Hydroxyethyl Starch Research Articles

Anti-inflammatory dressing based on hyaluronic acid and hydroxyethyl starch for wound healing

Eliminating persistent inflammation and choosing dressings that provide the best healing environment is key to promoting wound healing. Dynamic and reversible hydrogels have attracted much attention because of their capacity to adapt to irregular wound surfaces. Herein, oxidized hydroxyethyl starch (OHES) and hyaluronic acid (HA-ADH) were crosslinked via the dynamic acylhydrazone bond to form an anti-inflammatory function hydrogel (HA-ADH/OHES@XT) that could release xanthatin (XT) slowly. The HA-ADH/OHES hydrogels showed an appropriate gelation time, notable water-retaining capacity, self-healing, suitable biodegradability, and good biocompatibility for wound healing applications. In vivo experiments demonstrated that HA-ADH/OHES@XT hydrogels promoted tissue regeneration and wound healing at a rate of approximately 89.1 % on day 20 by reducing inflammation, increasing collagen deposition, and promoting re-epithelialization, indicating their great potential as a wound dressing.

Three Is a Magic Number: Tailored Clickable Chelators Used to Determine Optimal RGD-Peptide Multiplicity in αvβ6-Integrin Targeted 177Lu-Labeled Cancer Theranostics.

The cellular adhesion receptor αvβ6-integrin is highly expressed in many cancers, e.g., pancreatic, lung, head-and-neck, cervical, bladder, and esophageal carcinoma. Multimerization of αvβ6-integrin-specific RGD peptides increases the target affinity and retention but affects biodistribution and pharmacokinetics. Amide formation of the terminal carboxylic acid moieties of the square-symmetrical bifunctional chelator DOTPI with 3-azidopropylamine yields derivatives with 4, 3, and 2 terminal azides and zero, 1, and 2 remaining carboxylic acids, respectively, whereby formation of the 2-cis-isomer is preferred according to NMR investigation of the Eu(III)-complexes. Cu(II)-catalyzed alkyne-azide cycloaddition (CuAAC) of the alkyne-functionalized αvβ6-integrin binding peptide cyclo[YRGDLAYp(NMe)K(pent-4-ynoic amide)] (Tyr2) yields the respective di-, tri-, and tetrameric conjugates for Lu-177-labeling. In mice bearing αvβ6-integrin-expressing xenografts of H2009 (human lung adenocarcinoma) cells, the Lu-177-labeled trimer's tumor-to-blood ratio of 112 exceeds that of the tetramer (10.4) and the dimer (54). Co-infusion of gelofusine (succinylated gelatin) reduces the renal uptake of the trimer by 89%, resulting in a 10-fold better tumor-to-kidney ratio, while no improvement of that ratio is observed with arginine/lysine, para-aminohippuric acid (PAH), and hydroxyethyl starch (HES) coinfusions. Since the Lu-177-labeled Tyr2-trimer outperforms the dimer and the tetramer, such trimers are considered the best lead structures for the ongoing development of αvβ6-integrin targeted anticancer theranostics.

Efficacy of 6% Hydroxyethyl Starch and 2% Lidocaine in Reducing the Pain of Propofol Injection: A randomised, placebo-controlled trial.

