Pmsa predicted fluid responsiveness before a fluid bolus was infused during general anesthesia. Pmsa also indicated the fluid responsiveness prior to anesthesia induction and even how many fluid boluses would be needed until SV no longer increased by ≥ 10%. However, the overall discriminating capacity of Pmsa to predict fluid responsiveness was not impressive. The ROC curves yielded confidence intervals that were statistically significant but only with modest margins.
We used the fluid-induced responses in Pmsa to estimate how much the anesthesia-induced reduction in the vascular compliance increased the "unstressed" blood volume, which is the fraction of the intravascular volume that does not generate pressure . Fig. 4 shows that 1.2 L of blood would be needed to restore Pmsa to its pre-anesthesia level.
The research works by Arthur Guyton from the 1950s link circulatory volume with pressure and flow. The central concept is the mean circulatory filling pressure (Pmcf), which is the pressure that in develops in vascular system if the blood flow is quickly stopped. A closely related variable is the mean systemic filling pressure (Pms) which denotes the pressure when equilibrated throughout the systemic circulation . The Pms and Pmcf values are usually similar and are often used interchangeably.
The driving force for venous return (dVR) is the difference between Pms and the right atrial pressure, which is measured clinically as the CVP. Thus, a high CVP operates as a resistor to the venous return, which governs CO. The flow gradient is stronger if Pms is high, which is expressed by the parameter denoted Eh, because the resistance to flow by the CVP then becomes less important. One may say that Eh is a measure of how effectively a volume change increases the CO.
The likelihood of fluid responsiveness was higher when Pmsa was low. This is logical, as Pmsa reflects the "stressed" blood volume and the vascular compliance. The fluid-induced increases in Pmsa did not differ significantly between responders and non-responders, and this was also expected because the same fluid volume was given to all patients.
The dVR and Eh decreased by 30–40% after the induction of general anesthesia, which was reflected in a drop in stroke volume by 35%. By contrast, Pmsa only decreased by 25%, as shown in Fig. 4. This difference can be explained by the increase in CVP, which is mostly likely due to the positive-pressure that was initiated as soon as patients were anesthetized. This suggests that 2/3 of the reduction of the SV could be accounted for by an anesthesia-induced increase in the vascular compliance. The resistance to venous return (RVR) is not expected to change during hyper- or hypovolemia , and only small changes were found in the present study.
"Unstressed" blood volume
The "unstressed" blood volume is usually obtained from the intercept of the y-axis (volume) at zero pressure in a vascular compliance plot . Fig. 4 shows this type of plot, but it is based on only the changes within the narrow interval of the present measurements. Here, the horizontal shift between the baseline Pmsa and the compliance curve indicated the increase in the "unstressed" blood volume due to general anesthesia. This is the volume that the anesthetist aims to compensate using intravenous fluid.
The particularly pronounced blood volume response to the first bolus infusion is probably due to the capillary refill that always occurs in response to the decrease in arterial pressure accompanying anesthesia induction, even in the absence of intravenous fluid administration . Capillary refill is also the reason why the first post-induction Pmsa could not be used in Fig. 4, as the blood volume change was not zero and no matching hemoglobin value was available.
Overall, the bolus infusions expanded the blood volume by more than the infused amount. This is reasonable, as the colloid osmotic pressure of the fluid is 33% higher than normal blood plasma . However, the intravenous retention of the infused fluid, being higher for colloids than for crystalloids, is unlikely to matter much for the present calculations.
Crystalloid fluid might even offer an alternative way to estimate the anesthesia-induced increase of the "unstressed" volume. Kinetic analysis of hemodilution curves in women scheduled for abdominal hysterectomy showed that capillary leakage of fluid was arrested when 1.24 L (16.6 ml/kg) of Ringer´s had been infused, which is similar to the value found here . This finding suggests that a low Pmsa counteracts the capillary leakage of fluid when the blood volume is expanded by crystalloid fluid.
The central idea of Guyton´s hemodynamics is that CO is determined by the venous return, whereas the heart plays a permissive role . Despite critical views, this concept has received widespread attention among physiologists, anesthetists, and intensivists alike .
Basic studies have been performed in pigs, where Pms has been derived by ventilatory maneuvers [21, 22] and, recently, with extracorporeal membrane oxygenation .
Attempts to use Pms in the clinic have been made over the past decade. Three methods are used. One is to calculate Pms when VR is suppressed by stepwise deep inspirations. The second is to arrest the circulatory flow in one arm by inflating a blood pressure cuff and then to obtain Pms when the arterial and venous pressures have become equal. The third method is to calculate the Pms analog called Pmsa, which was the approach used in the present work.
Comparisons between these methods in cardiac surgery have shown, in one study, acceptable agreement between Pms values, but good agreement between changes in effective blood volume . Meijs et al. compared inspiratory holds with Pmsa in cardiac surgery and found the methods to be interchangeable .
Cecconi et al. measured Guyton´s hemodynamic parameters in 39 postoperative patients who received different vasoactive therapies and respiratory support . The Pmsa showed great variability and did not increase in response to a fluid bolus consisting of either crystalloid or colloid fluids.
A review by Cooke et al. supports our finding that Pmsa is lower in fluid responders than in non-responders . However, fluid challenges and passive leg raising increased Pmsa more in the responders, and by a greater incremental change than we found. These differences may be due the anesthetized state of our patients.
CO was measured by the arterial waveform pulse contour analysis implemented in the FloTrac/Vigileo system. This hemodynamic monitor can be used in conscious patients, but it is uncalibrated and may then have a higher coefficient of variation than is observed with calibrated monitors .
The data were collected in the clinical setting, and the occasionally high SV apparent at baseline may be due to preoperative stress.
The strengths of the study include the uniform anesthetization of the patients and their freedom from acute disease. All patients also received the same fluid treatment. Sampling was carefully timed by a single set of investigators. No adrenergic drugs were used, as they may affect vascular tone and Pmsa .
The original patient series included 25 additional patients who received volume loading with Ringer´s solution in addition to the 86 who received colloid. Those who received Ringer were not included, as 3 ml/kg of crystalloid could not adequately challenge fluid responsiveness . Only 20% of these patients showed fluid responsiveness during the first bolus infusion, which is 1/3 of the fraction of patients who received the colloid bolus.