As expected, sepsis patients had lower baseline albumin levels, presumably following increased vasopermeability, and MAP, but higher HR and cardiac filling than non-sepsis patients. The latter may have resulted from myocardial depression, characteristic for severe sepsis, as shown by lower GEF and down- and rightward displacement of preload-recruitable stroke work [
10]. Nevertheless, the haemodynamic response to fluid loading was similar to that in non-sepsis, in disagreement with the literature [
10]. The slope of preload-recruitable stroke work did not differ among fluid types, suggesting unaltered cardiac function during fluid loading, so that the differences between fluid types in cardiac output responses were primarily caused by differences in filling. However, a rise in LVSWI that, in contrast to cardiac filling and output, seemed somewhat greater in saline loading in sepsis than in non-sepsis patients can be explained in part by a greater effect on SVI. The greater cardiac filling and output with colloid than with saline loading maintained in sepsis argue against increased vasopermeability that may increase (rapid) equilibration of infused proteins and artificial colloids with the extravascular space and thereby limit intravascular retention of fluids, but such effect in more severely ill septic patients with higher permeability cannot be excluded [
1,
7,
8,
12]. Neither can we exclude slowly increased extravasation of colloids in sepsis, even though nearly complete equilibration between the intra- and extravascular space is expected within 90 min [
7]. The similar COP in sepsis and non-sepsis after colloid fluid loading agrees with the literature showing that colloid/albumin solutions are able to increase, at least transiently, low COP/albumin in critically ill patients with sepsis and shock [
6,
7,
12]. Our results may also help explain a potential survival benefit of albumin over saline resuscitation in sepsis [
3]. In animal experiments, authors [
13,
14] found that, even in sepsis and shock, colloids were effective, and even more so than crystalloids, in maintaining COP, cardiac filling and output. Otherwise, that colloids, per unit volume and time, are better able to recruit cardiac preload than are rapidly extravasating crystalloid solutions is in line with our previous study in cardiovascular surgery patients with less elevated permeability [
9,
19]. When using crystalloids, two to four times more fluid may be required to restore and maintain intravascular fluid volume compared with colloids, although true evidence is scarce [
1,
5‐
7,
9]. Our results agree with this idea, even in septic clinical hypovolaemia, since the difference in cardiac output increase multiplied by the difference in volume infused was three for colloids versus saline. The ratio in the SAFE study comparing albumin with saline resuscitation was 1:1.3 [
3], however. This can be explained by either insufficient need for fluid resuscitation, severely increased permeability, poor monitoring and guidance of therapy, or combinations thereof. The current data finally indicate that our clinical criteria were useful in selecting patients with, on average, a linear increase in cardiac output upon fluid loading in the steep part of the cardiac function curve.
The limitations of our study include the coincidental imbalance in haemoglobin and CVP between fluid types at baseline. The latter can be explained by a coincidental imbalance in PEEP and the effect of transmitted airway pressure on atmospheric-pressure-referenced CVP. We did not measure mixed venous SO
2, which may be lower than S
cvO
2. However, changes may be similar, so that the unchanged VO
2 is probably true. The increase in DO
2 did not differ among fluid types since higher cardiac output was offset by greater haemodilution after colloid than saline loading. The relatively high S
cvO
2 values and low lactate levels may otherwise imply adequate tissue oxygenation. Admittedly, the number of patients in this study was relatively small, but sufficient for analyses of fluid pathophysiology, the principal aim, rather than therapy, of our study. Finally, we cannot exclude that infusion of even more saline, for instance guided by GEDVI [
18], would have resulted in greater rises in preload-recruitable CI and LVSWI. By comparing (and pooling) different, roughly iso-oncotic colloid fluids, our study carries the advantage over others, in which only one or two colloid fluid types were studied [
3,
4,
6,
7,
12,
13,
18], of evaluating the contribution of COP independently of other fluid properties. Finally, most studies, unlike ours, did not separate effects in sepsis from those in non-sepsis [
2,
3,
6].
In conclusion, fluid loading with colloids results in a greater linear increase in cardiac filling, output and stroke work than does saline loading, in both septic and non-septic clinical hypovolaemia, in spite of myocardial depression and presumably increased vasopermeability potentially decreasing the effects of colloid fluid loading in the former.