Analysis of outcomes of single-unit cord blood transplantation with umbilical cord blood units processed with two different red blood cell sedimentation reagents.

BACKGROUND: Various processing methodologies are routinely used to reduce volume and red blood cell content of umbilical cord blood (UCB) units collected for hematopoietic stem cell transplantation. There is limited information regarding effects of UCB processing techniques on clinical outcomes. STUDY DESIGN AND METHODS: Retrospective data analysis compared laboratory and clinical outcomes following single-unit UCB transplantation performed between 1999 and 2015. All UCB units were from St. Louis Cord Blood Bank and all were manually processed with either Hetastarch processed cord blood units (HCB) (n = 661) or PrepaCyte processed cord blood units (PCB) (n = 84). Additional sensitivity analysis focused on units transplanted from 2010 to 2015 and included 105 HCB and 84 PCB. RESULTS: There were no significant differences in patient characteristics between the two groups. Pre-freeze total nucleated and CD34+ cell counts, cell doses/kg of recipient weight, and total colony-forming units (CFUs) were higher in PCB compared with HCB. Post-thaw, the PCB group had a significantly better total nucleated cell recovery, while there were no significant differences in cell viability, CFU recovery, or CD34+ cell recovery. Primary analysis demonstrated faster neutrophil and platelet engraftment for PCB but no differences in overall survival (OS), whereas sensitivity analysis found no effect of processing method on engraftment, but better OS in the HCB group compared with PCB group. CONCLUSION: The UCB processing method had no significant impact on engraftment. However, we cannot completely exclude the effect of processing method on OS. Additional studies may be warranted to investigate the potential impact of the PCB processing method on clinical outcomes.

Addition of Drag-Reducing Polymers to Colloid Resuscitation Fluid Enhances Cerebral Microcirculation and Tissue Oxygenation After Traumatic Brain Injury Complicated by Hemorrhagic Shock.

Hemorrhagic shock (HS) is a severe complication of traumatic brain injury (TBI) that doubles mortality due to severely compromised microvascular cerebral blood flow (mvCBF) and oxygen delivery reduction, as a result of hypotension. Volume expansion with resuscitation fluids (RF) for HS does not improve microvascular CBF (mvCBF); moreover, it aggravates brain edema. We showed that the addition of drag-reducing polymers (DRP) to crystalloid RF (lactated Ringer's) significantly improves mvCBF, oxygen supply, and neuronal survival in rats suffering TBI+HS. Here, we compared the effects of colloid RF (Hetastarch) with DRP (HES-DRP) and without (HES). Fluid percussion TBI (1.5 ATA, 50 ms) was induced in rats and followed by controlled HS to a mean arterial pressure (MAP) of 40 mmHg. HES or HES-DRP was infused to restore MAP to 60 mmHg for 1 h (prehospital period), followed by blood reinfusion to a MAP of 70 mmHg (hospital period). In vivo two-photon microscopy was used to monitor cerebral microvascular blood flow, tissue hypoxia (NADH), and neuronal necrosis (i.v. propidium iodide) for 5 h after TBI+HS, followed by postmortem DiI vascular painting. Temperature, MAP, blood gases, and electrolytes were monitored. Statistical analyses were done using GraphPad Prism by Student's t-test or Kolmogorov-Smirnov test, where appropriate. TBI+HS compromised mvCBF and tissue oxygen supply due to capillary microthrombosis. HES-DRP improved mvCBF and tissue oxygenation (p < 0.05) better than HES. The number of dead neurons in the HES-DRP was significantly less than in the HES group: 76.1 ± 8.9 vs. 178.5 ± 10.3 per 0.075 mm3 (P < 0.05). Postmortem visualization of painted vessels revealed vast microthrombosis in both hemispheres that were 33 ± 2% less in HES-DRP vs. HES (p < 0.05). Thus, resuscitation after TBI+HS using HES-DRP effectively restores mvCBF and reduces hypoxia, microthrombosis, and neuronal necrosis compared to HES. HES-DRP is more neuroprotective than lactated Ringer's with DRP and requires an infusion of a smaller volume, which reduces the development of hypervolemia-induced brain edema.

Improved Cerebral Perfusion Pressure and Microcirculation by Drag Reducing Polymer-Enforced Resuscitation Fluid After Traumatic Brain Injury and Hemorrhagic Shock.