Propofol administration is associated with pain, mediated by the activation of vascular endothelium. Hydroxyethyl starch (HES) inhibits endothelial membrane activation by various nociceptive substances. Thus, this study hypothesised that pre-administration of HES can reduce pain on propofol administration. This study aimed to compare the proportion of patients with no pain on propofol administration and to compare the severity of pain and any change in pre- and post-induction haemodynamic variables. This prospective, randomised, placebo-controlled clinical trial was conducted at Chirayu Medical College & Hospital, Bhopal, India, between August 2023 and December 2023 and included patients undergoing elective surgery under general anaesthesia. Patients were randomly assigned to 3 groups to receive either 100 mL of 6% HES followed by propofol (Group HES), 100 mL normal saline (NS) followed by propofol premixed with 2% lidocaine (Group L) or 100 mL NS followed by propofol induction (Group P). A total of 339 patients were included. The proportion of patients with no pain on propofol injection was significantly higher in the HES group (n = 75) than in the lignocaine (n = 33) and placebo (n = 13) groups (P <0.0001 each). The median pain scores were 0 (interquartile range [IQR]: 0-1), 1 (IQR: 0-1) and 2 (IQR: 2-3) in the HES, lignocaine and placebo groups, respectively. The proportion of patients with moderate (n = 44) and severe (n = 48) pain scores was significantly higher in the placebo group than in the HES and lignocaine groups (P <0.0001 each). The proportion of patients experiencing pain on propofol injection was found to be significantly less with the pre-administration of 100 mL 6% HES compared to the pre-administration of lidocaine.

Risks and Harms to Physicians Reporting Hematologic Adverse Drug Reactions (ADRs) to Health Authorities

Background : The Southern Network on Adverse Reports group (SONAR) has previously identified severe risks and harms to physicians who reported serious ADRs to Heath Authorities related to solid-tumor oncology pharmaceuticals. (eClinMed, PLOS One, Journal of Scientific and Professional Integrity) We investigated whether similar risks and harms occurred to clinicians/scientists who reported hematology-associated ADRS. Methods: Quotes were abstracted from media coverage or Health Authority hearings for individual hematology drugs. Results : Risks and harms were reported in regulatory agency or government agency meetings by eight clinician/scientists physicians who led phase-3 pharmaceutical-sponsored clinical trials (Olivieri N (U Toronto, NEJM 1996, Singh G, Stanford, unpublished 2004), Buse J (U of North Carolina, unpublished 1999, Henke M (Abteilung Universitatsklinik, Lancet 2003, Mangano D (UCSF, NEJM 2005), Topol E and Nissen S (Cleveland Clinic JAMA 2004), meta-analyses (n = 2) (Bennett C (Northwestern, JAMA 2008, Mangano D (UCSF, NEJM 2006); database analyses (n = 1) (Mangano D (UCSF, NEJM 2004), case-control studies (n = 1) (Brass L, Yale, NEJM 2005) and an independent safety review (n = 1) (Solomon S, Harvard, JAMA 2005) including lawsuits, loss of job, public harassment and loss of grants. Three physicians lost academic positions (Topol, Olivieri, Mangano), two physicians lost federal grants (Olivieri, Bennett), and one FDA scientist (Graham) was demoted. ADR findings resulted in drug removal (n = 7; Vioxx, Avandia, Bextra, Celebrex, Trasylol, Phenyl propanolamine, Hydroxy-ethyl starch), revised indications (n = 2) (Procrit, Aranesp 2007, 2008, 2010)) or 10-year delay in FDA-approval (n = 1) (Fereprox). Median time from FDA approval to ADR identification was 8 years (Range, 4 years (Bextra) to 62 years PPA)). Numbers of persons reportedly seriously injured or dying from 1 ADR was 10,00 (Procrit)- 270,000 (Vioxx) (median 120,000). Manufacturer allegations that resulted in pharmaceutical companies actions included violation of secrecy agreement (n = 2) (Fererpox, PPAs) and public reporting of proprietary data (n = 11). Pharmaceutical companies paid $600,000 (Fereprox) to $5.8 billion (Vioxx) in fines and settlements. Discussion: Twelve physicians experienced severe threats and/or harms after reporting hematologic-associated ADRs to Health Authorities and/or in major publications. We suggest physicians not sign secrecy agreements that might jeopardize public safety (as currently established by almost all US medical universities) and should partner with independent drug safety monitoring boards (DSMBs) on ADR evaluations to monitor safety concerns of drugs and medical devices.

