The effect of anaesthesia and adrenergic therapy on the distribution and elimination of a crystalloid solution studied by volume kinetic analysis

Abstract: Intravenous fluid therapy is a mandatory treasure during anaesthesia and surgery. It is sometimes combined with adrenergic therapy to maintain haemodynamic stability. It is of great importance to know how the body handles the distribution of fluid in these circumstances in order to minimize the risk of fluid overload. The objective of this thesis was to examine intravenous fluid handling by studying changes in cardiovascular parameters and by using a volume kinetic method to analyze fluid volumes in the body. Methods: In Paper I we studied whether anaesthesia and surgery affect the sensitivity of the À-2 adrenergic receptor in vivo. 10 patients and 10 volunteers were given an intravenous infusion of epinephrine (50 Êg/kg/min). Both cardiovascular and biochemical changes were measured for which the ratios of the areas under the curve were calculated. In Paper II an animal model was used to evaluate how different adrenergic stimuli affect the distribution and elimination of crystalloid fluid bolus. The impact of three different drugs (dopamine 50 Êg/kg/min, isoprenaline 0.1 Êg/kg/min and phenylephrine 3 Êg/kg/min ) on the relationship between plasma dilution and haemodynamics was evaluated. The plasma dilution (an index of volume expansion) was studied using volume kinetic analysis. Paper III studied the initial effect of spinal and general anaesthesia on the distribution and elimination of crystalloid fluid loads. The volume kinetic model was fitted to data from a total of 20 patients who received 20 ml/kg BW of Ringer's acetate iv. The haemodynamic changes were also recorded. In Paper IV three different intravenous fluid regimens (a bolus of 5ml/kg BW of Ringer's acetate, 2 ml/kg BW of dextran I and a continuous infusion of Ringer's acetate 15 ml/kg BW over 40 min) were given during the induction of spinal anaesthesia to prevent arterial hypotension. A total of 75 patients were studied using haemodynamic measurements and volume kinetic analysis. The anaesthetic agent isoflurane has earlier been shown in air animal model to promote extravascular accumulation of crystalloid fluid and, in Paper V, thirty patients undergoing thyroid surgery were randomly anaesthetized with isoflurane or propofol (controls) respectively, to evaluate whether isoflurane also promotes extravascular accumulation in a human model given 25 ml/kg BW of Ringer Ls acetate. The volume kinetic model was again used to analyse the distribution and elimination of fluid. Results: The response to epinephrine (Paper I) measured as the AUC (area under the curve) of P-cAMP divided by the AUC for Pepinephrine, was more pronounced in the patient group than among the controls (p<0.02). This was reflected in greater hypokalaemic and hyperglycaemic responses (p<0.0004). All results indicate air increased adrenergic response during the first hour of abdominal surgery. All adrenergic drugs (Paper II) changed the baseline of the haemodynamic parameters. Alpha stimulus (phenylephrine) promoted renal excretion of fluid at the expense of fluid. distribution to the periphery (p<0.05 vs. controls) while beta stimulus (isoprenaline) had the opposite effect. Normal saline caused an increase in atrial, arterial pressures and in cardiac output. These increases showed a linear correlation with the plasma dilution, which was strong for both the phenylephrine and control groups. The volume kinetics in Paper III showed that the induction of anaesthesia resulted in similar changes in both groups. The elimination of fluid was significantly reduced (p<0.003) and the distribution of fluid from a central fluid space to a peripheral one was halved (p<0.01). Both types of anaesthesia decreased the mean arterial pressure significantly, and general anaesthesia to a higher degree than spinal anaesthesia (p<0.05). A computer simulation of the obtained kinetic data suggested that a small i.v. fluid load given immediately following the induction of spinal anaesthesia could be more effective in preventing hypotension and this was confirmed in 5 additional patients. In Paper IV there were no differences between the groups and the mean arterial pressure decreased by approximately 26%. The freight of the block was the only factor that correlated with the drop in blood pressure. Patient discomfort (nausea, swearing) was inure common in the dextran 1 and control groups. Volume kinetic analysis showed that the bolus regimens diluted plasma by 10% and, in the control group, by almost 20%. The dilution-time curve shows no apparent elimination during the bolus experiments, but the patients still had a diuresis. Fluid must therefore have been recruited front the periphery. Plasma dilution in Paper V increased to 30% during the infusion and then remained half as high throughout the experiment. Urinary excretion during the experiment amounted to only 11% of infused volume. The amount of water loss through extra vascular retention and evaporation was equal in both groups and amounted to 2.0-2.2 ml/min. Conclusion: Abdominal surgery under general anaesthesia for one hour does not cause desensitization of adrenergic receptors. Anaesthesia causes air accumulation of infused fluid in a central compartment by reducing the tendency for distribution to a peripheral compartment. Urinary excretion is markedly reduced. Both these facts contribute to a prolonged plasma dilution by crystalloid solutions. By adding an adrenergic drug, the distribution and elimination of such a fluid can be changed. Alpha stimuli cause a centralization of fluid. and promote diuresis, while beta stimuli have the opposite effect. lsoflurane does riot cause a greater extravascular accumulation of fluid. than propofol.