Hemorrhagic shock (HS) after traumatic brain injury (TBI) reduces cerebral perfusion pressure (CPP) and cerebral blood flow (CBF), increasing hypoxia and doubling mortality. Volume expansion with resuscitation fluids (RFs) for HS does not improve CBF and tissue oxygen, while hypervolemia exacerbates brain edema and elevates intracranial pressure (ICP). We tested whether drag-reducing polymers (DRPs), added to isotonic Hetastarch (HES), would improve CBF but prevent ICP increase. TBI was induced in rats by fluid percussion, followed by controlled hemorrhage to mean arterial pressure (MAP) = 40 mmHg. HES-DRP or HES was infused to MAP = 60 mmHg for 1 h, followed by blood reinfusion to MAP = 70 mmHg. Temperature, MAP, ICP, cortical Doppler flux, blood gases, and electrolytes were monitored. Microvascular CBF, tissue hypoxia, and neuronal necrosis were monitored by two-photon laser scanning microscopy 5 h after TBI/HS. TBI/HS reduced CPP and CBF, causing tissue hypoxia. HES-DRP (1.9 ± 0.8 mL) more than HES (4.5 ± 1.8 mL) improved CBF and tissue oxygenation (p < 0.05). In the HES group, ICP increased to 23 ± 4 mmHg (p < 0.05) but in HES-DRP to 12 ± 2 mmHg. The number of dead neurons, microthrombosis, and the contusion volume in HES-DRP were significantly less than in the HES group (p < 0.05). HES-DRP required a smaller volume, which reduced ICP and brain edema.

[Effect and underling mechanism of 6% hydroxyethyl starch 130/0.4 on serum albumen in trauma orthopedic patients during operation].

Objective: To investigate the effect of 6% hydroxyethyl starch 130/0.4(HES) on protein in severe trauma orthopedic patients after acute hemodilution. Methods: Fourty-eight severe trauma patients who met the inclusion criteria were selected from June 2018 to December 2018 in Yantaishan Hospital, and were randomly divided into two groups (n=24): group A and group B. Group A was ringer's sodium lactate control group, and group B was HES treatment group. After the tracheal intubation, the patients of group A were infused with 10% blood volume of sodium lactate ringer at 0.5 ml·kg(-1)·min(-1), and the patients in group B were infused with 10% blood volume of HES at 0.5 ml·kg(-1)·min(-1). Total protein (TP), human serum albumin (HSA), numbers of circulating endothelium cells (CEC), C-reactive protein (CRP), and serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10 and IL-6 were measured immediately after acute hemodilution (T(0)), 24 hours (T(1)) and 48 hours (T(2)) after acute hemodilution. After infusion into human body, HES bond to HSA, and fluorescence spectroscopy was used to analyze the binding relationship between HES and HSA in order to further study the effects of HES on HSA. Results: The HSA, TP, CEC, TNF-α, IL-6, IL-10, CRP at T(0) of group A were (38±5) g/L, (66±5) g/L, (5.5±0.4)/0.9 µl, (24±5) µg/L, (8.9±0.8) µg/L, (44±6) µg/L, (13.6±1.4) mg/L; While at T(1) were (33±5) g/L, (60±6) g/L, (10.2±0.7)/0.9 µl, (87±9) µg/L, (38.8±2.3) µg/L, (57±7) µg/L, (23.4±2.4) mg/L. The HSA, TP, CEC, TNF-α, IL-6, IL-10, CRP at T(0) of group B were(38±4)g/L, (66±5) g/L, (5.4±0.6)/0.9 µl, (24±6) µg/L, (9.1±0.9) µg/L, (45±6) µg/L, (13.4±1.8) mg/L; While at T(1) were (35±5)g/L, (62±5)g/L, (7.4±0.6)/0.9 µl, (70±8) µg/L, (29.5±3.1) µg/L, (72±6) µg/L, (19.7±2.2) mg/L. HSA and TP decreased at T(1) in group A as compared with T(0) (P<0.05), contrarily CEC increased significantly at T(1), TNF-ɑ, IL-6, IL-10 and CRP augmented at T(1) and T(2) in two groups (P<0.05). In comparison with the patients of group A, CEC decreased significantly at T(1) (P<0.05). TNF-ɑ, IL-6, CRP reduced significantly at T(1) and T(2) (P<0.05), but IL-10 increased at T(1) and T(2) in group B (P<0.05). The secondary structure of HSA changed after HES was added in the HES solution. The fluorescence intensity of HSA decreased with the increase of HES concentration,which suggested that HES induced HSA fluorescence quenching. HES could bind to Trp-214 residue in HSA at a molecular ration of 1∶1. Conclusions: 6% HES reduces the occurrence of low protein level in severe trauma patients after operation. HES could bind to Trp-214 amino acid residue in HSA and form the complex at a molecular ratio of 1∶1. The formation of HES-HSA complex increases the volume of HES, avoids the vascular leakage, protects the vascular endothelial cells, and induces anti-inflammatory immunity in the patients with capillary syndrome.

