The Effect of Gender on Compensatory Neuromuscular Response to Upper Airway Obstruction in Normal Subjects Under Midazolam General Anesthesia

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Abstract
Upper airway patency may be compromised during sleep and anesthesia by either anatomical alterations (mechanical properties) or disturbances in the neural control (compensatory neuromuscular responses). The pathophysiology of upper airway obstruction during anesthesia may differ between men and women. Recently, we reported that the upper airway mechanical properties were comparable with those found during natural nonrapid eye movement sleep, as evaluated by measurements of passive critical closing pressure (PCRIT) and upstream resistance (RUS) during midazolam sedation. In this study, we compared the effects of gender on compensatory neuromuscular responses to upper airway obstruction during midazolam general anesthesia. Thirty-two subjects (14 men and 18 women) were studied. We constructed pressure-flow relationships to evaluate PCRIT and RUS during midazolam anesthesia. The midazolam anesthesia was induced with an initial dose of midazolam (0.07–0.08 mg/kg bolus) and maintained by midazolam infusion (0.3–0.4 μg · kg−1 · min−1), and the level of anesthesia was assessed by Ramsay score (Level 5) and Observer’s Assessment of Alertness/Sedation score (Level 2). Polysomnographic and hemodynamic variables were monitored while nasal pressure (via mask), inspiratory air flow (via pneumotachograph), and genioglossal electromyograph (EMGGG) were recorded. PCRIT was obtained in both the passive condition, under conditions of decreased EMGGG (passive PCRIT), and in an active condition, whereas EMGGG was increased (active PCRIT). The difference between the active PCRIT and passive PCRIT (ΔPCRITP − A) was calculated in each subject to determine the compensatory neuromuscular response. The difference between the active PCRIT and passive PCRIT (ΔPCRITA − P) was significantly greater in women than in men (4.6 ± 2.8 cm H2O and 2.2 ± 1.7 cm H2O, respectively; P < 0.01), suggesting greater compensatory neuromuscular response to upper airway obstruction independent of arousal. We demonstrate that the arousal-independent compensatory neuromuscular responses to upper airway obstruction during midazolam anesthesia were partially maintained in women, and that gender may be a major determinant of the strength of compensatory responses during anesthesia.