Voluven treatment could induce NLRP3 inflammasome-mediated pyroptosis of bone marrow-derived macrophages.

The aim of this study was to investigate the influence of Voluven on the NLRP3 inflammasome-mediated pyroptosis in bone marrow-derived macrophage (BMDM). Separated BMDMs were cultured and treated with different concentration of Voluven (0, 0.1, and 0.5 µg) dissolved in 10 µL 0.9% NaCl solution for 24 h. Both wild-type and nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)-/- C57BL/6J mice (n = 18) were intravenously injected with 0.2 mL of 0%, 5%, and 10% Voluven through femoral vein, respectively. Pyroptosis was inspected with flow cytometry. The mRNA levels of NLRP3 and caspase-1 were detected with quantitative real-time polymerase chain reaction (qRT-PCR). The levels of NLRP3, pro-caspase-1, and cleaved caspase-1 (p10) in serum were determined with Western blot. The expression of IL-17A in peripheral blood CD4+ T cells was analyzed with flow cytometry. The expression of cleaved caspase-1 (p10) in mice spleens was inspected with immunofluorescence. Compared with control group, the ratio of pyroptosis in all Voluven-treated groups rose significantly. The levels of NLRP3 and caspase-1 were increased after Voluven treatment. The expression of interleukin (IL)-17A in Voluven-treated CD4+ T cells was also increased, exhibiting a dose-dependent pattern. In wild-type mice, Voluven-treated mice had higher levels of IL-17A, NLRP3, and cleaved caspase-1 (p10) in a dose-dependent manner. The effects of Voluven were diminished in NLRP3-/- mice.

Prevention of heterotopic ossification: an experimental study using a plasma expander in a murine model.

BACKGROUND: Heterotopic ossification (HO) is a frequent complication following orthopedic and trauma surgery. It often leads to substantial morbidity as many affected patients suffer from pain and joint contractures. Current prophylactic measures include nonsteroidal anti-inflammatory drugs (NSAID) and local radiation. However, several disadvantages such as delayed fracture healing and impaired ossification have been reported. For this reason, a novel approach for prevention of HO was searched for. We hypothesized that systemic administration of hydroxyethyl starch (HES), a substance known to influence microcirculation, would reduce formation of HO in a murine model. METHODS: A pre-established murine model was used where HO has been shown to develop following Achilles tendon tenotomy. Twenty CD1 mice were randomly assigned to a control (n = 10) or treatment group (n = 10). The treatment group received two intravenous HES injections perioperatively, while the control group underwent tenotomy only. After ten weeks, the mice were euthanized and micro CT scans of the hind limbs were performed. HO was manually identified and quantitatively assessed. A Wilcoxon rank sum test was used for comparison of both groups. RESULTS: The mean heterotopic bone volume in the control group was significantly larger compared to the HES group (2.276 mm(3) vs. 0.271 mm(3), p = 0.005). A reduction of mean ectopic bone volume of 88 % was found following administration of HES. CONCLUSION: A substantial reduction of HO formation was found following perioperative short-term administration of HES. This work represents a preliminary study, necessitating further studies before drawing ultimate conclusions. However, this simple addition to current prophylactic measures might lead to a more effective prevention of HO in the future.

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.

A Comparison Between the Effects of Preloading with Ringer's Solution and Voluven on Hemodynamic Changes in Patients Undergoing Elective Cesarean Section Under Spinal Anesthesia.

INTRODUCTION: The most common complications after spinal anesthesia for Cesarean section is hypotension. Administration of intravenous crystalloid or colloid fluid before the induction of anesthesia is a way to prevent it. AIM: The aim of this study was to compare the effects of preloading with ringer's solution and Voluven on hemodynamic changes in patients underwent elective Caesarean section under spinal anesthesia. METHODS: This study was conducted on 70 pregnant women. They were randomly divided into two groups of 35. Group I received 10 ml/kg Ringer's solution (R group) and group II received 10 ml/kg Voluven (V group) over 15 min before spinal anesthesia. Mean SBP, DBP, MAP, HR, SPO2, mean Apgar of newborn at 1 and 5 minutes after birth, mean blood pH and analysis of umbilical venous blood gases of newborns, prevalence of nausea and vomiting, and the rate of shivering and its severity were recorded in the both groups. RESULTS: Blood pH and analysis of blood gases and Apgar of newborn at 1 and 5 minutes after birth were similar in both groups. Shivering did not differ significantly between the two groups. Level of anesthesia and the incidence of nausea and vomiting in the R group were significantly higher than those in the V group (P=0.041 and P=0.029, respectively). CONCLUSION: The administration of both crystalloid and colloid fluids were effective in preventing the hypotension, although the use of Voluven was preferred to Ringer with respect to the level of the blockade and the incidence of nausea and vomiting.

The Effects of Hydroxyethyl Starch 6% and Crystalloid on Volume Preloading Changes following Spinal Anesthesia.

