Comparison of dextran and albumin on blood coagulation in patients undergoing major gynaecological surgery.

BACKGROUND: Hydroxyethyl starches have been withdrawn from the European market. In Sweden, dextran was the main colloid until 2000, when starches overtook the market. After the recent 6S-trial, it was suggested that dextran could be reinstituted, but concerns for greater coagulopathy, bleeding and anaphylaxis still remain. An experimental study from our department indicated that isovolemic substitution of dextran-70 did not derange the von Willebrand function more than albumin 5%, considering the fact that dextran is hyperoncotic in comparison to albumin 5% and, therefore, induces a greater plasma volume expansion and thereby a greater dilutional coagulopathy. METHODS: Eighteen patients undergoing major gynaecological surgery were assigned to receive either 5% albumin or 6% dextran-70 with 9 patients in each group. Standard coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and platelet count, viscoelastic coagulation test thromboelastometry (ROTEM) and the Multiplate platelet aggregation test were used to test for coagulation defects at different time points perioperatively. Blood loss, blood loss replacement data and haemodynamic parameters were retrieved from anaesthetic and postoperative charts. A local departmental fluid and transfusion/infusion protocol assured haemoglobin > 90 g/l and mean arterial pressure > 65 mmHg with Ringer's acetate in addition to the colloid use. RESULTS: There were no differences in demographic data between the groups. The tissue factor-activated (EXTEM) clot-structure parameter ROTEM A10 was decreased significantly in the dextran group as compared to the albumin group after the infusion of 500 ml of either colloid solution. The PT and aPTT were significantly prolonged, and the platelet count decreased postoperatively in the dextran group, whereas albumin only deranged fibrinogen levels as compared to preoperative levels. There were no differences in Multiplate platelet aggregometry, amount of haemorrhage or transfusion of blood components between the groups. CONCLUSIONS: Standard plasma-based coagulation tests, platelet count and whole blood viscoelastic clot structure are affected by 6% dextran-70 to a greater extent than by 5% albumin, but platelet aggregation is not. Future studies should use more advanced haemodynamic monitoring to assess isovolemic plasma volume expansion with dextran and whether this affects haemostasis to a lesser degree.

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.

Prostacyclin reduces plasma volume loss after skeletal muscle trauma in the rat.

BACKGROUND: Trauma induces transcapillary leakage of fluid and proteins because of increased microvascular permeability. Based on studies showing that prostacyclin (PGI2) has permeability-reducing properties, in the present study, we investigated whether PGI2 reduces plasma volume (PV) loss after a nonhemorrhagic trauma. METHODS: The study was performed on anesthetized Sprague-Dawley rats exposed to a controlled standardized blunt trauma to the abdominal rectus muscle. Thereafter, the animals were randomized to treatment with either PGI2 (2 ng/kg per minute) or 0.9% NaCl. PV was estimated before and 3 hours after the trauma using I-albumin as tracer. In separate experiments, the transcapillary escape rate of I-albumin was calculated and plasma concentrations of cytokines were measured after both treatments. RESULTS: Average PV at baseline was 41.6 mL/kg ± 2.5 mL/kg and 42.3 mL/kg ± 1.7 mL/kg in the PGI2 and NaCl animals, respectively. PV was decreased by 22% ± 8% in the NaCl animals and by 11% ± 9% in the PGI2 animals 3 hours after the trauma (p < 0.05). Trauma induced a decrease in mean arterial blood pressure and an increase in hematocrit in both groups. There were no differences in urine production and mean arterial blood pressure between the PGI2 and NaCl animals. The transcapillary escape rate for albumin was calculated for one hour starting 30 minutes after the trauma and was 15.1% ± 2.4% per hour in the PGI2 animals and 17.4% ± 3.3% per hour in the NaCl animals (p = 0.09). Interleukin 6 concentration 3 hours after the trauma was lower in the PGI2 animals than in the NaCl animals (p < 0.05). CONCLUSION: We conclude that PGI2 attenuates PV loss after blunt muscle trauma. The vascular effects of PGI2 are associated with a modulation of the trauma-induced inflammatory response.

Effect of charge on microvascular permeability in early experimental sepsis in the rat.

A key feature of sepsis is hypovolemia due to increased microvascular permeability. It has been suggested that the negative charge of albumin and of the endothelial glycocalyx is important for maintenance of the normally low permeability for albumin. Here we tested the hypothesis that charge effects contribute to the increased permeability in sepsis. Transcapillary escape rate (TER) and initial distribution volume for (125)I-labeled bovine serum albumin (BSA, isoelectric point pH 4.6) and for (131)I-labeled charge modified BSA (cBSA, average isoelectric point, pH 7.1) was measured 3h after sepsis was induced by cecal ligation and incision (CLI) (n=11) and in control animals (n=12). The importance of charge for permeability in sepsis was estimated by comparing the ratio between TER for cBSA and TER for BSA during control conditions to that after CLI. Plasma concentration of the glycocalyx component glycosaminoglycans (GAGs) was measured in separate control and CLI animals. The initial distribution volume for BSA and cBSA in control animals was 38 ± 3 ml/kg and 47 ± 4 mL/kg and decreased by 17% and 19%, respectively, following CLI. TER for BSA increased from 16.7 ± 4.1% in the controls to 20.1 ± 1.9% following CLI. Corresponding values for cBSA were 26.7 ± 5.6% and 29.8 ± 3.5%, respectively. The ratio between TER for cBSA and TER for BSA was 1.62 ± 0.1 in the control group and 1.49 ± 0.1 following CLI (p<0.05). Plasma GAG concentrations were higher in CLI animals than in the control group. We conclude that CLI induce hypovolemia secondary to increased microvascular permeability. Negative charge contributes to the normally low permeability of albumin and the importance of charge is decreased in early experimental sepsis. The observed charge effects are associated with CLI-induced breakdown of the glycocalyx.

A model for evaluating the effects of blunt skeletal muscle trauma on microvascular permeability and plasma volume in the rat.

The objective of the present study was to develop an experimental model suitable for studying the effects of a nonhemorrhagic soft tissue trauma on plasma volume (PV) and microvascular permeability. Anesthetized Sprague-Dawley rats were exposed to a sham procedure or a laparotomy followed by a standardized trauma to the abdominal rectus muscle. We evaluated the effects of trauma on transcapillary escape rate and on PV (3 h after trauma) using 125I-albumin as tracer and on edema formation in the traumatized muscle with a wet- versus dry-weight method. The effects of the trauma on the cytokines IFN-gamma, IL-4, IL-6, IL-10, and TNF-alpha were investigated 1 and 3 h after trauma in a separate group. Transcapillary escape rate was 13.9% per hour in the sham animals compared with 18.5% per hour in the traumatized animals (P < 0.05). Because arterial and venous blood pressures were not altered by the trauma, the change in transcapillary escape rate most likely reflects a change in microvascular permeability. Plasma volume decreased from 42 mL/kg at baseline to 31 mL/kg at the end of the experiments (P < 0.05) in the trauma group, whereas PV remained unchanged in the sham group. Only 15% of the PV loss could be referred to edema in the traumatized muscle. Trauma induced a significant increase in IL-6 and IL-10 after 1 h. We conclude that the present nonhemorrhagic trauma induces an increase in microvascular permeability in the traumatized tissue and in other parts of the body, resulting in hypovolemia. The model may be used for the evaluation of different therapeutic interventions aimed at the correction of hypovolemia.