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Background: Perioperative fluid management - including the type, dose, and timing of administration -directly affects patient outcome after major surgery. The objective of fluid administration is to optimize intravascular fluid status to maintain adequate tissue perfusion. There is continuing controversy around the perioperative use of crystalloid versus colloid fluids. Unfortunately, the importance of fluid volume, which significantly influences the benefit-to-risk ratio of each chosen solution, has often been overlooked in this debate., Main Text: The volume of fluid administered during the perioperative period can influence the incidence and severity of postoperative complications. Regrettably, there is still huge variability in fluid administration practices, both intra-and inter-individual, among clinicians. Goal-directed fluid therapy (GDFT), aimed at optimizing flow-related variables, has been demonstrated to have some clinical benefit and has been recommended by multiple professional societies. However, this approach has failed to achieve widespread adoption. A closed-loop fluid administration system designed to assist anesthesia providers in consistently applying GDFT strategies has recently been developed and tested. Such an approach may change the crystalloid versus colloid debate. Because colloid solutions have a more profound effect on intravascular volume and longer plasma persistence, their use in this more "controlled" context could be associated with a lower fluid balance, and potentially improved patient outcome. Additionally, most studies that have assessed the impact of a GDFT strategy on the outcome of high-risk surgical patients have used hydroxyethyl starch (HES) solutions in their protocols. Some of these studies have demonstrated beneficial effects, while none of them has reported severe complications., Conclusions: The type and volume of fluid used for perioperative management need to be individualized according to the patient's hemodynamic status and clinical condition. The amount of fluid given should be guided by well-defined physiologic targets. Compliance with a predefined hemodynamic protocol may be optimized by using a computerized system. The type of fluid should also be individualized, as should any drug therapy, with careful consideration of timing and dose. It is our perspective that HES solutions remain a valid option for fluid therapy in the perioperative context because of their effects on blood volume and their reasonable benefit/risk profile.

Background & Aims: Blood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output., Methods: Healthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging., Results: Ten of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index., Conclusions: A smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid., Trial Registration: The protocol was registered with the European Union Drug Regulating Authorities Clinical Trials Database (https://eudract.ema.europa.eu) (EudraCT No. 2013-003260-32)., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Crystalloid fluid requires 30 min for complete distribution throughout the extracellular fluid space and tends to cause long-standing peripheral edema. A kinetic analysis of the distribution of Ringer's acetate with increasing infusion rates was performed to obtain a better understanding of these characteristics of crystalloids., Methods: Data were retrieved from six studies in which 76 volunteers and preoperative patients had received between 300 ml and 2375 ml of Ringer's acetate solution at a rate of 20-80 ml/min (0.33-0.83 ml/min/kg). Serial measurements of the blood hemoglobin concentration were used as inputs in a kinetic analysis based on a two-volume model with micro-constants, using software for nonlinear mixed effects., Results: The micro-constants describing distribution (k12) and elimination (k10) were unchanged when the rate of infusion increased, with half-times of 16 and 26 min, respectively. In contrast, the micro-constant describing how rapidly the already distributed fluid left the peripheral space (k21) decreased by 90% when the fluid was infused more rapidly, corresponding to an increase in the half-time from 3 to 30 min. The central volume of distribution (V(c)) doubled., Conclusion: The return of Ringer's acetate from the peripheral fluid compartment to the plasma was slower with high than with low infusion rates. Edema is a normal consequence of plasma volume expansion with this fluid, even in healthy volunteers. The results are consistent with the view that the viscoelastic properties of the interstitial matrix are responsible for the distribution and redistribution characteristics of crystalloid fluid., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Introduction: The objective of this study was to test whether stroke volume (SV) variations in response to a fixed mini-fluid challenge (ΔSV100) measured by impedance cardiography (ICG) could predict an increase in arterial pressure with volume expansion in spontaneously breathing patients under spinal anaesthesia., Methods: Thirty-four patients, monitored by ICG who required intravenous fluid to expand their circulating volume during surgery under spinal anaesthesia, were studied. Haemodynamic variables and bioimpedance indices (blood pressure, SV, cardiac output [CO]) were measured before and after fluid challenge with 100mL of crystalloid, and before/after volume expansion. Responders were defined by ≥15% increase in systolic arterial pressure (SAP) after infusion of 500 mL of crystalloid solution., Results: SAP increased by ≥15% in 20 (59%) of the 34 patients. SAP, SV, and CO increased and HR decreased only in responders. SV variations in response to mini-fluid challenge and volume expansion differed between patients who showed arterial responsiveness and those in whom SAP did not increase with volume expansion (11.6% [9.1-19.3] versus 2.5% [1.3-7], P<0.001, and 22.4% [11.7-36.6] versus 0.9 [0-5.5], P<0.001, respectively). ΔSV100 predicted an increase of arterial pressure with an area under the receiver operating characteristic (AUC) curve of 0.89 (CI95%: 0.73-0.97, P<0.001). The cut-off was 5%. Baseline SAP and HR were not predictive of arterial responsiveness (P>0.05)., Conclusion: A ΔSV100 over 5% accurately predicted arterial pressure response to volume expansion during surgery., (Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Acute normovolemic hemodilution (ANH) and volume loading (VL) are standard blood-sparing procedures. However, VL is associated with hypervolemia, which may cause tissue edema, cardiopulmonary complications and a prolonged hospital stay. The body reacts to hypervolemia with release of atrial natriuretic peptide (ANP) from the heart. ANP has been shown to deteriorate the endothelial glycocalyx, a vital part of the vascular permeability barrier. The aim of the present study was to evaluate and compare ANP release and damage to the glycocalyx during ANH and VL., Methods: ANH or VL with 6% hydroxyethyl starch 130/0.4 was administered prior to elective surgery in patients of good cardiopulmonary health (n =9 in each group). We measured concentrations of ANP in plasma and of three main constituent parts of the glycocalyx (hyaluronan, heparan sulfate and syndecan 1) in serum before and after ANH or VL. Heparan sulfate and syndecan 1 levels in urine were also determined., Results: In contrast to ANH, VL (20 ml/kg) induced a significant release of ANP (approximately +100%, P <0.05) and increased the serum concentration of two glycocalyx constituents, hyaluronan and syndecan 1 (both by about 80%, P <0.05). Elevation of syndecan 1 was also detected in the urine of patients undergoing VL, but no increase was found in patients undergoing ANH. Heparan sulfate levels were not influenced by either procedure., Conclusion: These data suggest that hypervolemia increases the release of ANP and causes enhanced shedding of the endothelial glycocalyx. This perturbation must be expected to impair the vascular barrier, implying that VL may not be as safe as generally assumed and that it should be critically evaluated.

Background: Although 5% albumin (human serum albumin [HSA]) is widely used in cardiac surgery children, synthetic colloids may provide a valuable alternative. This study compared 6% hydroxyethyl starch (HES) 130/0.4 with HSA for volume replacement in this population., Methods: The study was a two-center, randomized, controlled, parallel-group, double-blind trial performed in children aged 2-12 yr undergoing elective surgery for congenital heart disease under extracorporeal circulation. The primary objective was to demonstrate equivalence between HES and HSA with regard to the total volume of colloid infusion for intraoperative volume replacement including priming of the extracorporeal circuitery., Results: In the per-protocol population, mean volume of colloid required until end of surgery was (mean ± SD) 36.6 ± 11.8 ml/kg body weight in the HES group (N = 29) and 37.0 ± 11.9 ml/kg body weight in the HSA group (N = 26; ratio of means HES/HSA = 0.98 [95% CI, 0.84-1.16]). Intraoperative fluid balance was less positive in the HES group (P = 0.047). No difference was found regarding hemodynamics, the use of vasoactive and inotropic drugs. Blood loss, erythrocytes transfusion, and renal function were not different between groups. The incidence of adverse events up to postoperative day 28 did not differ between the groups., Conclusions: In pediatric cardiac surgery, HES showed equivalence to HSA with regard to volume replacement therapy in children aged from 2 to 12 yr. Although there was no suggestion of an imbalance of safety measures between HES and HSA, the study was not powered to provide any firm conclusions about safety of tetrastarch in this population.

