Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 vs. 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS study. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery. A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock. Resuscitation with hydroxyethyl starch improves renal function and lactate clearance in penetrating trauma in a randomized controlled study: the FIRST trial (Fluids in Resuscitation of Severe Trauma). Volume therapy in the critically ill: is there a difference? Hydroxyethyl starch (HES) does not directly affect renal function in patients with no prior renal impairment. Efficacy of hetastarch in the resuscitation of patients with multisystem trauma and shock. A total balanced volume replacement strategy using a new balanced hydoxyethyl starch preparation (6% HES 130/0.42) in patients undergoing major abdominal surgery. Hemodynamic effects of 6% and 10% hydroxyethyl starch solutions versus 4% albumin solution in septic patients. Hydroxyethyl starch resuscitation reduces the risk of intra-abdominal hypertension in severe acute pancreatitis. Therapeutic influence of 20 % albumin versus 6% hydroxyethylstarch on extravascular lung water in septic patients: a randomized controlled trial. [Comparison of postoperative volume therapy in heart surgery patients]. Fluid resuscitation in the management of early septic shock (FINESS): a randomized controlled feasibility trial. A prospective randomized study to evaluate the renal impact of surgical revascularization strategy in diabetic patients. A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis. [The study of hypertonic saline and hydroxyethyl starch treating severe sepsis]. Volume therapy with a new hydroxyethyl starch solution in cardiac surgical patients before cardiopulmonary bypass. N-acetylcysteine does not prevent hepatorenal ischaemia-reperfusion injury in patients undergoing orthotopic liver transplantation. [The influence of lactate Ringer solution versus hydroxyethyl starch on coagulation and fibrinolytic system in patients with septic shock]. [Volume replacement with a new hydroxyethyl starch preparation (3 percent HES 200/0.5) in heart surgery]. Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new starch preparation with gelatin. Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction. Safety of HES 130/0.4 (Voluven(R)) in patients with preoperative renal dysfunction undergoing abdominal aortic surgery: a prospective, randomized, controlled, parallel-group multicentre trial. The influence of different intravascular volume replacement regimens on renal function in the elderly. Fluid resuscitation with colloids of different molecular weight in septic shock. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. Does the type of volume therapy influence endothelial-related coagulation in the critically ill? Continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD)--what is the procedure of choice in critically ill patients? Comparison of the acute hemodynamic effects of hypertonic or colloid infusions immediately after mitral valve repair. Randomized trial of volume expansion with albumin or saline in children with severe malaria: preliminary evidence of albumin benefit. The effects of albumin versus hydroxyethyl starch solution on cardiorespiratory and circulatory variables in critically ill patients.
ABSTRACT: INTRODUCTION: Inadequate initial treatment and delayed hemodynamic stabilization (HDS) may be associated with increased risk of death in severe sepsis patients. METHODS: In order to compare the hemodynamic efficacy and safety of 6% HES 130/0.4 and NaCl 0.9% for HDS in patients with severe sepsis, we designed a prospective, multicenter, active-controlled, double-blind, randomized study in intensive care units. RESULTS: 174 out of 196 patients reached HDS (88 and 86 patients for HES and NaCl, respectively). Significantly less HES was used to reach HDS vs. NaCl (1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group (mean difference = -331± 1,033, 95% CI -640 to -21, P = 0.0185). Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl, respectively. Total quantity of study drug infused over four consecutive days, ICU and hospital LOS, and area under the curve of SOFA score were comparable. Acute renal failure occurred in 24 (24.5%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454). There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality, coagulation, or pruritus up to 90 days after treatment initiation. CONCLUSION: Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups. CLINICALTRIALS.GOV: NCT00464204. Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.
                In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization.
                Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline.
                Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.). The value of human albumin (HA) for treating hypovolemia is controversial. Less expensive alternatives such as hydroxyethyl starch (HES) are sometimes refused because of unwanted side effects. We prospectively randomized 50 patients older than 70 years old undergoing major abdominal surgery to receive either 5% HA (n = 25) or a third generation HES preparation (6% HES 130/0.4; n = 25) when mean arterial blood pressure was <60 mm Hg and central venous pressure was <10 mm Hg. Hemodynamics, inflammation (interleukin-6), endothelial activation-integrity (adhesion molecules), coagulation (thrombelastography), and renal function (including kidney-specific proteins) were monitored after the induction of anesthesia, after surgery, 5 h in the intensive care unit, and on the first postoperative day. HA patients received 3960 +/- 590 mL of HA and 5070 +/- 1030 mL of Ringer's lactate solution, and HES patients received 3500 +/- 530 mL of HES and 4550 +/- 880 mL of Ringer's lactate solution. Total protein remained normal only in the HA-treated patients. No significant differences (P > 0.1) between the groups were seen with regard to hemodynamics, coagulation, and kidney function. Plasma levels of interleukin-6 and soluble adhesion molecules were significantly (P < 0.05) higher in the HA- than in the HES-treated patients. We conclude that HA in elderly patients undergoing major abdominal surgery can easily be replaced by a modern HES preparation. Because of the decreased inflammatory response and endothelial activation-injury, HES 130/0.4 seems to be the more appropriate fluid strategy for these patients. High volume hemofiltration (HVHF) has shown potential benefits in septic animals and a few reports suggested a hemodynamic improvement in humans. However, randomized studies are still lacking. Our goal was to evaluate the hemodynamic effects of HVHF in septic shock patients with acute renal failure (ARF).
                Prospective randomized study in an intensive care unit (ICU).
                Twenty patients with septic shock and ARF.
                Patients were randomized to either high volume hemofiltration [HVHF 65 ml/(kg h)] or low volume hemofiltration [LVHF 35 ml/(kg h). Vasopressor dose was adjusted to reach a mean arterial pressure (MAP) > 65 mmHg.
                We performed six hourly measurements of MAP, norepinephrine dose, PaO(2)/FiO(2) and lactate, and four daily urine output and logistic organ dysfunction (LOD) score. Baseline characteristics of the two groups were comparable on randomization. Mean norepinephrine dose decreased more rapidly after 24 h of HVHF treatment compared to LVHF treatment (P = 0.004) whereas lactate and PaO(2)/FiO(2) did not differ between the two treatment groups. During the 4-day follow-up, urine output was slightly increased in the HVHF group (P = 0.059) but the LOD score evolution was not different. Duration of mechanical ventilation, renal replacement therapy and ICU length of stay were also comparable. Survival on day 28 was not affected.
