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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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available., Methods: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product., Results: At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB ( p < 0.01)., Conclusion: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “œwork of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Objective: To describe and compare prothrombin time (PT), activated partial thromboplastin time (aPTT), thromboelastography (TEG), HCT, and platelet count measurements in a hemorrhage/over-resuscitation model., Design: Randomized crossover study., Setting: University teaching hospital., Animals: Six cats., Interventions: Anesthetized cats underwent 3 treatments at 2-month intervals. The treatments were as follows: NHR-no controlled hemorrhage and sham resuscitation; LRS-controlled hemorrhage and lactated Ringer's solution (LRS) for resuscitation; and Voluven-controlled hemorrhage and 6% tetrastarch 130/0.4 for resuscitation. The LRS and Voluven were administered at 60 and 20 mL/kg/h, respectively, for 120 minutes. Blood samples were drawn for PT, aPTT, TEG, HCT, and platelet count measurements at a healthy check (T - 7d), after controlled hemorrhage (T0), at 60 and 120 minutes of resuscitation (T60 and T120), and at 24 hours after completion of resuscitation (T24h). Data were analyzed using a general linear mixed model approach (significance was P < 0.05)., Measurements and Main Results: Total median blood loss (controlled hemorrhage and blood sampling from T0 to T120) at T120 was 11.4, 31.0, and 30.8 mL/kg for NHR, LRS, and Voluven, respectively. PT and aPTT during LRS and Voluven were prolonged at T60 and T120 compared to NHR (P < 0.001). On TEG, the reaction time, kinetic time, and alpha-angle were within reference intervals for cats at all time points in all treatments, while maximum amplitude was less than the reference interval (40 mm) at T0, T60, and T120 during Voluven and at T60 and T120 during LRS compared to NHR (both P < 0.001). The HCT and platelet count were significantly lower at T60 and T120 during LRS and Voluven compared to NHR (P < 0.001)., Conclusions: Hypocoagulopathy was observed during hemorrhage and liberal fluid resuscitation. Prolongation of PT and aPPT and decreased clot strength may have been caused by hemodilution and platelet loss., (© 2024 The Author(s). Journal of Veterinary Emergency and Critical Care published by Wiley Periodicals LLC on behalf of Veterinary Emergency and Critical Care Society.)

Introduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs., Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated., Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about -23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice., Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment., Competing Interests: The authors declare no conflicts of interest related to this study., (© 2024 Luo et al.)

Purpose: Colloid and/or co-load may be more effective than crystalloid for preventing postspinal anesthesia hypotension. We tested five different prophylactic norepinephrine dosages combined with colloid co-load infusion in patients receiving cesarean section and spinal anesthesia., Methods: Patients were randomly allocated to receive different prophylactic norepinephrine dosages (0 [NE 0 group], 0.025 [NE 25 group], 0.05 [NE 50 group], 0.075 [NE 75 group], or 0.1 [NE 100 group] µg/kg/min) combined with 500 mL 6% hydroxyethyl starch (130/0.4) immediately following spinal anesthesia (n = 35 per group). The primary endpoint was the incidence of postspinal anesthesia hypotension (systolic blood pressure [SBP] < 80% of baseline). Secondary endpoints included severe hypotension, bradycardia, nausea or vomiting, hypertension, SBP stability control versus baseline, the 50% (effective dose, ED50) and 90% (ED90) dose effective for preventing postspinal anesthesia hypotension, Apgar scores, and umbilical cord blood gases., Results: The incidence of postspinal anesthesia hypotension was 48.6%, 31.3%, 17.1%, 14.3%, and 5.7% in the respective groups. As the prophylactic norepinephrine dosage increased, the incidence of postspinal anesthesia hypotension declined (p < 0.001), and SBP remained stable relative to baseline (median performance error [MDPE], p < 0.001; median absolute performance error [MDAPE], p = 0.001). The ED50 and ED90 values were -0.006 (95% CI -0.046-0.013) and 0.081 (95% CI 0.063-0.119) µg/kg/min. Other endpoints were comparable across the groups., Conclusion: An initial prophylactic norepinephrine dosage of 0.05 µg/kg/min combined with 500 mL 6% hydroxyethyl starch (130/0.4) co-load infusion was optimal for preventing postspinal anesthesia hypotension during cesarean section., Trial Registration: NCT05133817, registration date: 12 Nov, 2021., (© 2023. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)

Objective: Severe traumatic shock is one of the leading causes of death in young adults. A large number of studies have shown that effective volumetry resuscitation on the basis of controlled injury can not only increase the success rate of early resuscitation but also reduce systemic inflammatory response and improve the cure rate of severe traumatic shock. The study explored the effects of hydroxyethyl starch (HES) on the survival rate, lymphocyte function and proliferation of rats with traumatic shock, and the potential mechanisms., Methods: Traumatic shock was constructed in rats as experimental model, and liquid resuscitation was performed using HES and lactated Ringer's (LR). 24-h mortality was recorded, and lymphocytes were isolated. The expressions of signaling pathway factors was detected by qPCR and Western blot. ELISA was performed to determine the expression of interleukin 6 (IL-6) and tumor necrosis factor- α (TNF- α ) in cell supernatant., Results: HES for fluid resuscitation augmented the survival of traumatic shock rats, upregulated the expressions of MEK and ERK1/2, and downregulated the expressions of IL-6 and TNF- α . However, inhibition of ERK signaling pathway reversed the effect of HES on the immune improvement and the 24-h survival rate of the traumatic shock rats ( P < 0.05)., Conclusion: HES could exert the anti-inflammatory effects on lymphocytes by mediating the phosphorylation of proteins of the ERK signaling pathway. HSE demonstrated a high efficacy in effectively treating traumatic shock, thus could be used in clinical practice., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Yun Liu et al.)

Background: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated., Methods: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus., Results: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229)., Conclusions: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Background: Hydroxyethyl starch (HES) 130 is a frequently used fluid to replace intravascular losses during surgery or trauma. In the past years, several trials performed in critically ill patients have raised questions regarding the safety of this product. Our aim in this meta-analysis was to evaluate the safety and efficacy of 6% HES during surgery and in trauma., Methods: This systematic review and meta-analysis was registered at PROSPERO (CRD42018100379). We included 85 fully published articles from 1980 to June 2018 according to the protocol and three additional recent articles up to June 2020 in English, French, German, and Spanish reporting on prospective, randomised, and controlled clinical trials applying volume therapy with HES 130/0.4 or HES 130/0.42, including combinations with crystalloids, to patients undergoing surgery. Comparators were albumin, gelatin, and crystalloids only. A meta-analysis could not be performed for the two trauma studies as there was only one study that reported data on endpoints of interest., Results: Surgical patients treated with HES had lower postoperative serum creatinine (P<0.001) and showed no differences in renal dysfunction, renal failure, or renal replacement therapy. Although there was practically no further difference in the colloids albumin or gelatin, the use of HES improved haemodynamic stability, reduced need for vasopressors (P<0.001), and decreased length of hospital stay (P<0.001) compared with the use of crystalloids alone., Conclusions: HES was shown to be safe and efficacious in the perioperative setting. Results of the present meta-analysis suggest that when used with adequate indication, a combination of intravenous fluid therapy with crystalloids and volume replacement with HES as colloid has clinically beneficial effects over using crystalloids only., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: We aimed to evaluate the effect of third-generation hydroxyethyl starch (6% HES 130/0.4) on hemostasis and perioperative blood loss in patients undergoing off-pump coronary artery bypass (OPCAB) with continuation of preoperative aspirin., Methods: Forty-nine consecutive patients, who underwent OPCAB at a single institution between November 1, 2014 and March 31, 2016, were included. Coagulation tests, including thromboelastometry and clinical data of all patients, retrospectively were collected from anesthesia and medical records., Results: The total amount of intraoperative crystalloid and HES was 2057.5 ± 771.6 mL (N = 32) and 1090.6 ± 645.0 mL (N = 32), respectively. In the coagulation pathway, the change ratio of fibrinogen concentration, prothrombin time, and fibrinogen thromboelastometry-maximum clot firmness (FIBTEM-MCF) significantly correlated with HES (P < 0.001, P = 0.00131, and P < 0.001, respectively), but not with crystalloid. In the coagulation pathway concerning interaction with platelets, the change ratio of platelet count, extrinsic thromboelastometry-clotting formation time (EXTEM-CFT), and EXTEM-MCF significantly were correlated with HES (P < 0.001, P < 0.001, and P < 0.001, respectively), but not with crystalloid. At chest closure, the hematocrit decreased in a dose-dependent manner with HES (P < 0.001), but not with crystalloid administration. There was an association between the change ratio of hematocrit and EXTEM-MCF (P = 0.00122). However, intra-postoperative blood loss was not correlated with HES 130/0.4 or crystalloid administration., Conclusion: We found that 6% HES 130/0.4 prolonged coagulation testing in a dose-dependent manner due to hemodilution but did not increase blood loss in patients undergoing OPCAB with continuation of preoperative aspirin.

