The rational choice of a plasma substitute for states of hypovolaemia depends partly on its colloid osmotic pressure (COP). We have measured the COP of 108 samples of plasma substitute across selectively permeable membranes which retain molecules greater than 10,000 dalton (COP10) and 50,000 dalton (COP50) the ratio COP50/COP10 providing a potential index of diffusibility of the smaller molecules across capillary membranes. 6% Hespan solution showed a particularly favourable COP50/COP10 ratio at 0.58 indicating a potential for good retention in the circulation whilst 3.5% Haemaccel showed a COP50/COP10 ratio of 0.18 indicating a potential for marked transcapillary diffusion, especially in states of capillary leak. In patients with normal capillary permeability both Gelofusine and Dextran 110 are likely to show adequate retention in the circulation with a COP50/COP10 ratio of 0.37 and 0.39 respectively. These are comparable to the retention of 4.5% human albumin (0.36) but all of the plasma substitutes tested, with the exception of Haemaccel, provided a higher COP across both membranes than 4.5% human albumin solution. An in vivo comparison of these plasma substitutes is required to confirm the advantages of macromolecular colloids in states of capillary leak.
We have used a 2.2 MHz continuous-wave Doppler blood velocity meter (Bach-Simpson BVM 202) to measure ascending aortic blood velocity and acceleration, and have obtained from the velocity signal a noninvasive measure of stroke volume and cardiac output by combining the Doppler technique with M-mode echocardiography. In two separate studies we have systematically altered the loading conditions of the heart with lower body pressure; and the inotropic state of the heart with dobutamine (5 micrograms . kg-1 . min-1), and documented the changes in mean velocity (MV), maximum acceleration (MA), stroke volume (SV), cardiac output (CO) and left ventricular end-diastolic dimension (EDD) (M-mode echocardiography). Application of lower body pressure to subjects in a 30 degrees head-up tilt position caused a systematic increase in preload, as shown by a 9% increase in EDD, which raised SV by a maximum of 33% (p less than or equal to 0.001) and CO by 32% (p less than or equal to 0.01), thus showing a classical Starling response; whilst there was relatively little increase in MA. Conversely, infusion of dobutamine, an inotropic agent, caused a 29.2% increase in MA (p less than or equal to 0.01) with minimal increase in SV. Thus, the ability to measure ascending aortic blood velocity allows noninvasive monitoring of changes in both inotropic state and Starling function, with considerable ease and rapidity.
Plasma colloid osmotic pressure (COP) has been calculated from both serum albumin concentration and plasma total protein concentration. These values have been compared to those measured directly using a membrane-transducer oncometer in a group of normal subjects, in a group of critically-ill patients with a variety of primary diagnoses and in a group of hypovolaemic patients before and after plasma volume replacement with 6% hydroxyethyl starch solution. In the normal samples, COP calculated from albumin (COPalb) underestimated the measured COP (COPm) by mean of 2.0 mmHg (p less than 0.002), with correlation coefficient r = 0.39(n/s). Similarly, the COPalb underestimated COPm by a mean of 5.7 mmHg (p less than 0.001) in the critically ill patient group; r = 0.38 (p less than 0.02). Furthermore, in the patients receiving plasma volume replacement serum albumin concentration fell by 13.1% (p less than 0.001) whilst COPm increased by 11.5% (p less than 0.002). In the normal subjects COP calculated from total protein concentration (COPtp) underestimated the COPm by 1.5 mmHg (p less than 0.02) with r = 0.65 (p less than 0.01). Conversely, in the patient samples, mean COPtp overestimated COPm by 3.5 mmHg (p less than 0.001) with r = 0.73 (p less than 0.002). We conclude that COPalb is an inadequate estimate of COPm particularly in patients where its use may have important clinical consequences. COPtp provides a reasonable estimate of COPm in normal subjects but in patients samples, where albumin: globulin ratio is low COPtp overestimates substantially in many cases. We advocate the direct measurement of COP in critically-ill patients.
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