Incidence of postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis.

BACKGROUND: Trials suggest that the use of i.v. hydroxyethyl starch (HES) solutions is associ-ated with increased risk of death and acute kidney injury (AKI) in critically ill patients. It is uncertain whether similar adverse effects occur in surgical patients. METHODS: Systematic review and meta-analysis of trials in which patients were randomly allocated to 6% HES solutions or alternative i.v. fluids in patients undergoing surgery. Ovid Medline, Embase, Cinhal, and Cochrane Database of Systematic Reviews were searched for trials comparing 6% HES with clinically relevant non-starch comparator. The primary end-point was hospital mortality. Secondary endpoints were requirement for renal replacement therapy (RRT) and author-defined AKI. Pre-defined subgroups were cardiac and non-cardiac surgery. RESULTS: Four hundred and fifty-six papers were identified; of which 19 met the inclusion criteria. In total, 1567 patients were included in the analysis. Dichotomous outcomes were expressed as a difference of proportions [risk difference (RD)]. There was no difference in hospital mortality [RD 0.00, 95% confidence interval (CI) -0.02, 0.02], requirement for RRT (RD -0.01, 95% CI -0.04, 0.02), or AKI (RD 0.02, 95% CI -0.02 to 0.06) between compared arms overall or in predefined subgroups. CONCLUSIONS: We did not identify any differences in the incidence of death or AKI in surgical patients receiving 6% HES. Included studies were small with low event rates and low risk of heterogeneity. Narrow CIs suggest that these findings are valid. Given the absence of demonstrable benefit, we are unable to recommend the use of 6% HES solution in surgical patients.

Comparative evaluation of the effects of hydroxyethyl starch on coagulation state of patients during brain tumor surgeries in comparison to crystalloids by thromboelastography.

BACKGROUND: Hypercoagulability has been reported in primary brain tumors which can lead to thrombotic complications. Hydroxyethyl starch (hetastarch) is a synthetic colloid solution with adverse effects on blood coagulation. The aim of this study was to evaluate the protective effect of hetastarch in reducing thromboembolic events in these patients. MATERIALS AND METHODS: In a double-blinded clinical trial, 60 brain tumor surgery patients were randomly divided into two groups and given 10 mL/kg hetastarch or normal saline during surgery. Blood coagulation was compared before and after infusion of these fluids within and between groups by thromboelastography (TEG). RESULTS: There were no significant differences in bleeding (P = 0.126), duration of surgery (P = 0.504), and fluid intake (0.09L) between the two groups. Percentage of changes in R (R: Time to initiate fibrin formation), K (K: Measure of the speed taken to reach a specific level of clot strength), and Ly30 (Ly30: Percent of fibrin distraction after 30 minutes of clot formation) in the crystalloid group were -20.61 ± 26.46, -30.02 ± 49.10, and 1.27 ± 22.63, and that in the colloid group were 22.10 ± 26.11, 41.79 ± 37.15, and 59.09 ± 37.12, respectively. Deterioration in hemostasis during and after surgery was not observed. CONCLUSION: There was a reduction in the speed of clot formation and increase in clot lysis in the hetastarch group. Coagulability was decreased in the colloid group. Infusion of 10 mL/kg hetastarch in brain tumor resection surgeries can probably decrease susceptibility of these patients to deep vein thrombosis (DVT) and thromboembolic events.

Effect of the colloids gelatin and HES 130/0.4 on blood coagulation in cardiac surgery patients: a randomized controlled trial.