                HVHF decreased vasopressor requirement and tended to increase urine output in septic shock patients with renal failure. However, a larger trial is required to confirm our results and perhaps to show a benefit in survival. The role of fluids in trauma resuscitation is controversial. We compared resuscitation with 0.9% saline vs hydroxyethyl starch, HES 130/0.4, in severe trauma with respect to resuscitation, fluid volume, gastrointestinal recovery, renal function, and blood product requirements.
                Randomized, controlled, double-blind study of severely injured patients requiring >3 litres of fluid resuscitation. Blunt and penetrating trauma were randomized separately. Patients were followed up for 30 days.
                A total of 115 patients were randomized; of which, 109 were studied. For patients with penetrating trauma (n=67), the mean (sd) fluid requirements were 5.1 (2.7) litres in the HES group and 7.4 (4.3) litres in the saline group (P<0.001). In blunt trauma (n=42), there was no difference in study fluid requirements, but the HES group required significantly more blood products [packed red blood cell volumes 2943 (1628) vs 1473 (1071) ml, P=0.005] and was more severely injured than the saline group (median injury severity score 29.5 vs 18; P=0.01). Haemodynamic data were similar, but, in the penetrating group, plasma lactate concentrations were lower over the first 4 h (P=0.029) and on day 1 with HES than with saline [2.1 (1.4) vs 3.2 (2.2) mmol litre⁻¹; P=0.017]. There was no difference between any groups in time to recovery of bowel function or mortality. In penetrating trauma, renal injury occurred more frequently in the saline group than the HES group (16% vs 0%; P=0.018). In penetrating trauma, maximum sequential organ function scores were lower with HES than with saline (median 2.4 vs 4.5, P=0.012). No differences were seen in safety measures in the blunt trauma patients.
                In penetrating trauma, HES provided significantly better lactate clearance and less renal injury than saline. No firm conclusions could be drawn for blunt trauma. Study registration: ISRCTN 42061860. There are still several concerns about the extensive and prolonged use of hydroxyethylstarch solution (HES) in critically ill patients. The effects of volume replacement with HES over 5 days on hemodynamics, laboratory data, and organ function were compared with volume therapy using human albumin (HA).
                Prospective, randomized study.
                Clinical investigations on a surgical intensive care unit (ICU) of a university hospital.
                150 traumatized patients (injury severity score > 15) and 150 postoperative patients with sepsis were analyzed.
                Either 10% low-molecular weight HES (HES-trauma, n = 75; HES-sepsis, n = 75) or 20% HA (HA-trauma, n = 75; HA-sepsis, n = 75) was given for 5 days to maintain the pulmonary capillary wedge pressure (PCWP) between 12 and 15 torr. The entire management of therapy of the patients was performed by physicians who were not involved in the study and blinded to the infusion regimen.
                In addition to extensive cardiorespiratory monitoring, several routine laboratory parameters for assessing pulmonary, renal, hepatic, and coagulation function were analyzed from arterial blood samples on the day of admission to the ICU and on the day of sepsis diagnosis, respectively ("baseline" value) and daily over the following 5 days. Mortality during and after the study did not differ significantly between the infusion groups. There were also no differences between the incidence of pulmonary, renal, or hepatic failure in the two subgroups. Mean arterial pressure, heart rate, and PCWP were similar in both subgroups, whereas cardiac index, oxygen delivery index, oxygen consumption index, and the ratio between the partial pressure of oxygen in arterial blood and fractional inspired oxygen were higher in the HES- than in the HA-treated groups. Standard coagulation parameters did not differ, albumin concentration increased significantly in both HA groups, and lactate concentrations decreased only in the HES-sepsis patients (from 2.8 +/- 0.5 to 1.5 +/- 0.4 mg/dl). Volume replacement using albumin was significantly (p < 0.001) more costly than therapy with HES.
                Volume therapy with 10% HES for 5 days in the ICU patient showed no disadvantages compared with an infusion regimen using 20% albumin. Volume replacement using HES may even be associated with improved hemodynamics. HES appears to be a valuable and significantly cheaper alternative to albumin--even for prolonged volume therapy in the critically ill patient. To examine the effects of hydroxyethyl starch (HES) on renal function.
                Randomized, controlled trial.
                Operating theatre of a university hospital.
                60 ASA physical status I and II male patients undergoing middle ear surgery.
                Patients received either lactated Ringer's solution (LRS) or one of three HES solutions. The HES solutions were administered in a dose of 15 mL/kg bodyweight (bw), the Ringer's solution in a dose of 60 mL/kg bw, after induction of anesthesia over a period of one hour.
                Blood and urine samples for hormone and enzyme tests were obtained at defined times before, during, and after surgery. Urine excretion, glomerular filtration rate (GFR), renal plasma flow, and routine hemodynamic parameters were measured simultaneously.
                There were no significant intergroup differences regarding GFR, renal plasma flow, or tubular and glomerular integrity as measured by specific proteins and enzymes (alpha-1-microglobulin, Tamm-Horsfall-protein, immunoglobulin G, and N-acetyl-beta-D-glucosaminidase). Arginine vasopressin decreased in all groups during and following anesthesia, aldosterone and plasma renin activity decreased only in the HES groups, and angiotensin II decreased only in the HES 200/0.5 group. Central venous pressure increased during fluid administration in the LRS group and returned to baseline sooner in the HES groups.
                Hydroxyethyl starch administration appears to be risk-free with regard to renal function in patients without preexisting renal dysfunction who undergo general anesthesia. The relevance of the decrease in aldosterone following HES therapy needs further investigation. A prospective trial of 6% hetastarch (HES) v 5% plasma protein fraction (PPF) as the colloid component of intravenous (IV) fluid resuscitation was conducted in 32 patients with multisystem trauma and/or hemorrhagic shock. Patient age, mechanism and pattern of injury, and IV fluid requirements were similar in both groups. No intergroup differences were noted in indexes of hepatic, pulmonary, or renal function or in the incidence of infection. The frequency of other complications, including bleeding diatheses, and mortality were identical in the two groups. Although this investigation should be viewed as a pilot study, our results suggest that, compared with PPF, HES in large volumes is a safe, effective colloid solution in the resuscitation of patients with multisystem trauma and/or hemorrhagic shock. Further study of HES in a larger number of patients is warranted by these findings. The kind of fluid for correcting hypovolaemia is still a focus of debate. In a prospective, randomized, controlled and double-blind study in patients undergoing major abdominal surgery, a total balanced volume replacement strategy including a new balanced hydroxyethyl starch (HES) solution was compared with a conventional, non-balanced fluid regimen.