The Effects of Albumin 20% and Hydroxyethyl Starch 6% on Bleeding and Interleukin-6 Levels as Priming Solutions for Cardiopulmonary Bypass: A Randomized Controlled Trial

Background: Cardiopulmonary bypass (CPB) can adversely affect coagulation and systemic inflammatory response. Given that the optimal strategy for priming CPB in cardiac surgery remains a matter of debate, this study aimed to investigate the effects of albumin 20% and hydroxyethyl starch 6% as priming solutions on bleeding and interleukin-6 (IL-6) levels during CPB. Methods: This randomized clinical trial involved 40 patients undergoing coronary artery bypass surgery at Shahid Chamran Hospital between July 2021 and July 2022. Participants were assigned to 2 groups: the first group received 50 mL of albumin 20% as the priming solution for the CPB circuit, while the second group received 500 mL of hydroxyethyl starch 6%. Bleeding and IL-6 levels were assessed before and after the intervention. Results: The albumin group comprised 80.0% men and 20.0% women, with a mean age of 66.45±5.84 years. The hydroxyethyl starch 6% group consisted of 85.0% men and 15.0% women, with a mean age of 63.05±5.92 years (P&gt;0.05). The findings revealed that 12 hours after CPB, the IL-6 level in the hydroxyethyl starch 6% group (mean: 171.6±77.71 pg/mL) was significantly higher than that in the albumin group (mean: 105.8±36.45 pg/mL; P=0.002). At 48 hours after CPB, the mean bleeding was not significantly different between the groups (P=0.950). Conclusion: Albumin 20% was more effective than hydroxyethyl starch 6% concerning IL-6 levels. However, no significant differences in bleeding were observed between the groups at 48 hours post-CPB.

Peri-Interventional Hemodynamic Management Strategies for Percutaneous Chemosaturation of the Liver in Metastatic Cancer.

Background: Hepatic chemosaturation for inoperable liver tumors is a palliative treatment option with a beneficial effect on survival. However, the procedure regularly leads to circulatory failure during the filtration phase, and hemodynamic management is challenging. Our study aimed to compare two different strategies for hemodynamic management during chemosaturation to develop hypotheses for improving patient care and reducing peri-interventional morbidity. Methods: We conducted a single-center retrospective cohort study including 66 procedures of chemosaturation between May 2016 and March 2024. Procedures were divided into two groups: group 1 was managed with norepinephrine as the only vasopressor and liberal use of hydroxyethyl starch (HES). Group 2 was managed with norepinephrine and vasopressin and the preferred use of balanced crystalloids. We compared these two groups with respect to hemodynamic parameters, laboratory values, and post-interventional complications. Results: The heart rate was highest and the mean arterial pressure (MAP) was lowest during the filtration phase in both groups (p = 0.868, p = 0.270). The vasoactive inotropic score (VIS) was significantly higher in group 2 during the filtration phase (31.5 vs. 89, p < 0.001). Group 1 received significantly more HES overall (1000 mL vs. 0 mL, p < 0.001). Lactate levels at admission to the ICU were higher in group 1 (22.9 vs. 14.45 mg/dL, p = 0.041). Platelet counts were lower in group 2 from directly after chemosaturation through day 2 (p = 0.022, p = 0.001, p = 0.032). The INR differed significantly directly after chemosaturation (1.13 vs. 1.26, p = 0.015). Overall, group 1 received significantly more blood products peri-interventionally. There were two bleedings and one ischemic stroke in the overall cohort. There was no peri-interventional mortality. Conclusions: Advanced hemodynamic management ensures low peri-interventional mortality and morbidity. High-dose vasopressors, including vasopressin and the preferred use of balanced crystalloids, are sufficient to stabilize circulatory function during chemosaturation.

