Description of pulmonary propofol kinetics and of the influence of propofol on flow distribution with a recirculatory model

J.A. Kuipers, F. Boer, W. Olieman, A.G.L. Burm, J.G.Bovill. Department of Anaesthesiology, Leiden University Medical Center, Leiden,The Netherlands

Background

Propofol influences haemodynamics and possibly causes a re-distribution of blood flow. The principal site of propofol elimination is the liver and thus diversion of the flow from the liver could alter it’s hepatic elimination. Furthermore, the clearance of propofol from the plasma exceeds hepatic blood flow and the lung is thought to contribute to its elimination¹. Both flow re-distribution and pulmonary uptake or pulmonary elimination cannot be identified with a classical 3-compartmental model. In this study we examined the ability of a recirculatory model to identify propofol-induced flow re-distribution and pulmonary propofol behaviour in sheep.

Methods

Ten sheep, suspended in a hammock, with two semi-permanent catheters in the right internal jugular vein for propofol and indocyanine green (ICG) injection and one in the carotid artery for arterial sampling, received three injections of 25 mg ICG and one injection of 4 mg/kg propofol. The first injection of ICG was given to describe the baseline parameters of the circulation. The second ICG injection was given simultaneously with the propofol injection for measurement of the intravascular recirculatory parameters and to allow the identification of the lung compartment. A third ICG injection at different times after propofol injection was given to measure the influence of propofol on the intravascular parameters. The arterial concentration-time curves of ICG were analysed with a recirculatory model². The parameters of the model of the first and third ICG injection were compared with a paired t-test to identify propofol-induced flow re-distribution and differences in distribution volumes. The pulmonary uptake and elimination of propofol were analysed using the central part of the recirculatory model, which for propofol included a pulmonary compartment from which propofol could be eliminated (figure).

Results

Propofol caused a significant (-24%) decrease of the cardiac output (table; values are mean ± SD). In the recirculatory model for ICG this decrease was accompanied by a significant decrease of the flow to the fast compartment, maintenance of the flow to the slow compartment and an increase in elimination clearance of ICG. The distribution of the total blood volume (Vss) over the central and peripheral parts of the circulation was unaffected by propofol administration. For propofol a pulmonary tissue compartment of 0.47 ± 0.16 litres was found. A significant amount of the propofol was eliminated in the central part of the model which includes heart and lungs. During the first-pass 30% of the bolus dose of propofol was eliminated in the lungs.

Parameters	Baseline	t = 13-30 min
CO (l/min)	5.04 ± 0.76	3.85 ± 0.91^*
Clnd_f (l/min)	3.00 ± 1.07	1.39 ± 0.79^*
Clnd_s (l/min)	1.08 ± 0.69	1.47 ± 1.13
Clel (l/min)	0.79 ± 0.30	1.00 ± 0.29^*
Vss (l)	2.24 ± 0.25	2.03 ± 0.45
Vcentral (l)	0.67 ± 0.14	0.54 ± 0.10
Vnd_f (l)	0.90 ± 0.40	0.51 ± 0.41
Vnd_s (l)	0.67 ± 0.19	0.99 ± 0.52

^* Different from parameters at baseline, p<0.05 for paired t-test

Conclusions

The reduction in cardiac output by propofol resulted in a decreased flow to the fast ICG compartment, while the flow to the slow ICG compartment was maintained. It is assumed that the splanchnic circulation, draining to the liver, belongs to the slow non-distributive peripheral compartment. For propofol a large pulmonary tissue compartment and extrahepatic elimination was identified. Recirculatory modelling can be used to identify both drug-induced flow re-distribution and pulmonary uptake and elimination.

References

1. Br. J Anaesth 68: 183-186, 1992

2. JPET 278: 1050-1057, 1996 .