                In Group A (n = 15), a new balanced 6% HES 130/0.42 was given along with a balanced crystalloid solution; in Group B (n = 15), an unbalanced conventional HES 130/0.42 plus an unbalanced crystalloid (saline solution) were administered. Volume was given when mean arterial pressure (MAP) was <65 mmHg and central venous pressure (CVP) minus positive end-expiratoric pressure (PEEP) level was <10 mmHg. Haemodynamics, acid-base status, coagulation (thrombelastography (TEG)) and kidney function (including kidney-specific proteins, N-acetyl-beta-d-glucosaminidase (beta-NAG) and alpha-1-microglobulin) were measured after induction of anaesthesia, at the end of surgery, 5 and 24 h after surgery.
                Group A received 3533 +/- 1302 mL of HES and 5333 +/- 1063 mL of crystalloids, in Group B, 3866 +/- 1674 mL of HES and 5966 +/- 1202 mL of crystalloids were given. Haemodynamics, laboratory data, TEG data and kidney function were without significant differences between the groups. Cl- concentration and base excess (-5 +/- 2.4 mmol L-1 vs. 0.4 +/- 2.4 mmol L-1) were significantly higher in patients of Group B than of Group A.
                A complete balanced volume replacement strategy including a new balanced HES preparation resulted in significantly less derangement in acid-base status compared with a non-balanced volume replacement regimen. The new HES preparation showed no negative effects on coagulation and kidney function. To compare the hemodynamic effects of two different concentrations of pentastarch hydroxyethyl starch (HES; 200/0.5) solutions with a 4% human albumin solution for fluid resuscitation.
                Open-label, randomized, controlled study.
                Medical-surgical intensive care unit.
                34 consecutive, hemodynamically stable, adult patients with sepsis and suspected hypovolemia.
                Patients received a 400 mL infusion of either 10% HES (n = 11), 6% HES (n = 10), or 4% albumin (n = 13) over 40 minutes.
                Hemodynamic and blood data were collected 40, 70, 100, and 160 minutes after the start of the fluid challenge.
                Cardiac index, stroke volume index, and left ventricular stroke work index increased more in the 10% HES group than the 6% HES or albumin groups (P < 0.05). Oxygen delivery increased only in the 10% HES group. A decrease in hemoglobin concentration occurred in all three groups but was greatest in the 10% HES group.
                HES is as effective as albumin for volume resuscitation in septic patients. This study aimed to address whether hydroxyethyl starch (HES) is beneficial for intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) in early stages.
                Forty-one patients with SAP were randomized to HES group (n = 20) and the Ringer's lactate (RL) group (n = 21). The groups received 6% HES 130/0.4 for 8 days and RL solution without colloid, respectively. The primary end point was the IAP. The secondary end points were fluid balance, major organ complications, the Acute Physiology and Chronic Heath Evaluation II score, and the serum levels of C-reactive protein, interleukin-6, and interleukin-8.
                The characteristics of baseline data were similar in the 2 groups. In the HES group, the IAP was significantly lower in 2 to 7 days, and fewer patients received mechanical ventilation (15.0% vs 47.6%). A negative fluid balance was observed earlier in the HES group than in the RL group (2.5 ± 2.2 vs 4.0 ± 2.5 days).
                Fluid resuscitation with HES in the early stages of SAP can decrease the risk of intra-abdominal hypertension and reduce the use of mechanical ventilation. Recent studies demonstrated that extravascular lung water (EVLW) is a reliable and independent marker for outcome. The primary therapeutically goal in critically ill patients is to resuscitate and retain adequate organ perfusion by fluid administration, where is necessary to achieve adequate intravascular filling, but avoid initiation of pulmonary edema.
                Patients with severe sepsis were randomly allocated to a group treated with 20% Albumin 100 ml every 12 hours (ALB; n = 30) or with 6% hydroxyethylstarch 130/0, 4 250 ml every 6 hours (HES; n = 26). Both treatments were completed by crystalloids or norephinephrin as necessary. We analyzed amount of developed EVLW, and relation with mortality, PaO2/FiO2 and alveolo-arterial oxygen difference.
                We observed significantly greater decrease of EVLW when compared with baseline during whole monitored period of 72 hours in ALB group in contrast to HES patients (p < 0.05). Despite no significant changes of EVLW in HES group, we noted improve of PaO2/FiO2 and AaDO2 in both groups. We did not observed significant difference in mortality.
                The present study results show can summarize that albumin reduces in a higher amount and earlier the extravascular lung water than HES, but this reduction was not associated with improvement of oxygenation functions, which was better in HES group. Patients who have undergone cardiac surgery with use of extracorporeal circulation frequently reveal marked hypovolaemia in spite of a highly positive fluid balance. This is thought to be due to transient microvascular damage and extravascular fluid shift. Further volume replacement to achieve haemodynamic stability in the postoperative period may cause fluid overload and congestive heart failure. The present study was designed to investigate whether this fluid overload could be avoided by using a hypertonic-hyperoncotic solution (group I: HHL, 10% hydroxyethylstarch 200/0.5 in 7.2% saline) instead of two different standard colloid solutions (group II: HA, 5% albumin; group III: HES, 6% hydroxyethylstarch in 0.9% saline).
                Twenty-one patients meeting our criteria for hypovolaemia immediately after cardiac surgery were randomly assigned to three groups. Patients in group I received HHL in increments of 150 ml, while patients in group II and group III were given HA and HES respectively in increments of 500 ml until hypovolemia was corrected. Haemodynamic assessment was done using a pulmonary artery thermodilution catheter. Intra- and extravascular volumes, including extravascular lung water (EVLW), intrathoracic blood volume (ITBV), and total blood volume (TBV) were measured by the double indicator technique using lung water software (COLD-System, Pulsion, Munich, Germany).