Purpose: Sudden sensorineural hearing loss, briefly sudden deafness (SD), in the elderly remains less investigated despite rapidly aging population in most countries around the world. This study investigated whether aging process affects the treatment outcome of SD in the elderly., Patients and Methods: Eighty patients with SD, comprising 40 geriatric patients aged >65 years and 40 non-geriatric patients aged 55-64 years, were enrolled in this study. All patients underwent an inner ear test battery including audiometry, and cervical vestibular-evoked myogenic potential (cVEMP), ocular VEMP (oVEMP), and caloric tests., Results: Pre-treatment mean hearing level in the geriatric group (94 ± 16 dB) did not significantly differ from non-geriatric group (89 ± 20 dB). After treatment for 3 months, mean hearing gain in the geriatric group (22 ± 18 dB) with an improvement rate of 65%, did not significantly differ from non-geriatric group (21 ± 28 dB) with 58% improvement rate. Both inter-subject and intra-subject analyses revealed that the aging process greatly influenced the cVEMP and oVEMP responses, while less influenced the caloric responses., Conclusion: The treatment outcome of SD in geriatric patients aged >65 years did not significantly differ from that in non-geriatric patients aged 55-64 years, indicating that aging process did not affect treatment outcome of SD. Unlike treatment outcome for the presbycusis is unsatisfactory, treatment outcome for the elderly with SD could be favorable., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To evaluate the effects of 6% hydroxyethyl starch 130/0.4 (HES) and a polyionic isotonic crystalloid (CRYS) on standard coagulation tests and rotational thromboelastometry (ROTEM) in dogs with spontaneous hemoperitoneum (SHP)., Design: Prospective randomized open-label clinical study., Setting: University teaching hospital., Animals: Forty-two client-owned dogs presented with SHP., Interventions: Dogs diagnosed with SHP and hypovolemic shock were randomly allocated to receive HES (10 mL/kg, n = 22) or CRYS (30 mL/kg, n = 20) intravenously over 20 minutes for hemodynamic stabilization., Measurements and Main Results: Parameters measured before (T 0 ) and after (T 1 ) treatment were HCT, platelet counts, prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and extrinsic activated (EXTEM), intrinsic activated (INTEM), and extrinsic activated with platelet inhibition ROTEM assays. Data were analyzed as absolute values and as the percentage change from T 0 to T 1 . No significant differences between groups were detected in any variable at T 0 , and for HCT, platelet counts, prothrombin time, activated thromboplastin time, and fibrinogen concentrations at T 1 . Clot formation time in EXTEM was significantly prolonged (P = 0.037), and maximum clot firmness was significantly decreased (P = 0.038) in the HES group compared to the CRYS group at T 1 . The percentage change in EXTEM clotting time (P = 0.012) and INTEM clot formation time (P = 0.031) was greater after HES than CRYS. Lysis indices remained at 100% for all ROTEM assays in both groups., Conclusion: Compared to a 3-fold volume of CRYS, administration of HES was associated with impairment in ROTEM parameters in dogs with SHP, but no evidence of hyperfibrinolysis was detected., (© Veterinary Emergency and Critical Care Society 2020.)

Background: Hydroxyethyl starch (HES, 6% 130/0.4) has been used as a volume expander for the treatment of cerebral hypoperfusion in acute ischemic stroke. Although HES use was associated with renal failure in sepsis or critical illness, it still remains to be elucidated whether HES is linked to renal adverse events in patients with acute ischemic stroke., Methods: A total of 524 patients with acute ischemic stroke within 7 days of onset were included between January 2012 and May 2016. Renal function on admission and follow-up on day 7 ± 2 was assessed using serum creatinine (SCr) and estimated glomerular filtration rate (eGFR). Propensity score matching (PSM) was used to perform a 1:1 matched-pair analysis to minimize the group differences caused by covariates. The percentage of patients with new-onset acute renal injury (AKI) using the Kidney Disease: Improving Global Outcomes or good functional outcome (modified Rankin Scale 0-2) at 90 days were compared between HES cohort and controls., Results: Among the included patients (mean age, 68.6 years; male, 56.5%), 81 patients (15.5%) were HES cohort (median cumulative dose, 1,450 mL). Baseline renal function was better in HES cohort compared to that in the controls (SCr, 0.87 ± 0.43 mg/dL vs. 1.15 ± 1.15 mg/dL, P < 0.001; eGFR, 86.91 ± 24.27 mL/min vs. 74.55 ± 29.58 mL/min, P < 0.001), which became not significant in PSM cohort (72 pairs). The percentage of new-onset AKI did not differ between the HES cohort and controls (1.4% vs. 1.4%, P = 1.000). In addition, new-onset AKI was not related to HES (odds ratio, 1.422; 95% confidence interval, 0.072-28.068; P = 0.817) after adjusting for confounders. HES cohort tended to have higher percentage of good functional outcome at 90 days compared to controls, which failed to reach statistical significance (68.1% vs. 54.2%, P = 0.087)., Conclusion: A low cumulative dose of HES was not associated with renal adverse events in patients with acute ischemic stroke., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: We aimed to evaluate the effect of limited volume of hydroxyethyl starch (HES) administration on postoperative renal function in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB)., Methods: One thousand six hundred fifty-seven patients undergoing cardiac surgery under CPB over two years were included. The patients were divided according to the amount of HES administrated during the first 2 days post-surgery; moderate dose HES (≥20 ml/kg) versus low dose HES (< 20 ml/kg). Outcomes were compared by using inverse probability weighting., Results: Incidence of acute kidney injury (AKI) was higher in the moderate HES group (p = .02). However, new renal replacement therapy (RRT) (P = .30) and early mortality (p = .97) was similar between the groups. When adjusted, the moderate HES use was associated with AKI (OR, 1.66; 95% CI, 1.12-2.44; p = .01), but did not increase the risk of new RRT (OR, 1.27; 95% CI, 0.71-2.18; p = .40) or early mortality (HR, 0.73; 95% CI, 0.29-1.81; p = .50)., Conclusions: The moderate dose administration of HES (≥20 ml/kg) in the postoperative period following cardiac surgery might be associated with the risk of AKI. However, it was not associated with serious adverse outcomes such as new RRT or mortality. Further randomized controlled studies are needed to validate study results.

Objective: To evaluate the effects of 2 constant rate infusions of hydroxyethyl starch (HES) 130/0.4 on plasma colloid osmotic pressure (COP) in hypoalbuminemic dogs., Design: Prospective, randomized clinical trial., Animals: A total of 24 client-owned dogs., Interventions: Hypoalbuminemic euvolemic dogs (albumin < 20 g/L [<2 g/dL]) with normal perfusion parameters requiring IV fluid therapy were enrolled. In addition to crystalloid, HES 130/0.4 was administered as a constant rate infusion over 24 hours at 1 mL/kg/h (group 1, n = 15) or at 2 mL/kg/h (group 2, n = 9), in order to support plasma COP. Before infusion, a blood sample was collected to perform CBC, serum electrophoresis, and serologic tests for some infective diseases. Plasma COP, albumin concentration, PCV, and total plasma protein concentration were evaluated serially at baseline (T0) and then at 6, 12, and 24 hours after the start of infusion, and a multilevel model was performed for these parameters to detect statistically significant differences between the 2 groups., Measurement and Main Results: Twenty-four dogs were included. No statistically significant differences in COP were found between the 2 groups; however, a high level of variability has been identified within the single individual. Among the other laboratory analyses, PCV was significantly decreased in group 1 at T12 and T24 compared with T0 (P < 0.001) and total plasma protein concentration was significantly increased in group 2 at T12 and T24 compared with T0 (P < 0.008)., Conclusion: No significant effect on plasma COP was found following infusion with HES 130/0.4 at doses of 1 mL/kg/h and 2 mL/kg/h for 24 hours to hypoalbuminemic dogs. The administered concomitant dose of crystalloids, underlying disease, and small sample size were all potential confounding factors., (© Veterinary Emergency and Critical Care Society 2020.)