Unlabelled: It is common knowledge that arterial hypotension is a one of most prevalent pathology of early neonatal period and it causes severe neurological complications. Purpose of the prospective randomized open study was to assess the efficacy of HES 130/0.4 (6% Voluven) as a start medicine for arterial hypotension in early neonatal period in comparison with normal saline solution (0.9% NaCl)., Materials and Methods: the study was held from January 2010 to September 2011. Newborns of the ICU with arterial hypotension on the first day of life were included into the study. Acute haemorrhage was an exclusion criterion. Routine monitoring of arterial pressure, heart rate and diuresis was carried out in all newborns. pH, pCO2, pO2 blood glucose, lactate and BE levels were measured before and after the treatment. Echocardiography, examination of regional blood flow in anterior cerebral artery, renal artery and mesenteric artery was held HES 130/0.4 (6% Voluven) and saline solution (0.9% NaCl) were used Parameters of haemostasis, biochemical and haematological analysis monitored after the solutions use. Time of arterial pressure normalization and duration of the treatment positive effect were recorded Episodes of hypotension, amount of cardiotonics per day and per 7 days and duration of cardiotonics administration were recorded as well., Results: 6% Voluven infusion both to 0.9% NaCl infusion normalizes the regional circulation. Furthermore it increases the blood pH and diuresis. Lactate level normalization occurred only after 6% Voluven infusion. There was not change of serum sodium level. Liver enzymes, C-protein, prothrombin index were same in both groups of patients. 6% Voluven use in newborns with extremely low birth weight was accompanied with increasing of creatinine level, prolongation of activated partial thromboplastin time and increasing of intraventricular hemorrhage rate. Newborns with weight over 1000 gram did not have these complications. Voluven advantage in comparison with saline solution is a decreasing of cardiotonics administration in patients with weight over 1000 gram., Conclusions: 6% Voluven is more effective than 0.9% NaCl for increasing of cardiac output, myocardial contractile ability and diuresis, normalization of liquid balance and lactate level, decreasing of cardiotonics amount. 6% Voluven can be recommended for arterial hypotension treatment in newborns with weight over 1000 gram both to normal saline solution especially in case of shock.

Objective: The purpose of this study was to determine whether changes in PETCO2 and exhaled CO2 (VCO2) can predict fluid responsiveness after a preload challenge., Design: A retrospective review of prospectively recorded data., Setting: A medical intensive care unit of a university-affiliated tertiary care hospital., Participants: Mechanically ventilated patients undergoing a preload challenge., Interventions: In the authors' intensive care unit, fluid responsiveness is determined by a passive leg raising (PLR) maneuver and/or a 500-mL crystalloid challenge. An increase in the stroke volume index >10% as measured by a NICOM bioreactance cardiac output monitor (Cheetah Medical, Inc, Vancouver, WA) is used to determine fluid responsiveness. PETCO2 and volumetric capnography (VCO2) were monitored via a combined CO2 and flow sensor capnostat (Respironics NM3 Monitor; Philips Healthcare, Eindhoven, Netherlands). Patients were mechanically ventilated with tidal volumes controlled at 8 mL/kg, allowing for consistent minute ventilation., Measurements and Main Results: During the study period, 44 challenges (10 PLR and 34 fluid boluses) were performed on 34 patients. There were 24 (54%) positive "fluid" responses. PETCO2 increased by 5.9% ± 7.6% in the responders compared with 1.4% ± 4.4% in the nonresponders (p = 0.02). Similarly, VCO2 increased by 11.0% ± 8.6% in the responders compared with 0.8% ± 5.6% in the nonresponders (p = 0.001). The area under the receiver operating characteristic curve was 0.67 (95% confidence interval, 0.48-0.80) for PETCO2 and 0.79 (95% confidence interval, 0.63-0.89) for VCO2. PETCO2 and VCO2 were predictive of fluid responsiveness only in those patients without underlying lung disease. The stroke volume variation was 15.8 ± 3.7 in the responders compared with 13.6 ± 4.8 in the nonresponders (p = 0.15)., Conclusions: Dynamic changes in PETCO2 and VCO2 may be used as adjunctive indicators of fluid responsiveness in patients without underlying lung disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: The turnover of Ringer´s solutions is greatly dependent on the physiological situation, such as the presence of dehydration or anaesthesia. The present study evaluates whether the kinetics is affected by previous infusion of colloid fluid., Methods: Ten male volunteers with a mean age of 22 years underwent three infusion experiments, on separate days and in random order. The experiments included 10 mL/kg of 6% hydroxyethyl starch 130/0.4 (Voluven™), 20 mL/kg of Ringer's acetate, and a combination of both, where Ringer´s was administered 75 minutes after the starch infusion ended. The kinetics of the volume expansion was analysed by non-linear least- squares regression, based on urinary excretion and serial measurement of blood haemoglobin concentration for up to 420 minutes., Results: The mean volume of distribution of the starch was 3.12 L which agreed well with the plasma volume (3.14 L) estimated by anthropometry. The volume expansion following the infusion of starch showed monoexponential elimination kinetics with a half-life of two hours. Two interaction effects were found when Ringer´s acetate was infused after the starch. First, there was a higher tendency for Ringer´s acetate to distribute to a peripheral compartment at the expense of the plasma volume expansion. The translocated amount of Ringer´s was 70% higher when HES had been infused earlier. Second, the elimination half-life of Ringer´s acetate was five times longer when administered after the starch (88 versus 497 minutes, P<0.02)., Conclusions: Starch promoted peripheral accumulation of the later infused Ringer´s acetate solution and markedly prolonged the elimination half-life., Trial Registration: ClinicalTrials.gov: NCT01195025.

