Flumazenil abolishes midazolam-induced increase in the work of nasal breathing

To evaluate the effects of midazolam sedation followed by flumazenil antagonism on the work of nasal breathing in normal humans.

We measured minute ventilation through the nasal route, respiratory frequency, nasal resistance (Rn) and the work of nasal breathing under three conditions: awake, during midazolam sedation, and after flumazenil antagonism in eight healthy human subjects. A custom-made, partitioned face mask enabled nasal and oral airflow to be measured separately. To calculate Rn and the work of nasal breathing, nasal mask and oropharyngeal pressure was also measured.

Total resistive work spent on the upstream segment of the nasal route per minute (Wn) (J x min(-1)) was greater during midazolam sedation (3.6 +/- 2.9) than while awake (1.6 +/- 0.9) and after flumazenil antagonism (1.7 +/- 0.6), respectively (mean +/- SD) (P < 0.05). Total resistive work spent on the upstream segment of nasal breathing (WnNnE) (JxL(-1)) increased from 0.31 +/- 0.14 to 0.75 +/- 0.61 after midazolam administration (P < 0.05) and decreased to 0.31 +/- 0.10 after flumazenil. Following midazolam administration, a strong correlation was observed between changes in WnNnE and changes in Rn r = 0.852, P < 0.0001), whereas there was no correlation between changes in Wn and changes in Rn r = 0.159, P = 0.279).

The work of breathing spent on the upstream segment of the nasal route increases during midazolam sedation and returns to baseline after flumazenil antagonism.