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Midazolam
Midazolam has the advantage over other benzodiazepines in that it is water soluble at a
suitable pH; at physiological pH it becomes highly lipophilic permitting rapid transfer across
the blood-brain barrier. This has resulted in the possibility of using midazolam by three other
routes: intranasal, buccal and intramuscular. Midazolam (10 mg in 2 ml) squirted around the
buccal mucosa is more effective than rectal diazepam (10 mg) in acute seizures in children,
and is easier to administer. By this route, the maximum concentration is reached by 30
minutes (although the pharmacodynamic response may be quicker), and the bioavailability is
75%. Intranasal midazolam has also been used successfully; a dose of 0.2 mg/kg intranasally
results in a maximum serum concentration in 12 minutes with a bioavailability of 55%.
Bioavailability after intramuscular injection is about 80100%, and peak levels are reached
after about 25 minutes although there is marked individual variation.

Midazolam has very short distribution and elimination half-lives. Its action is thus short-lived,
and there is a strong tendency to relapse following a single bolus injection. Its kinetic
characteristics and its smaller volume of distribution make it the benzodiazepine of choice
for use as an infusion, as it has less propensity to accumulate. In the intensive care setting,
midazolam can have a greater half-life and volume of distribution due to hepatic impairment.
Midazolam exhibits the same toxic effects as other benzodiazepines, including sedation,
hypotension, and cardiorespiratory depression. Respiratory arrest may occur occasionally,
even after intramuscular injection, so careful monitoring is imperative.

Midazolam is given in premonitory status epilepticus intramuscularly, rectally, buccally or
intranasally at a dose of 510 mg (in children 0.150.3 mg/kg), which can be repeated once
after 15 minutes or so. As an intravenous infusion on the intensive care unit, it should be
given as a loading dose of approximately 0.15 mg/kg followed by an infusion of 0.050.4
mg/kg/h. Midazolam is available in 5 ml ampoules containing 2 mg/ml or 2 ml ampoules
containing 5 mg/ml.

Lorazepam
Lorazepam has a lesser volume of distribution and is less lipid soluble than diazepam. Its
pharmacokinetic characteristics result in a slower onset of action, but a longer duration of
action. Lorazepam is indicated in the early stage of status epilepticus only, where its lack of
accumulation in lipid stores, strong cerebral binding, and long duration of action due to its
distribution half-life are very significant advantages over diazepam. The pharmacology and
clinical effects of lorazepam have been well characterised in adults, children, and the
newborn, and the drug has been the subject of large-scale clinical trials. Lorazepam is
remarkably effective in controlling seizures in the early stage of status epilepticus. Its main
disadvantage is the rapid development of tolerance. Initial injections of lorazepam are
effective for about 12 hours (longer than with diazepam), but repeated doses are much less
effective, and the drug has no place as long-term therapy. Lorazepam has sedative effects
shared by all the benzodiazepine drugs used in status epilepticus, but sudden hypotension or
respiratory collapse is less likely because of its relative lipid insolubility and the lack of
accumulation after single bolus injections.

Lorazepam is administered by intravenous bolus injection. As distribution is slow, the rate of
injection is not critical. In adults, a bolus dose of 0.07 mg/kg (to a maximum of 4 mg) is
given, and this can be repeated once after 20 minutes if no effect has been observed. In
children under ten years, bolus doses of 0.1 mg/kg are recommended. Long-term infusion of
lorazepam should not be used. It is usually available as a 1 ml ampoule containing 4 mg of
lorazepam.