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

Abstract

PurposeSedatives 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 MethodsIn 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.ResultsIncreased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce50(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).ConclusionThe 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.

A Debate on Surgical and Nonsurgical Approaches for Obstructive Sleep Apnea: A Comprehensive Review

“…Patients with OSA should be examined for possible anatomic abnormalities of the upper airway, which may complicate laryngoscopy and/or intubation. Careful preoxygenation is needed and opioids should be used sparingly, while isoflurane should be avoided and muscle relaxants should be calculated for an ideal body wight [ 25 ]. Some studies have advanced the idea that in order to avoid limitation of the functional residual capacity of the lungs (FRC) by an elevated diaphragm, obese patients should be extubated in sitting or lateral positions; however, in selected cases, prolonged intubation or ventilation is recommended.…”

A Simulation Study of Propofol Effect-Site Concentration for Appropriate Sedation in Pediatric Patients Undergoing Brain MRI: Pharmacodynamic Analysis

“… 17 18 However, its narrow therapeutic window and the vulnerability of patients to its sedative effects might quickly lead to unintended deep anesthesia with loss of protective reflexes upon even small increases in dosage. 19 20 An appropriate low dosage of propofol that ensures an adequate depth of sleep for the successful completion MRI would probably help minimize these adverse events. When the Ce of propofol for appropriate sedation is unknown, there is no alternative for the dosing strategy, other than depending entirely on the experience of the clinician.…”