OBJECTIVE: The choice of the prime solution for cardiopulmonary bypass can play an important role in limiting the effect on blood coagulation, but it is still unclear what the effect of colloids on blood coagulation is. The aim of this study was to investigate the effect of synthetic colloids on blood loss and blood coagulation in patients after on-pump coronary artery bypass graft (CABG) procedures. METHODS: Sixty elective, on-pump CABG patients were randomly assigned to receive the prime solutions lactated Ringer's solution combined with hydroxyethyl starch 130/0.4 (HES, 6% Volulyte, Fresenius Kabi Nederland BV, Zeist, the Netherlands) (HES group) or gelatin (Gelofusin(®), B Braun Melsung AG, Melsungen, Germany) (Gelo group). Blood loss was assessed using post-operative chest tube output; secondary endpoints were number of blood component transfusions, routine coagulation test values and rotation thromboelastometry values (Rotem(®) delta, Pentapharm GmbH, Munich, Germany). RESULTS: Total post-operative chest tube output was 500 ± 420 ml in the HES group versus 465 ± 390 ml in the Gelo group (p = 0.48). No significant differences were observed in any of the routine coagulation tests values, thromboelastometry parameters or number of blood component transfusions between the groups. CONCLUSIONS: In this randomized, controlled trial of adults after on-pump CABG procedures, there was no significant difference in blood loss or blood coagulation between the HES group and the Gelo group.

Evaluation of the hydroxyethyl starch stabilizing agent, Vetstarch, in the preservation of canine cerebrospinal fluid samples.

BACKGROUND: A challenge of cerebrospinal fluid (CSF) analysis is the time-dependent degradation of nucleated cells, impeding accurate interpretation. CSF additives have been used to delay cell degradation; however, stabilizing agents, including serum, can alter microprotein levels. OBJECTIVES: This study aimed to determine if the hydroxyethyl starch, Vetstarch, is effective at preserving nucleated cell morphology in CSF compared with the saline diluent or serum without altering microprotein levels. METHODS: CSF samples were collected from 26 dogs. Samples were divided into four aliquots. One aliquot was analyzed immediately (control). The remaining three aliquots were mixed with either saline, fetal calf serum, or Vetstarch before storage at 4°C. Nucleated cell differentials, protein concentrations, and cell morphology scores were analyzed 48 hours later. A cell morphology score of 1 indicated no cellular degeneration; a score of 4 indicated severe degeneration. RESULTS: Samples stored in serum, saline, and Vetstarch exhibited poorer mean (±SD) morphology scores (2.4 ± 0.7, 2.6 ± 0.8, and 2.7 ± 0.9, respectively) compared with controls (1.9 ± 0.4). Samples stored in saline and Vetstarch demonstrated higher percentages of unrecognizable cells, with a median of 28 (range 0-100) and 27 (0-100), respectively; samples stored in serum had a median of 14 (range 0-67) unrecognizable. Microprotein levels of samples stored in Vetstarch were dependent on the method of protein analysis. Serum significantly increased microprotein levels. CONCLUSIONS: Vetstarch does not reduce time-dependent cellular degeneration compared with the saline diluent or serum and is, therefore, not recommended as a stabilizing agent for canine cerebrospinal fluid.

The Crystalloid Co-Load: Clinically as Effective as Colloid Preload for Preventing Hypotension from Spinal Anaesthesia for Caesarean Delivery.

OBJECTIVE: Colloid preloading diminishes post-spinal hypotension. However, whether colloid preloading is superior to crystalloid co-loading is uncertain. In this retrospective study, we compared the effects of a colloid preload versus a crystalloid co-load on vasopressor requirements and maternal haemodynamics among women undergoing elective caesarean delivery (CD) with spinal anaesthesia. METHODS: We extracted data from the medical records of 160 healthy women who underwent elective CD with spinal anaesthesia at an academic obstetric centre before and after an institutional fluid-loading protocol change. Patients received a 500 mL 6% hydroxyethyl starch preload or a 1000 mL crystalloid co-load. The primary outcome was the total phenylephrine dose administered from spinal block placement to delivery. RESULTS: Our cohort comprised 79 women in the colloid group and 77 women in the crystalloid group. The mean phenylephrine use was significantly lower in the colloid group than in the crystalloid group (489±403 µg vs. 647±464 µg, respectively, p=0.02). The maximal drop in systolic blood pressure was greater in the colloid group than in the crystalloid group (36±20 mmHg vs. 29±16 mmHg, respectively, p=0.02). There were no clinically significant differences between the groups in heart rate, blood loss, temperature and Apgar scores. CONCLUSION: Vasopressor use was lower in colloid preloading than in crystalloid co-loading. However, differences in all outcome measures were minimal and likely clinically insignificant, suggesting that both fluid-loading techniques are appropriate to use for the prevention of spinal hypotension in women undergoing CD.

Trials in adult critical care that show increased mortality of the new intervention: Inevitable or preventable mishaps?

