Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China.

STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.

Investigation of treatment volume versus circulating blood volume during Rheocarna treatment.

INTRODUCTION: Rheocarna's therapeutic effect is associated with fibrinogen (Fib) and low-density lipoprotein cholesterol (LDL-C) adsorptive removal. This study aimed to retrospectively investigate the association between treatment volume (TV) and circulating blood volume (CBV) and the Fib removal rate (Fib-RR) and LDL-C-RR. METHODS: CBV and TV/CBV, cut-off value (CO value), and area under the receiver operating characteristic (ROC) curve (AUC) were calculated. The Fib-RR and LDL-C-RR at the midterm and end of treatment were compared. The groups were further categorized into three groups with TV/CBV lower than or higher than the CO value at the midterm and end (midterm/end; Group L: lower than/lower than CO; Group L/H: lower than/higher than CO; Group H: higher than/higher than CO), and the Fib-RR and LDL-RR of each group at the midterm and end were compared. RESULTS: ROC analysis revealed a TV of 1.480 times the BV as CO value, which showed a maximum Youden index predicting a Fib-RR of 20% (AUC: 0.828). Among the three groups, Group L and Group L/H demonstrated significantly higher Fib-RR and LDL-C-RR at the end of the study than in the midterm, while Group H exhibited no difference. CONCLUSION: The results reveal that a treatment volume of 1.5 times the circulating blood volume is a sufficient solute removal capacity in the Rheocarna-enabled cases.

Effect of a single small volume fluid bolus with balanced or un-balanced fluids on chloride and acid-base status: a prospective randomized pilot study (the FLURES-trial).

OBJECTIVE: To compare the short-term effects on acid base, electrolyte status and urine output of a single fluid bolus of saline to that of the balanced solution Plasmalyte® in critically ill patients. METHODS: Prospective, randomized, controlled trial. Adult patients (≥ 18 years) admitted to the ICU receiving a fluid bolus were randomized to receive 1 L of saline (NaCl 0.9%, Baxter) or a balanced fluid [Plasmalyte® (Baxter)]. Blood samples and urine output were collected just before (T0), just after (T1), 2 h after (T2) (only for urinary output) and three hours after termination of the fluid bolus (T4). The effect of fluid boluses on serum chloride, apparent strong ion difference, base excess, urinary output and blood pressure or vasopressor need were analyzed. MAIN RESULTS: Patients who received a 1 L saline fluid bolus had a significant increase in serum chloride (1.60; 95% CI 1.10 to 2.10; P < 0.001) and short-term decrease in apparent strong ion difference (- 1.85; 95% CI - 2.71 to - 0.99; P < 0.001) and base excess (- 0.90; 95% CI - 1.31 to - 0.50; P < 0.001). We observed a 17% increase in patients developing hyperchloremia in the saline group (0.17; 95% CI 0.05 to 0.29; P = 0.005). No significant difference in urinary output, blood pressure or vasopressor need was observed in either group. CONCLUSION: Even a single, small bolus of saline, administered to critically ill patients, causes a significant increase in chloride concentration and a decrease in apparent strong ion difference and base excess, and an increase in the number of patients developing hyperchloremia. No difference in effect on urinary output, blood pressure or vasopressor need was observed between the two groups. EUDRACT NUMBER: 2014-001005-41; date of registration: 28/10/2014. LOCAL EC APPROVAL: EC project number 2014/038.

Polyoxazoline-conjugated porcine serum albumin as an artificial plasma expander for dogs.

Veterinary medicine has made tremendous progress for domestic dogs, which are irreplaceable family members enriching human life. Nevertheless, no adequate supply system exists for their blood products. This study examined the synthesis, structure, safety, and efficacy of poly(2-ethyl-2-oxazoline)-conjugated porcine serum albumin (POx-PSA) as an artificial plasma expander for dogs. The aqueous POx-PSA solution showed moderately high colloid osmotic pressure and good blood cell compatibility. Actually, lyophilized powder stored for 1 year can regenerate into a homogeneous solution. The circulation half-life of POx-PSA in rats was 2.1-fold longer than that of naked PSA. Rats produced neither anti-PSA IgG antibody nor anti-POx IgG antibody, which suggests excellent immunological stealth properties of POx-PSA. Complete resuscitation of hemorrhagic shock in rats was achieved soon after injection of POx-PSA solution. Serum biochemistry tests and histopathological observations indicated no abnormality in the related organs. When POx-PSA was administered to dogs intravenously, (i) no serum biochemical or hematological alteration was observed, also (ii) no overt deterioration of animal health was observed. These results indicate that POx-PSA has potential as an artificial plasma expander for dogs.

