Clinical pharmacology of lorazepam

As a preanesthetic medication, lorazepam is available for oral, intravenous, or intramuscular administration. A parenteral dose of 0.04 to 0.06 mg per kg has been shown to be most effective as a preanesthetic medication in terms of antianxiety and antirecall effect (Table 1). Lorazepam has as its predominant advantage over other benzodiazepines the ability to produce anterograde amnesia reliably and for a relatively long duration. From an anesthesia standpoint, the drug finds its major usage as a premedicant or adjuvant (administered in the peri-induction period) to minimize the possibility of recall of unpleasant events during anesthesia and surgery. This is especially germane in patients who are unable to tolerate a sufficient depth of anesthesia to provide this amnesic effect on the basis of anesthetic agent alone. Quite often these patients are critically ill, and from a physiologic standpoint, their cardiovascular systems are unable to tolerate or adapt to moderate to deep anesthetic concentrations of the inhalation anesthetic agents. Even though the metabolic products of lorazepam are not active, the duration of action of this drug dictates that it not be used in the outpatient setting. Indeed, the drug probably should not be used in patients whose expected hospital stay is less than 72 hours. It appears that thrombosis or phlebitis after intravenous injection of lorazepam is less than with diazepam, especially if the drug is injected in small hand or arm veins. Most side effects of lorazepam are associated with central nervous system depression, are dose-related, and fairly predictable. Adverse central nervous system effects may be reversed by administration of physostigmine, but it is worthwhile to note that the duration of action of physostigmine, and repeated administration of physostigmine may be necessary. Lorazepam appears to be acceptable to both physicians and patients. There do not appear to be any obvious adverse interactions between lorazepam and other medications commonly used in anesthesia practice. Nevertheless, it appears that the major value of lorazepam to the anesthesiologist's armamentarium is its ability to prevent recall in appropriate situations.