Diazepam

Diazepam31,33,34,40-42 has a time honoured place as a drug of first choice in premonitory or early stages of status epilepticus. Its pharmacology and clinical effects have been extensively studied in adults, children, and the newborn, and it has been shown to be highly effective in a wide range of status epilepticus types. Diazepam can be given by intravenous bolus injections or by the rectal route in the premonitory stage, and has a rapid onset of action. Sufficient cerebral levels are reached within one minute of a standard intravenous injection, and rectal administration produces peak levels at about 20 minutes. Diazepam has a redistribution half-life of approximately 20 minutes with a large volume of distribution of 1-2 L/kg, and an elimination half-life of 20-40 hours. The drug is thus rapidly redistributed, and has a relatively short duration of action after a single intravenous injection. After repeated dosing, as drug concentrations in the peripheral compartments increase, this redistribution does not occur. Thus repeated bolus injections produce higher peak levels which persist, carrying an attendant risk of sudden and unexpected CNS depression and cardiorespiratory collapse. Diazepam is metabolised by hepatic microsomal enzymes. Respiratory depression, hypotension, and sedation are the principal side effects. Sudden apnoea can occur, especially after repeated injections or if the injection is administered at too fast a rate.

Bolus intravenous doses of diazepam should be given in an undiluted form at a rate not exceeding 2-5 mg/min, using the Diazemuls formulation. Diazepam may be given rectally, either in its intravenous preparation infused from a syringe via a plastic catheter, or as the ready made, proprietary, rectal tube preparation Stesolid, which is a convenient and easy method. Diazepam suppositories should not be used, as absorption is too slow. The adult bolus intravenous or rectal dose in status epilepticus is 10-20 mg, and additional 10 mg doses can be given at 15 minute intervals, to a maximum of 40 mg. In children, the equivalent bolus dose is 0-2-0-3 mg/kg. A continuous infusion of benzodiazepine has also been used, but there is now little place for this mode of administration. The solution should be freshly prepared, and no drugs should be admixed. The usual intravenous formulation is as an emulsion (Diazemuls) in a 1 ml ampoule containing 5 mg/ml or as a solution in 2 ml ampoules containing 5 mg/ml. Stesolid is the usual rectal formulation - a 2 5 ml rectal tube containing 5 mg or 10 mg diazepam. The intravenous solution can also be instilled rectally.

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