Solubility, distribution and transport of halothane in blood
Creators: name: Pang, Yew Choi
Publisher: name: University of British Columbia
Year: 2010

description: Halothane (1,1,1-trifluoro-2-bromo-2-chloroethane) is a commonly employed general anaesthetic. A direct injection gas-liquid chromatographic procedure was developed to quantitatively estimate the halothane concentration of blood and other aqueous fluids. This used a specially designed external injection port which obviated a preliminary separation of the anaesthetic from the aqueous phase. The method was extended to include quantitative estimation of methoxyflurane (1,l-dichloro-2,2-difluoroethyl-methylether), diethylether and ethanol over the approximate range 1-100 mg/100 ml. This analytical method was used to investigate the quantitative interaction of halothane with major human blood components and the distribution of halothane between cells and plasma. The results obtained with an equilibrium dialysis technique developed for this study showed that haemoglobin, albumin, red cell membranes and triglyceride-rich micelles (chylomicrons and VLDL), but not y-globulin, contribute significantly to the solubility, and thus the transport, of halothane in blood. A significant amount of halothane is also dissolved in the aqueous phase. The results suggest that halothane interacts with a finite number of surface sites on haemoglobin and albumin. When the aqueous phase was saturated with halothane, the average number of halothane molecules bound per haemoglobin and albumin molecule was approximately 5 and 20 respectively. In the case of triglyceride-rich micelles and red cell membranes, the halothane molecules appeared to be located within the hydrophobic core, since the amount of halothane solubilized by the micelles and membrane increased with increasing free halothane concentration without showing evidence of saturation of hydrophobic sites. The results obtained from the equilibrium dialysis studies were used to calculate the distribution of halothane between the cells and plasma. This distribution was also experimentally determined by analysis of the halothane concentration in the plasma after centrifugation of whole blood samples equilibrated with halothane. There was reasonable agreement between the results obtained by the two methods. The uptake and distribution of halothane in dog blood at different inspired levels of halothane was studied by analysing the concentration of halothane in whole blood and plasma of arterial and mixed venous blood at different times after the induction of anaesthesia. Generally, a steady state was reached approximately 2 hours after induction. The time required for the distribution of halothane between the plasma and cells appeared to be much shorter than the time required to attain the steady state. This suggested that the distribution of halothane between blood components calculated from the results of the equilibrium dialysis studies is applicable to blood in vivo during anaesthesia. The arterial blood halothane concentration calculated by combining the experimentally determined end-tidal halothane partial pressure and literature values for the blood gas partition coefficient are different from those determined experimentally. This suggested that halothane in the alveoli and halothane in the arterial blood were not in thermodynamic equilibrium, as commonly accepted.