Background: Hydroxyethyl Starch (HES) 130/0.4 (6%) is a commonly used intravascular volume expander with anti-inflammatory and antioxidant properties. In this study, we aimed to compare the histopathologic activity of HES 130/0.4 (6%) with various widely-used agents in pleurodesis., Methods: Forty male Wistar-Albino rats were divided into five groups: controls, povidone-iodine recipients (PI group), sterile talcum recipients (Talcum group), autologous blood recipients (AB group) and HES 130/0.4 (6%) recipients (HES group). Thirty days after application of agents, pleural and lung tissues were resected. Evaluation was performed via macroscopic scoring (adhesion) and specimens were stained with H&E for microscopic examination (inflammation and fibrosis)., Results: HES recipients had significantly higher adhesion compared to controls (lower grade 0, higher grade 1 frequency vs. controls), they were found to have significantly lower frequency of grade 2 adhesion (vs. PI, Talc and AB) and grade 3 adhesion (vs. AB), indicating that the adhesion-generating properties of HES were only superior to the control group. HES recipients had significantly higher inflammatory grades compared to controls (lower grade 0, higher grade 1 frequency), while they had lower grades compared to the PI, Talc and AB groups. Although the PI, Talc and AB groups were statistically similar in most comparisons, we observed a trend towards higher success with the use of Talc and especially AB., Conclusion: Our results do not support a role for HES in pleurodesis. We believe that the autologous blood method remains as an effective and successful procedure without side effects.

Background: Excessive perioperative fluid administration may result in iatrogenic endothelial dysfunction and tissue edema, transducing inflammatory markers into the bloodstream. Colloids remain longer in the circulation, requiring less volume to reach similar hemodynamic endpoints compared to crystalloids. Thus, we tested the hypothesis that a goal-directed colloid regimen attenuates the inflammatory response compared to a goal-directed crystalloid regime., Methods: Patients undergoing moderate- to high-risk open abdominal surgery were randomly assigned to goal-directed lactated Ringer's solution (n = 58) or a hydroxyethyl starch 6% 130/0.4 (n = 62) fluid regimen. Our primary outcome was perioperative levels of pro- and anti-inflammatory cytokines. Secondary outcome was perioperative levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP). Measurements were performed preoperatively, immediate postoperatively, on postoperative day one, two and four., Results: The areas under the curve of Interleukin (IL) 6 (p = 0.60), IL 8 (p = 0.46), IL 10 (p = 0.68) and tumor necrosis factor α (p = 0.47) levels did not differ significantly between the groups. WBC, CRP and PCT values were also comparable. LBP, although significantly higher in the crystalloid group, remained in the normal range. Patients assigned to crystalloids received a median (IQR) amount of 3905 mL (2880-5288) of crystalloid. Patients assigned to colloids received 1557 mL (1207-2116) of crystalloid and 1250 mL (750-1938) of colloid., Conclusion: Cytokine and inflammatory marker levels did not differ between goal-directed crystalloid and colloid administration after moderate to high-risk abdominal surgery., Trial Registration: ClinicalTrials.gov ( NCT00517127 ). Registered 16th August 2007.

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: N-terminal pro brain natriuretic peptide (NT-proBNP) and troponin T are released during myocardial wall stress and/or ischemia and are strong predictors for postoperative cardiovascular complications. However, the relative effects of goal-directed, intravenous administration of crystalloid compared to colloid solutions on NT-proBNP and troponin T, especially in relatively healthy patients undergoing moderate- to high-risk noncardiac surgery, remains unclear. Thus, we evaluated in this sub-study the effect of a goal-directed crystalloid versus a goal-directed colloid fluid regimen on postoperative maximum NT-proBNP concentration. We further evaluated the incidence of myocardial injury after noncardiac surgery (MINS) between both study groups., Methods: Thirty patients were randomly assigned to receive additional intravenous fluid boluses of 6% hydroxyethyl starch 130/0.4 and 30 patients to receive lactated Ringer's solution. Intraoperative fluid management was guided by oesophageal Doppler-according to a previously published algorithm. The primary outcome were differences in postoperative maximum NT-proBNP (maxNT-proBNP) between both groups. As our secondary outcome we evaluated the incidence of MINS between both study groups. We defined maxNT-proBNP as the maximum value measured within 2 h after surgery and on the first and second postoperative day., Results: In total 56 patients were analysed. There was no significant difference in postoperative maximum NT-proBNP between the colloid group (258.7 ng/L (IQR 199.4 to 782.1)) and the crystalloid group (440.3 ng/L (IQR 177.9 to 691.2)) during the first 2 postoperative days (P = 0.29). Five patients in the colloid group and 7 patients in the crystalloid group developed MINS (P = 0.75)., Conclusions: Based on this relatively small study goal-directed colloid administration did not decrease postoperative maxNT-proBNP concentration as compared to goal-directed crystalloid administration., Trial Registration: ClinicalTrials.gov ( NCT01195883 ) Registered on 6th September 2010.

This study aimed to investigate the relationship between intravascular volume and intracardiac filling pressures in stable HF patients with reduced ejection fraction (HFrEF). A total of 40 HFrEF patients (LVEF 36 ± 10%) (10 subjects with a pulmonary artery catheter) underwent intravascular volume expansion with 1 L hydroxyl-ethyl-starch over 3 h with coinciding intravascular volume measurements (technetium (99 tc)-labeled red blood cell technique). Intravascular blood volume increased from 5.0 ± 1.0 L to 5.7 ± 1.0 L (p < 0.0001). No change in clinical status, echocardiographic indices, or cardiac filling pressures was noticed. Invasively measured right atrial pressure and pulmonary arterial wedge pressure increased significantly immediately after start of infusion (4 ± 2 mmHg to 8 ± 4 mmHg; p = 0.01 and 10 ± 3 mmHg to 15 ± 6 mmHg; p = 0.01, respectively), decreased afterwards, and remained stable for 3 h (6 ± 2 mmHg and 14 ± 4 mmHg, respectively). The accuracy of cardiac filling pressure estimates to predict intravascular volume expansion was low (all AUC < 0.65).

Synthetic colloids are commonly administered to dogs to treat absolute or relative hypovolaemia. Voluven® (tetrastarch 130/0.4) and Gelofusine® (succinylated gelatin) are available to veterinarians in South Africa. In humans, use of these products has caused acid-base derangements, changes in haematology and impaired haemostasis. We aimed to investigate these effects in healthy normovolaemic dogs. Eight healthy adult beagle dogs underwent a cross-over study, receiving Voluven® or Gelofusine® (10 mL/kg/h for 120 min) once each with a 14-day washout between treatments. Dogs were premedicated with dexmedetomidine (10 µg/kg intramuscularly). Anaesthesia was induced with propofol and the dogs were maintained with isoflurane-in-oxygen. The anaesthetised dogs were connected to a multi-parameter monitor to monitor physiological parameters throughout. Catheters placed in a jugular vein and dorsal metatarsal artery allowed sampling of venous and arterial blood. Blood was collected immediately prior to commencement of colloid infusion, after 60 min infusion and at the end of infusion (120 min) to allow for arterial blood gas analysis, haematology and coagulation testing (activated partial thromboplastin time [aPTT], prothrombin time [PT] and thromboelastography [TEG]). There was no effect, between treatments or over time, on blood pH. The haemoglobin concentration, erythrocyte count and haematocrit decreased significantly over time (all p 0.01), with no differences between treatments, and remained within normal clinical ranges. There were no differences between treatments or over time for the TEG, aPTT and PT tests of haemostasis. At the dose studied, Voluven® and Gelofusine® had comparably negligible effects on blood acid-base balance and coagulation in normovolaemic dogs.

