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

Koo BN, Shin S, Kim SY, Kang YR, Jeong KH, Han DW - Yonsei Med. J. (2015)

Bottom Line: 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).Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT

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 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).

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.

No MeSH data available.


Related in: MedlinePlus

Description of the raw data. Observer's Assessment of Alertness/Sedation score (A) and airway obstruction score (B) versus propofol effect-site concentration.
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Figure 1: Description of the raw data. Observer's Assessment of Alertness/Sedation score (A) and airway obstruction score (B) versus propofol effect-site concentration.

Mentions: Twenty-five patients who met the selection criteria were studied. Demographics of the enrolled patients are summarized in Table 2. Relations between propofol Ce and the observed sedation and airway obstruction scores are shown in Fig. 1. Increments in propofol Ce were associated with increased depth of sedation and airway obstruction (Fig. 1) and decreased values of BIS (Fig. 2). The sedation and airway obstruction effects were best described with a sigmoidal Emax model using propofol Ce. The estimated model parameters of the ultimately selected pharmacodynamic model and bootstrap estimates for each level of sedation and airway obstruction are summarized in Table 3. Based on our observations, all sedation- and airway obstruction-related parameters were estimated with adequate precision (relative standard error <50%) and were also reliable, as they were within the 95% confidence intervals of the bootstrap estimates. The predicted Ce50(m) values corresponding to sedation scores (m) ≥2, 3, 4, and 5 were 1.61, 1.78, 1.91, and 2.17 µg/mL, respectively. The predicted Ce50(m) values corresponding to airway-obstruction scores (m) ≥2, 3, and 4 were 1.53, 1.64, and 2.09 µg/mL, respectively. Significant correlations were found between AHI and Ce50(4) for airway obstruction with a negative slope (p<0.0001) and AHI and BMI with a positive slope (p<0.0001), as shown in Fig. 3. The pharmacodynamic model including AHI significantly improved the performance of the base model based on the likelihood ratio test, decreasing the minimum value of the objective function from 507.0 to 501.4 (p=0.018). Considering that AHI was the only factor that showed correlation with propofol Ce50(4) for airway obstruction, we included this as a covariate in our model (Table 3). Typical probability curves of population data for each sedation and airway-obstruction score are shown in Fig. 4. The effect of AHI on the probability of an airway obstruction score of 4, as evaluated by estimation, is presented in Fig. 5. Propofol Ce50(4) values in patients with AHI scores of 10, 40, and 70 were predicted to be 2.41, 2.05, and 1.81 µg/mL, respectively.


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

Koo BN, Shin S, Kim SY, Kang YR, Jeong KH, Han DW - Yonsei Med. J. (2015)

Description of the raw data. Observer's Assessment of Alertness/Sedation score (A) and airway obstruction score (B) versus propofol effect-site concentration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4541675&req=5

Figure 1: Description of the raw data. Observer's Assessment of Alertness/Sedation score (A) and airway obstruction score (B) versus propofol effect-site concentration.
Mentions: Twenty-five patients who met the selection criteria were studied. Demographics of the enrolled patients are summarized in Table 2. Relations between propofol Ce and the observed sedation and airway obstruction scores are shown in Fig. 1. Increments in propofol Ce were associated with increased depth of sedation and airway obstruction (Fig. 1) and decreased values of BIS (Fig. 2). The sedation and airway obstruction effects were best described with a sigmoidal Emax model using propofol Ce. The estimated model parameters of the ultimately selected pharmacodynamic model and bootstrap estimates for each level of sedation and airway obstruction are summarized in Table 3. Based on our observations, all sedation- and airway obstruction-related parameters were estimated with adequate precision (relative standard error <50%) and were also reliable, as they were within the 95% confidence intervals of the bootstrap estimates. The predicted Ce50(m) values corresponding to sedation scores (m) ≥2, 3, 4, and 5 were 1.61, 1.78, 1.91, and 2.17 µg/mL, respectively. The predicted Ce50(m) values corresponding to airway-obstruction scores (m) ≥2, 3, and 4 were 1.53, 1.64, and 2.09 µg/mL, respectively. Significant correlations were found between AHI and Ce50(4) for airway obstruction with a negative slope (p<0.0001) and AHI and BMI with a positive slope (p<0.0001), as shown in Fig. 3. The pharmacodynamic model including AHI significantly improved the performance of the base model based on the likelihood ratio test, decreasing the minimum value of the objective function from 507.0 to 501.4 (p=0.018). Considering that AHI was the only factor that showed correlation with propofol Ce50(4) for airway obstruction, we included this as a covariate in our model (Table 3). Typical probability curves of population data for each sedation and airway-obstruction score are shown in Fig. 4. The effect of AHI on the probability of an airway obstruction score of 4, as evaluated by estimation, is presented in Fig. 5. Propofol Ce50(4) values in patients with AHI scores of 10, 40, and 70 were predicted to be 2.41, 2.05, and 1.81 µg/mL, respectively.

Bottom Line: 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).Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.

ABSTRACT

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 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).

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.

No MeSH data available.


Related in: MedlinePlus