Background: Plasma expander (PE) based on polyethylene glycol (PEG) conjugated to albumin has shown positive results maintaining blood volume during hemodilution and restoring blood volume during resuscitation from hemorrhagic shock. Polyethylene glycol conjugation to human serum albumin (HSA), PEG-HSA, increases size, weight, and colloidal osmotic pressure, with minor effects on solution viscosity., Methods: This study was designed to test the hypothesis that PEG-HSA (2 g/dL) produced by direct PEGylation chemistry improves cardiac function during 2 experimental models, (i) moderate hemodilution and (ii) resuscitation from hemorrhagic shock, compared with a conventional colloidal PE (Dextran 70 kd [Dx70], 6 g/dL). Cardiac function was studied using a miniaturized pressure volume conductance catheter implanted in the left ventricle and evaluated in terms of cardiac indices derived from the pressure volume measurements., Results: Polyethylene glycol-HSA increased cardiac output, stroke volume, and stroke work and decreased systemic vascular resistance compared with Dx70 in both experimental models. The improvements induced by PEG-HSA in cardiac function were sustained over the observation time. Polyethylene glycol-HSA cardiac mechanoenergetics changes are the result of increased energy transferred per stroke and decreased resistance of the vasculature connecting the heart. In summary, PEG-HSA decreased left ventricle ejection impedance., Conclusion: Ejection of blood diluted with PEG-HSA presented a reduced load to the heart, increased contractile function, and lowered the energy consumed per unit volume compared with Dx70. Our results emphasize the importance of heart function as a parameter to be included in the evaluation changes induced by new PEs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Objectives: Hydroxyethyl starch (HES) 130/0.4 is considered an effective plasma expander when compared to crystalloids. There is controversy around its superiority regarding hemodynamic optimization and about possible detrimental effects on coagulation. The aim of this study was to compare the effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in adult patients under spinal anesthesia regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes., Methods: In this randomized, controlled trial, 48 patients scheduled for hip arthroplasty with spinal anesthesia were randomized into two groups: 24 patients were allocated to receive a preload of 15 mL.kg(-1) of HES 130/0.4 and 24 patients received a preload of 30 mL.kg(-1) lactated Ringer solution before surgery. Hemodynamic measurements, hemoglobin concentrations, biochemical parameters and coagulation tests were evaluated in three periods during surgical procedure. Patients received medical follow-up during their hospital stay and up to postoperative 30 days. Primary outcome was the requirement of red blood cell transfusion between groups during hospital stay. Secondary outcome were hemodynamic parameters, length of hospital stay, mortality and occurrence of clinical postoperative complications., Results: Red blood cell transfusion was required in 17% of patients in the HES group and in 46% in the Ringer group (p = .029). Postoperative infections were more frequently observed in the Ringer group (17%) compared to the HES group (0), p = .037. There were no significant differences between groups in mortality, hospital length of stay and clinical complications other than infection., Conclusions: During hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated Ringer., (Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: This study aims to study changes in blood volume after 1 litre infusions of Gelofusine(®) [4% succinylated gelatine in 0.7% saline, weight-average molecular weight (MWw) 30 kDa] and Voluven(®) (6% hydroxyethyl starch in 0.9% saline, MWw 130 kDa) in the presence of increased capillary permeability., Methods: In this randomized double-blind study, adults undergoing laparoscopic cholecystectomy received 1 litre of Gelofusine(®) (n=12) or Voluven(®) (n=13) over 1 h at the induction of anaesthesia. No other fluids were given. Haematocrit, serum electrolytes, and osmolality were measured before infusion and hourly thereafter for 4 h. Changes in blood volume were calculated from changes in haematocrit. The urinary albumin:creatinine ratio (ACR) was measured before and after operation., Results: Baseline parameters before the two infusions were similar (P>0.050). The urinary ACR increased significantly after operation after Gelofusine(®) (P=0.011) and Voluven(®) (P=0.002), indicating increased capillary permeability. Voluven(®) produced a greater increase in serum chloride concentration (P=0.028) and a larger decrease in strong ion difference (P=0.009) than Gelofusine(®). There were no significant differences in changes in haematocrit (P=0.523) and blood volume (P=0.404) over the study period when the two infusions were compared, nor were there any differences in serum sodium, potassium, bicarbonate, and albumin concentrations (P>0.050). Urine output, sodium concentration, and osmolality were similar after the two infusions (P>0.050)., Conclusions: The blood volume-expanding effects of the two colloids were not significantly different, despite the increase in postoperative urinary ACR and the 100 kDa difference in MWw.

Aims: This study evaluated the hypothesis that exogenous nitric oxide (NO) supplementation during acute hemodilution with plasma expander (PE) provides beneficial effects on cardiac function., Main Methods: Acute hemodilution in golden Syrian hamsters was induced by a 40% of blood volume exchange with dextran 70 kDa. Intravascular NO supplementation after hemodilution was accomplished with a NO donor, diethylenetriamine NONOate (DETA NONOate). The test group was treated with DETA NONOate, while the control group received only vehicle. Left ventricular cardiac function was studied using pressure-volume measurements obtained with a miniaturized conductance catheter., Key Findings: Cardiac output increased to 122±5% and 107±1% of the baseline in the group treated with NO donor and the vehicle group, respectively. Stroke work per stroke volume (SW/SV) after hemodilution reduced to 90% of the baseline and the NO donor significantly reduced SW/SV compared to the vehicle. The minimum rate of pressure change (dP/dt(min)) was significantly lower in animals treated with the NO donor compared to vehicle treated animals. Systemic vascular resistance (SVR) decreased to 62±5% of the baseline in the NO donor group whereas the vehicle group SVR decreased to 83±5% of the baseline. Using intravital microscopy analysis of microvessel in the dorsal skinfold window chamber, we established that the NO donor group induced significant vasodilation compared to the vehicle group., Significance: NO supplementation in an acute hemodilution with PE has beneficial effects on cardiac performance. However, the NO supplementation effects with a NO donor are dose-independent and short-lasting., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Colloid fluids influence the coagulation system by diluting the plasma and, potentially, by exerting other effects that are unique for each fluid product. We hypothesised that changes in the coagulation measured at the end of surgery would be mainly governed by differences in half-life between the colloid fluids., Methods: Eighty-four patients were randomised to receive one of four colloids: HES 130/0.42/6:1 (Venofundin(®)), 130/0.4/9:1 (Voluven(®)), 200/0.5/5:1 (Haes-steril(®)) and 6% dextran 70 (Macrodex(®)). Blood samples were taken just before and after a preoperative 500 ml bolus, and also after subsequent elective hip replacement surgery. Volume expansion was estimated from the blood dilution and coagulation assessed by ROTEM, activated partial thromboplastin time, prothrombin international normalised ratio (PT-INR), D-dimer and thrombin-antithrombin complex (TAT)., Results: The blood volume expansion amounted to approximately 600 ml for all four colloids directly after infusion. Voluven(®) and Haes-steril(®) prolonged the aPT time and Venofundin(®) increased TAT. Although all colloids increased PT-INR and D-dimer, the ROTEM analyses showed that they consistently shortened the clotting time and weakened the clot strength. These effects were mainly unchanged after surgery, during which the haemorrhage averaged 500-600 ml. Macrodex(®) produced a stronger volume support at the end of the surgery (91% of infused volume; P<0.001) than the three starch solutions (42-60%)., Conclusions: All tested colloid fluids induced a mild hypercoagulable state with faster clotting, but with weaker clot strength. The additive influence of surgery was relatively small, and postoperative changes in coagulation were mainly due to differences in the half-life of each colloid., (© 2011 The Authors. Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.)

Background: Hemodynamic and global oxygen transport variables have failed to reflect splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock. Volemic expansion after fluid resuscitation is essential to improve global and regional oxygen in hemorrhagic shock. We hypothesized that, in contrast to conventional plasma expanders, the smaller volemic expansion from 7.5 NaCl/6% hydroxyethyl starch (HHES) solution administration in hemorrhagic shock may provide lesser systemic oxygen delivery and gastric perfusion. We used hemorrhaged dogs to compare intravascular volume expansion and the early systemic oxygenation and gastric perfusion effects of fixed fluid bolus administration, which are usually used in clinical situations with severe hemorrhage, of HHES, lactated Ringer (LR), and 6% hydroxyethyl starch (HES) solutions., Methods: Thirty dogs were bled (30 mL · kg(-1)) to hold mean arterial blood pressure at 40 to 50 mm Hg over 45 minutes and were resuscitated in 3 groups: LR (n = 10) at 3:1 ratio to shed blood; HES (mean molecular weight 130 kDa, degree of substitution 0.4) (n = 10) at 1:1 to shed blood; and HHES (n = 10), 4 mL · kg(-1). Intravascular volume expansion (Evans blue and hemoglobin dilution), hemodynamic, systemic oxygenation, venous-to-arterial CO(2) gradient (Pv-aCO(2)), and gastric intramucosal-arterial PCO(2) gradient (PCO(2) gap) variables were measured at baseline, after 45 minutes of hemorrhage, and 5, 45, and 90 minutes after fluid resuscitation., Results: HHES increased blood volume because of the high volume expansion efficiency, but intravascular volume expansion with this solution was the smallest of the solutions (P < 0.05). All 3 solutions induced a similar hemodynamic performance but HHES showed lower mixed venous PO(2) and higher systemic oxygenation extraction, Pv-aCO(2), and PCO(2) gap than LR and HES (P < 0.05)., Conclusions: In dogs submitted to pressure-guided hemorrhagic shock and fixed-volume resuscitation, the smaller intravascular volume expansion from HHES solutions provides worse recovery of systemic oxygenation and gastric perfusion compared with LR and HES solutions despite its high volume expansion efficiency, which was limited by low infused volume.