Multifunctional nanoplatform with near-infrared triggered nitric-oxide release for enhanced tumor ferroptosis

Ferroptosis has emerged as a promising strategy for cancer treatment. Nevertheless, the efficiency of ferroptosis-mediated therapy remains a challenge due to high glutathione (GSH) levels and insufficient endogenous hydrogen peroxide in the tumor microenvironment. Herein, we presented a nitric-oxide (NO) boost-GSH depletion strategy for enhanced ferroptosis therapy through a multifunctional nanoplatform with near-infrared (NIR) triggered NO release. The nanoplatform, IS@ATF, was designed that self-assembled by loading the NO donor L-arginine (L-Arg), ferroptosis inducer sorafenib (SRF), and indocyanine green (ICG) onto tannic acid (TA)-Fe3+‒metal-phenolic networks (MPNs) modified with hydroxyethyl starch. Inside the tumor, SRF could inhibit GSH biosynthesis, impair the activation of glutathione peroxidase 4, and disrupt the ferroptosis defensive system. In conjunction with TA-Fe3+‒MPNs, which has cascaded Fenton catalytic activity, it could navigate the lethal ferroptosis to cancer cells. Upon NIR laser irradiation, the ICG-generated ROS oxidated L-Arg to a substantial quantity of NO, which further depleted the intracellular GSH and caused LPO accumulation, enhancing cell ferroptosis. Moreover, ICG also serves as a photothermal agent that can produce hyperthermia when exposed to irradiation, further potentiating ferroptosis therapy. In addition, the nanoplatform showed significantly improved tumor therapeutic efficacy and anti-metastasis efficiency. This work thus demonstrated that utilizing NO boost-GSH depletion to enhance ferroptosis induction is a feasible and promising strategy for cancer treatment.Graphical abstract

Boosting Oxidative Stress with Hydroxyethyl Starch Smart Nanomedicines to Eliminate Cancer Stem Cells

Boosting Oxidative Stress with Hydroxyethyl Starch Smart Nanomedicines to Eliminate Cancer Stem Cells

Process Control of Multistep Surface Functionalization on Hydroxyethyl Starch Nanocapsules Determines the Reproducibility of the Biological Efficacy.

Nanocarrier synthesis is highly process-dependent, leading to potential batch-to-batch variability if it is not controlled at each step. This variability affects the reproducibility of subsequent biomodification, resulting in unpredictable biological effects, particularly for bioactive molecules such as interleukin-2 (IL-2). Inconsistent conjugation can lead to variable treatment outcomes and severe side effects. Therefore, precise control of each synthesis step is critical for ensuring a consistent quality and biological performance. Our study demonstrates that dividing nanocarrier synthesis into smaller, controlled steps improves reproducibility. Using this method, we achieved highly reproducible, concentration-dependent growth of CTLL-2 cells with hydroxyethyl starch (HES) nanocapsules functionalized with defined amounts of IL-2. We believe that such detailed, stepwise control in nanocarrier synthesis enhances batch consistency, improving the clinical applicability of the drug delivery systems.

Incidence and influential factors of postoperative pruritus in morphine-based intravenous patient-controlled analgesia

Background: Pruritus is a distressing symptom of systemic opioid analgesia that responds poorly to conventional antipruritus treatments. This study aimed to determine the incidence and risk factors for postoperative pruritus using intravenous patient-controlled analgesia (IV-PCA). Methods: Opioid-naïve patients who underwent morphine-based IV-PCA for postoperative pain at a tertiary center between January 1, 2020, and June 30, 2023, were included retrospectively. The primary outcome was pruritus within 72 h after surgery. Cumulative morphine consumption and pain numerical rating scores were measured to evaluate the potential impact of pruritus on postoperative pain control. Results: A total of 1,696 patients were enrolled, of whom 119 (7.0%) developed pruritus during the study period. Five independent factors for pruritus were identified, including intraoperative uses of hydroxyethyl starch solutions [adjusted odds ratio (aOR): 0.13, 95% confidence interval (CI): 0.04–0.43], lockout interval of IV-PCA (aOR: 0.50, 95% CI: 0.27–0.94, on base-2 logarithmic scale), droperidol addition to morphine solutions (aOR: 0.53, 95% CI: 0.35–0.81), cumulative morphine dose (aOR: 1.76, 95% CI: 1.47–2.12, on base-2 logarithmic scale), and postoperative uses of antihistamines (aOR: 2.90, 95% CI: 1.83–4.60) (c-statistic = 0.745). Patients with pruritus had higher postoperative morphine consumption (median: 67.5 mg, interquartile range: 38.3–94.0 vs. 38.0 mg, 21.0–65.4, p&lt;0.0001) but similar pain intensity compared to those without pruritus. Conclusion: Increasing the lockout interval and the droperidol regimen may protect patients from morphine-induced pruritus after IV-PCA. Further studies are warranted to clarify the mechanisms underlying the anti-pruritus effects of hydroxyethyl starch.