Background: Changes in blood haemoglobin concentration indicate plasma volume expansion following hydroxyethyl starch (HES) infusion, but may be affected by vascular tone and HES-induced shedding of the endothelial surface layer (ESL). We hypothesised that anaesthesia-induced hypotension enhances changes in plasma volume as assessed by blood haemoglobin concentration (ΔPV Hb , %) following HES infusion., Methods: Fifty-two patients undergoing abdominal surgery were randomised to receive a continuous infusion of saline (S group) or phenylephrine to restore vascular tone (P group) (n = 26 each). Both groups received an infusion of 8 mL/kg 6% HES solution after induction of general anaesthesia. We compared ΔPV Hb at the end of fluid infusion (15 minutes) and 15 minutes later (30 minutes) between the two groups. We assessed changes in ESL structure by measuring plasma concentrations of hyaluronate and syndecan-1. P < .05 was considered statistically significant., Results: Mean arterial blood pressure was lower in the S group approximately by 30-40% compared to the P group (P < .001). ΔPV Hb was larger in the S group compared to the P group at 15 minutes (24.9 [5.2] % vs 19.0 [5.2] %; P < .001) and 30 minutes (26.5 [5.9] % vs 16.9 [6.6] %; P < .001). There were no clinically significant differences in plasma concentrations of hyaluronate and syndecan-1 with time and between the groups., Conclusions: Increased volume expansion of circulating plasma following HES infusion in anaesthesia-induced hypotension compared to when blood pressure is restored by phenylephrine may result from an attenuation of transcapillary fluid filtration, rather than ESL shedding. UMIN Clinical Trial Registration Number: UMIN000017394 (http://www.umin.ac.jp/ctr/index.htm)., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Fluid therapy influences glycocalyx shedding; however, the effect of this intervention on glycocalyx shedding in patients with glioma remains unclear. In this study, we have investigated glycocalyx shedding and cerebral metabolism during colloid loading in patients with and without glioma., Methods: Forty patients undergoing general anesthesia were assigned to the glioma brain group (n = 20) or the normal brain group (n = 20); patients in the normal brain group were undergoing partial hepatectomy to treat liver cancer. All patients were subjected to 15 mL/kg hydroxyethyl starch (HES) loading after the induction of anesthesia. Glycocalyx shedding, reflected by syndecan-1 and heparan sulfate levels at the jugular venous bulb, was measured in both groups. We also evaluated cerebral metabolism parameters, including jugular venous oxygen saturation (SjvO 2 ), arterial-jugular venous differences in oxygen (CajvO 2 ), glucose (A-JvGD), lactate (A-JvLD), the cerebral extraction ratio for oxygen (CERO 2 ), and the oxygen-glucose index., Results: Our results showed that patients in the glioma brain group had lower preoperative basal syndecan-1 shedding in plasma than patients in the normal brain group. The hematocrit (Hct)-corrected syndecan-1 level was significantly increased after 15 mL/kg HES fluid administration (19.78 ± 3.83 ng/mL) compared with the Hct-correct baseline syndecan-1 level (15.67 ± 2.35 ng/mL) in patients in the glioma brain group. Similarly, for patients in the normal brain group, Hct-corrected syndecan-1 level was significantly increased after HES loading (34.71 ± 12.83 ng/mL) compared with the baseline syndecan-1 level (26.07 ± 12.52 ng/mL). However, there were no intergroup or intragroup differences in Hct-corrected heparan sulfate levels at any time point. Our study also showed that the SjvO 2 was lower and CajvO 2 and CERO 2 were higher in the glioma brain group at 30 min after HES loading. Intragroup analysis showed that CERO 2 and CajvO 2 increased after general anesthesia compared with the baseline values in the glioma brain group. In contrast, cerebral metabolism in the normal brain group was unchanged during perioperative period. There were no significant differences in oxygen-glucose index between the two groups throughout the study period., Conclusions: Preoperative 15 mL/kg HES loading had similar effects on systemic glycocalyx shedding in both the glioma brain and normal brain groups, although patients in the normal brain group had higher levels of plasma syndecan-1. Furthermore, the intraoperative anesthetic management may substantially influence cerebral metabolism in patients with glioma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Sufficient tissue oxygen tension may reduce the risk of postoperative wound infections. Supplemental administration of crystalloids increases subcutaneous oxygen tension (P sq o 2 ). Colloids remain longer in the intravascular system and might therefore increase P sq o 2 even more than crystalloids. Therefore, we tested the hypothesis that goal-directed colloid administration increases the perioperative P sq o 2 more compared with crystalloid administration., Methods: We randomly assigned 80 patients undergoing elective open abdominal surgery to receive fluid boluses of hydroxyethyl starch (HES) or lactated Ringer's (LR) solution guided by oesophageal Doppler. Intraoperative P sq o 2 was measured in the upper arm. After operation, we measured the P sq o 2 in the upper arm and in the surgical wound., Results: Forty patients were enrolled in each group. Patients in the colloid group received HES solution 750 ml (500; 1000) and LR solution 1500 ml (1000; 2000). Patients in the crystalloid group received LR solution 2825 ml (2000; 3960). The goal-directed administration of colloids did not improve intraoperative P sq o 2 in the arm compared with crystalloid administration (11.4 kPa [9.0; 16.6] vs 11.2 kPa [8.6; 15.1], respectively; P=0.58). Postoperative arm P sq o 2 was 8.1 kPa (6.5; 9.6) in the colloid group and 7.3 kPa (5.7; 9.1) in the crystalloid group (P=0.11). Postoperative surgical wound P sq o 2 was 10.7 kPa (8.6; 13.4) in the colloid group and 10.1 kPa (8.1; 12.7) in the crystalloid group (P=0.68)., Conclusions: Goal-directed colloid administration did not increase P sq o 2 compared with goal-directed crystalloid administration in patients undergoing open abdominal surgery., Clinical Trial Registration: NCT00517127., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: Hemodynamic management during low central venous pressure (L-CVP)-assisted hepatectomy involves fluid restriction during resection and fluid resuscitation after resection. Recently, high stroke volume variation (SVV) has been reported as an alternative to L-CVP for reducing blood loss during a hepatectomy. The current study evaluated the impact of a newly implemented SVV-based goal-directed therapy (GDT) protocol on blood loss during hepatectomy., Methods: We conducted a before-after comparative study, which included L-CVP-assisted hepatectomy cases (control group) and GDT-assisted hepatectomy cases (intervention group). The GDT protocol included SVV, cardiac index, and mean arterial pressure as hemodynamic parameters. The target SVV ranges were ≥ 13% and ≤ 12% before and after the resection, respectively. The primary endpoint was the proportion of patients whose blood loss was < 400 mL (median of our hepatectomy cases) in the GDT group, and it was compared to a predefined threshold of 50%. We also investigated factors associated with blood loss using multiple regression analysis., Results: We included 66 patients in the control group and 50 in the GDT group. In the GDT group, the median blood loss was 220 mL and 36 patients (72%) lost < 400 mL blood. This was significantly greater than 50% (P < 0.001). Post-resection GDT-guided fluid optimization reduced positive intraoperative fluid balance compared to that achieved by the conventional fluid therapy used in the control. Multiple regression analysis showed that GDT application, epidural anesthesia, operative time, and hydroxyethyl-starch infusion volume were associated with blood loss., Conclusion: Compared to conventional management, SVV-guided GDT may reduce blood loss during hepatectomies.

Purpose: To investigate the effects of the combination of centhaquin and 6% hydroxyethyl starch 130/0.4 (HES 130/0.4) in a swine model of hemorrhagic shock., Methods: Twenty Landrace-Large White pigs were instrumented and subjected to hemorrhagic shock. The animals were randomly allocated in two experimental groups, the control (group CO, n = 10) and the centhaquin groups (0.015 mg/kg, n = 10, group CH). Acute hemorrhage was induced by stepwise blood withdrawal (18 mL/min) from the internal jugular vein until MAP decreased to 40-45 mmHg, whereas anesthesia remained constant. All animals received HES 130/0.4 solution in the resuscitation phase until their mean arterial pressure (MAP) reached 90% of the baseline. The animals were observed for 60 min, during which no further resuscitation was attempted., Results: The total amount of blood and the bleeding time did not differ significantly between group CO and group CH (120 ± 13 vs. 120 ± 14 mL, p = 0.6; 20 ± 2 vs. 20 ± 1 min, p = 0.62, respectively). During the hemorrhagic phase, only a difference in heart rate (97.6 ± 4.4 vs. 128.4 ± 3.6 beats/min, p = 0.038) was observed between the two groups. The time required to reach the target MAP was significantly shorter in the centhaquin group compared to controls (13.7 ± 0.4 vs. 19.6 ± 0.84 min, p = 0.012). During the resuscitation phase, a statistical significant difference was observed in MAP (75.2 ± 1.6 vs. 89.8 ± 2.1 mmHg, p = 0.02) between group CO and group CH. During the observation phase, a statistical significant difference was observed in SVR (1109 ± 32.65 vs. 774.6 ± 21.82 dyn s/cm 5 , p = 0.039) and cardiac output (5.82 ± 0.31 vs. 6.9 ± 0.78 L/min, p = 0.027) between the two groups. Two animals of group CO and seven animals of group CH survived for 24 h (p = 0.008). We observed a marked increase in microvascular capillary permeability in group CO compared to group CH, with the wet/dry weight ratio being significantly higher in group CO compared to group CH (4.8 ± 1.6 vs. 3.08 ± 0.6, p < 0.001)., Conclusions: The combination of centhaquin 0.015 mg/kg and HES 130/0.4 resulted in shorter time to target MAP, lower wet-to-dry ratio, and better survival rates after resuscitation from hemorrhagic shock.