Perioperative colloids: From theory to practice.

INTRODUCTION: Fluid administration is the cornerstone in hypovolemic patient's reanimation. Clinical guidelines restrict colloid administration favouring crystalloids. Currently, we don't know exactly which is the daily clinical practice during the perioperative period. The objective of this study is to describe perioperative use of colloids analysing possible reasons aiming to use them. MATERIAL AND METHODS: Prospective, cross-section, national, multicentre observational study. Fluid Day sub-study. We enrolled all patient's older than 18 years old who underwent surgery during the 24 h of the 2-days study (February, 2019, 18th and 20th). We registered demographic data, comorbidities, anaesthetic and surgical procedure data, fluids administered, perioperative bleeding and monitoring type used during the perioperative period. RESULTS: A total of 5928 cases were analysed and 542 patients (9.1%) received any type of colloids, being hydroxiethyl-starch the most frequently used (5.1%). Patients receiving colloids suffered more longing surgery (150 [90-255] vs. 75 [45-120] min), were urgently operated (13.7 vs. 7.5%) and were more frequent classified as high risk (22 vs. 4.8%). Their recovery was mostly in critical care units (45.1 vs.15.8%). Patients with bleeding less than 500 ml received colloids in a percentage of 5.9 versus 45.9% when this figure was overcome. Patients who received colloids were anaemic more frequently: 29.4 vs. 16.3%. Colloids administration had a higher risk for transfusion (OR 15.7). Advanced monitoring also increased the risk for receiving colloids (OR 9.43). CONCLUSIONS: In our environment with routine clinical practice, colloids administration is limited and close linked to perioperative bleeding.

Utility of 6% hydroxyethyl starch 130/0.4 in oral cancer surgeries with a duration of over 6 hours: A retrospective case-control study.

To evaluate the utility of 6% hydroxyethyl starch (HES) 130/0.4 in oral cancer surgeries with durations over 6 hours. Using a case-control study design, the investigators enrolled patients who underwent oral cancer surgery involving osteotomy or manipulation near the major blood vessels at the Department of Orofacial Surgery in our hospital between 2017 and 2020. The predictor variable was 6% HES130/0.4. Outcomes included in-out balance and other postoperative parameters pertaining to circulatory maintenance (blood loss, urine volume, infusion volume, blood transfusion volume, albumin dose, hemoglobin levels, blood albumin levels, and doses of vasopressors used to maintain blood pressure), as well as pre- and postoperative renal function, pH, bicarbonate levels, and base excess. Changes in renal function were evaluated by assessing blood urea nitrogen and creatinine levels before surgery and at 1 and 7 days postoperatively. The Mann-Whitney U test was used for between-group comparisons, and Student t test was used for intragroup comparisons. The statistical significance was set at P < .05. A total of 65 patients underwent oral cancer surgery with a duration over 6 hours during the study period. The administration of 6% HES130/0.4 at 22.1 ± 7.5 mL/kg/day did not increase blood loss or the blood transfusion volume. Moreover, patients who were administered 6% HES130/0.4 had a significantly larger mean urine volume and infusion volume than those who were not administered 6% HES130/0.4. The infusion therapy could maintain the urine volume and did not worsen renal function. The results of this study showed that administration of 6% HES130/0.4 at a dose lower than 25 mL/kg in patients undergoing oral cancer surgery over 6 hours was effective for circulation maintenance but did not increase the intraoperative blood loss or transfusion volume. This treatment did not cause any dilutional metabolic acidosis or renal dysfunction.

Limiting calcium overload after cardiac arrest: The role of human albumin in controlled automated reperfusion of the whole body.

