Blood volume in patients likely to be preload responsive: a post hoc analysis of a randomized controlled trial.

BACKGROUND: Preload responsive postoperative patients with signs of inadequate organ perfusion are commonly assumed to be hypovolemic and therefore treated with fluids to increase preload. However, preload is influenced not only by blood volume, but also by venous vascular tone and the contribution of these factors to preload responsiveness in this setting is unknown. Based on this, the objective of this study was to investigate blood volume status in preload-responsive postoperative patients. METHODS: Data from a clinical trial including postoperative patients after major abdominal surgery were analyzed. Patients with signs of inadequate organ perfusion and with data from a passive leg raising test (PLR) were included. An increase in pulse pressure by ≥ 9% was used to identify patients likely to be preload responsive. Blood volume was calculated from plasma volume measured using radiolabelled albumin and hematocrit. Patients with a blood volume of at least 10% above or below estimated normal volume were considered hyper- and hypovolemic, respectively. RESULTS: A total of 63 patients were included in the study. Median (IQR) blood volume in the total was 57 (50-65) ml/kg, and change in pulse pressure after PLR was 14 (7-24)%. A total of 43 patients were preload responsive. Of these patients, 44% were hypovolemic, 28% euvolemic and 28% hypervolemic. CONCLUSIONS: A large fraction of postoperative patients with signs of hypoperfusion that are likely to be preload responsive, are hypervolemic. In these patients, treatments other than fluid administration may be a more rational approach to increase cardiac output. Trial registration EudraCT 2013-004446-42.

Albumin infusion rate and plasma volume expansion: a randomized clinical trial in postoperative patients after major surgery.

BACKGROUND: Optimal infusion rate of colloids in patients with suspected hypovolemia is unknown, and the primary objective of the present study was to test if plasma volume expansion by 5% albumin is greater if fluid is administered slowly rather than rapidly. METHODS: Patients with signs of hypoperfusion after major abdominal surgery were randomized to intravenous infusion of 5% albumin at a dose of 10 ml/kg (ideal body weight) either rapidly (30 min) or slowly (180 min). Plasma volume was measured using radiolabeled albumin at baseline, at 30 min, and at 180 min after the start of infusion. Primary outcome was change in plasma volume from the start of infusion to 180 min after the start of infusion. Secondary outcomes included the change in the area under the plasma volume curve and transcapillary escape rate (TER) for albumin from 180 to 240 min after the start of albumin infusion. RESULTS: A total of 33 and 31 patients were included in the analysis in the slow and rapid groups, respectively. The change in plasma volume from the start of infusion to 180 min did not differ between the slow and rapid infusion groups (7.4 ± 2.6 vs. 6.5 ± 4.1 ml/kg; absolute difference, 0.9 ml/kg [95%CI, - 0.8 to 2.6], P = 0.301). Change in the area under the plasma volume curve was smaller in the slow than in the rapid infusion group and was 866 ± 341 and 1226 ± 419 min ml/kg, respectively, P < 0.001. TER for albumin did not differ and was 5.3 ± 3.1%/h and 5.4 ± 3%/h in the slow and in the rapid infusion groups, respectively, P = 0.931. CONCLUSIONS: This study does not support our hypothesis that a slow infusion of colloid results in a greater plasma volume expansion than a rapid infusion. Instead, our result of a smaller change in the area under the plasma volume curve indicates that a slow infusion results in a less efficient plasma volume expansion, but further studies are required to confirm this finding. A rapid infusion has no effect on vascular leak as measured after completion of the infusion. TRIAL REGISTRATION: EudraCT2013-004446-42 registered December 23, 2014.

Effect of ringers acetate in different doses on plasma volume in rat models of hypovolemia.