Several promising therapies assessed in the adult critically ill in large, multicenter randomized controlled trials (RCTs) were associated with significantly increased mortality in the intervention arms. Our hypothesis was that there would be wide ranges in sponsorship (industry or not), type(s) of intervention(s), use of DSMBs, presence of interim analyses and early stopping rules, absolute risk increase (ARI), and whether or not adequate prior proof-of-principle Phase II studies were done of RCTs that found increased mortality rates of the intervention compared to control groups. We reviewed RCTs that showed a statistically significant increased mortality rate in the intervention compared to control group(s). We recorded source of sponsorship, sample sizes, types of interventions, mortality rates, ARI (as well as odds ratios, relative risks and number needed to harm), whether there were pre-specified interim analyses and early stopping rules, and whether or not there were prior proof-of-principle (also known as Phase II) RCTs. Ten RCTs (four industry sponsored) of many interventions (high oxygen delivery, diaspirin cross-linked hemoglobin, growth hormone, methylprednisolone, hetastarch, high-frequency oscillation ventilation, intensive insulin, NOS inhibition, and beta-2 adrenergic agonist, TNF-α receptor) included 19,126 patients and were associated with wide ranges of intervention versus control group mortality rates (25.7-59 %, mean 29.9 vs 17-49 %, mean 25 %, respectively) yielding ARIs of 2.6-29 % (mean 5 %). All but two RCTs had pre-specified interim analyses, and seven RCTs were stopped early. All RCTs were preceded by published proof-of-principle RCT(s), two by the same group. Seven interventions (except diaspirin cross-linked hemoglobin and the NOS inhibitor) were available for use clinically at the time of the pivotal RCT. Common, clinically available interventions used in the critically ill were associated with increased mortality in large, pivotal RCTs even though safety was often addressed by interim analyses and early stopping rules.

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.

The effects of tranexamic acid and 6% hydroxyethyl starch (HES) solution (130/0.4) on postoperative bleeding in coronary artery bypass graft (CABG) surgery.

BACKGROUND: The addition of 6% hydroxyethyl starch (HES) into Ringer lactate priming solution may have adverse effects on hemostasis in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) with or without the use of tranexamic acid. METHODS: In a prospective, randomized clinical trial, 132 patients were assigned to receive 20 ml/kg of Ringer priming solution with or without tranexamic acid (TA) (Group RS-TA, n=34 and Group RS-noTA, n=32) or 10 ml/kg of 6% HES plus 10 ml/kg of RS priming solution with or without intravenous tranexamic acid (Group HES-TA, n=35 and Group HES-noTA, n=31). Estimated blood loss, chest tube drainage, amount of blood products, hemoglobin, hematocrit, platelet and coagulation parameters were examined before and 24 hour after surgery. RESULTS: For Group HES with tranexamic acid, when compared to other groups, estimated blood loss, postoperative 24 hour drainage loss and blood product transfusions were less (P=0.023; P=0.003; P=0.001; respectively) and hemoglobin, hematocrit values at 12 and 24 hours after surgery increased in comparison to other groups (P=0.041, P=0.034, P=0.004, P=0.001; respectively). Platelet concentrations were similar between groups (P>0.05). CONCLUSIONS: In CABG, the administration of tranexamic acid in HES 130/0.4 prime solution study group decreased estimated blood loss and chest tube drainage in comparison to patients receving Ringer prime solution with or without tranexamic acid postoperatively however, no effects on renal functions or postoperative complications were shown.

Hydroxyethyl starch: a review of pharmacokinetics, pharmacodynamics, current products, and potential clinical risks, benefits, and use.

OBJECTIVE: To review and summarize the pharmacokinetics and pharmacodynamics of hydroxyethyl starch (HES), as well as reported risks and benefits of HES infusion, and to provide administration and monitoring recommendations for HES use in dogs and cats. DATA SOURCES: Veterinary and human peer-reviewed medical literature, including scientific reviews, clinical and laboratory research articles, and authors' clinical experience. SUMMARY: HES solutions are the most frequently used synthetic colloid plasma volume expanders in human and veterinary medicine. The majority of research in human medicine has focused on the adverse effects of HES infusion, with emphasis on acute kidney injury and coagulation derangements. The studies often differ in or fail to report factors, such as the type, amount, interval, and concentration of HES administered; the patient population studied; or concurrent fluids administered. Currently, there is no definitive clinical evidence that the reported adverse effects of HES use in human medicine occur in veterinary species. There is little information available on HES administration techniques or simultaneous administration of additional fluids in human and veterinary medicine. The rationale for HES use in small animals has been largely extrapolated from human medical studies and guidelines. A controlled approach to intravenous fluid resuscitation using crystalloid and HES volumes titrated to reach desired resuscitation end point parameters is outlined for small animal practitioners. CONCLUSION: The extrapolation of data from human studies directly to small animals should be done with the knowledge that there may be species variations and different pharmacokinetics with different HES solutions. Veterinary reports indicate that bolus and continuous rate infusions of 6% hetastarch solutions at moderate doses are well tolerated in feline and canine subjects. Further research in domesticated species is necessary to better define and expand the knowledge regarding use of HES solutions in small animal medicine.