BACKGROUND: Regarding the overall inadequate results after cardiopulmonary resuscitation, the development of new treatment concepts is urgently needed. Controlled Automated Reperfusion of the whoLe body (CARL) represents a therapy bundle to control the conditions of reperfusion and the composition of the reperfusate after cardiac arrest (CA). The aim of this study was to investigate the plasma expander's role in the CARL priming solution and examine its mechanism of action. METHODS: Viscosity, osmolality, colloid osmotic pressure (COP), pH and calcium binding of different priming solutions were measured in vitro and compared to in vivo data. N = 16 pigs were allocated to receive CARL following 20 min of untreated CA with either human albumin 20% (HA, N = 8) or gelatin polysuccinate 4% (GP, N = 8). Blood gas analyses were performed during the first hour of reperfusion and catecholamine and fluid requirements were recorded. Neurological outcome was assessed by neurological deficit scoring (NDS) on the seventh day. RESULTS: In vitro, addition of HA to the CARL priming solution resulted in higher COP and higher calcium-binding than GP. In vivo, treatment with HA led to greater reduction of ionized calcium and higher extracorporeal flows within the first 30 min of reperfusion with no difference in catecholamine support and fluid requirement. Seven-day survival of 75% with no difference in NDS was observed in both groups. CONCLUSIONS: Our data show that the plasma expander in the CARL priming solution has a significant effect on the initial reperfusate and can potentially influence the course of resuscitation. However, seven-day survival and NDS did not differ between groups.

Manipulation of Nitric Oxide Levels via a Modified Hydroxyethyl Starch Molecule.

INTRODUCTION: Although the improving effect of nitric oxide (NO) donors has experimentally been demonstrated in shock, there are still no NO donor medications clinically available. Thiol-nitrosothiol-hydroxyethyl starch (S-NO-HES) is a novel molecule consisting of NO coupled to a thiolated derivative of hydroxyethyl starch (HES). It was aimed to assess the ability of S-NO-HES to serve as an NO donor under a variety of in vitro simulated physiologic conditions, which might be the first step to qualify this molecule as a novel type of NO donor-fluid. METHODS: We studied the effect of temperature on NO-releasing properties of S-NO-HES in blood, at 34°C, 37°C, and 41°C. Ascorbic acid (Asc) and amylase were also tested in a medium environment. In addition, we evaluated the activity of S-NO-HES in the isolated aortic ring and Langendorff-perfused heart setup. RESULTS: The NO release property of S-NO-HES was found at any temperature. Asc led to a significant increase in the production of NO compared to S-NO-HES incubation (P < 0.05). The addition of amylase together with Asc to the medium further increased the release of NO (P < 0.05). S-NO-HES exerted significant vasodilatory effects on phenylephrine precontracted aortic rings that were dose-dependent (P < 0.01). Furthermore, S-NO-HES significantly increased the heart rate and additionally reduced the duration of the cardiac action potential, as indicated by a reduction of QTc-B values (P < 0.01). CONCLUSIONS: We demonstrated for the first time that the S-NO-HES molecule exhibited its NO-releasing effects. The effectiveness of this new NO donor to substitute NO deficiency under septic conditions or in other indications needs to be studied.

Impact of colloids or crystalloids in renal function assessed by NGAL and KIM-1 after hysterectomy: randomized controlled trial

Abstract Background Hydroxyethyl starches are colloids used in fluid therapy that may reduce volume infusion compared with crystalloids, but they can affect renal function in critical care patients. This study aims to assess renal effects of starches using renal biomarkers in the perioperative setting. Methods This prospective, controlled, randomized study compared Hydroxyethyl starch 6% (HES) with Ringer's lactate (RL) in hysterectomy. Each episode of mean arterial pressure (MAP) below 60 mmHg guided the fluid replacement protocol. The RL group received 300 mL bolus of RL solution while the HES group received 150 mL of HES solution. All patients received RL (2 mL.kg−1.h−1) intraoperatively to replace insensible losses. Blood and urine samples were collected at three time points (preoperatively, 24 hours, and 40 days postoperatively) to assess urinary NGAL and KIM-1, as primary outcome, and other markers of renal function. Results Seventy patients were randomized and 60 completed the study. The RL group received a higher crystalloid volume (1,277 ± 812.7 mL vs. 630.4 ± 310.2 mL; p= 0.0002) with a higher fluid balance (780 ± 720 mL vs. 430 ± 440 mL; p= 0.03) and fluid overload (11.7% ± 10.4% vs. 7.0% ± 6.3%; p= 0.04) compared to the HES group. NGAL and KIM-1 did not differ between groups at each time point, however both biomarkers increased 24 hours postoperatively and returned to preoperative levels after 40 days in both groups. Conclusion HES did not increase renal biomarkers following open hysterectomy compared to RL. Moreover, HES provided better hemodynamic parameters using less volume, and reduced postoperative fluid balance and fluid overload.

