PURPOSE: Midazolam is a rapidly acting benzodiazepine commonly used for conscious sedation during medical procedures, such as fiberoptic bronchoscopy. Midazolam is metabolized in the liver by cytochrome P4503A (CYP3A) enzymes. Recent guidelines suggest that midazolam should not be used concomitantly with Protease Inhibitors (PI) because PI's inhibit CYP3A enzymes, theoretically increasing sedation and the potential for serious adverse effects. The purpose of the present study is to investigate whether there is evidence of prolonged sedation and increased adverse effects among individuals taking PI's who receive intravenous midazolam during bronchoscopy.
METHODS: HIV-seropositive and seronegative subjects receiving midazolam for conscious sedation during bronchoscopy were included in this analysis. All subjects were stable outpatients undergoing bronchoalveolar lavage for a prospective research investigation. The time from the administration of midazolam to the re-attainment of baseline level of consciousness, and nadir values for pulse, respiratory rate, and blood pressure were analyzed. Values for HIV-seropositive subjects using PI's (HIV+/PI+) were compared to both HIV-seropositive subjects not using PI's (HIV+/PI-) and to HIV-seronegative subjects (HIV-).
RESULTS: 36 HIV-seronegative subjects and 23 HIV-seropositive subjects were included. Eleven of the HIV-seropositive subjects were on PI's while the other twelve were on no or other anti-retroviral therapy. Mean midazolam doses were not different between the three groups (p = 0.43): HIV+/PI+ = 4.1mg(±1.1); HIV+/PI- = 4.4mg(±1.0); HIV- = 4.7mg(±1.5). The time from the administration of midazolam to the re-attainment of baseline level of consciousness was not significantly different among the three groups (p = 0.19): HIV+/PI+ = 54.1 minutes(±45.0); HIV+/PI- = 44.7 minutes(±30.6) ; HIV- = 34.4 minutes(±28.2). Additionally, nadir values for respiratory rate, pulse and blood pressure were similar between the three groups. No serious adverse events occurred.
CONCLUSION: There is no evidence of prolonged sedation or increased adverse effects among HIV-seropositive individuals treated with PI's who receive intravenous midazolam during bronchoscopy.
CLINICAL IMPLICATIONS: Intravenous use of midazolam in patients on PI's is safe during bronchoscopy and these results should influence guidelines and bronchoscopic sedation policies.
DISCLOSURE: Carmen Rosario, None.