The effect of remifentanil on respiratory variability, evaluated with dynamic modeling

Mitsis, G. D., Governo, R. J. M., Rogers, R. and Pattinson, K. T. S. (2009) The effect of remifentanil on respiratory variability, evaluated with dynamic modeling. Journal of Applied Physiology, 106 (4). pp. 1038-1049. ISSN 8750-7587

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Abstract

Opioid drugs disrupt signaling in the brain stem respiratory network affecting respiratory rhythm. We evaluated the influence of a steady-state infusion of a model opioid, remifentanil, on respiratory variability during spontaneous respiration in a group of 11 healthy human volunteers. We used dynamic linear and nonlinear models to examine the effects of remifentanil on both directions of the ventilatory loop, i.e., on the influence of natural variations in end-tidal carbon dioxide (Pet(CO(2))) on ventilatory variability, which was assessed by tidal volume (Vt) and breath-to-breath ventilation (i.e., the ratio of tidal volume over total breath time Vt/Ttot), and vice versa. Breath-by-breath recordings of expired CO(2) and respiration were made during a target-controlled infusion of remifentanil for 15 min at estimated effect site (i.e., brain tissue) concentrations of 0, 0.7, 1.1, and 1.5 ng/ml, respectively. Remifentanil caused a profound increase in the duration of expiration. The obtained models revealed a decrease in the strength of the dynamic effect of Pet(CO(2)) variability on Vt (the "controller" part of the ventilatory loop) and a more pronounced increase in the effect of Vt variability on Pet(CO(2)) (the "plant" part of the loop). Nonlinear models explained these dynamic interrelationships better than linear models. Our approach allows detailed investigation of drug effects in the resting state at the systems level using noninvasive and minimally perturbing experimental protocols, which can closely represent real-life clinical situations.

Item Type: Article
Additional Information: IDS Number: 427AW
Keywords: CARBON-DIOXIDE; VENTILATORY VARIABILITY; BIOLOGICAL-SYSTEMS; BREATHING PATTERN; CHAOTIC DYNAMICS; HUMANS; DEPRESSION; SLEEP; PHARMACOKINETICS; PHARMACODYNAMICS
Schools and Departments: Brighton and Sussex Medical School > Clinical and Laboratory Investigation
Subjects: G Geography. Anthropology. Recreation > GV Recreation. Leisure > GV0557 Sports
Q Science > QP Physiology
R Medicine > RC Internal medicine
Depositing User: Tracey O'Gorman
Date Deposited: 24 Aug 2011 14:23
Last Modified: 17 Jun 2013 15:37
URI: http://sro.sussex.ac.uk/id/eprint/7154
Google Scholar:11 Citations
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