Kinetics of 5% and 20% albumin: A controlled crossover trial in volunteers.

BACKGROUND: Albumin for intravenous infusion is marketed in two concentrations, 20% and 5%, but how they compare with regard to plasma volume expansion over time is unclear. METHODS: In a prospective crossover study, 12 volunteers received 3 ml kg-1 of 20% albumin and, on another occasion, 12 ml kg-1 of 5% albumin over 30 min. Hence, equivalent amounts of albumin were given. Blood was collected on 15 occasions over 6 h. Mass balance and volume kinetics were used to estimate the plasma volume expansion and the capillary leakage of albumin and fluid based on measurements of blood hemoglobin, plasma albumin, and the colloid osmotic pressure. RESULTS: The greatest plasma volume expansion was 16.0 ± 6.4% (mean ± SD) with 20% albumin and 19.0 ± 5.2% with 5% albumin (p < .03). The volume expansion with 20% albumin corresponded to twice the infused volume. One third of the 5% albumin volume quickly leaked out of the plasma, probably because of the higher colloid osmotic pressure of the volunteer plasma (mean, 24.5 mmHg) than the albumin solution (19.1 mmHg). At 6 h, the capillary leakage amounted to 42 ± 15% and 47 ± 11% of the administered albumin with the 20% and 5% preparations, respectively (p = .28). The corresponding urine outputs were 547 (316-780) ml and 687 (626-1080) ml (median and interquartile range; p = .24). CONCLUSION: The most important difference between the fluids was a dehydrating effect of 20% albumin when the same albumin mass was administered.

In vitro effect of hydroxyethyl starch on coagulation in dogs as assessed by dynamic viscoelastic coagulometry.

OBJECTIVE: To evaluate the effect of 6% hydroxyethyl starch (HES) 670/0.75 and 6% HES 130/0.4 dilution of canine whole blood on coagulation using dynamic viscoelastic coagulometry (DVC). ANIMALS: 56 healthy adult dogs. PROCEDURES: 2 blood samples were obtained from each dog and randomized to 1 of 7 groups-undiluted or 2 dilutions (1:3 or 1:10) of 3 different fluids: saline (0.9% NaCl) solution, 6% HES 670/0.75, or 6% HES 130/0.4. Dilutions were calculated to simulate approximately a 10- or 30-mL/kg body weight IV bolus of each fluid. DVC was performed on each sample. Coagulation parameters compared between groups included clot rate (CR), platelet function (PF), and activated clotting time. RESULTS: Dilution with saline solution did not significantly affect coagulation, while dilution with HES 670/0.75 and HES 130/0.4 caused a dose-dependent significant decrease in CR (1:3 HES 670/0.75, P = 0.007; 1:10 HES 670/0.75, P = 0.002; 1:3 HES130/0.4, P < 0.0001; and 1:10 HES 130/0.4, P = 0.0003) and PF (1:3 HES 670/0.75, P < 0.0001; 1:10 HES 670/0.75, P < 0.0001; 1:3 HES130/0.4, P < 0.0001; and 1:10 HES 130/0.4, P = 0.0015). CLINICAL RELEVANCE: Dilution of canine blood with HES 670/0.75 and HES 130/0.4, at clinically relevant doses (10 and 30 mL/kg), led to significant hypocoagulability beyond dilutional effect. This was, in part, due to impaired PF, which was significantly greater with HES 670/0.75. Further research using DVC to assess the effects of HES on coagulation in dogs, ideally with clinical conditions warranting HES administration, is needed.

