On the modeling of drug induced respiratory depression in the non-steady-state

Caruso, Antonello L G; Bouillon, Thomas W; Schumacher, Peter M; Morari, Manfred (2008). On the modeling of drug induced respiratory depression in the non-steady-state. IEEE Engineering in Medicine and Biology Society conference proceedings, 2008, pp. 5564-5568. Piscataway, N.J.: IEEE Service Center 10.1109/IEMBS.2008.4650475

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The ability of anesthetic agents to provide adequate analgesia and sedation is limited by the ventilatory depression associated with overdosing in spontaneously breathing patients. Therefore, quantitation of drug induced ventilatory depression is a pharmacokinetic-pharmacodynamic problem relevant to the practice of anesthesia. Although several studies describe the effect of respiratory depressant drugs on isolated endpoints, an integrated description of drug induced respiratory depression with parameters identifiable from clinically available data is not available. This study proposes a physiological model of CO2 disposition, ventilatory regulation, and the effects of anesthetic agents on the control of breathing. The predictive performance of the model is evaluated through simulations aimed at reproducing experimental observations of drug induced hypercarbia and hypoventilation associated with intravenous administration of a fast-onset, highly potent anesthetic mu agonist (including previously unpublished experimental data determined after administration of 1 mg alfentanil bolus). The proposed model structure has substantial descriptive capability and can provide clinically relevant predictions of respiratory inhibition in the non-steady-state to enhance safety of drug delivery in the anesthetic practice.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy

UniBE Contributor:

Bouillon, Thomas Winfried and Schumacher, Peter






IEEE Service Center




Jeannie Wurz

Date Deposited:

04 Oct 2013 15:03

Last Modified:

23 Jan 2018 12:17

Publisher DOI:


PubMed ID:


Web of Science ID:



https://boris.unibe.ch/id/eprint/27292 (FactScience: 105919)

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