Sidestream dark field video microscopy demonstrates shelf-stable blood products preserve the endothelial glycocalyx in a canine hemorrhagic shock model.

To utilize sidestream dark field video microscopic technology to evaluate the endothelium in a canine hemorrhagic shock and resuscitation model. 6 purpose-bred adult dogs were anesthetized, instrumented, and subjected to hemorrhagic shock from September 2021 through June 2022. Each dog was resuscitated with 5 resuscitation strategies in an experimental crossover design study: (1) lactated Ringer's solution (LRS) and hydroxyethyl starch (HES) solution; (2) canine chilled whole blood (CWB); (3) canine fresh frozen plasma (FFP) and packed RBCs (pRBC); (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC); or (5) HBOC/FDP and canine lyophilized platelets. Sidestream dark field video microscopic evaluation was performed at 5 time points: commencement, after hemorrhage, after shock, after resuscitation (T135), and conclusion (T180). There was a significant difference between the perfused boundary region (PBR) measurements when comparing the LRS/HES resuscitation arm to the CWB and FFP/pRBC resuscitation arms at T180. A significant difference in PBR was appreciated in the LRS/HES arm at T135 and T180 compared to its baseline. No other significant differences in PBR were appreciated when resuscitation arms were compared longitudinally or to each other. Shelf-stable blood products preserved the endothelial glycocalyx similarly to CWB and pRBC/FFP as evaluated by sidestream dark field video microscopy. Lactated Ringer and HES solutions did not adequately preserve the endothelial glycocalyx compared to CWB and pRBC/FFP. Shelf-stable blood products are a viable option to preserve the endothelial glycocalyx when used during hemorrhagic resuscitation in dogs.

Hydroxyethyl Starch, a Synthetic Colloid Used to Restore Blood Volume, Attenuates Shear-Induced Distortion but Accelerates the Convection of Sodium Hyaluronic Acid

Hydroxyethyl Starch, a Synthetic Colloid Used to Restore Blood Volume, Attenuates Shear-Induced Distortion but Accelerates the Convection of Sodium Hyaluronic Acid

Volume therapy: which preparation for which situation?

The most commonly used fluids for volume therapy are crystalloids and colloids. Crystalloids comprise 0.9% sodium chloride and balanced crystalloids (BC). Colloids can be divided into artificial colloids and human albumin (anatural colloid). Large studies show advantages for BC over 0.9% NaCl with respect to renal endpoints, probably due to the unphysiologically high chloride content of 0.9% NaCl. However, other studies, such as the BaSICS and PLUS trials, showed no significant differences in mortality in aheterogeneous population. Despite this, meta-analyses suggest advantages for BC. Therefore, BC should be preferred, especially in patients at increased risk of acute kidney injury, with acidemia and/or hyperchloremia. Except for specific indications (e.g., in patients with cirrhosis, sepsis resuscitation after initial volume therapy with BC), albumin should not be used. There is clear evidence of harm from hydroxyethyl starch in intensive care patients.