BACKGROUND: Even though crystalloids are the first choice for fluid resuscitation in hemodynamically unstable patients, their potency as plasma volume expanders in hypovolemia of different etiologies is largely unknown. The objective of the study was to investigate dose-response curves of a crystalloid in hypovolemia induced by either sepsis or hemorrhagic shock. RESULTS: Rats were randomized to resuscitation with Ringers acetate at a dose 10, 30, 50, 75, or 100 ml/kg at 4 h after induction of sepsis by cecal ligation and puncture (CLP) or 2.5 h after a 30 ml/kg hemorrhage. Plasma volume (125I-albumin) was the primary outcome. Plasma volume decreased by about 11.8 (IQR 9.9-14.5) ml/kg relative baseline after CLP and increased dose-dependently by at most 5.8 (IQR 3.3-7.0) ml/kg in the 100 ml/kg group at 15 min after resuscitation. In the hemorrhage group, the plasma volume increased by at most 13.8 (IQR 7.1-15.0) ml/kg in 100 ml/kg group. Blood volumes at baseline, calculated using hematocrit and plasma volumes, were 72.4 (IQR 68.2-79.5) ml/kg in sepsis group and 71.1 (IQR 69.1-74.7) ml/kg in hemorrhage group. At 15 min after resuscitation with a dose of 100 ml/kg blood volumes increased to 54.8 (IQR 52.5-57.7) ml/kg and ; 49.6 (IQR 45.3-56.4) ml/kg, in the sepsis and hemorrhage groups, respectively. Plasma volume expansion as the percentage of dose at 15 min was 5.9 (IQR 2.5-8.8)% and 14.5 (IQR 12.1-20.0)% in the sepsis and hemorrhage groups, respectively. At 60 min, average plasma volume as the percentage of dose had decreased to 2.9 (IQR ([-2.9] - 8.3)% (P = 0.006) in the sepsis group whereas no change was detected in the hemorrhage group. A dose-dependent decrease in the plasma oncotic pressure, which was more marked in sepsis, was detected at 60 min after resuscitation. CONCLUSIONS: We conclude that the efficacy of Ringers acetate as a plasma volume expander is context dependent and that plasma volume expansion is lower than previously realized across a wide range of doses. Ringers acetate decreases plasma oncotic pressure in sepsis, in part, by mechanisms other than dilution.

The importance of albumin infusion rate for plasma volume expansion following major abdominal surgery - AIR: study protocol for a randomised controlled trial.

BACKGROUND: Administration of fluids to restore normovolaemia is one of the most common therapeutic interventions performed peri-operatively and in the critically ill, but no study has evaluated the importance of infusion rate for the plasma volume-expanding effect of a resuscitation fluid. The present study is designed to test the hypothesis that a slow infusion of resuscitation fluid results in better plasma volume expansion than a rapid infusion. METHODS/DESIGN: The study is a single-centre, assessor-blinded, parallel-group, randomised prospective study. Patients over 40 years of age admitted to the post-operative care unit after a Whipple procedure or major gynaecological surgery and presenting with signs of hypovolaemia are eligible for inclusion. Patients are randomised in a 1:1 fashion with no stratification to either rapid (30 minutes) or slow (180 minutes) infusion of 5% albumin at a dose of 10 ml/kg ideal body weight. Plasma volume is measured using 125I human serum albumin at baseline (prior to albumin infusion) as well as at 30 minutes and 180 minutes after infusion start. The primary endpoint is change in plasma volume from baseline to 180 minutes after the start of 5% albumin infusion. Secondary endpoints include the integral of plasma volume over time from baseline to 180 minutes after the start of the infusion and transcapillary escape rate of albumin (%/h) from 180 minutes to 240 minutes after the start of albumin infusion. In addition, diuresis, change in central venous oxygen saturation, lactate and blood pressure will be evaluated. A total of 70 patients will be included in the study, and the study has 80% power to detect a difference of 4 ml/kg in plasma volume expansion between the two groups. DISCUSSION: The present study is the first clinical investigation of the importance of infusion rate for the plasma volume-expanding effect of a resuscitation fluid. TRIAL REGISTRATION: EudraCT identifier: 2013-004446-42 . Registration date: 20 December 2013. ClinicalTrials.gov identifier: NCT02728921 . Registration date: 31 March 2016.

