23. BENZODIAZEPINES

Benzodiazepines include diazepam, midazolam, nitrazepam, clonazepam and lorazepam. Their actions include sedation, amnesia, reduced anxiety and an anticonvulsant action. They are not analgesics and must not be given to quieten a patient postoperatively who is in pain. They must also be used with great care for patients who are agitated after surgery. The anaesthetist must exclude other causes of agitation, especially hypoxia. Benzodiazepines will cause dose-dependent respiratory depression. They will reduce both the tidal volume and respiratory rate. Benzodiazepines are very rarely required postoperatively unless they are used to treat convulsions.

Diazepam

Diazepam is insoluble in water. When dissolved in ethylene glycol it causes pain on intravenous injection and thombophlebitis. This is not a problem with the emulsion of diazepam in soya bean oil. Diazepam has been used for sedation, as an anticonvulsant and for premedication. It is rapidly absorbed orally with peak concentrations in adults within 1 hour (premedication 0.1 to 0.2 mg/kg). Intramuscular injection is very painful and absorption may be unpredictable so it should be avoided. The anticonvulsant dose of diazepam is 0.25 mg/kg intravenously.

Midazolam

Midazolam is a water-soluble benzodiazepine. Compared to diazepam, it is two to thee times as potent. Midazolam is rapidly absorbed from the gastrointestinal tract but about 50% undergoes liver metabolism before entering the circulation (first pass effect). Midazolam is a very good drug for premedication in children. It may be given orally 30 minutes before surgery (0.5 mg/kg up to 10 mg), mixed with apple juice or any clear fluid. Midazolam can be given intranasally (0.3 mg/kg) or intra-muscularly (0.1 mg/kg). Doses of 1 to 2 mg (up to 0.1 mg/kg) are used for sedation in adults. Compared to diazepam, midazolam produces a more rapid onset with greater amnesia and less postoperative sedation.

Flumazenil

Flumazenil is a benzodiazepine antagonist. It will reverse the sedation and respiratory depression however it has a short duration (1 to 2 hours) of action and a patient may need repeated doses (0.2 mg intravenously repeated slowly up to 1 to 2 mg) if re-sedation occurs.