Midazolam is a short-acting water-soluble benzodiazepine (at pH less than 4), a member of a new class of imidazobenzodiazepine derivatives. At physiological pH the drug becomes much more lipid soluble. Water solubility minimises pain on injection and venous thrombosis compared with diazepam administered in organic solvent. Midazolam is a hypnotic-sedative drug with anxiolytic and marked amnestic properties. To date it has been used mostly by the intravenous route, for sedation in dentistry and endoscopic procedures and as an adjunct to local anaesthetic techniques. It has proved less reliable than thiopentone, but preferable to diazepam, as an intravenous induction agent and is unlikely to replace the other well established drugs. However, due to the cardiorespiratory stability following its administration, midazolam is useful for anaesthetic induction in poor-risk, elderly and cardiac patients. The short elimination half-life (1.5-3.5h) and the absence of clinically important long acting metabolites make midazolam suitable for long term infusion as a sedative and amnestic for intensive care, but clinical trials have yet to be completed. Thus, a combination of properties make midazolam a useful addition to the benzodiazepine group.

Midazolam. A review of its pharmacological properties and therapeutic use

Ro 21-3981 is a newly synthesized water soluble benzodiazepine derivative. Its pharmacological properties are similar to diazepam. This investigation was designed to establish the effective induction dosage of Ro 21-3981 and to compare it with diazepam for induction of anaesthesia. The ED50 for Ro 21-3981 induction is 0.15 mg/kg and ED100 is 0.2 mg/kg. Ro 21-3981 is one and one-half times as potent as diazepam (0.3 rng/kg) and more rapid in action. There is significantly less pain on injection with Ro 21-3981 as compared to diazepam. Cardiovascular stability and apnoea were observed with both drugs. Ro 21-3981 is a promising anaesthetic induction drug that merits further human study.

https://link.springer.com/content/pdf/10.1007%2FBF03004881.pdf

Comparison of two benzodiazepines for anaesthesia induction: midazolam and diazepam.

Drug therapy. Benzodiazepines (first of two parts).

One hundred and eighty-five patients were allocated at random to receive pethidine with diazepam (in an emulsion), or pethidine with midazolam i.v. as sedation for upper gastrointestinal endpscopy. Sedation and conditions for examination were comparable and satisfactory in both groups. Midazolam produced more amnmia (P=

A randomized comparison of midazolam and diazepam for sedation in upper gastrointestinal endoscopy

Midazolam (Ro 21-3981), a new water-soluble benzodiazepine which can be used for the induction of anaesthesia, has two important advantages over diazepam: a short duration of action and absence of vascular irritation when administered i.v. (Conner, Katz and Pagano, 1978; Reves et al., 1979). The effects of the administration of midazolam i.v. on the central nervous and cardiovascular systems were determined in healthy volunteers and an assessment of the use of this drug as an induction agent for general anaesthesia was made.

W.H.K. Haslett

Papers

THE BENZODIAZEPINES: A review of their actions and uses relative to anaesthetic practice