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

Purpose: To evaluate the effects of midazolam sedation followed by flumazenil antagonism on the work of nasal breathing in normal humans. Methods: We measured minute ventilation through the nasal route, respiratory frequency, nasal resistance (R-n) 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 R-n and the work of nasal breathing, nasal mask and oropharyngeal pressure was also measured. Results: Total resistive work spent on the upstream segment of the nasal route per minute (W-n) (J.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 (W-n/V-nE) (J.L-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 W-n/V-nE and changes in (R-n r = 0.852, P < 0.0001), whereas there was no correlation between changes in W-n and changes in (R-n = 0.159, P = 0.279). Conclusion: The work of breathing spent on the upstream segment of the nasal route increases during midazolam sedation and returns to baseline after flumazenil antagonism.