Remimazolam

Last updated on 04 Sep 2025

Ah man, I just wish there was a version of midazolam that was shorter and cleaner, that I could use for sedation and maybe a bit of general anaesthesia now and again, that doesn't depend on organ function for breakdown and doesn't accumulate.

BOOM.

Wish granted.

Or is it?

Let's take a look.

What are the properties of the ideal sedation agent?

Speed

Rapid predictable onset
Easy titration to effect
Short, context-insensitive offset
Rapid recovery and discharge

Safety

Wide therapeutic window
Readily available reversal agent
Minimal respiratory depression
Minimal cardiovascular depression
Maintained airway reflexes
Hypoallergenic
Compatible with other medications

Pharmacokinetics

Organ-independent metabolism
Inactive metabolites with no accumulation

Effects

Anxiolysis
Anterograde amnesia
Comfort
Cooperative sedation
Analgesia

You can also add in things like 'cheap and easy to manufacture, stable in storage and transit at room temperature, doesn't degrade when exposed to light, compatible with normal plastic giving sets...' etc. etc.

Midazolam and propofol each hit a fair few of these targets, and remimazolam seeks to hit even more, providing the titratability and rapid offset of propofol, the amnesia and anxiolysis of midazolam, the organ independence of remifentanil and all with the safety of a reversal agent too.

CNS-7056

CNS 7056 (now known as remimazolam) hit the news in 2007 after it was found to act in a similar but shorter way than midazolam, with the added benefit of organ-independent metabolism.

It seems to:

Provide faster offset than midazolam and propofol
Give deeper sedation than midazolam
Have a less dose-dependent effect and less pain on injection than propofol
Cause much less apnoea than remifentanil

Note that it doesn't kick in any quicker than midazolam, it's just shorter in duration of action.

How it looks

As you can see from the image below, it's essentially midazolam with a backpack and a different pair of sunglasses on.

Ester group side chain
Chloride switched for bromide
No fluoride
Position change for a couple of nitrogens

It's a benzodiazepine

As a quick recap, benzodiazepines act on the GABAa receptor in the CNS, facilitating the opening of a chloride ion channel, leading to chloride influx, hyperpolarisation and therefore reduced neuronal activity.

Benzos have a dose-dependent effect, starting with anxiolysis, then moving through sedation to hypnosis with increasing doses, allowing them to be used as general anaesthetics at much higher doses.

The stats

Brand names

Byfavo - USA, Canada, Australia, South Korea
Anerem - Japan
Ruima - China
Aptimyda - Europe

Class and presentation

Ultra short acting Benzodiazepine
Esterified analogue of midazolam
Presented as a single use 20mg lyophilised powder
Reconstituted in 8.2 ml of normal saline to make 2.5 mg/ml solution with pH 2.9-3.9
Keeps for 48 hours in the fridge once reconstituted

Mechanism and dose

Positive allosteric modulator of GABAa receptor
Chloride influx and hyperpolarisation
Anxiolytic and sedative

Nothing new here.

Dose

5 mg IV over 1 minute for procedural sedation
2.5 mg every two minutes as needed to top up
0.2-0.4 mg/kg for general anaesthesia (off label)
Studies are ongoing for ICU sedation

I want to know its molecular formula

Of course you do

C21H19BrN4O2
Molecular weight 439.3, but the besylate is 597.5

So it's a carbohydrate with a sneaky bromine and a couple of nitrogens right?

Wrong - it's actually this

[4H-imidazol[1,2-a][1,4]benzodiazepine-4-propionic acid, 8-bromo-1-methyl-6-(2-pyridinyl)-(4S)-methyl ester, benzenesulphonate (1:1)]

So yeah, do with that what you will.

Administration

IV push
Incompatible with Ringer's lactate or acetated solutions

Distribution

Peak sedation 3.5 mins after IV bolus
91% protein bound
Volume of distribution 0.8 L/kg

Metabolism

Dose-independent hydrolysis by non-specific tissue esterases
To an inactive carboxylic acid
Organ-independent clearance

This means at all reasonable doses, you'll see consistent first order metabolism with no accumulation.

Elimination

Clearance 1.2 L/min
Half life of 7-8 minutes
Context sensitive half time of less than 10 minutes after 2 hour infusion

Reversal

Flumazenil 200 mcg - 500mcg will fully reverse within 2 minutes

Contraindications and warnings

Known allergy to benzodiazepines or dextran 20 (excipient)
Severe liver disease is a relative contraindication
Reduce dose in pregnancy by 30 - 50%

So is it any good?

It seems to be, the following results have been posited:

Faster recovery with less hypotension and similar success rates to propofol for colonoscopy
Faster procedure time and much faster recovery compared to midazolam for bronchoscopy
Similar sedation with much less haemodynamic compromise than propofol for cardioversion

💡

Its major advantage over propofol is that it can be reversed by flumazenil.

It's probably not useful as a single-shot anxiolytic premed, as it will likely wear off before the procedure has even started. However as a bolus for conscious sedation for a short procedure, where you don't want the cardiovascular instability of propofol or apnoea of strong opioids, it seems to be a great choice.

It may also be a good option for high risk (very obese) patients who are often denied sedation for risk of apnoea and loss of airway.

Here's how benzos work

Sedation top tips

Always have adequate monitoring and emergency airway equipment available
Have an answer to 'what is my plan if this patient goes deeper than anticipated?'
Use capnography to help guide your dosing, not saturations
When using anything more than minimal sedation, the sedationist should not also be doing the procedure
Start low and go slow - you can always give more
Sedation isn't analgesia, so consider short acting opioids or local anaesthetic for painful or stimulating procedures
BIS or processed EEG is not validated for benzodiazepine or ketamine sedation
If you're using ketamine, and the patient yawns, that's the time to decide whether you're waking up or giving more
No driving, machinery or legal decisions for at least 24 hours after sedation (the patient, not you)