                Correction of hypovolaemia-related haemodynamic parameters and restoration of normal TBV were achieved by 236 +/- 80 ml of HHL (group I), 857 +/- 244 ml of HA (group II) and 1000 +/- 0 ml of HES (group III) respectively. TBV increased significantly in each group, compared to baseline values. EVLW did not change significantly in any group. We found that the volume-augmenting effect of HHL per millilitre infused solution was more than four times that of HA and HES, primarily as a result of increasing plasma osmolality due to an increase of plasma sodium levels. This pronounced effect on intravascular volume of HHL lasted for only 2 h following infusion, however, and did not lead to any unwanted side effects. In the period between 2 and 20 h after primary volume replacement, further fluid therapy with colloids and crystalloids, guided by clinical signs of hypovolaemia, was necessary in each group of patients. The overall fluid requirements for the first 20 h after operation did not differ among the three resuscitation regimens.
                We found that HHL is a safe and effective solution for acute correction of hypovolaemia after cardiac surgery. The advantages of a smaller initial volume load by HHL cannot be maintained for longer than 2 h. It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome. This randomized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarch vs normal saline in early septic shock, powered for a difference in mortality.
                At three Canadian and one New Zealand academic centre, 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria, infectious source, and persistent hypotension after >or= 1 L of crystalloid fluid were recruited. Feasibility measures were patient recruitment, blinding of the study fluids, and acceptability of the goal directed algorithms. Boluses of blinded normal saline or pentastarch (500 mL - maximum 3 L or 28 mL x kg(-1)) were administered within goal directed care for the first 12 hr.
                Of 161 patients screened, 121 were excluded and 40 patients were enrolled, for a recruitment rate of 0.75 patients/site/month. Only 57% of physicians and 54% of nurses correctly guessed the study fluid (P = 0.46 and P = 0.67, respectively). The goal directed algorithms were acceptable to 97% of physicians.
                The ability to recruit patients in this pilot randomized controlled trial was below expectations. Blinding of study fluids was adequate, and resuscitation algorithms were acceptable to most physicians. Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock. Acute kidney injury (AKI) is a major postoperative complication following cardiac surgery. Diabetes mellitus is a major cause of nephropathy and end-stage renal failure. We aimed to evaluate the occurrence of adverse renal outcomes, in diabetic patients, between on-pump (CPB) and off-pump (OPCAB) coronary artery bypass graft (CABG). Seventy-one diabetic patients (36 and 35 patients in the CPB and OPCAB groups, respectively) were enrolled in a prospective randomized study. Renal tubular and glomerular functions, were monitored preoperatively and over five consecutive days. There was no significant difference between the groups in terms of age, gender, New York Heart Association class, Canadian Cardiovascular Society functional classification of angina grade and number of CABG. Intensive care unit stay, duration of intubation, hospital stay and bleeding were significantly higher in the CPB group. No significant differences in plasmatic creatinine, urinary creatinine, creatinine clearance, proteinuria or osmolality were detected. A significant rise in urinary albumine excretion occurred in both groups peaking on the operative day; for the on-pump CABG group (10±5 vs. 48±57; P=0.015) and for the OPCAB group (11±6 vs. 37±59; P=0.04). Values were less important in the OPCAB group and return to the baseline was faster than in the CPB group. OPCAB attenuates sub-clinical AKI, in diabetic patients. The mortality of patients with acute renal failure (ARF) remains high, and in several large studies approaches 60%. This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years, despite the introduction of major advances in monitoring and treatment. Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality. This study investigates the potential role of the dialysis membrane on patient outcome in a prospective multicenter study of 153 patients with ARF requiring dialysis. The membrane assignment was made in alternating order and was limited to membranes with low complement activation (Biocompatible [BCM]) and cellulosic, high complement activation (Bioincompatible [BICM]). Both types of membranes were low-flux membranes. Patients were dialyzed with the assigned membrane until recovery, discharge from hospital, or death. The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis. A logistic regression analysis was used to adjust for the APACHE II score. The results of the study showed a statistically significant difference in survival (57% in patients on BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in patients on BICM and 43% in patients on BICM; P = 0.001). These differences were particularly marked in the patients who were nonoliguric (>400 ml/d of urine output) at initiation of the study. In the subset of patients who were nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric after initiating dialysis on a BICM membrane, in contrast to 44% who were initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF, particularly those who are nonoliguric at the time of initiation of dialysis. To evaluate the effect of 7.5% hypertonic saline (HS) and 6% hydroxyethyl starch (HES) 130/0.4 on early fluid resuscitation for severe sepsis.
                Prospective randomized control trial was carried out in intensive care unit (ICU) of the Affiliated Hospital of Jianghan University. One hundred and thirty five patients with severe sepsis were randomly divided into three groups, each group consisted of 45 patients. Patients in HS+HES group received lactated Ringer solution following 4 ml/kg of 7.5% HS and 6% HES 130/0.4 500 ml, those in HES group received lactated Ringer solution following 6% HES 130/0.4 500 ml, and those in the lactated Ringer group (RL group) received lactated Ringer solution only.Mean arterial pressure (MAP), oxygenation index (PaO₂/FiO₂),arterial lactate (Lac),lactate clearance rate, acute physiology and chronic health evaluation II(APACHEII) score,fluid infusion volume, urine output as well as incidence of multiple organ dysfunction syndrome (MODS), and mortality were compared among three groups at 6 hours and 24 hours after ICU admission.
                At 6 hours after ICU admission,MAP[mm Hg (1 mm Hg=0.133 kPa): 68.7 ± 3.0], PaO₂/FiO₂(mm Hg: 262.2 ± 17.4), lactate clearance rate [(21 ± 4)%] in HS+HES group were significantly higher than those in HES group [MAP: 63.8 ± 3.5,PaO(2)/FiO(2): 252.0 ± 21.2, lactate clearance rate: (11 ± 2)%] and RL group [MAP: 62.6 ± 3.6, PaO₂/FiO₂:248.4 ± 17.0,lactate clearance rate: (9 ± 1)%, all P <0.01]. Arterial Lac in HS+HES group (mmol/L: 3.5 ± 0.7) was significantly lower than that in HES group (4.1 ± 0.7) and RL group (4.0 ± 0.7, both P <0.01). There was no significant difference in APACHE II score between HS+HES group (13.2 ± 1.9) and HES group (14.0 ± 1.6), and the APACHEII score in HS+HES group was significantly lower than that in RL group (15.2 ± 1.7, P <0.01). At 24 hours after ICU admission, PaO₂/FiO₂ (mm Hg: 303.3 ± 17.3) was significantly higher in HS+HES group than that in HES group (282.9 ± 21.1) and RL group (268.9 ± 15.2, both P <0.01). There was no significant difference in MAP, arterial Lac, lactate clearance rate and APACHEII score among three groups. At 6 hours and 24 hours after ICU admission, fluid infusion volume in HS+HES group (ml, 6 hours: 1 877.8 ± 215.2, 24 hours: 5 475.6 ± 208.8) was markedly less than that in HES group (6 hours: 2 505.6 ± 276.2, 24 hours: 6 383.3 ± 287.4) and RL group (6 hours: 3 496.7 ± 325.5,24 hours: 7 439.6 ± 229.6), yet urine output in HS+HES group (ml, 6 hours: 294.2 ± 36.9, 24 hours : 2 793.8 ± 37.1) was significantly higher than that in HES group (6 hours: 248.9 ± 25.3, 24 hours : 2 248.9 ± 25.3) and RL group (6 hours: 178.9 ± 14.8, 24 hours: 2 000.4 ± 147.0, all P <0.01). The incidence of MODS in HS+HES group (6.7%) was statistically lower than that in RL group (28.9%, P <0.05), while no obvious difference was found between HS+HES group and HES group (17.8%, P >0.05). There was no significant difference in mortality among three groups (HS+HES group: 2.2%, HES group: 4.4%, RL group: 8.9%, all P >0.05).
