Prothrombin and activated partial thromboplastin times, thromboelastography, hematocrit, and platelet count in a feline hemorrhage/over-resuscitation model using lactated Ringer's solution or 6% tetrastarch 130/0.4.

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.

Combined Hydroxyethyl Starch Luteolin Nanocrystals for Effective Anti-Hyperuricemia Effect in Mice Model.

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.

Comparison of shelf-stable and conventional resuscitation products in a canine model of hemorrhagic shock.

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.

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.

Hydroxyethyl Starch Improves the Prognosis of Rats with Traumatic Shock via Activation of the ERK Signaling Pathway in Lymphocytes.

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.

Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery.

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.

Third-Generation Hydroxyethyl Starch Causes Dose-Dependent Coagulopathy in Patients Undergoing Off-Pump Coronary Artery Bypass with Continuation of Preoperative Aspirin.

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.

Safety and efficacy of tetrastarches in surgery and trauma: a systematic review and meta-analysis of randomised controlled trials.

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.

Geriatric sudden deafness.

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.

A prospective randomized open-label trial on the comparative effects of 6% hydroxyethyl starch 130/0.4 versus polyionic isotonic crystalloids on coagulation parameters in dogs with spontaneous hemoperitoneum.

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 (T0 ) and after (T1 ) 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 T0 to T1 . No significant differences between groups were detected in any variable at T0 , and for HCT, platelet counts, prothrombin time, activated thromboplastin time, and fibrinogen concentrations at T1 . 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 T1 . 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.

Lack of Association between Low Cumulative Dose of Hydroxyethyl Starch and Acute Kidney Injury in Patients with Acute Ischemic Stroke.

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.

Impact of 6% balanced hydroxyethyl starch following cardiopulmonary bypass on renal function: a retrospective study.

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.

Evaluation of the effects of hydroxyethyl starch (130/0.4) administration as a constant rate infusion on plasma colloid osmotic pressure in hypoabluminemic dogs.

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.

Comparison of Hydroxyethyl starch 130/0.4 (6%) with commonly used agents in an experimental Pleurodesis model.

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.

The effect of intraoperative goal-directed crystalloid versus colloid administration on perioperative inflammatory markers - a substudy of a randomized controlled trial.

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.

Hydroxyethyl starch for perioperative goal-directed fluid therapy in 2020: a narrative review.

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.

A comparison of intraoperative goal-directed intravenous administration of crystalloid versus colloid solutions on the postoperative maximum N-terminal pro brain natriuretic peptide in patients undergoing moderate- to high-risk noncardiac surgery.

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.

Blood acid-base, haematological and haemostatic effects of hydroxyethyl starch (130/0.4) compared to succinylated gelatin colloid infusions in normovolaemic dogs.

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.