Platelet/white blood cell ratio in the prediction of postoperative acute kidney injury of patients

To investigate the risk factors and predictive value on acute kidney injury (AKI) following surgery, and to elucidate the relationship between platelet/white blood cell ratio (PWR) and AKI. A retrospective case-control study was conducted. The patients who underwent surgery admitted to Honghui Hospital of Xi'an Jiaotong University from January 2019 to January 2023 were enrolled. The patients who developed AKI during the postoperative hospital stay were categorized as the AKI group, while those with normal renal function or not meeting AKI criteria were categorized as the non-AKI group. Demographic information, clinical characteristics, perioperative medication usage, surgical related information, and preoperative and postoperative laboratory indicators were collected. Binary multivariate Logistic regression analysis was used to identify risk factors for postoperative AKI. Receiver operator characteristic curve (ROC curve) was plotted to assess the predictive efficacy of postoperative PWR for postoperative AKI. A total of 420 patients were enrolled finally, with 72 developing AKI during hospitalization and 348 not developing AKI. Compared with the non-AKI group, the patients in the AKI group had a higher proportion of hypertension and coronary heart disease, a more usage of angiotensin converting enzyme inhibitor (ACEI), mannitol and vancomycin but a less usage of hydroxyethyl starch, a longer duration from injury to surgery and postoperative hospital stay, a greater intraoperative blood transfusion volume, a lower preoperative albumin (Alb), blood sodium, blood chlorine but a higher serum creatinine (SCr), blood urea nitrogen (BUN)/Alb ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP), and a higher postoperative white blood cell count (WBC), BUN, SCr, BUN/Alb ratio, blood potassium, and blood phosphorus but a lower platelet count (PLT), PWR, and Alb. Binary multivariate Logistic regression analysis revealed that perioperative usage of hydroxyethyl starch [odds ratio (OR) = 8.595, 95% confidence interval (95%CI) was 4.112-17.964, P < 0.001], prolonged duration from injury to surgery (OR = 1.084, 95%CI was 1.034-1.137, P = 0.001), increased intraoperative blood transfusion volume (OR = 1.001, 95%CI was 1.000-1.002, P = 0.017) were risk factors for AKI following surgery, and increased postoperative PWR was protective factor (OR = 0.930, 95%CI was 0.894-0.967, P < 0.001). ROC curve analysis indicated that the area under the ROC curve (AUC) of postoperative PWR for predicting postoperative AKI was 0.684 (95%CI was 0.615-0.754); at the optimal cut-off value of 19.34, the sensitivity was 63.8%, and the specificity was 69.8%. Postoperative PWR is an independent risk factor for AKI in patients undergoing surgery. Postoperative PWR reduction in surgical patients can assist in predicting the occurrence of postoperative AKI.

Anesthetic protocol for exploratory laparotomy in giant anteater (myrmecophaga tridactyla): case report

The movement of the giant anteater (Myrmecophaga tridactyla) in search of water and food causes a large number of accidents. The objective of this study is to describe the anesthetic protocol used in an exploratory laparotomy to control internal bleeding in a giant anteater. The animal was treated at the “Luiz Quintiliano de Oliveira” Veterinary Hospital of the Araçatuba School of Veterinary Medicine (UNESP) with a history of being run over. Midazolam was administered to restrain and position the animal during the physical and ultrasound examination, tramadol hydrochloride as premedication, and ketamine and midazolam for induction. Finally, anesthesia was maintained under inhalation anesthesia with isoflurane. Bradycardia during the transoperative period was corrected with a bolus of hypertonic solution (7.5% NaCl) and hydroxyethyl starch (Voluven®). The animal showed a satisfactory anesthetic recovery. Therefore, it is concluded that the anesthetic protocol is declared adequate for this procedure in giant anteaters.