                7.5%HS and 6%HES 130/0.4 could improve the effect of early fluid resuscitation on severe sepsis, and it could lower the incidence of MODS. To compare the hemodynamic efficacy of a new hydroxyethyl starch (HES) preparation (130/0.4) with an HES 200/0.5 solution.
                Prospective, randomized, double-blind, phase II study.
                An urban, university-affiliated hospital.
                Twenty patients undergoing elective first-time cardiac surgery.
                After induction of anesthesia and before the start of surgery, a new HES 130/0.4 (molecular weight, 130,000 d; degree of substitution, 0.4) (n = 10) or HES 200/0.5 (molecular weight, 200,000 d; degree of substitution, 0.5) (n = 10) was infused (10 mL/kg) within 30 minutes when pulmonary capillary wedge pressure was less than 10 mmHg.
                Extensive hemodynamic monitoring was performed 30 and 60 minutes after the end of infusion. Then surgery was started. Standard laboratory parameters were measured before surgery and on the 1st postoperative day. A similar amount of HES was given in both groups (HES 130, 795+/-75 mL; HES 200, 820+/-90 mL). Filling pressures (central venous pressure, pulmonary capillary wedge pressure) and cardiac index increased similarly in both groups and remained significantly elevated 60 minutes after the end of infusion. All other hemodynamic parameters were similar between the two volume groups. Renal (creatinine) and hepatic function (aspartate aminotransferase, alanine aminotransferase) and hemostasis (platelet count, activated partial thromboplastin time, blood loss) were without group differences until the morning of the 1st postoperative day.
                The new 6% HES 130/0.4 was as effective as a 6% HES 200/0.5 preparation in regard to hemodynamic efficacy. No negative side effects on organ function were seen. The 6% HES 130/0.4 solution may become an alternative strategy for volume therapy in cardiac surgery. Glutathione (GSH) acts as a free radical scavenger that may be helpful in preventing reperfusion injury. N-acetylcysteine (NAC) replenishes GSH stores. The aims of this study were to evaluate the efficacy of NAC in improving liver graft performance and reducing the incidence of post-operative acute kidney injury (AKI).
                Our study was a randomized, double-blind, placebo-controlled trial of 100 patients; 50 received placebo and 50 received a loading dose of 140 mg/kg of intravenous (IV) NAC over 1 h followed by 70 mg/kg IV repeated every 4 h for a total of 12 doses. Both groups were followed up for 1 year post-orthotopic liver transplant (OLT). We recorded liver function tests, renal function tests, graft survival, patient survival, plasma GSH and duration of hospital and ICU stay. In addition to serum creatinine (SCr) levels, we analysed cystatin C and beta-trace as independent measures of glomerular filtration. All clinical data were recorded daily for the first week after the surgery, then on Days 14, 21, 30, 90 and 180 and at the end of the first year.
                IV NAC did not affect survival, graft function or risk of AKI. However, GSH levels were highly variable with only 50% of patients receiving NAC exhibiting increased levels and fewer patients developed AKI when GSH levels were increased. Additional risk factors for AKI in the post-transplant period were female gender (P = 0.05), increased baseline serum bilirubin (P = 0.004) and increased baseline SCr levels (P = 0.02).
                IV NAC was not effective in reducing renal or hepatic injury in the setting of liver transplantation. The dose and duration of NAC used, though higher than most renal protection studies, may have been ineffective for raising GSH levels in some patients. To investigate the influence of lactate Ringer solution (RL) versus hydroxyethyl starch 130/0.4 (HES130/0.4) solution on coagulation and fibrinolytic system in the patients with septic shock.
                Forty-two consecutive patients with septic shock diagnosed between September 2009 and June 2011 were randomized to two study groups: RL resuscitation group (RL group) with 20 patients, and HES130/0.4 resuscitation group (HES group) with 22 patients. In all of them peripheral blood was collected at four points of time: before resuscitation, 6, 12, 24 hours after resuscitation, and then prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of plasma tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI) were determined. Meanwhile, the patients' outcome and the length of intensive care unit stay (ICU-LOS) were recorded.
                ICU-LOS (days) in HES group was significantly shorter than the RL group (12.5 ± 8.8 vs. 17.1 ± 16.6, P < 0.01). Meanwhile, the volume of fluid (L: 2.77 ± 0.59) as well as vasoactive drugs [μg×kg(-1)×min(-1): 0.56 ± 0.15] used in the HES group were significantly lower than RL group (3.46 ± 0.73, 0.81 ± 0.41, both P < 0.01). In RL group, 12 patients died and 8 patients survived, while in HES group, 7 patients died and 15 patients survived, showing no difference between two groups. PT, APTT and the levels of t-PA showed no significant differences between two groups at different time points, but the levels of plasma PAI (μg/L) of the HES group decreased gradually, and was significantly lower than that before resuscitation and RL group at 24 hours after resuscitation (41.76 ± 25.95 vs. 89.11 ± 14.27, 55.08 ± 35.43, both P < 0.05).