The gelatin plasma substitute is often polydisperse and heterogenous, making it difficult to determine the elimination rate and half-life in the body. In this study, one method was developed based on quantitative determination of hydroxyproline derivatives. Two plasma substitutes were prepared by succinylation and genipin-crosslinking, respectively. After transfusion, the blood samples were hydrolyzed and derivatized, and then analyzed by HPLC. A two-phase exponential association equation was used for fitting the time-concentration curves. The results indicated that this method could be used for quantitative determination of gelatin in blood, and the pharmacokinetic parameters such as elimination rate and half-life.

Objective: Balanced fluids appear to be have advantages over unbalanced fluids for correcting hypovolemia. The effects of a new balanced hydroxyethyl starch (HES) were studied in cardiac surgery patients., Design: Prospective, randomized, unblinded study., Setting: Clinical study in a single cardiac surgery institution., Participants: Sixty patients undergoing elective cardiac surgery with cardiopulmonary bypass., Intervention: Patients received either a balanced 6% HES 130/0.4 plus a balanced crystalloid (n = 30) or an unbalanced HES-in-saline plus saline (n = 30) to keep cardiac index >2.5 L/min/m(2)., Measurements and Main Results: Base excess (BE), kidney function, inflammatory response (interleukins-6, -10), endothelial activation (intercellular adhesion molecule-1 [ICAM]), and coagulation (thromboelastometry, whole blood aggregation) were measured after induction of anesthesia, after surgery and 5 hours later, and at the 1st and 2nd postoperative days; 2,950 +/- 530 mL of balanced and 3,050 +/- 560 mL of unbalanced HES were given. BE was reduced significantly in the unbalanced group (from 1.11 +/- 0.71 mmol/L to -5.11 +/- 0.48 mmol/L after surgery) and remained unchanged in the balanced group. Balanced volume replacement resulted in significantly lower IL-6, IL-10, and ICAM plasma concentrations and lower urine concentrations of kidney-specific proteins than in the unbalanced group. After surgery, thromboelastometry data and platelet function were changed significantly in both groups; 5 hours thereafter they were significantly changed only in the unbalanced group., Conclusion: A plasma-adapted HES preparation in addition to a balanced crystalloid resulted in significantly less decline in BE, less increase in concentrations of kidney-specific proteins, less inflammatory response and endothelial damage, and fewer changes in hemostasis compared with an unbalanced fluid strategy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to investigate the effects of acute hypervolemic fluid infusion (AHFI) of 6% hydroxyethyl starch (HES) 130/0.4 or 4% succinylated gelatin (GEL) on hemostasis and the possible mechanisms., Methods: Thirty-six gastric cancer patients were randomized to receive AHFI of either HES, GEL or lactated Ringer's (RL) solution at the rate of 30 mL x kg(-1) x h( -1) from 20 minutes before to 40 minutes after induction of general anesthesia., Results: Group HES and GEL had significantly prolonged PT and aPTT, decreased VIII:C and vWF immediately after AHFI. Statistically prolonged reaction time and coagulation time, and decreased growth angle were seen immediately after HES infusion. Maximum amplitude decreased significantly in group HES and GEL immediately after and 4 hours after AHFI., Conclusion: Gelatin reduced clot quality associated with derangements of fibrin polymerization and HES 130/0.4 delayed initiation of sufficient thrombin generation to convert fibrinogen to fibrin and impaired platelet function.

Objective: To study the changes in blood volume and hormones controlling sodium and water homeostasis after infusions of 0.9% saline, Gelofusine (4% succinylated gelatin in 0.7% saline, weight-average molecular weight 30 kD), and Voluven (6% hydroxyethyl starch in 0.9% saline, weight-average molecular weight 130 kD) in healthy volunteers., Design: Randomized, three-way crossover study., Setting: University teaching hospital., Subjects: Ten healthy adult male volunteers., Interventions: Volunteers received 1-L infusions of 0.9% saline, Gelofusine, and Voluven over 1 hr on three occasions. Body weight, hematocrit, serum biochemistry, and plasma concentrations of vasopressin, aldosterone, brain natriuretic peptide, and total renin were measured before infusion and hourly thereafter for 6 hrs. Changes in body water, blood volume, and extravascular fluid volume were calculated., Measurements and Main Results: Although changes in body weight (total body water) after the infusions were similar, blood volume expansion by the two colloids was significantly greater than that produced by 0.9% saline (p < .01). At the end of infusions, 68%, 21%, and 16% of the infused volumes of 0.9% saline, Gelofusine, and Voluven, respectively, had escaped from the intravascular space to the extravascular space. Over the 6 hrs, the magnitude and duration of blood volume expansion by the two colloids were similar (p = .70). There were no significant differences in urinary volume, osmolality, and sodium content after the three infusions. Hormonal changes were similar after the three infusions, with the increase in natriuretic peptide being transient. The reduction in aldosterone and total renin concentrations was more sustained., Conclusions: The effects of Gelofusine and Voluven were similar despite the 100 kD difference in weight-average molecular weight. Excretion of an acute fluid load containing sodium and chloride may be dependent on a sustained suppression of the renin-angiotensin-aldosterone system rather than on natriuretic peptides.

Background: Hypotension after spinal anesthesia for cesarean delivery remains a major clinical problem. Fluid preloading regimens together with vasopressors have been used to reduce its incidence. Previous studies have used noninvasive arterial blood pressure measurement and vasopressor requirements to evaluate the effect of preload. We used a suprasternal Doppler flow technique to measure maternal cardiac output (CO) and corrected flow time (FTc, a measure of intravascular volume) before and after spinal anesthesia after 3 fluid preload regimens. We hypothesized that colloid solutions, compared with crystalloid, would produce the largest increase in CO and have the lowest incidence of hypotension., Methods: Sixty healthy term women scheduled for planned cesarean delivery under spinal anesthesia were recruited for this randomized, double-blind study. Baseline heart rate, systolic blood pressure (SBP), CO, and FTc were recorded in the left lateral tilt position. Patients were randomized to receive 1 of 3 fluid preload regimens given over 15 min: 1.5 L crystalloid (Hartman's solution), 0.5 L of 6% w/v hydroxyethyl starch (HES) solution (HES 0.5), or 1 L of 6% w/v HES solution (HES 1.0). Further measurements were made after fluid loading every 5 min for 30 min. After 30 min, spinal anesthesia was induced with hyperbaric bupivacaine 12.5 mg with fentanyl 15 microg and recordings were continued every 5 min for 20 min or until surgery started. The primary outcome, CO, was compared among groups. The incidence of hypotension (defined as a 20% reduction in SBP from the baseline), ephedrine use, and umbilical cord blood gases were also compared., Results: Patient characteristics, heart rate, SBP, and cord gases were similar among groups. Although CO and FTc increased after preload in all groups (P < 0.005), this was only maintained with HES 1.0 after spinal anesthesia (P < 0.005). There were no differences among groups in the incidence of hypotension (70% vs 35% vs 65% for Hartman's solution, HES 0.5, and HES 1.0, respectively; P = 0.069) or mean ephedrine dose (10.4 vs 5.7 vs 9.7 mg; P = 0.26)., Conclusion: Despite CO and FTc increases after fluid preload, particularly with HES 1.0 L, hypotension still occurred. The data suggest that CO increases after these preload regimens cannot compensate for reductions in arterial blood pressure after spinal anesthesia.

