Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil
Abstract Purpose Regulations have broadened to allow moderate sedation administration for gastrointestinal endoscopy by non-anesthesia personnel. The line between moderate and deep sedation is ambiguous. Deep sedation offers patient comfort as well as greater safety concerns. Unintended deep sedatio...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | BMC Pharmacology and Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40360-023-00642-5 |
| _version_ | 1797945771255922688 |
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| author | Jing-Yang Liou I-Ting Kuo Weng-Kuei Chang Chien-Kun Ting Mei-Yung Tsou |
| author_facet | Jing-Yang Liou I-Ting Kuo Weng-Kuei Chang Chien-Kun Ting Mei-Yung Tsou |
| author_sort | Jing-Yang Liou |
| collection | DOAJ |
| description | Abstract Purpose Regulations have broadened to allow moderate sedation administration for gastrointestinal endoscopy by non-anesthesia personnel. The line between moderate and deep sedation is ambiguous. Deep sedation offers patient comfort as well as greater safety concerns. Unintended deep sedation can occur if drug interactions are overlooked. We present a pharmacodynamic model for moderate sedation using midazolam, alfentanil and propofol. The model is suitable for training and devising rationales for appropriate dosing. Methods The study consists of two parts: modeling and validation. In modeling, patients scheduled for esophagogastroduodenoscopy (EGD) or colonoscopy sedation are enrolled. The modified observer’s assessment of alertness/sedation (MOAA/S) score < 4 is defined as loss of response to represent moderate sedation. Two patient groups receiving bronchoscopy or endoscopic retrograde cholangiopancreatography (ERCP) are used for validation. Model performance is assessed by receiver operating characteristic (ROC) curves and area under the curve (AUC). Simulations are performed to demonstrate how the model is used to rationally determine drug regimen for moderate sedation. Results Interaction between propofol and alfentanil is stronger than the other pairwise combinations. Additional synergy is observed with three drugs. ROC AUC is 0.83 for the modeling group, and 0.96 and 0.93 for ERCP and bronchoscopy groups respectively. Model simulation suggests that 1 mg midazolam, 250 µg alfentanil and propofol maximally benefits from drug interactions and suitable for moderate sedation. Conclusion We demonstrate the accurate prediction of a three-drug response surface model for moderate sedation and simulation suggests a rational dosing strategy for moderate sedation with midazolam, alfentanil and propofol. |
| first_indexed | 2024-04-10T21:00:24Z |
| format | Article |
| id | doaj.art-d2cf2edc31914a5ebbeac76cdaf4c277 |
| institution | Directory Open Access Journal |
| issn | 2050-6511 |
| language | English |
| last_indexed | 2024-04-10T21:00:24Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pharmacology and Toxicology |
| spelling | doaj.art-d2cf2edc31914a5ebbeac76cdaf4c2772023-01-22T12:24:55ZengBMCBMC Pharmacology and Toxicology2050-65112023-01-0124111010.1186/s40360-023-00642-5Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanilJing-Yang Liou0I-Ting Kuo1Weng-Kuei Chang2Chien-Kun Ting3Mei-Yung Tsou4Department of Anesthesia, Taipei Veterans General HospitalDepartment of Anesthesia, Taipei Veterans General HospitalDepartment of Anesthesia, Taipei Veterans General HospitalDepartment of Anesthesia, Taipei Veterans General HospitalDepartment of Anesthesia, Taipei Veterans General HospitalAbstract Purpose Regulations have broadened to allow moderate sedation administration for gastrointestinal endoscopy by non-anesthesia personnel. The line between moderate and deep sedation is ambiguous. Deep sedation offers patient comfort as well as greater safety concerns. Unintended deep sedation can occur if drug interactions are overlooked. We present a pharmacodynamic model for moderate sedation using midazolam, alfentanil and propofol. The model is suitable for training and devising rationales for appropriate dosing. Methods The study consists of two parts: modeling and validation. In modeling, patients scheduled for esophagogastroduodenoscopy (EGD) or colonoscopy sedation are enrolled. The modified observer’s assessment of alertness/sedation (MOAA/S) score < 4 is defined as loss of response to represent moderate sedation. Two patient groups receiving bronchoscopy or endoscopic retrograde cholangiopancreatography (ERCP) are used for validation. Model performance is assessed by receiver operating characteristic (ROC) curves and area under the curve (AUC). Simulations are performed to demonstrate how the model is used to rationally determine drug regimen for moderate sedation. Results Interaction between propofol and alfentanil is stronger than the other pairwise combinations. Additional synergy is observed with three drugs. ROC AUC is 0.83 for the modeling group, and 0.96 and 0.93 for ERCP and bronchoscopy groups respectively. Model simulation suggests that 1 mg midazolam, 250 µg alfentanil and propofol maximally benefits from drug interactions and suitable for moderate sedation. Conclusion We demonstrate the accurate prediction of a three-drug response surface model for moderate sedation and simulation suggests a rational dosing strategy for moderate sedation with midazolam, alfentanil and propofol.https://doi.org/10.1186/s40360-023-00642-5EndoscopyModerate sedationPharmacodynamicsComputer Simulation |
| spellingShingle | Jing-Yang Liou I-Ting Kuo Weng-Kuei Chang Chien-Kun Ting Mei-Yung Tsou Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil BMC Pharmacology and Toxicology Endoscopy Moderate sedation Pharmacodynamics Computer Simulation |
| title | Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil |
| title_full | Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil |
| title_fullStr | Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil |
| title_full_unstemmed | Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil |
| title_short | Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil |
| title_sort | pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam propofol and alfentanil |
| topic | Endoscopy Moderate sedation Pharmacodynamics Computer Simulation |
| url | https://doi.org/10.1186/s40360-023-00642-5 |
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