Background and Aims: Viscous solutions provide a superior submucosal cushion for EMR. SIC-8000 (Eleview; Aries Pharmaceuticals, La Jolla, Calif) is a commercially available U.S. Food and Drug Administration-approved solution, but hetastarch is also advocated. We performed a randomized trial comparing SIC-8000 with hetastarch as submucosal injection agents for colorectal EMR., Methods: This was a single-center, double-blinded, randomized controlled trial performed at a tertiary referral center. Patients were referred to our center with flat or sessile lesions measuring ≥15 mm in size. The primary outcome measures were the Sydney resection quotient (SRQ) and the rate of en bloc resections. Secondary outcomes were total volume needed for a sufficient lift, number of resected pieces, and adverse events., Results: There were 158 patients with 159 adenomas (SIC-8000, 84; hetastarch, 75) and 57 serrated lesions (SIC-8000, 30; hetastarch, 27). SRQ was significantly better in the SIC-8000 group compared with hetastarch group (9.3 vs 8.1, P = .001). There was no difference in the proportion of lesions with en bloc resections. The total volume of injectate was significantly lower with SIC-8000 (14.8 mL vs 20.6 mL, P = .038)., Conclusions: SIC-8000 is superior to hetastarch for use during EMR in terms of SRQ and total volume needed, although the absolute differences were small. (Clinical trial registration number: NCT03350217.)., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Fluid responsiveness is an important factor to consider for fluid volume loading during major surgery. The effect of continuous vasopressor infusion on fluid responsiveness during prolonged major surgery is a concern., Objective: We hypothesised that continuous vasopressor infusion during major surgery might not exert significant effects on changes in stroke volume variation (SVV) following fluid bolus infusion, and thereby on fluid responsiveness., Design: Randomised controlled trial., Setting: University hospital from April 2014 to August 2016., Patients: Patients undergoing liver resection who were randomised to receive continuous intravenous infusion of phenylephrine (P group), norepinephrine (N group), or no vasopressor (C group) (n=17/group). Exclusion criteria were cardiac arrhythmia and severe cardiac, pulmonary or renal dysfunction., Intervention: Patients received 4 ml kg fluid boluses of 6% hydroxyethyl starch solution when SVV was at least 12%. Vasopressors were administered continuously to maintain the systemic vascular resistance index at more than 1900 dyn s cm m., Main Outcome Measures: Cardiac index and SVV were measured using the FloTrac/Vigileo system (Version 4.00). The number of fluid boluses with fluid responsiveness (i.e. >15% increase in cardiac index) was compared between groups using multilevel logistic regression analysis., Results: Numbers of fluid responsive boluses in the C, P and N groups were 12 (14%), 22 (34%) and 19 (27%), respectively. Odds ratios on fluid responsiveness for phenylephrine and norepinephrine compared with the control were 3.65 (97.5% confidence interval, 1.15 to 11.6; P = 0.012) and 2.56 (97.5% confidence interval, 0.82 to 8.00; P = 0.064), respectively. Decreases in SVV after fluid bolus infusion for the P and N groups were comparable with the C group (P = 0.23 and 0.53, respectively)., Conclusion: Continuous administration of phenylephrine increased fluid responsiveness during liver resection, suggesting complex effects of continuous vasopressor infusion involving changes in cardiac preload and afterload., Trial Registration: UMIN000011024.

Objective: To determine if low molecular weight synthetic colloid fluids administered to dogs interfere with refractometric estimates of total plasma protein (TPPr) and urine osmolality (UOsm)., Study Design: Experimental study., Animals: Eighteen healthy Greyhound dogs., Methods: Anaesthetized Greyhounds subjected to haemorrhage for 60 minutes were given 80 mL kg -1 of Plasma-Lyte 148 (CRYST), or 20 mL kg -1 of hydroxyethyl starch 130/0.4 (HES) or succinylated gelatine (GELO) (n = 6 per group) intravenously over 20 minutes. Refractometric (TPPr) and biuret total plasma protein (TPPb) were measured before haemorrhage (Baseline), at end of shock (Shock), immediately (T20), then 40 minutes (T60), 100 minutes (T120) and 160 minutes (T180) after fluid administration. Urine specific gravity (USG) and UOsm were measured at all time points except T20. Estimated UOsm (eUOsm) was calculated from USG. Bias and limits of agreement (LOA) for TPPr versus TPPb, and eUOsm versus UOsm were calculated at each time point., Results: For dogs given CRYST and GELO, median TPPr and TPPb decreased in parallel, with a small consistent TPP bias (CRYST range of bias, 0.38-0.67 g dL -1 ; GELO range of bias, 0.42-0.58 g dL -1 ). Dogs given HES showed divergence between median TPPr and TPPb after T20, with a peak bias at T20 of 1.62 g dL -1 (LOA 1.29-1.95). Dogs given HES and GELO had markedly increased USG [HES peak median USG at T180 of 1.119 (Q1-Q3 1.103-1.122); GELO peak median USG at T120 of 1.114 (Q1-Q3 1.082-1.119)], with large increases in bias between eUOsm and UOsm [HES peak bias at T60 of 2995 mOsm kg -1 (LOA 2032-3958 mOsm kg -1 ); GELO peak bias at T120 of 2465 mOsm kg -1 (LOA 940-3990 mOsm kg -1 )]., Conclusions and Clinical Relevance: Administration of HES and GELO to dogs with haemorrhagic shock interferes with refractometric measurements for at least 3 hours after administration., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Purpose : To compare the effects of fluid resuscitation with lactated Ringer's solution (LR) and saline-based 6% hydroxyethyl starch 130/0.4 (HES) on the inflammatory response and oxidative stress in the small intestine as well as on bacterial translocation to the liver. Methods: Sprague-Dawley rats were subjected to blood pressure-controlled hemorrhagic shock and then resuscitated with LR or HES. At 1, 3, 6, 12, and 24 hr after resuscitation, liver tissues were collected to count the bacterial colonies, and small intestines were harvested to analyze the levels of inflammatory (TNF-α and HO-1) and oxidative stress (MPO) mediators as well as the intestinal injury by immunohistochemistry, colorimetry and hematoxylin & eosin staining, respectively. Results: The expression level of TNF-α in the LR group was stable from 1 to 6 hr but decreased at 12 hr and then abruptly increased at 24 hr. The expression level of TNF-α in the LR group was significantly lower than that in the HES group, especially during the first 12 hr post-fluid infusion. MPO activity decreased to its lowest level at 3 hr but increased from 6 to 12 hr, with no difference at 24 hr between the two groups. Although a decreasing tendency was observed from 6 hr, HO-1 expression levels remained higher in the LR group than in the HES group at 12 and 24 hr, particularly at 12 hr. During the initial 12 hr, the LR group exhibited significantly lower colony-forming units in the liver tissues than the HES group. Chiu's score in the intestine decreased regardless of which resuscitative fluids were used. Conclusions: During early resuscitation (within 12 hr), LR may be superior to HES in reducing intestinal injuries by suppressing inflammatory and oxidative mediators.

Background and Objectives: Modern crystalloid and colloid solutions are balanced solutions which are increasingly used in perioperative period. However, studies investigating their negative effect on whole blood coagulation are missing, and vivid debate is going on about which solution has the minimal coagulopathy effect. The aim of our study was to assess the effect of modern fluid solutions on whole blood coagulation using rotational thromboelastometry., Methods: Blood samples were obtained from 30 patients during knee arthroscopy before and after administration of 500mL of crystalloid, Hydroxyethyl Starch and gelatin according to the randomization. Rotational thromboelastometry (Extem, Intem and Fibtem tests) was used to assess negative effect of fluid solutions on whole blood coagulation., Results: In Extem test, the initiation phase of fibrin clot formation represented by CT parameter was not influenced by any fluid solution (p>0.05). The speed of clot formation represented by CFT and α angle was impaired by Hydroxyethyl Starch and gelatin but not by crystalloids (p<0.05). The strength of formatted coagulum represented by MCF parameter was impaired both in Extem and Fibtem test by HES and in Fibtem also by crystalloids (p<0.05). Intem test was not negatively influenced by any crystalloid or colloid solution in any parameter (p>0.05)., Conclusion: Extem test appears to be sensitive to coagulopathy effect of modern colloids and crystalloids. Hydroxyethyl starch has the most obvious negative effect on clot formation followed by gelatin and finally by crystalloids. Intem test seems to be insensitive to adverse effect of modern colloids and crystalloids., (Copyright © 2019 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background: Hemorrhage remains the primary cause of preventable death in civilian and military trauma. The Committee on Tactical Combat Casualty Care recommends prehospital (PH) resuscitation with whole blood (WB). However, 6% hetastarch in lactated electrolyte (HEX) and crystalloids are more commonly available and used for PH resuscitation in military and civilian environments, respectively. The mechanistic benefits of PH WB resuscitation have not been well studied and remain to be elucidated., Study Design and Methods: The aim of this study was to evaluate the differences in simulated PH WB and HEX resuscitation, specifically with regards to coagulation, physiologic, and metabolic outcomes to better elucidate the mechanistic benefits of WB. In a randomized study, the physiologic, coagulation, and metabolic responses to simulated PH WB (n = 12) or HEX (n = 12) were evaluated in a nonhuman primate model of severe polytraumatic hemorrhagic shock., Results: Notable findings included 1) equivalence of shock reversal between simulated PH WB and HEX treatment groups as determined by hemodynamics and base deficit and 2) prevention of coagulopathy at simulated hospital arrival with initial WB resuscitation as determined by viscoelastic and plasmatic coagulation assays., Conclusion: The major benefit of WB, as compared to HEX, in simulated PH resuscitation appears to be prevention of coagulopathy at hospital arrival. Both fluids effectively reversed shock in this model, implying that efficacious provision preload (cardiac output support and hence oxygen delivery) and coagulation proteins (prevention of coagulopathy) are mechanisms underlying WB's effectiveness in early resuscitation of hemorrhagic shock., (© 2019 AABB.)

