On the modeling of drug induced respiratory depression in the non-steady-state.
Annu Int Conf IEEE Eng Med Biol Soc
; 2008: 5564-8, 2008.
Article
in En
| MEDLINE
| ID: mdl-19163978
ABSTRACT
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associated with intravenous administration of a fast-onset, highly potent anesthetic mu agonist (including previously unpublished experimental data determined after administration of 1 mg alfentanil bolus).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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Therapy, Computer-Assisted
/
Carbon Dioxide
/
Alfentanil
/
Respiratory Mechanics
/
Models, Biological
Type of study:
Prognostic_studies
Limits:
Humans
/
Male
Language:
En
Journal:
Annu Int Conf IEEE Eng Med Biol Soc
Year:
2008
Document type:
Article
Affiliation country:
Switzerland