Drug-induced respiratory depression: an integrated model of drug effects on the hypercapnic and hypoxic drive

Caruso, Antonello L G; Bouillon, Thomas W; Schumacher, Peter M; Luginbuhl, Martin; Morari, Manfred (2007). Drug-induced respiratory depression: an integrated model of drug effects on the hypercapnic and hypoxic drive. Clinical lymphoma & myeloma, 2007, pp. 4259-4263. Dallas, Tex.: Cancer Information Group 10.1109/IEMBS.2007.4353277

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Drug-induced respiratory depression is a common side effect of the agents used in anesthesia practice to provide analgesia and sedation. Depression of the ventilatory drive in the spontaneously breathing patient can lead to severe cardiorespiratory events and it is considered a primary cause of morbidity. Reliable predictions of respiratory inhibition in the clinical setting would therefore provide a valuable means to improve the safety of drug delivery. Although multiple studies investigated the regulation of breathing in man both in the presence and absence of ventilatory depressant drugs, a unified description of respiratory pharmacodynamics is not available. This study proposes a mathematical model of human metabolism and cardiorespiratory regulation integrating several isolated physiological and pharmacological aspects of acute drug-induced ventilatory depression into a single theoretical framework. The description of respiratory regulation has a parsimonious yet comprehensive structure with substantial predictive capability. Simulations relative to the synergistic interaction of the hypercarbic and hypoxic respiratory drive and the global effect of drugs on the control of breathing are in good agreement with published experimental data. Besides providing clinically relevant predictions of respiratory depression, the model can also serve as a test bed to investigate issues of drug tolerability and dose finding/control under non-steady-state conditions.

Item Type:	Journal Article (Original Article)
Division/Institute:	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, Schumacher, Peter
ISSN:	1557-9190
ISBN:	18002943
Publisher:	Cancer Information Group
Language:	English
Submitter:	Jeannie Wurz
Date Deposited:	04 Oct 2013 14:57
Last Modified:	05 Dec 2022 14:17
Publisher DOI:	10.1109/IEMBS.2007.4353277
PubMed ID:	18002943
Web of Science ID:	000253467003119
URI:	https://boris.unibe.ch/id/eprint/24568 (FactScience: 51543)