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Midazolam (Versed), diazepam (Valium), and lo-razepam (Ativan) are benzodiazepine derivatives that are useful in anesthesia. Midazolam is the most popular of these agents for the induction of anesthesia. Its pop-ularity is related to its aqueous solubility and to its short duration of action, which permits a prompt return of psychomotor competence. Unlike midazolam, lor-azepam and diazepam are not water soluble and must be formulated in propylene glycol; the latter is irritating to the vasculature on parenteral administration.
Benzodiazepines are useful as orally administered premedications. They are also used intravenously in doses that produce conscious sedation rather than hyp-nosis. Sedated patients tolerate unpleasant procedures (e.g., wound repair, bronchoscopy, angiography) while maintaining cardiorespiratory function and the ability to respond to tactile stimulation or verbal commands.
Midazolam has a shorter half-life (t1/2 = 1.3â€“2.2 hours) than either diazepam (t1/2 = 30 hours) or lor-azepam and is not converted in the liver to active metabolites, as is diazepam. Thus, use of midazolam re-sults in a more rapid return to psychomotor compe-tence. Doses may need to be lowered by at least 30% in older patients and in those premedicated with opioids or other sedative drugs.
The benzodiazepines, when given by slow IV infusion to induce anesthesia, have minimal influences on the car-diovascular and respiratory systems. Thus, they may be logical substitutes for barbiturates in poor-risk patients who cannot tolerate cardiovascular depression. In other respects, they appear pharmacologically similar to the barbiturates. IV administration causes unconsciousness without analgesia; skeletal muscle relaxation is inade-quate for intubation or short surgical procedures. Consequently, when these characteristics of anesthetic management are desired, benzodiazepines must be coadministered with appropriate analgesic drugs and neuromuscular blocking agents.
The popularity of the benzodiazepines as an anes-thetic supplement in cardiac surgery is related to their amnesic potential. They can ensure unawareness during the initial period, when the anesthetics are being diluted in the fluid of the bypass circuit. Lorazepam is often chosen for this purpose because it is longer acting and more potent than either midazolam or diazepam. Benzodiazepine administration may cause amnesia even when used in doses that do not produce uncon-sciousness. Antegrade amnesia may occur with the doses that are used to relieve preoperative anxiety.
Flumazenil (Romazicon) is a benzodiazepine antago-nist that specifically reverses the respiratory depression and hypnosis produced by the benzodiazepine receptor agonists. Its block of the amnesic effect of the agonists is less reliable. Flumazenil is particularly useful when an overdose of benzodiazepines has occurred. It is also em-ployed when a benzodiazepine has been used to pro-duce conscious sedation and rapid recovery of psy-chomotor competency is desirable. To avoid resedation, flumazenil may require administration by intravenous infusion.
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