Effects of fresh frozen plasma, Ringer's acetate and albumin on plasma volume and on circulating glycocalyx components following haemorrhagic shock in rats.

BACKGROUND: Early use of fresh frozen plasma (FFP) in haemorrhagic shock is associated with improved outcome. This effect may partly be due to protection of the endothelial glycocalyx and/or secondary to a superior efficacy of FFP as a plasma volume expander compared to crystalloids. The objective of the present study was to investigate if protection of the glycocalyx by FFP can be demonstrated when potential differences in plasma volume (PV) following resuscitation are accounted for. METHODS: Rats were subjected to a volume-controlled haemorrhage (30 ml/kg). At 2.5 h after haemorrhage, animals were randomized to resuscitation with FFP (37.5 ml/kg), albumin (30 ml/kg) or Ringer's acetate (RA) (135 ml/kg, 4.5 times the bleed volume). PV was measured 2 h after completion of resuscitation using (125)I-albumin and effects on endothelial glycocalyx were evaluated by measuring circulating heparan sulphate and syndecan-1. Hemodynamic effects of resuscitation were evaluated by measuring lactate and mean arterial pressure (MAP). RESULTS: Resuscitation with FFP or albumin resulted in plasma volume expansion equalling the blood loss (to 55 ± 5 ml/kg and 54 ± 4 ml/kg (mean ± S.D.), respectively), whereas plasma volume expansion in RA group was lower (to 42 ± 7 ml/kg). Plasma concentration of heparan sulphate was lower in the FFP and albumin groups than in the RA group at 2 h after resuscitation. After correcting for differences in plasma volume, no significant difference in circulating amount of heparan sulphate was detected between the FFP and albumin groups (2879 ± 1075 µg/kg and 3318 ± 1814 µg/kg, respectively, P = 0.4) and the RA group (3731 ± 777 µg/kg). No differences between the groups in plasma concentration or amount of circulating syndecan-1 were detected after resuscitation. After resuscitation, MAP was higher in the FFP and albumin groups than in the RA group. Lactate did not differ between the FFP and RA groups after resuscitation. CONCLUSIONS: Improved outcome in trauma by FFP could in part be explained by better plasma volume expansion compared to crystalloids. The decrease in plasma concentration of markers of glycocalyx degradation after resuscitation with FFP are largely secondary to differences in plasma volume and may not accurately reflect effects of FFP on the glycocalyx.

Plasma volume expansion with 5% albumin compared to Ringer's acetate during normal and increased microvascular permeability in the rat.

BACKGROUND: It is believed that the effectiveness of colloids as plasma volume expanders is dependent on the endothelial permeability for macromolecules. The objective of this study was to test the hypothesis that the plasma volume expanding effect of 5% albumin relative to that of a crystalloid solution is reduced if microvascular permeability is increased. METHODS: A control group was resuscitated with either 5% albumin (8 ml/kg) or Ringer's acetate (36 ml/kg) immediately after a hemorrhage of 8 ml/kg (n = 29). In a second group, permeability was increased by inducing sepsis through cecal ligation and incision (n = 28). Three hours after cecal ligation and incision, the animals were resuscitated with either 5% albumin in a ratio of 1:1 relative to the volume of lost plasma, or Ringer's acetate in a ratio of 4.5:1. RESULTS: In the hemorrhage group, plasma volumes at 15 min after resuscitation with albumin or Ringer's acetate had increased by 9.8 ± 2.6 ml/kg (mean ± SD) and 7.4 ± 2.9 ml/kg and were similar at 2 and 4 h. Plasma volume 3 h after cecal ligation and incision had decreased by approximately 7 ml/kg, and at 15 min after resuscitation with albumin or Ringer's acetate it had increased by 5.7 ± 2.9 and 2.4 ± 3.0 ml/kg, respectively (P < 0.05). At 2 and 4 h after resuscitation, plasma volumes did not differ between the groups. CONCLUSION: This study does not support the hypothesis that the plasma-volume-expanding effect of albumin relative to that of crystalloids is decreased under conditions characterized by increased permeability.