Purpose: We investigated the safety and efficacy of administering hydroxyethyl starch 6% 130/0.4/9 (HES130/0.4/9) versus 5% human serum albumin (HSA), perioperatively, to patients undergoing thoracic esophagectomy with 3-field lymph-node dissection for esophageal cancer., Methods: The subjects of this study were 262 patients, scheduled to undergo thoracic esophagectomy for esophageal cancer, who were assigned to one of two groups based on the fluid replacement therapy. We compared the intraoperative and immediate postoperative hemodynamics and incidence of complications in the two groups., Results: Neither group suffered any adverse events. No significant differences were observed in systolic/diastolic blood pressure, heart rate, incidence of postoperative complications, postoperative urine output, or serum creatinine levels, between the groups. A mild postoperative increase (×1.5 increase) in serum creatinine levels was seen in 9.5% and 9.5% of patients in the HSA and HES130/0.4/9 groups, respectively (p = 0.99), and a moderate postoperative increase (×2.0 increase) was seen in 4.4% and 3.1%, respectively (p = 0.84). Univariate and multivariate analyses revealed that the administration of hydroxyethyl starch was not associated with a postoperative increase in serum creatinine levels., Conclusion: Hydroxyethyl starch 6% 130/0.4/9 was well tolerated and comparable to albumin with respect to its effect on renal function during thoracic esophagectomy with 3-field lymph-node dissection.

Objective: To describe the frequency of renal tubular vacuolization (RTV) as a surrogate of osmotic nephrosis and assess hyperosmolar agents as predictors of RTV severity., Design: Retrospective study (February 2004-October 2014)., Setting: Veterinary teaching hospital., Animals: Fifty-three client-owned, critically ill dogs that had a postmortem examination., Interventions: None., Measurements and Main Results: The frequency, severity, and location of RTV were determined in small group of critically ill dogs postmortem. Logistic regression was performed to assess cumulative 6% HES (670/0.75) and mannitol dose as predictors for RTV severity with presenting serum creatinine concentration, cumulative furosemide dose, and duration of hospitalization as covariates. RTV was noted in 45 (85%) of 53 critically ill dogs and was most commonly located to the medullary rays (68%). Cumulative 6% HES (670/0.75) dose (P = 0.009) and presenting serum creatinine concentration (P = 0.027) were significant predictors of RTV severity. For every 1 mL/kg increase in 6% HES (670/0.75) dose that a dog received, there was 1.6% increased chance of having more severe RTV (OR 1.016; 95% CI 1.004-1.029). In addition, for every 88.4 μmol/L (1 mg/dL) increase in presenting serum creatinine, there was a 22.7% increased chance of having more severe RTV (OR 1.227; 95% CI 1.023-1.472). Cumulative mannitol (P = 0.548) and furosemide (P = 0.136) doses were not significant predictors of RTV severity., Conclusion: In a small group of critically ill dogs, there was a high frequency of RTV identified on postmortem examination. Administration of 6% HES (670/0.75) and presenting serum creatinine concentration were significant predictors of RTV severity. Larger prospective studies are needed to determine the etiology and significance of RTV in dogs., (© Veterinary Emergency and Critical Care Society 2019.)

Objective: To evaluate changes in serum creatinine and chloride concentrations in anesthetized dogs that received 6% hydroxyethyl starch (HES) 670/0.7., Design: Retrospective case series, 2002-2015., Setting: University veterinary teaching hospital., Animals: Two hundred forty-four client-owned dogs undergoing general anesthesia that received an HES solution., Interventions: None., Measurements and Main Results: Medical records of dogs that received an HES solution (6%, 670/0.7) while under general anesthesia during the study period were reviewed. Information obtained from the medical record included patient signalment, reason for anesthesia or diagnosis, body weight, amount of HES solution administered, pre- and postanesthesia creatinine value, pre- and postanesthesia chloride value, and day interval between measurements. Corrected chloride values were used for all statistical analysis. Dogs received a median dose of 6.3 mL/kg hetastarch during anesthesia. Median preanesthesia creatinine and corrected chloride values were 79.5 μmol/L (0.9 mg/dL) (range 8.8-689.5 μmol/L [0.1-7.8 mg/dL]) and 111 mmol/L (111 mEq/L) (range 80-123 mmol/L [80-123 mg/dL]), respectively. Median postanesthesia creatinine was 57.4 μmol/L (0.65 mg/dL) (8.8-716 μmol/L [0.1-8.1 mg/dL]). Median postanesthesia corrected chloride was 115 mmol/L (115 mEq/L) (range 87.5-129.6 mmol/L [87.5-129.6 mEq/L]). Mann-Whitney test analysis revealed a significant decrease in creatinine (Δ Cr 17.7 μmol/L [0.2 mg/dL], P < 0.01) and a significant increase in corrected chloride (Δ Cl 4.1 mmol/L [4.1mEq/L], P < 0.01) between pre- and postanesthesia values., Conclusions: In a mixed population of hospitalized dogs undergoing general anesthesia that received a median dose of 6 mL/kg of HES, creatinine was lower and chloride was higher in the postanesthetic than in the preanesthetic period. The clinical significance of these changes and the role that HES administration played in them relative to concurrent therapies is unknown., (© Veterinary Emergency and Critical Care Society 2019.)

Introduction: Balanced fluid replacement solutions can possibly reduce the risks for electrolyte imbalances, for acid-base imbalances, and thus for renal failure. To assess the intraoperative change of base excess (BE) and chloride in serum after treatment with either a balanced gelatine/electrolyte solution or a non-balanced gelatine/electrolyte solution, a prospective, controlled, randomized, double-blind, dual centre phase III study was conducted in two tertiary care university hospitals in Germany., Material and Methods: 40 patients of both sexes, aged 18 to 90 years, who were scheduled to undergo elective abdominal surgery with assumed intraoperative volume requirement of at least 15 mL/kg body weight gelatine solution were included. Administration of study drug was performed intravenously according to patients need. The trigger for volume replacement was a central venous pressure (CVP) minus positive end-expiratory pressure (PEEP) <10 mmHg (CVP <10 mmHg). The crystalloid:colloid ratio was 1:1 intra- and postoperatively. The targets for volume replacement were a CVP between 10 and 14 mmHg minus PEEP after treatment with vasoactive agent and mean arterial pressure (MAP) > 65 mmHg., Results: The primary endpoints, intraoperative changes of base excess -2.59 ± 2.25 (median: -2.65) mmol/L (balanced group) and -4.79 ± 2.38 (median: -4.70) mmol/L (non-balanced group)) or serum chloride 2.4 ± 1.9 (median: 3.0) mmol/L and 5.2 ± 3.1 (median: 5.0) mmol/L were significantly different (p = 0.0117 and p = 0.0045, respectively). In both groups (each n = 20) the investigational product administration in terms of volume and infusion rate was comparable throughout the course of the study, i.e. before, during and after surgery., Discussion: Balanced gelatine solution 4% combined with a balanced electrolyte solution demonstrated significant smaller impact on blood gas analytic parameters in the primary endpoints BE and serum chloride when compared to a non-balanced gelatine solution 4% combined with NaCl 0.9%. No marked treatment differences were observed with respect to haemodynamics, coagulation and renal function., Trial Registration: ClinicalTrials.gov (NCT01515397) and clinicaltrialsregister.eu, EudraCT number 2010-018524-58., Competing Interests: This study was supported by a restricted grant of B. Braun Meldungen AG, Germany. GM received honoria for consulting and research grants by B. Braun Melsungen AG and Adrenomed, lecture fees by B. Braun Melsungen AG. KZ has received payments for lectures and consulting from B. Braun Melsungen AG and Fresenius Kabi as well as funding for a clinical trial. PM has received payments for lectures and consulting from B. Braun Melsungen AG and Fresenius Kabi as well as funding for a clinical trial. RR received honoria for consulting from Fresenius; he received lecture fees from Fresenius and B. Braun Melsungen AG and is Editor-in-Chief of Der Anaesthesist and editor of the European Journal of Anaesthesiology. TS received honoria for board membership by Astellas Pharma GmbH, lecture fees by Astellas Pharma, Bayer Health Care, B. Braun Melsungen AG and Astra Zeneca and research grants by Bayer Health Care and Astellas Pharma GmbH. All the other authors declare that they have no competing interests. This does not alter our adherence to PLOS One policies on sharing data and materials.

