Pharmacodynamic Estimate of Propofol-Induced Sedation and Airway Obstruction Effects in Obstructive Sleep Apnea-Hypopnea Syndrome

Purpose

Sedatives must be carefully titrated for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) as oversedation may lead to disastrous respiratory outcomes. This study aimed to investigate the relations between the effect-site concentration (Ce) of propofol and sedation and airway obstruction levels in patients with OSAHS.

Materials and Methods

In 25 patients with OSAHS, sedation was induced by 2% propofol using target-controlled infusion. Sedation and airway obstruction levels were assessed using the Observer''s Assessment of Alertness/Sedation Scale and a four-category scale, respectively. The relationships between propofol Ce and sedation and airway obstruction were evaluated using a sigmoid Emax model. Pharmacodynamic modeling incorporating covariates was performed using the Nonlinear Mixed Effects Modeling VII software.

Results

Increased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce_50(m) (Ce associated with 50% probability of an effect≥m) for sedation scores (m≥2, 3, 4, and 5) and airway-obstruction scores (m≥2, 3, and 4) were 1.61, 1.78, 1.91, and 2.17 µg/mL and 1.53, 1.64, and 2.09 µg/mL, respectively. Including the apnea-hypopnea index (AHI) as a covariate in the analysis of Ce₅₀₍₄₎ for airway obstruction significantly improved the performance of the basic model (p<0.05).

Conclusion

The probability of each sedation and airway obstruction score was properly described using a sigmoid Emax model with a narrow therapeutic range of propofol Ce in OSAHS patients. Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.