Background: Voluven (hydroxyethyl starch [HES] 130/0.4), a new generation of HES product with low molecular weight, has been widely used for the treatment of traumatic and hemorrhagic shock in clinics. However, no data are available whether it affects the balance of cerebral oxygen supply and consumption when applied to resuscitate hemorrhagic shock. The purpose of this study was to address this question in rabbits subjected to a severe hemorrhagic shock., Methods: In New Zealand rabbits, an acute hemorrhagic shock was induced by withdrawing 45% to 50% of total blood volume from the femoral vein in 10 minutes when the mean arterial pressure was reduced to 60% of the baseline level. Thirty minutes after the hemorrhage, animals were infused with either an equal amount of Voluven (group V) or a tripled amount of lactated Ringer's solution (group R). The saturation of oxygen was obtained in arterial (Sao2) and venous (SjvO2) blood samples from the femoral artery and jugular bulb, respectively. Arterial oxygen content (Cao2), jugular oxygen content (CjvO2), arteriovenous oxygen difference (AVDO2), and cerebral oxygen extraction rate (CERO2) were calculated accordingly to evaluate the oxygenation state in the brain., Results: Levels of SjvO2 and CjvO2 were decreased after hemorrhagic shock, and there were increases in AVDO2 and CERO2 values. After resuscitation, the SjvO2, AVDO2, and CERO2 levels in group V were quickly recovered to the basal levels, whereas the values in group R remained in the abnormal levels (p < 0.05). There were significant differences between the groups in their SjvO2 and CERO2 levels at 30 minutes after resuscitation. In addition, the mean arterial pressure was restored to the basal levels in group V but not in group R after resuscitation (p < 0.05)., Conclusion: We conclude that early infusion of Voluven is beneficial for maintenance of the hemodynamic stability and for the balance of cerebral oxygen supply and consumption during the resuscitation of acute hemorrhagic shock.

Background: Hypotension is the most common cardiovascular response to spinal anesthesia. We compared the effects of crystalloid/colloid versus crystalloid administration before spinal anesthesia on cardiac output (CO) in elderly patients undergoing transurethral resection of the prostate., Methods: Sixty male ASA I-III patients were randomized to one of three groups the control group received no intravascular volume preload, the saline group received 500 mL saline, and the hydroxyethyl starch (HES) group received 500 mL of saline plus 500 mL of 6% HES 130/0.4 within 20 min before spinal anesthesia. Mean arterial blood pressure (MAP) and heart rate, CO, and stroke volume were recorded with a thoracic electrical bioimpedance device., Results: MAP significantly decreased from baseline in the control group (from 104 +/- 20 mm Hg to 88 +/- 11 mm Hg [P = 0.005]) and was significantly lower than in the HES group (from 107 +/- 13 mm Hg to 97 +/- 12 mm Hg [P = 0.001]). In the saline group, MAP decreased (103 +/- 14 mm Hg to 92 +/- 17 mm Hg) with no significant differences compared with the control and HES groups. CO decreased significantly in the control group (from 4.9 +/- 1.6 L/min to 3.8 +/- 0.9 L/min [P = 0.002]) and was significantly lower than in the HES patients in whom CO increased significantly after volume preload (from 5.2 +/- 1.23 L/min to 6.2 +/- 1.43 L/min [P = 0.003]) and remained at baseline level until the end of the study., Conclusion: Intravascular volume preload with saline plus HES prevented a decrease of CO, but did not prevent spinal anesthesia-induced hypotension in elderly patients undergoing transurethral resection of the prostate.

Objective: To determine the differential influence of molecular weight and the degree of substitution of HES solutions on pharmacodynamics and pharmacokinetics including organ storage in a model of acute hemodilution in pigs., Design: Prospective controlled randomized animal trial., Interventions: After bleeding, 20 ml/kg, animals were substituted with 6% HES preparations (200/0.62, 200/0.5, and 100/0.5)., Measurements and Results: We did not observe any significant differences in the ability to sufficiently achieve plasma volume expansion and restoration of macrocirculation, nor maintenance of indicators of microcirculation between the groups. Urine production was significantly higher in HES-treated animals and highest in animals substituted with HES 100/0.5. Plasma clearance was measured under steady-state conditions with significantly reduced clearance for the HES 200/0.62 group compared with HES 100/0.5 and HES 200/0.5 (6.6 vs. 13.2 and 13.9 ml/min; P < or = 0.001), thus being dependent on the degree of substitution. Even after only 6 h, the amount of infused HES not detectable in either blood or urine was significantly higher in HES 200/0.62-treated animals (50.7% compared with HES 200/0.5 (28.8%), P = 0.020 and HES 100/0.5 (28.4%), P = 0.018), with its proportion rising over time. Finally, we could demonstrate considerable amounts of all HES solutions being stored in liver, kidney, lung, spleen and lymph nodes., Conclusions: All preparations analyzed sufficiently restored macro- and microcirculation; however, for all solutions relevant tissue storage of HES was observed after only 6 h.

Background: Artificial oxygen carriers such as perfluorocarbon (PFC) emulsions have reached Phase III clinical trials as alternatives to homologous blood, but their rheologic effects have not been characterized. In this study, the rheologic effects of PFC emulsion in the presence of clinically used volume expanders were investigated., Study Design and Methods: The effects of a new PFC emulsion (small droplet size with narrow size distribution) at two PFC concentrations (4 and 8 g/dL) on plasma and whole-blood viscosity in the presence of human albumin solution (HAS), hydroxyethyl starch (HES), or modified fluid gelatin (MFG) were investigated. Three hematocrit (Hct) levels were investigated: 30, 20, and 13 percent. Plasma, PFC emulsions, and whole-blood viscosity, with a Couette viscometer, and RBC elongation, with an ektacytometer, were measured for shear rates of 0.2 to 128 per second., Results: The two PFC concentrations increased plasma and whole-blood viscosities. Viscosity values similar to physiologic ones (Hct level, 40%) were observed at: 1) Hct level of 13 percent, with 4 or 8 g per dL MFG-PFC; 2) Hct level of 20 percent, with 4 g per dL MFG-PFC; and 3) Hct level of 30 percent, with 4 g per dL HES-PFC and 4 and 8 g per dL HAS-PFC. RBC deformability was unchanged., Conclusion: It is concluded that this new PFC emulsion increases plasma and blood viscosity and that among the three studied volume expanders, the interaction with MFG can result in viscosity values above the physiologic one even at low Hct values. The possible consequences of the increased viscosity at low Hct values are discussed.

Adequate restoration of intravascular volume remains an important therapeutic manoeuvre in managing the surgical, medical and the critically ill intensive care patient. Definition of the ideal volume replacement strategy still remains one of the burning problems. The choice between colloid and crystalloid solutions continues to generate controversy. The highly controversial crystalloid/colloid dispute has been enlarged to a colloid/colloid debate because aside of the natural colloid albumin several non-protein (synthetic) colloids are available as plasma substitutes (e.g. dextrans, gelatins, hydroxyethyl starch [HES] solutions). Due to their varying physico-chemical properties, these solutions widely differ with regard to their pharmacokinetic and pharmacodynamic properties as well as to their hemodynamic efficacy and side-effects. HES is the most intensively studied plasma substitute. The different HES preparations are defined by concentration, molar substitution (MS), mean molecular weight (MW), and the C2/C6 ratio of substitution. Two new HES specification, a third-generation HES with a lower Mw and a lower MS (6% HES 130/0.4) than all other HES preparation and a first-generation HES prepared in a balanced solution, may be promising by improving the therapy of the hypovolemic patient. Albumin cannot be recommended for correction of hypovolemia because of ist extreme costs and because it can easily be replaced by other no-protein colloids. Dextrans should also not be used any more due to the negative effects on coagulation and its high anaphylactic potency. The historical crystalloid/colloid controversy has been focused primarily on outcome. There is increasing evidence that outcome (mortality) is not the correct measure when assessing the ideal volume replacement strategy. New concepts about critical care such as organ perfusion and organ function, the role of inflammation, immunological aspects, and wound healing may change this point of view. Volume replacement has been hitherto often based on art, dogma and personal beliefs. Further well-performed studies in this area will help more to shed new light on the ideal volume replacement strategy of the hypovolemic patient than more meta-analyses that are pooling old-to-very old studies to solve this problem.