                Both RL and HES130/0.4 fluid resuscitation did not affect the outcome of the patients with septic shock, but the resuscitation efficiency of HES130/0.4 is much better than RL. Both type of fluids did not show the effect on coagulability of the septic patients, but colloid fluid resuscitation may protect the vascular endothelial cell, reduce the inhibition of fibrinolytic system, and alleviate hypercoagulability state of patients in early stage. In a randomized study including 55 patients undergoing elective aorto-coronary bypass surgery efficacy of a low concentrated hydroxyethylstarch (3% HES 200/0.5) was tested after extracorporeal circulation (ECC). All patients received 1,000 ml autologous washed erythrocytes (cell saver) and 400 ml fresh frozen plasma (FFP). Thereafter patients were randomized into 4 groups. Hemodynamic parameters, laboratory parameters as well as extravascular lung water (EVLW - double indicator dilution technique) were measured before ECC as well as before and after infusion therapy. With regard to hemodynamic efficiency and the change in laboratory data no relevant differences between group I, II and III could be seen. EVLW-measurement demonstrated the lowest increase in lung water after infusion of HES; simultaneously pulmonary gas exchange was less compromised in comparison to the other infusion groups. 3% HES 200/0.5 solution can be considered as an effective volume substitute with short intravascular retention time, which seems to be of advantage in patients coming off extracorporeal circulation. There is continuing concern on the influence of hydroxethyl starch (HES) on renal function.
                Prospective, randomized study.
                University-affiliated medical center.
                Forty consecutive patients aged >70 years undergoing cardiac surgery using cardiopulmonary bypass.
                Either low-molecular HES (mean molecular weight: 130 kD) with low degree of substitution (0.4) (6% HES 130/0.4) (n=20) or gelatin ( n=20) was given after induction of anesthesia until the 2nd postoperative day (POD) to keep central venous pressure between 12-14 mmHg.
                Creatinine clearance (CC) and fractional sodium clearance (FSC) were measured. N-acetyl-beta-D-glucosamidase, alpha-1-microglobulin, glutathione transferase-pi, and glutathione transferase-alpha were measured from urine specimens. Measurements were made after induction of anesthesia, at the end of surgery, and at the first and the second POD. More gelatin (total: 4150+/-490 ml) than HES 130/0.4 (total: 3450+/-450 ml) was infused within the study. CC and FSC were without differences between the two groups. All measured kidney-specific proteins were almost within normal range at baseline. They increased significantly after surgery, however, without significant group differences. At the 2nd POD, kidney-specific proteins had returned almost to normal values. None of the patients developed acute renal failure.
                Sensitive markers of kidney dysfunction increased in our elderly patients indicating moderate alterations in kidney integrity during cardiac surgery. The two volume replacement regimens did not differ with regard to kidney integrity in elderly patients undergoing cardiac surgery. Activation of thrombin and of the coagulation system plays an important role in the pathophysiology of sepsis-associated organ dysfunction. Antithrombin III (AT III) is a natural inhibitor of thrombin, a central procoagulatory factor with pleiotropic activities. Experimental supplementation of AT III improved coagulation parameters and ameliorated organ dysfunction. To determine whether long-term AT III supplementation has beneficial effects on organ function, we conducted a randomized, prospective study in surgical patients with severe sepsis. The study evaluated the long-term effect of AT III supplementation (duration of treatment: 14 days). After randomization (AT III vs. control group), AT III was infused continuously over 14 days to obtain plasma AT III activities > 120%. Forty consecutive patients were recruited (20 AT III/20 control group). Eleven patients had a rapid fatal course and did not met the criterion of a 14 day treatment period. From these 11 patients, 8 patients (5 AT III/3 control group) died within 72 h due to septic shock. The remaining 14 AT III patients and 15 controls survived 14 days and showed no differences in baseline parameters of organ function. AT III caused a disappearance of disseminated intravascular coagulation (DIC) in all patients with DIC, whereas in control patients, the frequency of DIC remained constant (p < .05). In AT III patients a progressive increase in oxygenation index (PaO2/FiO2 ratio) and a continuous decrease in pulmonary hypertension index (mean pulmonary artery pressure/mean arterial pressure (PAP/MAP) ratio) indicated an improvement of lung function (p < .05 vs. control). AT III prevented the continuous rise in total serum bilirubin concentration observed in control patients and diminished the frequency of artificial renal support therapy (p < .05). Long-term supplementation with AT III may improve lung function and prevent the development of septic liver and kidney failure in patients with severe sepsis. Patients with impaired renal function are at risk of developing renal dysfunction after abdominal aortic surgery. This study investigated the safety profile of a recent medium-molecular-weight hydroxyethyl starch (HES) preparation with a low molar substitution (HES 130/0.4) in this sensitive patient group.
                Sixty-five patients were randomly allocated to receive either 6% hydroxyethyl starch (Voluven); n = 32) or 3% gelatin (Plasmion); n = 33) for perioperative volume substitution. At baseline, renal function was impaired in all study patients as indicated by a measured creatinine clearance < 80 mL min(-1). The main renal safety parameter was the peak increase in serum creatinine up to day 6 after surgery.
                Both treatment groups were compared for non-inferiority (pre-defined non-inferiority range hydroxyethyl starch < gelatin + 17.68 micromol L(-1) or 0.2 mg dL(-1). Other renal safety parameters included minimum postoperative creatinine clearance, incidence of oliguria and adverse events of the renal system. Baseline characteristics, surgical procedures and the mean total infusion volume were comparable. Non-inferiority of hydroxyethyl starch vs. gelatin could be shown by means of the appropriate non-parametric one-sided 95% CI for the difference hydroxyethyl starch-gelatin [-infinity, 11 micromol L(-1)]. Oliguria was encountered in three patients of the hydroxyethyl starch and four of the gelatin treatment group. One patient receiving gelatin required dialysis secondary to surgical complications. Two patients of each treatment group died.
