[Therapy of paradoxical reactions to midazolam in regional anesthesia]

Many patients fear being awake in the operating room, and the acceptance of regional anesthesia is often made dependent on the promise of adequate sedation. With the introduction of the short-acting benzodiazepine (bzdp) midazolam, it seemed possible to achieve induction and maintainance of sleep throughout an operative procedure. This substance may, however, occasionally result in a "paradoxical reaction" (PR) characterized by agitated excitement, mental confusion, and uncooperativeness. We have treated this condition successfully with physostigmine, as documented here in two case reports where a possible interaction between promethazine and midazolam may have been responsible for the PR. The symptoms resemble some of those seen in the central anticholinergic syndrome, as further implied by the therapeutic effect of physostigmine, but an etiological difference may exist. A direct anticholinergic effect of bzdp's is described only following excessive doses. An indirect effect may result from the impact on GABA-receptors, which have been identified as structurally related to the bzdp receptors. Physostigmine itself is not bound at the bzdp receptor, but has been shown to block the binding of bzdp's to their receptors and to reverse sedation from midazolam, perhaps through an indirect stimulatory effect. Previous case reports have indicated the effect of physostigmine in reversing PR following various bzdp's. Without treatment, a PR during regional anesthesia frequently makes general anesthesia necessary in order to immobilize the patient sufficiently to make surgery possible.(ABSTRACT TRUNCATED AT 250 WORDS)