In this prospective, randomized, open controlled study we compared the effects on net red blood cell loss of 6% hydroxyethyl starch 130/0.4 (HES: n = 64) and 3% modified fluid gelatin (GEL: n = 68) administered for intravascular volume management in patients undergoing coronary surgery. Blood losses were calculated from determination of circulating blood volume and measurement of preoperative and postoperative hematocrit. Amount of colloids that could be administered was limited to 50 mL/kg. If additional fluids were required, balanced crystalloid solution was used. Anesthetic and surgical techniques were standardized. Both groups were similar with regard to demographic and intraoperative variables. Total study drug was 48.9 +/- 17.2 mL/kg in the HES group and 48.9 +/- 14.6 mL/kg in the GEL group. Total red blood cell loss was 544 +/- 305 mL in the HES group and 504 +/- 327 mL the GEL group. Measured blood losses were also similar in both groups (HES, 19.4 +/- 12.3 mL/kg; GEL, 19.2 +/- 14.5 mL/kg). Exposure to allogeneic blood product was comparable in both groups. In the conditions of the present study, HES 130/0.4 up to 50 mL/kg is a valuable alternative to modified fluid gelatin for plasma volume expansion during and after cardiac surgery.

Upon exposure to hypotonic medium, skate red blood cells swell and then reduce their volume by releasing organic osmolytes and associated water. The regulatory volume decrease is inhibited by stilbenes and anion exchange inhibitors, suggesting involvement of the red blood cell anion exchanger skAE1. To determine the role of tyrosine phosphorylation, red blood cells were volume expanded with and without prior treatment with the tyrosine kinase inhibitor piceatannol. At the concentration used, 130 microM, piceatannol nearly completely inhibits p72(syk), a tyrosine kinase previously shown to phosphorylate skAE1 (M. W. Musch, E. H. Hubert, and L. Goldstein. J Biol Chem 274: 7923-7928, 1999). Hyposmotic-induced volume expansion stimulated association of p72(syk) with a light membrane fraction of skate red blood cells. Piceatannol did not inhibit this association but decreased hyposmotically stimulated increased skAE1 tyrosine phophorylation. Movement of skAE1 from an intracellular to a surface detergent-resistant membrane domain and tetramer formation were not inhibited by piceatannol treatment. Two effects of hyposmotic-induced volume expansion, decreased band 4.1 binding and increased ankyrin, were both inhibited by piceatannol. These results suggest that at least one event requiring p72(syk) activation is pivotal for hyposmotic-induced increased transport; however, steps that do not require tyrosine phosphorylation may also play a role.

Objective: The purpose of this study was to investigate the effect of plasma volume expansion on the pulsatility indices of the fetal umbilical and middle cerebral arteries., Study Design: Two hundred sixteen patients with severe preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, hypertension-related fetal growth restriction, and gestational ages between 24 and 34 completed weeks of gestation were assigned randomly for temporizing treatment with plasma volume expansion (n = 111 patients; 250 mL hydroxyethyl starch 6% twice daily in 4 hours, and NaCl 0.9% between doses of hydroxyethyl starch and with intravenous medication) or without plasma volume expansion (n = 105; only NaCl 0.9% when necessary with medication). Measurements of the pulsatility index of the umbilical and middle cerebral arteries were performed at admission, after 16 to 48 hours, 60 to 120 hours, and 7 to 11 days., Results: Median gestational age was 30 weeks in both groups. Infused volumes of plasma volume expansion in the treatment group (total median, 813 mL/d) were associated with a significant decrease of hemoglobin concentration. Changes from baseline measurements of the umbilical and middle cerebral arteries were not different between the groups nor within subgroups during the first 7 to 11 days., Conclusion: Plasma volume expansion did not influence the pulsatility indices of the umbilical and middle cerebral arteries.

Background: Recent reports indicated negative effects of hydroxyethylstarch (HES) on renal function. The goal of this large scale retrospective study was to detect whether there was an association between postoperative deterioration of renal function and the use of HES 200 kD, 0.5 DS in the cardiac surgery setting., Methods: Retrospective analysis of daily collected data in 3124 patients who underwent coronary artery bypass and/or valvular surgery. Three groups were compared according to differences in fluid therapy: --GEL: gelatin was used as priming fluid of extracorporeal circulation (ECC) and for postoperative filling (n = 1276). --MIX: HES was used as priming fluid of ECC an gelatin was used for postoperative filling (n = 1008). --HES: HES was used as priming fluid of ECC and for postoperative filling (n = 840)., Main Results: There were no significant differences in postoperative serum creatinine concentrations between the 3 groups: GEL: 12,2 +/- 0,5 mg/l; MIX: 12,3 +/- 0.5 mg/l; HES: 12,3 +/- 0.6 mg/l. The need for postoperative extrarenal epuration was not significantly different between the 3 periods: GEL: 2,9%; MIX: 3,1%; HES: 3,8%., Conclusion: The use of HES 200 kD, 0.5 DS in cardiac surgery does not seem to be associated with a clinically significant deterioration of postoperative renal function.

We studied the distribution and elimination of an IV infusion of 20 mL/kg of acetated Ringer's solution (approximately 1500 mL) over 60 min in 12 women undergoing laparoscopic cholecystectomy. A plasma dilution of 4.2% developed during the induction of general anesthesia, even though fluid was withheld. The additional plasma dilution induced by the subsequent volume expansion was slightly larger than expected from previous volunteer experiments and averaged 18%. The diuretic response to intravascular fluid administration was small, and only 20% of the infused fluid had been excreted 4 h later. Volume kinetic analysis showed that the IV fluid expanded a central body fluid space by 3.2 L. The clearance constants for distribution and elimination averaged 115 mL/min and 6.8 mL/min, respectively. These data represent a half-life of the fluid in the patients that is 17 times longer (median, 4.5 h) than the half-life of the plasma dilution (16 min), indicating a strong tendency to the formation of peripheral edema. A nomogram based on the kinetic variables suggests that infusion rates should be relatively rapid early on during surgery but slower later. This strategy creates a constant plasma dilution at any desired level without causing undue peripheral accumulation of fluid.

Background: The authors studied the influence of alpha, beta, and dopaminergic catecholamines on blood volume expansion in conscious normovolemic sheep before, during, and after a bolus infusion of a crystalloid., Methods: A 0.9% NaCl bolus (24 ml/kg in 20 min) was infused in four paired experiments each: no drug, dopamine infusion (50 microg . kg . min), isoproterenol infusion (0.1 microg . kg . min), and phenylephrine infusion (3 microg . kg . min). Blood volume expansion was calculated by the dilution of blood hemoglobin concentration., Results: Dopamine had little effect on peak blood volume expansion (12.7 +/- 0.9 ml/kg) compared with 0.9% NaCl (13.0 +/- 2.7 ml/kg); in contrast, isoproterenol augmented blood volume expansion (18.5 +/- 1.8 ml/kg), and phenylephrine reduced blood volume expansion (8.9 +/- 1.4 ml/kg). Two hours after the 0.9% NaCl bolus, sustained blood volume expansion was greatest in the isoproterenol protocol (12.2 ml/kg), whereas the dopamine protocol (6.8 ml/kg) remained similar to the control protocol (4.1 ml/kg), and the phenylephrine protocol had a net volume loss (-1.9 ml/kg). Some blood volume expansion differences were attributed to changes in renal function as phenylephrine infusion increased urinary output, whereas isoproterenol was associated with antidiuresis. However, dopamine caused diuresis and sustained augmentation of blood volume., Conclusion: Catecholamines can alter the intravascular volume expansion of fluid therapy. beta-Receptor (isoproterenol) stimulation augmented blood volume expansion, whereas alpha (phenylephrine) stimulation reduced blood volume expansion. Combined dopaminergic, beta, and possibly alpha stimulation with dopamine augmented blood volume expansion and cardiac output while inducing diuresis.

