Use of Dynamic Negative Airway Pressure (DNAP) to Assess Sedative-induced Upper Airway Obstruction

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Abstract
Background: Traditional methods of assessing ventilatory effects of sedative agents do not measure their propensity to cause upper airway obstruction (UAO). The primary objective of this study was to develop a method, using dynamic negative airway pressure (DNAP), for replicating UAO during deep sedation. Methods: A state of deep sedation (defined as an Observer Assessment of Alertness and Sedation score of 3 and a bispectral index < 80) was attained in 10 healthy volunteers, aged 19-41, using midazolam. Volunteers breathed through a chamber connected to a regulated source of negative pressure that was gradually adjusted downward to produce UAO based on maximal inspiratory flow. The study consisted of three phases: A control phase while awake, a study phase during midazolam deep sedation, and a recovery phase after flumazenil administration. Results: During the control phase no subject demonstrated airway obstruction at negative pressures to -30-cm H2O. All subjects exhibited complete UAO during DNAP episodes while sedated. Negative pressures required to cause complete UAO (Pcrit) ranged from -2 to -14 cm H2O. After administration of flumazenil, all subjects attained full consciousness within 5 min and did not demonstrate UAO at negative pressures to -30-cm H2O. Conclusions: Dynamic Negative Airway Pressure is a useful method for provoking midazolam-induced UAO, and may potentially be used to compare the potential for different sedatives and patient factors to cause UAO. Flumazenil was completely effective in reversing the potential for midazolam to cause UAO.