Lactated Ringers, albumin and mannitol as priming during cardiopulmonary bypass reduces pulmonary edema in rats compared with hydroxyethyl starch

BackgroundEndothelial disorders with edema formation and microcirculatory perfusion disturbances are common in cardiac surgery with cardiopulmonary bypass (CPB) and contribute to disturbed tissue oxygenation resulting in organ dysfunction. Albumin is protective for the endothelium and could be a useful additive to CPB circuit priming. Therefore, this study aimed to compare organ edema and microcirculatory perfusion in rats on CPB primed with lactated Ringers, albumin and mannitol (LR/albumin/mannitol) compared to 6% hydroxyethyl starch (HES).ResultsMale rats were subjected to 75 min of CPB primed with either LR/albumin/mannitol or with 6% HES. Renal and lung edema were determined by wet/dry weight ratio. Pulmonary wet/dry weight ratio was lower in rats on CPB primed with LR/albumin/mannitol compared to HES (4.77 [4.44–5.25] vs. 5.33 [5.06–6.33], p = 0.032), whereas renal wet/dry weight ratio did not differ between groups (4.57 [4.41–4.75] vs. 4.51 [4.47–4.73], p = 0.813). Cremaster microcirculatory perfusion was assessed before, during and after CPB with intravital microscopy. CPB immediately impaired microcirculatory perfusion compared to baseline (LR/albumin/mannitol: 2 [1–7] vs. 14 [12–16] vessels per recording, p = 0.008; HES: 4 [2–6] vs. 12 [10–13] vessels per recording, p = 0.037), which persisted after weaning from CPB without differences between groups (LR/albumin/mannitol: 5 [1–9] vs. HES: 1 [0–4], p = 0.926). In addition, rats on CPB primed with LR/albumin/mannitol required less fluids to reach sufficient flow rates (0.5 [0.0–5.0] mL vs. 9 [4.5–10.0], p < 0.001) and phenylephrine (20 [0–40] µg vs. 90 [40–200], p = 0.004). Circulating markers for inflammation (interleukin 6 and 10), adhesion (ICAM-1), glycocalyx shedding (syndecan-1) and renal injury (NGAL) were determined by ELISA or Luminex. Circulating interleukin-6 (16 [13–25] vs. 33 [24–51] ng/mL, p = 0.006), interleukin-10 (434 [295–782] vs. 2120 [1309–3408] pg/ml, p < 0.0001), syndecan-1 (5 [3–7] vs. 15 [11–16] ng/mL, p < 0.001) and NGAL (555 [375–1078] vs. 2200 [835–3671] ng/mL, p = 0.008) were lower in rats on CPB primed with LR/albumin/mannitol compared to HES.ConclusionCPB priming with LR, albumin and mannitol resulted in less pulmonary edema, renal injury, inflammation and glycocalyx degradation compared to 6% HES. Furthermore, it enhanced hemodynamic stability compared with HES. Further research is needed to explore the specific role of albumin as a beneficial additive in CPB priming.

Bioreactance noninvasive cardiac output monitoring in euvolemic adult horses subjected with 7.2% saline and 6% hydroxyethyl starch (130/0.4) solution infusions.

To compare the ability of bioreactance noninvasive cardiac output (BR-NICO) with thermodilution cardiac output (TDCO) for the measurement of cardiac output (CO) in healthy adult horses receiving 2 different IV volume replacement solutions. Prospective randomized crossover study from September to November 2021. University teaching hospital. Six university-owned adult horses. Horses were randomly assigned to receive 7.2% hypertonic saline solution (HSS) or 6% hydroxyethyl starch (130/0.4) solution (HETA). BR-NICO and TDCO were measured simultaneously at baseline, 10, 20, 30, 40, 50, 60, 90, and 120minutes before fluid administration and again at the same times after starting a bolus infusion of IV volume replacers. All solutions were administered within 10minutes. BR-NICO and TDCO were strongly correlated (Pearson r2=0.93; P<0.01). Regression analysis showed the relationship between TDCO and BR-NICO was BR-NICO=0.48×TDCO+0.6. For the corrected BR-NICO values, the Bland-Altman agreement mean bias and lower/upper limits of agreement were -0.62 and -5.3 to 3.9L/min, respectively. Lin's concordance (95% confidence interval) between methods was 0.894 (0.825-1.097). Compared with baseline, HSS increased the CO at 10 and 20minutes (TDCO and BR-NICO). Compared with baseline, HETA decreased the CO at 10 and 20minutes (TDCO and BR-NICO) and increased the CO at 90 (TDCO only) and 120minutes (TDCO and BR-NICO). BR-NICO strongly agreed with TDCO in the measurement of CO in healthy unsedated adult horses. HSS administration significantly increased CO in the first 30minutes, while HETA initially decreased CO at 10minutes but increased CO to above baseline values by 90minutes.