Background: After head trauma, hypertonic saline lowers intracranial pressure (ICP) and preserves or increases cerebral perfusion pressure (CPP). Hypertonic saline has not been studied in patients with increased ICP due to subarachnoid haemorrhage (SAH). The aim of this study was to evaluate the effects on elevated ICP and on CPP in patients critically ill from SAH., Methods: Critically ill SAH-patients needing urgent treatment for an elevated ICP, but otherwise stable, were included in this study. We infused 7.2% saline in 6% hydroxyethyl starch (HyperHAES((R)) Fresenius Kabi AG, Bad Homburg v.d.h., Germany) 2 ml kg(-1) during 20 min in 10 episodes of ICP > 20 mmHg in seven patients with SAH. Our primary outcome variables were changes in ICP and CPP during and for 3 h after this infusion., Results: All interventions resulted in decreased ICP and elevation of CPP. The mean value for maximum ICP decrease in percent of baseline was 58% (range 43-83%, P = 0.002), which occurred at mean 40 min (range 25-90 min) after start of infusion. The mean percent peak increase in CPP was 26% (range 16-32%, P = 0.002). After 210 min, ICP was 35% lower than baseline (range 19-39%, P = 0.008). Serum sodium increase was mean 6.6 mmol l(-1) (range 5-9 mmol l(-1)) 30 min after start of infusion., Conclusions: 7.2% saline in 6% hydroxyethyl starch is an effective and safe therapy for intracranial hypertension after SAH. We demonstrate that an infusion of 2 ml kg(-1) during 20 min has a predictable and clinically significant beneficial effect on ICP and CPP. The effect was still present 3 h after end of infusion. Rebound ICP-increase was not observed within 3 h.

Hepatorenal syndrome (HRS) is a functional renal disorder complicating decompensated cirrhosis. Treatments to date, except liver transplantation, have been able to improve but not normalize renal function. The aim of this study was to determine the efficacy of transjugular intrahepatic portosystemic stent shunt (TIPS) as a treatment for type 1 HRS in ascitic cirrhotic patients, following improvement in systemic hemodynamics with a combination of midodrine, octreotide, and albumin (medical treatment). Fourteen ascitic cirrhotic patients with type 1 HRS received medical therapy until their serum creatinine reached below 135 micromol/L for at least 3 days, followed by a TIPS if there were no contraindications. Patients were assessed before and after medical treatment, as well as at 1 week and 1, 3, 6, and 12 months post-TIPS with measurements of renal function, sodium handling, systemic hemodynamics, central blood volume, and hormonal markers. Medical therapy for 14 +/- 3 days improved renal function (serum creatinine: 233 +/- 29 micromol/L vs. 112 +/- 8 micromol/L, P =.001) and renal sodium excretion (5 +/- 2 mmol/d vs. 9 +/- 2 mmol/d, P =.002) in 10 of the 14 patients. TIPS insertion in five of the responders further improved renal function and sodium excretion, so that by 12 months post-TIPS, glomerular filtration rate (96 +/- 20 mL/min, P <.01 vs. pre-TIPS) and urinary sodium excretion (119 +/- 15 mmol/d, P <.01 vs. pre-TIPS) were normal, associated with normalization of plasma renin and aldosterone levels and elimination of ascites. In conclusion, TIPS is an effective treatment for type 1 HRS in suitable patients with cirrhosis and ascites, following the improvement of renal function with combination therapy of midodrine, octreotide, and albumin.

Background: Hypertonic saline-dextran (HSD) has been utilized for small-volume resuscitation in acute circulatory shock. However, HSD has also been reported to induce myocardial depression. The aim of this study was to examine the effects of HSD on cardiac performance and splanchnic perfusion in a low cardiac output model based on experimental cardiac tamponade., Methods: Seven anaesthetized, mechanically ventilated pigs of both sexes (weight 24 +/- 2 kg, mean +/- SEM) completed a randomized, cross-over protocol. A low cardiac output state was established by intrapericardial infusion of dextran. Animals were resuscitated by bolus infusions (4 ml kg(-1) in 2 min) of either 7.5% hypertonic saline-dextran or Ringer's acetated solution (RAc) and then observed during tamponade (20 min) and following its release (40 min). Central haemodynamics, portal venous (QPV) and renal arterial (QRA) flows were measured together with gastric, jejunal, hepatic and renal laser-Doppler flowmetry., Results: Resuscitation using HSD in a low cardiac output state completely restored QPV and improved gastric, jejunal, hepatic and renal microcirculation as assessed by laser-Doppler flowmetry while no significant effect was observed in QRA. No such beneficial effects could be observed when animals were resuscitated using RAc. The improved haemodynamic state by HSD was maintained following release of cardiac tamponade while perfusion in RAc resuscitated animals returned to baseline or even remained depressed (hepatic and renal microcirculation). No signs of cardiodepression by HSD were observed., Conclusion: Resuscitation using HSD in a low cardiac output state restored splanchnic perfusion and microcirculation without any signs of cardiodepression.

Unlabelled: Definition of the "ideal" intravascular fluid volume replacement strategy still remains a critical problem. This article analyzes studies on volume replacement by using a MEDLINE search of the past 3 years (from January 1, 2000, to December 12, 2002). Forty original studies in humans with a total of 2454 subjects were identified. Five studies were performed in volunteers (n = 113); the other 35 studies (n = 2341) were performed in a variety of patients (e.g., cardiac surgery, trauma patients, children, and intensive care unit patients). The influence of different volume replacement regimens on coagulation was one of the major topics of interest (16 studies with 1183 subjects), and other studies focused on metabolic state, alterations in macro- and microcirculation, volume distribution, and organ function (e.g., kidney function and splanchnic perfusion). Among all synthetic colloids, hydroxyethyl starch (HES) was the solution most often studied. Two new HES preparations have been approved (Hextend), a balanced hetastarch solution, and a new third-generation HES [130/0.4]). Only two studies used albumin, and no superiority of albumin was found over less expensive synthetic colloids. In almost all studies, the outcome either was no end-point or was not reported. Volume replacement has often been hitherto based on dogma and personal beliefs. Future well performed studies in this area will hopefully help to shed new light on the ideal volume replacement strategy., Implications: By using a MEDLINE search covering the last 3 yr, the present knowledge on volume replacement regimens was analyzed. Forty studies in humans were identified. New hydroxyethyl starch preparations have shed light on this topic, whereas no additional data supporting the use of albumin have been presented.