                As we found no drug-related adverse effects of hydroxyethyl starch on renal function, we conclude that the choice of the colloid had no impact on renal safety parameters and outcome in patients with decreased renal function undergoing elective abdominal aortic surgery. Elderly patients are at risk of developing renal dysfunction. Synthetic colloids are often used perioperatively, but they may have detrimental effects on renal function. In a prospective, randomized study, we assessed the influence of different intravascular volume replacement regimens on renal function in elderly (>65 yr) and younger (< 65 yr) patients without preoperative renal dysfunction who were undergoing major abdominal surgery. Either 6% low molecular weight hydroxyethyl starch (HES) solution (mean molecular weight 70,000 D, degree of substitution 0.5; HES 70/0.5) [each group n = 10]), 6% medium-molecular weight HES (molecular weight 200,000 D, degree of substitution 0.5 (HES 200/0.5) [each group n = 10]), or modified gelatin (molecular weight 35,000 D [each group n = 10]) was administered to maintain mean arterial blood pressure >65 mm Hg and central venous pressure between 10 and 14 mm Hg. After the induction of anesthesia (T0); at the end of surgery (T1); 4 h after surgery (T2); and on the first (T3), second (T4), and third postoperative days (T5), alpha1-microglobulin (alpha1-M), N-acetyl-beta-glucosaminidase, fractional sodium clearance, and creatinine clearance (CC) were measured. Colloids (1300-3000 mL) were infused until the first postoperative day. At T0, urine concentrations of alpha1-M were higher in the elderly than in the younger patients in all groups (P < 0.05). alpha1-M remained increased only in the gelatin group. N-acetyl-beta-glucosaminidase and fractional sodium clearance were not affected during the study period in any groups. At baseline, CC was significantly higher in the younger than in the elderly patients, but CC did not decrease in any of the intravascular volume replacement groups. We conclude that intravascular volume therapy with gelatin and two different HES preparations did not adversely affect renal function in elderly patients without preoperative renal malfunction.
                We studied the influence of three different intravascular volume replacement regimens on renal function in elderly patients without renal dysfunction who were undergoing major abdominal surgery. Two hydroxyethyl starch and one gelatin preparation were administered perioperatively to maintain stable hemodynamics. As assessed by sensitive markers of renal function, all three regimens can be used safely for volume replacement without risking significant renal dysfunction. The aim of this study was to investigate the short-term effect of fluid resuscitation with 4% modified fluid gelatine (GEL) versus 6% hydroxyethyl starch (HES) on haemodynamics and oxygenation in patients with septic shock and acute lung injury (ALI).
                Prospective randomised clinical trial.
                Twenty-bed intensive care unit in a university hospital.
                Thirty hypovolemic patients (intrathoracic blood volume index, ITBVI <850 ml/m(2)) in septic shock with ALI were randomised into HES (mean molecular weight: 200,000 Dalton, degree of substitution 0.6) and GEL (mean molecular weight: 30,000 Dalton) groups (15 patients each).
                For fluid resuscitation 250 ml/15 min boluses (max. 1,000 ml) were given until the end point of ITBVI >900 ml/m(2) was reached. Repeated haemodynamic measurements were done at baseline (t(b)), at the end point (t(ep)) then at 30 min and 60 min after the end point was reached (t(30), t(60)). Cardiac output, stroke volume, extravascular lung water (EVLW), and oxygen delivery was determined at each assessment point. For statistical analysis two-way ANOVA was used.
                ITBVI, cardiac index, and oxygen delivery index increased significantly at t(ep) and remained elevated for t(30) and t(60), but there was no significant difference between the two groups. The increase in the ITBVI by 100 ml of infusion was similar in both groups (HES: 26+/-19 ml/m(2) vs GEL: 30+/-19 ml/m(2)). EVLW, remained unchanged, and there was no significant difference between the groups (HES, t(b): 8+/-6, t(60): 8+/-6; GEL, t(b): 8+/-3, t(60): 8+/-3 ml/kg). The PaO(2)/FiO(2) did not change significantly over time or between groups (HES, t(b): 207+/-114, t(60): 189+/-78; GEL, t(b): 182+/-85, t(60): 182+/-85 mmHg).
                The results of this study indicate that both HES and GEL infusions caused similar short-term change in ITBVI in septic shock, without increasing EVLW or worsening oxygenation. The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids.
                In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points.
                The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate.
                The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.)
                2008 Massachusetts Medical Society The endothelium plays an important role in the regulation of haemostasis by producing substances such as thrombomodulin (TM). The influence of long-term volume replacement with different types of fluid on the TM-protein C-protein S system was investigated in a prospective, randomized study. Thirty trauma patients and 30 patients suffering from sepsis after major surgery received either 10% low-molecular weight (LMW) hydroxyethylstarch solution (HES-trauma, n = 15; HES-sepsis, n = 15) or 20% human albumin (HA-trauma, n = 15; HA-sepsis, n = 15) for 5 days to maintain central venous pressure (CVP) between 12 and 16 mm Hg. Plasma concentrations of TM, protein C, (free) protein S and thrombin-antithrombin (TAT) were measured in arterial blood samples obtained on the day of admission to the intensive care unit or on the day of diagnosis of sepsis and over the next 5 days. There were no differences between HA- and HES-treated trauma patients. Protein C and protein S also did not differ between HA- and HES-treatments. At baseline, TM plasma concentrations were increased to > 40 micrograms litre-1 in both sepsis groups only. In the HA-sepsis group, TM increased significantly (from 48.1 (SD 13.9) to 68.4 (13.0) micrograms litre-1), whereas it remained almost unchanged in the HES-sepsis group. In HES-sepsis patients, protein C (from 51.0 (10.1) to 71.9 (8.9)%) and protein S (from 19.0 (6.0) to 40.8 (11.4)%) increased significantly during the study, whereas both remained reduced in HA-patients. TAT (indicating intravascular coagulation) did not differ between the two fluid groups. We conclude that in trauma patients, the type of volume therapy had no influence on the TM-protein C-protein S system. In sepsis patients, volume therapy with HES was beneficial, whereas infusion of HA had no substantial positive effect on endothelial-associated coagulation. Although at present there is no prospective randomized study which could show significantly better survival of patients on continuous procedures, the majority of intensivists advocate this technique of renal function replacement due to generally accepted opinion that it has less effect on circulation of already hemodynamically unstable patients. In our prospective randomized study with 104 patients, we also did not observe any difference in 28 days survival, in total survival, as well as in circulatory instability between two treatment modalities. Even in subgroup of 80 patients with sepsis and septic shock there were no difference in survival. Sepsis was the underlying disorder in 52 and septic shock in 28 patients out of 104 patients analyzed in this study. Our prospective randomized study did not show a statistically significant difference between the two methods of renal replacement therapy. Survival rates were not affected and neither was the occurrence of hemodynamic instability. We believe that both methods are complementary; IHD for faster elimination of electrolytes and waste products elimination, CRRT for regulation of higher calories requirements and for hemodynamically unstable patients. The expectations that one method is superior to the other in the term of better survival have not been corroborated by the current data available in the literature. The choice of the method should be individualized. ARF, which is an integral part of MOF, is a problem frequently encountered in critically ill patient treated in the ICU, but outcome of these patients depends closely on the control of basic event. Evaluation of each of the supportive procedures is therefore hindered by the fact that the underlying disease has the crucial effect on survival and the type of supportive procedure less so. To determine the acute hemodynamic effect of hypertonic saline and/or colloid solutions as volume resuscitation in postoperative mitral valve repair patients.