Intraoperative goal-directed hemodynamic therapy through fluid administration to optimize the stroke volume: A meta-analysis of randomized controlled trials

ObjectiveTo evaluate the clinical impact of optimizing stroke volume (SV) through fluid administration as part of goal-directed hemodynamic therapy (GDHT) in adult patients undergoing elective major abdominal surgery. MethodsThis systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered in the PROSPERO database in January 2024. The intervention was defined as intraoperative GDHT based on the optimization or maximization of SV through fluid challenges, or by using dynamic indices of fluid responsiveness, including stroke volume variation, pulse pressure variation, and plethysmography variation index compared to usual fluid management. The primary outcome was postoperative complications. Secondary outcome variables included postoperative acute kidney injury (AKI), length of stay (LOS), intraoperative fluid administration, and 30-day mortality. ResultsA total of 29 randomized controlled trials (RCTs) met the inclusion criteria. There were no significant differences in the incidence of postoperative complications (RR 0.89; 95% CI, 0.78–1.00), postoperative AKI (OR 0.97; (95% IC, 0.55–1.70), and mortality (OR 0.80; 95% CI, 0.50–1.29). GDHT was associated with a reduced LOS compared to usual care (SMD: −0.17 [−0.32; −0.03]). The subgroup in which hydroxyethyl starch was used for hemodynamic optimization was associated with fewer complications (RR 0.79; 95% CI, 0.65–0.94), whereas the subgroup of patients in whom crystalloids were used was associated with an increased risk of postoperative complications (RR 1.08; 95% CI, 1.04–1.12). ConclusionsIn adults undergoing major surgery, goal-directed hemodynamic therapy focused on fluid-based stroke volume optimization did not reduce postoperative morbidity and mortality.

Effect of hydroxyethyl starch (Voluven ® 6% 130/0.4) on blood glucose levels during orthopaedic lower limb surgery under spinal anaesthesia – a prospective, randomised controlled trial

Effect of hydroxyethyl starch (Voluven ^® 6% 130/0.4) on blood glucose levels during orthopaedic lower limb surgery under spinal anaesthesia – a prospective, randomised controlled trial

Role of Heavy Water in Modified University of Wisconsin Solution for Extended Cold Storage of Rat Liver

To resolve the critical donor shortage worldwide, enlarging the potential donor pool to include expanded criteria donors is necessary. Despite numerous attempts to establish new preservation solutions, no dramatic innovation has occurred since University of Wisconsin (UW) solution displaced Euro Collins’ solution; UW solution remains the global gold standard. We previously developed a heavy water (D2O)–containing organ storage solution, Dsol, which is effective for livers subjected to extended cold storage (CS), and reported its effectiveness. Dsol is a modified UW solution; however, the substances or conditions that exhibit a synergistic or additive effect with D2O are unclear. Here we made UWD solution by removing hydroxyethyl starch (HES) from and adding 30%-D2O to UW solution, and compared the effects of these solutions. After 48 hours of CS, the livers were reperfused at 37 °C on an isolated perfused rat liver apparatus, and their perfusion kinetics, functions, and injuries were compared. In the UW group, portal vein resistance significantly increased and the oxygen consumption rate and bile production decreased; in contrast, these changes were suppressed in the UWD group. Organ expansion and liver damage progressed in both groups. These results confirmed that the removal of HES from and addition of D2O to the UW solution reduced CS-induced cellular function impairments and microcirculatory disorders. However, to reduce injury during reperfusion after CS, it is necessary to provide conditions that inhibit injury progression after reperfusion.