Objective: To investigate the association between synthetic colloids and biomarkers of acute kidney injury (AKI) in dogs with hemorrhagic shock., Design: Experimental interventional study., Setting: University., Animals: Twenty-four healthy ex-racing Greyhounds., Interventions: Anesthetized Greyhounds subjected to hemorrhage for 60 min were resuscitated with 20 mL/kg of fresh whole blood (FWB), 6% hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL/kg of isotonic crystalloid (CRYST) over 20 min (n = 6 per treatment). Concentrations of biomarkers of AKI were measured at baseline, end of hemorrhage, and at 40 (T60), 100 (T120), and 160 (T180) min after fluid bolus. Biomarkers included neutrophil gelatinase-associated lipocalin in urine and serum (uNGAL; sNGAL), and urine cystatin C (uCYSC), kidney injury molecule-1 (uKIM), clusterin (uCLUST), osteopontin, gamma-glutamyl transferase, monocyte chemoattractant protein-1 (uMCP), interleukin-6, interleukin-8, protein (uPROT), hyaluronan, and F 2 -isoprostanes. Renal histology was scored for tubular injury and microvesiculation. Biomarker fold-change from baseline was compared between groups using mixed effects models (Bonferroni-Holm corrected P<0.05). Frequencies of histology scores were compared by Fisher's exact test., Measurements and Main Results: In dogs treated with GELO, uNGAL fold-change was markedly greater compared with all other groups at T60, T120, and T180 (all P<0.001), and uCYSC was greater at T60 compared with CRYST (P<0.001), and at T120 and T180 compared with all other groups (all P<0.001). Smaller, albeit significant, between-group differences in uKIM, uCLUST, uMCP, and urine protein concentration were observed across the FWB, GELO, and HES groups, compared with CRYST. The GELO group more frequently had marked tubular microvesiculation than the other groups (P = 0.015) although tubular injury scores were comparable., Conclusion: In dogs with hemorrhagic shock, GELO was associated with greater magnitude increases in urine biomarkers of AKI and more frequent marked tubular microvesiculation, compared with FWB, CRYST, and HES., (© Veterinary Emergency and Critical Care Society 2019.)

Study Design: Retrospective analysis., Objective: The objective of this study was to investigate the effects of intraoperative balanced 6% hydroxyethyl starch (HES) 130/0.4 on postoperative blood loss and the coagulation profile., Summary of Background Data: The safety of colloid versus crystalloid transfusion for bleeding and coagulation during major spine surgery remains controversial and only a few studies exist. Thus, we compared the effects of balanced 6% HES 130/0.4 and crystalloid on postoperative bleeding and coagulation., Methods: Patients undergoing spine surgery between February 1, 2015 and February 28, 2017 were divided into 2 groups: patients receiving intraoperative balanced 6% HES 130/0.4 and patients receiving crystalloid. We compared the postoperative bleeding volume with changes in the coagulation profile and length of hospital stay between these 2 groups. Propensity score (PS)-matching and multivariate stepwise linear regression were performed., Results: A total of 169 patients who met the inclusion criteria were analyzed. The quantity of total colloid per patient was 10-15 mL/kg. A significant difference was observed in the total intraoperative transfused crystalloid volume between the 2 groups (colloid group, 1.394.6±1.414.0 mL; crystalloid group, 2.027.3±1.114.1 mL; P<0.001). Postoperative blood loss and coagulation profile changes were not significantly different in the 60 PS-matched paired patients. Furthermore, no differences in either postoperative transfusion requirement or length of hospital stay were observed between the groups. Multivariate stepwise linear regression revealed that operation time (β=0.549; P<0.001) and intraoperative transfusion of packed red blood cells (β=0.466; P=0.003) or fresh frozen plasma (β=-0.263; P=0.041) were independently associated with postoperative blood loss. However, intraoperative colloid administration was not a predictive factor., Conclusions: Intraoperative infusion of balanced 6% HES 130/0.4 in patients undergoing spine surgery presented clinically insignificant changes in postoperative blood loss and coagulation compared to crystalloid., Level of Evidence: Level III.

Background: To improve prognosis after esophageal surgery, intraoperative fluid optimization is important. Herein, we hypothesized that hydroxyethyl starch administration during esophagectomy reduce the total amount of fluid infused and it could have a positive effect on postoperative complication occurrence and mortality., Methods: All consecutive adult patients who underwent elective esophageal surgery for cancer were studied. The primary outcome was the development of composite complications including death, cardio-cerebrovascular complications, respiratory complications, renal complications, gastrointestinal complications, sepsis, empyema or abscess, and multi-organ failure. The relationship between perioperative variables and composite complication was evaluated using multivariable logistic regression., Results: Of 892 patients analyzed, composite complications developed in 271 (30.4%). The higher hydroxyethyl starch ratio in total fluid had a negative relationship with the total fluid infusion amount (r = - 0.256, P <  0.001). In multivariable analysis, intraoperatively administered total fluid per weight per hour (odds ratio, 1.248; 95% CI, 1.153-1.351; P <  0.001) and HES-to-crystalloid ratio (odds ratio, 2.125; 95% CI, 1.521-2.969; P <  0.001) were associated with increased risks of postoperative composite outcomes., Conclusions: Although hydroxyethyl starch administration reduces the total fluid infusion amount during esophageal surgery for cancer, intravenous hydroxyethyl starch infusion is associated with an increasing risk of postoperative composite complications.

We assessed whether perioperative fluid management with balanced solutions and a limited volume of hydroxyethyl starch (renal-protective fluid management [RPF] strategy) could improve renal outcomes after cardiovascular surgery.For this retrospective observational study, we evaluated 2613 patients who underwent cardiovascular surgery from January 1, 2010 to December 31, 2013. The control group were given intravenous fluids with saline-based solutions and unlimited volumes of hydroxyethyl starch solutions and the RPF group were given intravenous fluids with RPF. The primary outcome was the incidence of acute kidney injury (AKI) and chronic dialysis within 12 months after cardiovascular surgery. Multivariable regression and propensity analyses were performed to evaluate the association between perioperative fluid management strategy and postoperative renal outcomes.Postoperative AKI and chronic dialysis occurred in 213 (21.2%) and 5 (0.5%) patients in the RPF group compared with 696 (43.2%) and 38 (2.4%) patients in the control group, respectively. After adjustment, the RPF group was linked to a decreased risk of postoperative AKI, severe AKI, persistent AKI, use of renal replacement therapy, chronic kidney disease, chronic dialysis, and a shorter postoperative extubation time and intensive care unit, and hospital stay duration.The perioperative fluid management strategy with balanced solutions and a limited volume of hydroxyethyl starch was related to improved acute and 1-year renal and clinical outcomes after cardiovascular surgery. These findings indicate the need for further definitive clinical trials on perioperative fluid management strategy.

Objective: Establish whether the use of starch in hip arthroplasty is a risk factor for excessive surgical bleeding and requirement of red blood cell transfusion., Method: Analytical observational retrospective study in 240 patients who underwent primary total hip arthroplasty from January 2015 to January 2016. Two groups were formed: starch (94 patients) and non-starch (146 patients). Age, sex, body mass index, preoperative and postoperative hemoglobin, red cell transfusion and surgical bleeding was analyzed., Results: Starchy group had increased risk of excessive surgical bleeding (OR: 3.58; 95% CI: 2.05- 6.26) and red blood cells transfusion (OR: 3.12; 95% CI: 1.76 -5.5). In the starch group average surgical bleeding was 396 ml (SD: ± 234.94) and a decrease in hemoglobin of 4.6 g/dl (SD± 1.38). The control group had an average bleeding of 271.8 ml (SD: ± 139.22) and decrease in hemoglobin of 3.34 g/dl (SD: ± 1.4)., Discussion: The starch group had higher surgical bleeding and required more often red blood cells transfusion than the non-starch group. We suggest to take in account the possible complications related to the use hydroxyethyl starch., (Copyright: © 2019 Permanyer.)

Purpose: To examine the effect of discontinuing hydroxyethyl starch (HES) solutions on length of hospital stay, transfusion, risk of death, acute kidney injury (AKI), and dialysis., Methods: We conducted a historical cohort study of linked administrative and clinical databases in patients undergoing coronary artery bypass surgery (CABG) on cardiopulmonary bypass. We used propensity scores to match patients who did not receive HES (after discontinuation) with patients exposed to HES (before discontinuation) and also controlled for albumin exposure. Hospital length of stay (the primary outcome) was analyzed using Fine-Gray proportional hazard regression, with hospital discharge as the outcome and death as a competing risk. Adverse outcomes were compared between matched patients using conditional logistic regression., Results: We compared 1,085 propensity score-matched pairs (n = 2,170) from a pool of 2,757 patients. Discontinuation of HES was associated with shorter length of hospital stay, as evidenced by an increased probability of discharge (hazard ratio, 1.24; 95% confidence interval [CI], 1.14 to 1.35) and a reduced risk of red blood cell transfusion (odds ratio [OR], 0.68; 95% CI, 0.55 to 0.84), plasma transfusion (OR, 0.48; 95% CI, 0.34 to 0.66), and platelet transfusion (OR, 0.62; 95% CI, 0.44 to 0.87). Discontinuation of HES was not associated with in-hospital mortality (OR, 0.74; 95% CI, 0.36 to 1.54), AKI (OR, 0.84; 95% CI, 0.57 to 1.25), or dialysis (OR, 0.83; 95% CI, 0.25 to 2.73)., Conclusions: For patients undergoing CABG on cardiopulmonary bypass, discontinuation of HES was associated with reduced hospital length of stay and reduced blood product transfusion, without measurable change in renal failure, dialysis rate, or in-hospital mortality. Our results should be interpreted with caution, though we found no evidence of harms associated with discontinuing HES., Trial Registration: www.clinicaltrials.gov (NCT02329158); registered 31 December, 2014.