Background: What is the effect of preoperative acute normovolemic hemodilution (ANH) with 6% hydroxyethyl starch (HES) 130/0.4 (Voluven) on blood volume?, Methods: In 10 patients undergoing radical hysterectomy, ANH was performed to a hematocrit of 21% using 6% HES 130/0.4 (Voluven) whereby a replacement of blood with 115% of colloid was planned. Plasma volume (indocyanine green dilution technique) and hematocrit were determined before, 30 and 60 min after ANH. Red cell volume (labelling erythrocytes with fluorescein) was determined before and 30 min after ANH., Results: After removal of 1,431+/-388 ml of blood and simultaneous replacement with 1,686+/-437 ml of colloid, blood volumes were 218+/-174 ml higher than before (at 105+/-4%). The volume effect was 98+/-12%, 30 min after ANH. Even 60 min after ANH, mean blood volumes were with 4,228+/-986 ml slightly higher than before ANH (102+/-5%). The hematocrit decreased disproportionally in relation to the residual intravascular volume. Consequently, estimating the volume effect from the changes in hematocrit led to an overestimation (about +30%)., Conclusion: Double label measurements of blood volume demonstrated that the volume effect of 6% HES 130/0.4 (Voluven) is about 100% in the course of ANH. The reason for the disproportionally large decrease in hematocrits could be the mobilization of a fraction of the plasma volume which was retained within the endothelial glycocalyx.

Unlabelled: Although the distribution of various crystalloid and colloid solutions at equilibrium has been well established, the acute peak expansion of intravascular volume that can be achieved with the rapid administration of crystalloid or colloid is unknown. We studied eight healthy male subjects in a two-part crossover trial designed to assess the maximal increase in intravascular volume achieved with 1000 mL of lactated Ringer's solution compared with the same volume of 6% Hetastarch. Subjects were made moderately hypovolemic by the withdrawal of 900 mL of blood, and then the crystalloid or colloid solution was rapidly infused over 5-7 min. Serial dilution of hematocrit was measured every 5 min for 30 min to determine changes in blood volume. Peak expansion of intravascular volume with lactated Ringer's solution was 630 +/- 127 mL, occurring immediately the rapid infusion was complete, whereas the peak expansion of intravascular volume with 6% Hetastarch was 1123 +/- 116 mL and occurred 5 min after the completion of the fluid infusion. The results were significantly different (P < 0.001). These results would suggest that even for very short periods of time, rapid infusion of colloid significantly more effectively increases blood volume and, by inference, cardiac output than the same volume of crystalloid, even if the crystalloid is administered very rapidly., Implications: Under conditions of moderate hypovolemia, the maximal acute intravascular volume expansion with the rapid infusion of 1000 mL of lactated Ringer's solution is slightly more than half that achieved with the same volume of 6% Hetastarch.

Objectives: Review of the physiological and clinical consequences of hyperchloraemic acidosis observed during plasma volume replacement using crystalloids and colloids., Data Sources: Data were searched in the Medline database after 1990 using the following key words: metabolic acidosis, crystalloids, colloids, albumin, gelatin, hydroxyethyl starch., Data Extraction: Publications before 1990 were selected for their historical value. Most of articles published after 1990 and all types including case report were accepted., Data Synthesis: Large volume infusion of isotonic solution can cause hyperchloraemic acidosis. Colloid plasma substitutes using saline solvent may be responsible for the same kind of acidosis with acidaemia. The anion gap is not modified in this case because of chloride increase. Physiological mechanism may be described using the Henderson-Hasselbach equation or the strong ion difference decrease (Stewart concept). Excessive chloride infusion is a major factor in this acid-base disorder and the term hyperchloraemic acidosis should be preferred to dilutional acidosis. When perioperative acidosis occurs, careful and complete analysis of acid-base disturbance should be made. The association of a normal anion gap, normal lactatemia, hyperchloraemia and acidaemia does not need specific treatment. Acidosis corrects spontaneously and slowly following chloride normalization. But any factor that may increase acidosis should be avoided., Conclusion: The use of balanced solution like lactated-Ringer solution instead of isotonic saline solution for fluid resuscitation, except for specific contra-indication as intracranial hypertension, may avoid hyperchloraemic acidosis. Potential risk of this acidosis led to the conception of a new colloid using balanced crystalloids solution as the solvent (Hextend).

Background: HES solutions provide a sterile, alternative colloidal fluid to albumin solutions and/or plasma in the management of patients who need plasma volume expansion. Solutions of HES are widely accepted internationally but are used only modestly in the United States, largely because of concerns over hemostasis., Study Design and Methods: A randomized, blinded, two-arm trial comparing the hemostatic effects of pentastarch versus hetastarch when infused in the clinically relevant dose of 90 g of HES dissolved in 1.5 L of saline was conducted. Multiple studies of fibrin clot formation, fibrinogen/fibrinolysis, and platelet (PLT) functions were performed before and on multiple occasions for 70 days following HES infusion., Results: Several significant abnormalities of hemostasis assay results occurred following HES infusions, with hetastarch causing significantly greater abnormalities than pentastarch. Individual clotting proteins and blood PLTs fell modestly because of plasma volume expansion and hemodilution. A fall in excess of that caused by hemodilution was demonstrated for von Willebrand factor antigen plus its associated FVIII and ristocetin cofactor activities. The partial thromboplastin time was prolonged, whereas the thrombin time was shortened. Plt function abnormalities were seen in most subjects to a modest degree. Studies of fibrinolysis were normal., Conclusions: Solutions of hetastarch produce significant abnormalities of some hemostasis laboratory results when infused at clinically relevant doses, but it is unlikely that the modest hemostatic abnormalities produced at these doses per se would lead to clinical bleeding. Hetastarch causes greater hemostatic abnormalities than pentastarch, and because both HES solutions have comparable plasma volume-expanding effects, it is reasonable to prefer pentastarch as a plasma volume expander.

Background: The impact of acute preoperative volume loading with colloids on blood volume has not been investigated sufficiently., Methods: Before surgery, in 20 patients undergoing major gynecologic procedures, volume loading was performed during anesthesia by infusing approximately 20 ml/kg of colloid at a rate of 90 ml/min (group I: 5% albumin solution; group II: 6% hetastarch solution; n = 10 each). Plasma volume (indocyanine green dilution technique), erythrocyte volume (labeling erythrocytes with fluorescein), hematocrit, total protein, and hetastarch plasma concentrations (group II) were measured before and 30 min after the end of infusion., Results: More than 1,350 ml of colloid (approximately 50% of the baseline plasma volume) were infused within 15 min. Thirty minutes after the infusion had been completed, blood volume was only 524 +/- 328 ml (group I) and 603 +/- 314 ml (group II) higher than before volume loading. The large vessel hematocrit (measured by centrifugation) dropped more than the whole body hematocrit, which was derived from double-label measurements of blood volume., Conclusions: The double-label measurements of blood volume performed showed that 30 min after the infusion of approximately 20 ml/kg of 5% albumin or 6% hetastarch solution (within 15 min), only mean 38 +/- 21% and 43 +/- 26%, respectively, of the volume applied remained in the intravascular space. Different, i.e., earlier or later, measuring points, different infusion volumes, infusion rates, plasma substitutes, or possibly different tracers for plasma volume measurement might lead to different results concerning the kinetics of fluid or colloid extravasation.

Background: There are several studies indicating a correlation between treatment with hydroxyethyl starch (HES) and pruritus. In order to see whether there is a possible dose-response relationship between HES and pruritus, we retrospectively studied 50 patients who had received HES in varying doses (cumulative dose 500-19500 ml) as hemodilution therapy after subarachnoid hemorrhage., Methods: Of 50 consecutive patients, 6 were excluded due to severe neurological sequelae. A questionnaire was sent to the remaining 44 patients at 6 months (5-12 months) median (range) after the end of HES treatment., Results: We received answers from 37 patients, of whom 54% reported pruritus. On average pruritus lasted for 15 weeks. There was significantly more pruritus in patients who received more than 5000 ml of HES versus those who received less than 5000 ml (P=0.023). Pruritus had a delayed onset and appeared as pruritic crises lasting for 2-30 min. It had a patchy distribution in most patients and no predilected locations. In 4 patients (20%) the pruritus lasted longer than 21 weeks., Conclusion: Our study indicates that there is a dose-dependency for the incidence of HES-induced pruritus, and that in some cases the pruritus may be severe and long-lasting.