Below I have included a chart showing the timing for the IM/IV benzos. Keep in mind that diazepam will have active metabolites that actually extend the duration of effect beyond the illustration in this chart.

https://coreem.net/core/parenteral-benzodiazepines/

Only midazolam and lorazepam can safely be co-administered in a syringe with haloperidol. Diazepam is prepared in a propylene glycol and ethanol solution, which can precipitate if combined in syringe with other drugs. This is largely irrelevant, as diazepam should not be administered IM. Each of these medications will result in a sedated patient for <$5.

In my practice I have started using midazolam more and have found satisfactory results. I use a rough rule of 1.5-2 mg of midazolam for every 1 mg of lorazepam that I would have otherwise given. This also allows for reassessment of your patient in a few hours, instead of providing a 6 hour nap. Next time you have an agitated patient, give midazolam a try!