Background: To compare the effects of intraoperative infusions of balanced electrolyte solution (BES)-based hydroxyethyl starch (HES) and saline-based albumin on metabolic acidosis and acid/base changes during major abdominal surgery conducted using Stewart's approach., Methods: Forty patients, aged 20-65 years, undergoing major abdominal surgery, were randomly assigned to the HES group (n = 20; received 500 ml of BES-based 6% HES 130/0.4) or the albumin group (n = 20; received 500 ml of normal saline-based 5% albumin). Acid-base parameters were measured and calculated using results obtained from arterial blood samples taken after anesthesia induction (T1), 2 hours after surgery commencement (T2), immediately after surgery (T3), and 1 hour after arriving at a postanesthetic care unit (T4)., Results: Arterial pH in the HES group was significantly higher than that in the albumin group at T3 (7.40 ± 0.04 vs. 7.38 ± 0.04, P = 0.043), and pH values exhibited significant intergroup difference over time (P = 0.002). Arterial pH was significantly lower at T3 and T4 in the HES group and at T2, T3, and T4 in the albumin group than at T1. Apparent strong ion difference (SIDa) was significantly lower at T2, T3, and T4 than at T1 in both groups. Total plasma weak nonvolatile acid (ATOT) was significantly lower in the HES group than in the albumin group at T2, T3 and T4 and exhibited a significant intergroup difference over time (P < 0.001)., Conclusions: BES-based 6% HES infusion was associated with lower arterial pH values at the end of surgery than saline-based 5% albumin infusion, but neither colloid caused clinically significant metabolic acidosis (defined as an arterial pH < 7.35).

We studied the effect of O-((((4-hydroxy-3,5-di(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl) benzyl)oxy)ethyl)-O-(2-hydroxyethyl)-(1→4)-α-D-glucan (D-HES, 80 mg/kg, intravenously) and reference preparation ethylmethylhydroxypyridine succinate (EMHP-S, 50 mg/kg, intravenously) on rat survival and neurological deficit in 24 h after transient global cerebral ischemia in Wistar rats. Intravenous administration of D-HES and EMHP-S significantly increased the number of survivors by 68 and 78%, respectively, in comparison with the control group. In groups treated with D-HES and EMHP-S, the number of animals with severe neurological deficit was significantly lower and the number of animals moderate or mild neurological deficit was significantly higher than in the control group.

Objective: This study was conducted since the effects of colloid solutions on the renal system remain controversial and need to be adequately studied in animals. We aimed to evaluate the effects of hydroxyethyl starch (Voluven) on the kidney tissue of rats with late renal failure due to ureteral obstruction., Materials and Methods: Rats were divided into four groups: Group C, control; Group HES, hydroxyethyl starch solution (HES) 130/0.4 (Voluven ® ); Group UUO, unilateral ureteral obstruction (UUO); and Group UUO-HES, UUO-HES 130/0.4 (Voluven ® ). In the groups with ureteral obstruction, the distal part of the right ureter was accessed and sutured through a lower abdominal incision under ketamine anesthesia. Any signs of late-stage renal failure were evaluated after three weeks. Rats in the HES group and the renal failure-HES group were administered with HES 130/0.4 as a single intravenous dose of 20 mL/kg. After a follow-up of 24 hours, intra-abdominal blood sample was collected, and the rats were sacrificed. Biochemical and histopathological parameters were then evaluated., Results: Ureteral obstruction significantly increased urea and creatinine levels. In addition, when the UUO-HES and HES groups were compared, the administration of HES increased urea and creatinine levels in the UUO-HES group. Nitric oxide enzyme activity and malondialdehyde levels have significantly increased in the UUO groups. In addition, HES significantly increased nitric oxide activity and malondialdehyde levels in the UUO-HES group, in comparison with the HES group. The activity of caspases 3 and 8 was significantly increased in the UUO groups. In addition, HES significantly increased the activity of caspases 3 and 8 in the UUO-HES group, in comparison with the HES group. Light microscopy revealed significant changes in the UUO groups, especially in the obstructed kidneys., Conclusion: If indicated, HES should be used with caution in cases of UUO, but not in the cases of bilateral ureteral obstruction. Other aspects of these findings, including the clinical significance and practical applications, merit further experimental and clinical investigation., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Effects of lactated Ringer's solution (LRS) and hetastarch 130/0.4 (HES) on colloid osmotic pressure (COP), plasma osmolality (OSM) and total protein (TP) were investigated in 18 inhalational-anaesthetised healthy horses. Horses received 4-6 ml/kg LRS (LRS; n=9) or HES (HES; n=9) from anaesthesia induction through 60 min, after which all were administered LRS. COP, TP and OSM were measured before premedication (baseline), postinduction and 30 (n=18), 60 (n=18), 90 (n=18) and 120 (n=12) minutes. Baseline COP, OSM and TP were not different between groups. TP decreased in both groups at all time points after induction. OSM increased from baseline in HES at 30, 60, 90 and 120 minutes. COP decreased at 30-120 minutes in LRS, and at 90 and 120 minutes in HES. Mean COP was higher in HES than LRS at 30 (18.8±0.5 vs 16.3±0.4 mmHg (P=0.001)), 60 (19.1±0.5 vs 15.9±0.4 mmHg (P<0.0001)) and 90 (17.4±0.5 vs 15.4±0.5 mmHg (P=0.005)) minutes. Sixty minutes of HES infusion increases OSM and transiently maintains COP compared with an equal volume of LRS in anaesthetised horses., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Hydroxyethyl starch (HES) solutions have shown their efficiency for intravascular volume expansion. A safety recommendation limiting their use in adult patients has recently been made., Objective: To assess the efficacy and adverse effects of HES when administered intra-operatively to paediatric patients., Design: Systematic review with meta-analyses. Data were analysed using classical mean differences [and their 95% confidence intervals (CIs)] and trial sequential analysis. A Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification was performed for all outcomes. Reviewers extracted valid data, including perioperative total fluid intakes, mortality, renal function, coagulation tests, blood loss and length of hospital and ICU stay., Data Sources: Searches were performed in databases (Pubmed, Embase, Cochrane central register of controlled trials), clinical trials register, and open access journals not indexed in major databases., Eligibility Criteria: Randomised controlled trials (RCTs) published before December 2016 involving paediatric patients who received 6% low molecular weight HES., Results: Nine RCTs involving 530 peri-operative paediatric patients were analysed. Compared with other fluids, HES did not significantly modify the amount of peri-operative fluid administered [mean difference 0.04; 95% CI (-1.76 to 1.84) ml kg], urine output [mean difference -33; 95% CI (-104 to 38) ml kg] or blood loss [mean difference -0.09; (-0.32 to 0.15) ml kg]. Trial sequential analysis determined that the outcomes for peri-operative fluid and urine output were underpowered. All results were graded as very low quality of evidence., Conclusion: Intravascular volume expansion with low molecular weight 6% HES did not appear to modify renal function, blood loss or transfusion when administered to children during the peri-operative period. However, given the lack of statistical power and the very low GRADE quality of evidence, more high-quality RCTs are needed to explore these outcomes.

Although postoperative renal dysfunction is relatively rare after cesarean delivery, preeclampsia is considered as the high-risk population. On the other hand, hydroxyethyl starch (HES) administration for preventing maternal hypotension induced by spinal anesthesia for cesarean delivery is a common practice. However, the effect of HES administration during cesarean delivery on postoperative kidney function in parturients with severe preeclampsia is not well investigated. We retrospectively reviewed both medical and anesthesia records of patients with severe preeclampsia who underwent cesarean delivery from January 2011 to December 2013. Preoperative blood examinations were compared with postoperative values. All parturients received 6% HES 70/0.5 for preventing anesthesia-induced hypotension or for volume resuscitation during cesarean delivery. A total of 87 severe preeclampsia parturients were underwent cesarean section during the period. The amounts of HES administration were 859 ± 206 mL. There was significant reduction in serum creatinine, from 0.70 ± 0.29 mg/dL preoperatively to 0.62 ± 0.17 mg/dL in 3-7 days after the cesarean. Only one patient had postoperatively elevated serum creatinine up to clinically significant level (from 0.64 mg/dL to 1.35 mg/kg).