Modelling of passive expiration in patients with adult respiratory distress syndrome.

The time-course of volume change during passive expiration preceded by an end-inspiratory hold was studied with a biexponential model in six adult respiratory distress syndrome (ARDS) patients. We measured the initial volumes and time constants of the fast (tau 1), and the slow (tau 2) compartments of expiration, as well as the static elastance of the respiratory system. The results were compared to those of 11 normal subjects. We observed that: 1) the biexponential model fitted closely the volume decay; 2) the fast compartment was responsible for 81 +/- 7% (ARDS) versus 84 +/- 10% (controls) of the total volume exhaled, with tau 1 = 0.35 +/- 0.11 s (ARDS) versus 0.50 +/- 0.22 s (controls); 3) the slow compartment contributed only 19 +/- 6% (ARDS) versus 16 +/- 7% (controls), with tau 2 = 4.67 +/- 2.38 s (ARDS) versus 3.27 +/- 1.54 s (controls); and 4) static elastance was higher in ARDS patients. The findings could be explained in terms of a four parameter viscoelastic model of the respiratory system.

A single-compartment model cannot describe passive expiration in intubated, paralysed humans.

The time-course of thoracic volume changes (respiratory inductive plethysmograph) during relaxed expiration was studied in 11 intubated, paralysed, mechanically ventilated subjects. The semilog volume-time curves show that expiration is governed by two apparently separate mechanisms: one causes emptying of most of the expired volume (approximately 80%) with a time constant of 0.50 +/- 0.22 s for a baseline tidal volume of 0.44 +/- 0.12 l (mean +/- SD) and 0.37 +/- 0.14 s when the tidal volume is reduced (VTP); the other contributes a relatively small amount to the expired volume over a significantly longer time, the time constant amounting to 3.27 +/- 1.54 s for baseline VT and 2.95 +/- 1.65 s for VTp. The first mechanism probably reflects the standard elastic and flow resistive properties of the respiratory system, while the second, slower compartment, is probably an expression of the viscoelastic properties of the pulmonary and chest wall tissues.

Pharmacokinetic interactions between theophylline and rioprostil.

The study is of double-blind crossover design. The effects of rioprostil, an analogue of prostaglandin E1, at a dose of 300 micrograms b.d., and placebo on the kinetic of slow-release theophylline are investigated. Eight healthy male volunteers participate in the study, each study period lasting for one week. During the first period, the doses of theophylline are altered in response to measured theophylline levels, 200 mg or 400 mg b.d. Regardless of placebo or rioprostil treatment, side effects appear before day 6 and are related specifically to theophylline administration. Blood samples are taken on days 4 and 5 to check steady-state plasma levels of theophylline and on days 6 and 7 to determine the main pharmacokinetic parameters. The same schedule is used for the second period of treatment. The achievement of steady-state concentration is verified. The mean pharmacokinetic parameters do not show a significant difference when slow-release theophylline is given alone or with rioprostil. These results are likely to be clinically relevant and, therefore, the theophylline dose should not be changed if rioprostil is prescribed at the same time as the theophylline.