BACKGROUND: Hypotension is one of the most common complications after spinal anesthesia for cesarean delivery. Normally, preloading with fluids, especially crystalloids, is used to prevention of hypotension. METHODS: In the present randomized clinical trial study, 120 parturients presenting for elective cesarean section with the American Society of Anesthesiologists Class I and II received either 15 cc normal saline or 7 cc/kg hydroxyethyl starch 6% (Voluven) fluid. Information regarding to systolic, diastolic, mean arterial pressure, and heart rate, incidence of hypotension, adverse effects, the total dose of atropine, and ephedrine were recorded in before and 3, 6, 9, 15, and 20 min after spinal anesthesia. Furthermore, Apgar score of newborn at the 1st and 5th min after birth was recorded. RESULTS: There was no significant difference in mean arterial pressure at different stages such as: Exactly after spinal and 3, 6, 15, and 20 min after spinal anesthesia between two groups (P > 0.05). Total dose of ephedrine and atropine were similar between groups (P > 0.05), respectively. There was no significant difference in Apgar score at the 1st and 5th min after birth between two groups. There were not any adverse effects of drugs in two groups. CONCLUSIONS: The results of this study show that hydroxyethyl starch 6% compared to normal saline are similar to prevent hypotension during spinal anesthesia for cesarean delivery.

Perioperative clinical and economic outcomes associated with replacing first-generation high molecular weight hydroxyethyl starch (Hextend®) with low molecular weight hydroxyethyl starch (Voluven®) at a large medical center.

BACKGROUND: Several plasma volume expander alternatives exist to enhance intravascular volume status in patients undergoing surgery. The optimal intravascular volume expander in the perioperative setting is currently unknown. Low molecular weight hetastarch, Voluven® (130/0.4), may have a better safety profile than high molecular weight hetastarch, Hextend® (450/0.7). We examined the clinical and cost outcomes of converting from Hextend® to Voluven® in a large tertiary medical center. METHODS: Using a large electronic database, we retrospectively compared two different time periods (2009 and 2010) where the availability of semisynthetic colloids changed. Perioperative and postoperative outcomes including the use of red blood cells (RBC), platelets and coagulation factors, length of stay in the postoperative acute care unit (PACU), intensive care unit and hospital, as well as 30-day and 1-year mortality were compared. In addition, direct acquisition costs of all intraoperative and PACU colloids and crystalloid use were determined. RESULTS: A total of 4,888 adult subjects were compared of which 1,878 received Hextend® (pre-conversion) and 2,759 received Voluven® (post-conversion) during two separate 7-month periods within 1 year apart, with the remainder receiving Plasmanate. The patients were similar in terms of patient demographics, preoperative comorbidities, ASA status, emergency surgery, types of surgery, intraoperative, and PACU times. In unadjusted outcomes, patients in the Hextend® group received more lactated Ringer's than in the Voluven® group (2,220 + 1,312 vs. 1,946 ± 1,097 ml; P < 0.0001). The use of albumin (Plasmanate) was reduced from 10.5% of patients to 1.1% when Voluven® was substituted for Hextend®. Unadjusted outcomes were similar in each group including hospital LOS, percent change from baseline creatinine and receipt of intraoperative and PACU blood product administration. However, overall unadjusted total fluid costs were greater in the Voluven® compared to Hextend® group ($116.7 compared to $59.3; P < 0.001). CONCLUSIONS: Conversion from Hextend® to Voluven® in the perioperative period resulted in decreased albumin use and was not associated with changes in clinical outcomes and short- and long-term mortality. The conversion was associated with decreases in crystalloid use and an increase in colloid use and hence IV fluid acquisition costs in the Voluven® group.

Normovolemic hemodilution using hydroxyethyl starch 130/0.4 (Voluven) in a Jehovah's Witness child requiring cardiopulmonary bypass for ventricular septal defect repair.

Surgical repair of congenital heart disease during cardiopulmonary bypass is common, and performing these complicated procedures in the absence of blood transfusions is especially challenging. A case of a Jehovah's Witness child who underwent surgical repair of a ventricular septal defect utilizing a new tetrastarch for autologous normovolemic hemodilution is reported. A successful operative repair was achieved without the need for non-autologous blood transfusion.

Effect of 6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride (Voluven®) on complications after subarachnoid hemorrhage: a retrospective analysis.

BACKGROUND: 6% Hydroxyethyl Starch 130/0.4 in 0.9% Sodium Chloride (Voluven®; 6% HES 130/0.4) is a colloid often used for fluid resuscitation in patients with subarachnoid hemorrhage (SAH), despite a lack of safety data for this use. The purpose of our study was to evaluate the effect of 6% HES 130/0.4 on major complications associated with SAH. METHODS: Medical records of all patients presenting between May 2010 and September 2012 with aneurysmal SAH were analyzed. Patients were divided in two groups based on the administration of 6% HES 130/0.4; HES group (n=57) and Non-HES group (n=72). The primary outcome included a composite of three major complications associated with SAH: Delayed Cerebral Ischemia (DCI), Hydrocephalus (HCP) requiring cerebrospinal fluid (CSF) shunting, and Rebleeding. RESULTS: The study groups were similar with respect to most characteristics except the incidences of hypertension, ischemic heart disease, Fisher grade and lowest hemoglobin during stay. The odds of developing the primary composite outcome was higher in the HES group [OR= 3.1(1.30-7.36), p=0.01]. The patients in the HES group had a significantly longer median duration of hospital (19 vs 14 days) and Neurointensive Care Unit stay (14 vs 10 days) compared to the Non HES group. CONCLUSION: We observed increased complications after SAH with 6% HES 130/0.4 (Voluven®) administration. An adequately powered prospective randomized controlled trial into the safety of 6% HES 130/0.4 in this patient population is warranted.