Human albumin and 6% hydroxyethyl starches (130/0.4) in cardiac surgery: a meta-analysis revisited.

BACKGROUND: A meta-analysis of randomized controlled trials was recently published in BMC Surgery that compared the use of human albumin with 6% hydroxyethyl starches 130/0.4 for cardiopulmonary bypass prime and perioperative fluid management in pediatric and adult cardiac surgery patients. The two plasma expanding solutions are described as equivalent for efficacy and safety outcomes, and, on that basis, the preferential use of hydroxyethyl starches 130/0.4 was recommended for economic reasons because of the higher unit costs of human albumin solutions. RESULTS: In addition to the fact that trials were mostly small, single-center studies and the number of total participants was low, making the meta-analysis underpowered for several outcomes, selective reporting of data for ICU length of stay was identified. Re-calculation of statistics at higher precision showed that ICU length of stay of patients in the human albumin group was significantly shorter than that of patients in the 6% hydroxyethyl starches 130/0.4 group (standard mean difference - 0.181, 95% confidence interval - 0.361 to - 0.001, P = 0.049), which may offset any proposed economic advantage of using 6% hydroxyethyl starches 130/0.4. At the same time, the renal safety of 6% hydroxyethyl starches 130/0.4 in surgical patients is under regulatory review. CONCLUSIONS: Underpowered trials and selective reporting may impair the validity of the meta-analysis. A more cautious conclusion about the interchangeability between human albumin and 6% hydroxyethyl starches 130/0.4 in cardiac surgery should have been reached.

Modified fluid gelatin 4% for perioperative volume replacement in pediatric patients (GPS): Results of a European prospective noninterventional multicenter study.

INTRODUCTION: Modified fluid gelatin 4% is approved for use in children, but there is still a surprising lack of clinical studies including large numbers of pediatric patients. Therefore, we performed a European prospective noninterventional multicenter study to evaluate the use of a modified fluid gelatin 4% in saline (sal-GEL) or an acetate-containing balanced electrolyte solution (bal-GEL) in children undergoing major pediatric surgery. AIMS: The primary aim was to assess the indications and dosing of modified fluid gelatin, and the secondary aim was to assess the safety and efficacy, focusing, in particular, on routinely collected clinical parameters. METHODS: Children aged up to 12 years with ASA risk scores of I-III receiving sal-GEL or bal-GEL were followed perioperatively. Demographic data, surgical procedures performed, anesthesia, hemodynamic and laboratory data, adverse events, and adverse drug reactions were documented using a standardized case report form. RESULTS: 601 children that were investigated at 13 European pediatric centers from May 2015 to March 2020 (sal-GEL 20.1%, bal-GEL 79.9%; mean age 29.1 ± 38.6 (range 0-144) months; body weight 12.1 ± 10.5 (1.4-70) kg) were included in the analysis. The most frequent indications for GEL infusion were hemodynamic instability without bleeding (76.0%), crystalloids alone not being sufficient for hemodynamic stabilization (55.7%), replacement of preoperative deficit (26.0%), and significant bleeding (13.0%). Mean infused GEL volume was 13.0 ± 5.3 (2.4-37.5) ml kg-1 . The total dose was affected by age, with higher doses in younger patients. After gelatin infusion, mean arterial pressure increased (mean change 8.5 ± 7.3 [95% CI: 8 to 9.1] mmHg), and the hemoglobin concentrations decreased significantly (mean change -1.1 ± 1.8 [95% CI: -1.2 to -0.9] g·dL-1 ). Acid-base parameters were more stable with bal-GEL. No serious adverse drug reactions directly related to gelatin (i.e., anaphylactoid reaction, clotting disorders, and renal failure) were observed. CONCLUSION: Moderate doses up to 20 ml kg-1 of modified fluid gelatin were infused most frequently to improve hemodynamic stability in children undergoing major pediatric surgery. The acid-base balance was more stable when gelatin in a balanced electrolyte solution was used instead of saline. No serious adverse drug reactions associated with gelatin were observed.