                Prospective, randomized trial.
                Postoperative cardiac intensive care unit of Broussais Hospital.
                Twenty-six patients who underwent mitral valve repair were prospectively studied. Two patients were excluded during the study.
                During the immediate postoperative period, when wedge pressure decreases to <8 mm Hg, patients were randomly assigned to receive 250 mL of either hypertonic saline 7.2%-hydroxyethyl starch 6% (molecular weight, 200,000; hydroxyethylation ratio, 0.5) solution (HS-HES group), hypertonic saline 7.2% solution (HS group), or hydroxyethyl starch 6% solution (HES group). The infusion was completed within 15 mins. No additional volume was infused throughout the study.
                Standard hemodynamic measurements and echocardiographic data demonstrated that HS-HES and HS induced a higher increase in left ventricular end-diastolic area than HES. In the HS-HES and HS groups, systemic vascular resistances decreased significantly and end-systolic area tended to decrease. In the HES group, systemic vascular resistances did not change and end-systolic area tended to increase. Accordingly, ejection fraction increased significantly by 21% and 18% with HS-HES (from 50.5 +/- 5.5 to 61.2 +/- 4.8) and HS (from 49.7 +/- 3.6 to 58.8 +/- 3.3), respectively, and did not change with HES. A major increase in cardiac index was observed after hypertonic solutions infusion, from 2.9 +/- 0.3 to 4.1 +/- 0.4 L/min/m2 in the HS-HES group and from 2.7 +/- 0.3 to 3.8 +/- 0.4 L/min/m2 in the HS group. Then, cardiac index progressively returned to baseline values within the 3 hrs after the infusion. No significant difference was observed between HS-HES and HS. In these groups, plasma sodium increased significantly after the infusion and remained higher than baseline values throughout the study. Adverse events were observed only with hypertonic solution administration: hypotensive episodes, sudden increases in pulmonary capillary wedge pressure, and ventricular arrhythmias. These side effects are likely attributable to a too-high dose and/or rate of infusion. All patients included in the study were discharged from the hospital before the 10th postoperative day.
                We conclude that in patients who have undergone mitral valve repair, postoperative infusion of hypertonic saline solutions increases left ventricular preload and left ventricular ejection fraction. The use of these hypertonic solutions may be of interest in patients with valvular cardiomyopathy. A titrated dose and a low rate of infusion may substantially improve the safety. Metabolic acidosis is the best predictor of death in children with severe falciparum malaria; however, its treatment presents a therapeutic dilemma, because acidosis and hypovolemia may coexist with coma, which can be associated with elevated intracranial pressure. We postulated that volume resuscitation with albumin might correct acidosis and hypovolemia with a lower risk of precipitating cerebral edema than crystalloid. In an open-label, randomized, controlled trial, we compared the safety of resuscitation with albumin to saline in Kenyan children with severe malaria.
                We randomly assigned children with severe malaria and metabolic acidosis (base deficit, >8 mmol/L) to receive fluid resuscitation with either 4.5% albumin or normal saline. A control (maintenance only) group was only included for patients with a base deficit of <15 mmol/L. The primary outcome measure was the percentage reduction in base deficit at 8 h. Secondary end points included death, the requirement for rescue therapies, and neurological sequelae in survivors.
                Of 150 children recruited for the trial, 61 received saline, 56 received albumin, and 33 served as control subjects. There was no significant difference in the resolution of acidosis between the groups; however, the mortality rate was significantly lower among patients who received albumin (3.6% [2 of 56 patients]) than among those who received saline (18% [11 of 61]; relative risk, 5.5; 95% confidence interval, 1.2-24.8; P=.013).
                In high-risk children with severe malaria and acidosis, fluid resuscitation with albumin may reduce mortality. Our study design did not enable us to determine whether saline administration is preferable to fluid restriction or whether saline administration is actually hazardous. Further studies are needed to confirm our findings before definitive treatment recommendations can be made. Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient. The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight (LMW) hydroxyethyl starch solution (HES) differs from that of human albumin (HA). According to a randomized sequence, 30 trauma patients (injury severity score [ISS] between 15 and 30) and 30 sepsis patients (secondary to major general surgery) received either 10% HES (mean molecular weight 200,000 daltons; HES trauma [n = 15], HES sepsis [n = 15]) or human albumin 20% (HA trauma [n = 15], HA sepsis [n = 15]) over 5 days to keep pulmonary capillary wedge pressure (PCWP) between 12 and 18 mm Hg. Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days. Gastric intramucosal pH (pHi) was measured by tonometry. Central venous pressure and PCWP were comparable within the subgroups (trauma/sepsis) throughout the entire study period. In the trauma patients, cardiac index (CI), oxygen consumption index (VO2I), and oxygen delivery index (DO2I), significantly increased only in the HES-treated patients. In the sepsis patients, CI, VO2I, and DO2I increased and remained higher than baseline only in the HES group (P < 0.01). Right ventricular ejection fraction (RVEF) was reduced (< 40%) in the HA patients and increased only in the HES patients (from 34% +/- 4% to 42% +/- 3%; P < 0.05). pHi remained normal (> 7.35) in both trauma groups and in the HES-treated sepsis patients. In the HA sepsis group, pH, decreased (> 7.20) within the study period (7.15 +/- 0.12 on Day 4), indicating deteriorated splanchnic perfusion. We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES. In both groups, volume replacement with HES even resulted in improved systemic hemodynamics. Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy.
Potential for increased risk of AKI should be considered when weighing the risks and benefits of HES for volume resuscitation, particularly in septic patients. Large studies with adequate follow-up are required to evaluate the renal safety of HES products in non-septic patient populations. RIFLE criteria should be applied to evaluate kidney function in future studies of HES and, where data is available, to re-analyse those studies already published. There is inadequate clinical data to address the claim that safety differences exist between different HES products.