Clinical controversies in the management of critically ill patients with severe sepsis: resuscitation fluids and glucose control.

Severe sepsis with multiple organ dysfunction remains the most common cause of death for patients treated in intensive care units. As there is no specific treatment for severe sepsis, current management consists of antibiotics, source control and the use of supportive therapies to sustain life while waiting for the adverse effects of sepsis-induced organ dysfunction to subside. Despite the central role of supportive therapies, few have been subjected to rigorous evaluation; two exceptions are the choice of resuscitation fluid and intensity of glucose control. Current data support the use of a crystalloid fluid with the addition of albumin when needed for fluid resuscitation. Administration of hydroxyethyl starch is harmful and should be avoided. Stress hyperglycemia should be treated when blood glucose concentration exceeds 180 mg/dL (10.0 mmol/L) and when insulin therapy is needed it should be targeted to a blood glucose concentration of 144-180 mg/dL (8-10 mmol/L).

Comparison Between the Effects of Ringer`s Lactate and Hydroxyethyl Starch on Hemodynamic Parameters After Spinal Anesthesia: A Randomized Clinical Trial.

BACKGROUND: Hypotension during spinal anesthesia is common and can lead to severe injuries and even death. Administration of crystalloid fluids is advised to prevent occurrence of hypotension; however its effectiveness is still the matter of arguments. OBJECTIVES: This study was designed to compare the effects of Ringer`s lactate and hydroxyethyl starch 6% on hemodynamic parameters after spinal anesthesia in patients undergoing orthopedic surgeries on lower limbs. PATIENTS AND METHODS: This randomized clinical trial was performed in Rasoul Akram Hospital, Tehran, Iran. 60 patients undergoing elective femoral fracture surgeries with spinal anesthesia were included in this study. Fitted patients were randomly divided into two equal groups. After entrance to the operation room and before spinal anesthesia, patients' hemodynamic parameters including systolic blood pressure (SBP), cardiac output (CO), and cardiac index (CI) were evaluated using monitoring electro-velocimetry set. In both groups, spinal anesthesia was performed using needle no. 25 and 3 mL of marcaine 0.5% in the sterile situation. None of the treatment group was aware of investigated group during the study. RESULTS: The baseline values of mentioned variables did not show a significant difference between two groups using t-test (P > 0.05). Also SBP, CI, and CO after intervention was not significantly different between two groups using t-test (P > 0.05). CONCLUSIONS: The result of present study on patients undergoing femoral fracture surgeries who received Hetastarch or Ringer`s lactate solutions showed that Hetastarch was not significantly more effective in compensation of hypotension induced by spinal anesthesia.

Volume replacement therapy during hip arthroplasty using hydroxyethyl starch (130/0.4) compared to lactated Ringer decreases allogeneic blood transfusion and postoperative infection.

BACKGROUND AND OBJECTIVES: Hydroxyethyl starch (HES) 130/0.4 is considered an effective plasma expander when compared to crystalloids. There is controversy around its superiority regarding hemodynamic optimization and about possible detrimental effects on coagulation. The aim of this study was to compare the effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in adult patients under spinal anesthesia regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. METHODS: In this randomized, controlled trial, 48 patients scheduled for hip arthroplasty with spinal anesthesia were randomized into two groups: 24 patients were allocated to receive a preload of 15 mL.kg(-1) of HES 130/0.4 and 24 patients received a preload of 30 mL.kg(-1) lactated Ringer solution before surgery. Hemodynamic measurements, hemoglobin concentrations, biochemical parameters and coagulation tests were evaluated in three periods during surgical procedure. Patients received medical follow-up during their hospital stay and up to postoperative 30 days. Primary outcome was the requirement of red blood cell transfusion between groups during hospital stay. Secondary outcome were hemodynamic parameters, length of hospital stay, mortality and occurrence of clinical postoperative complications. RESULTS: Red blood cell transfusion was required in 17% of patients in the HES group and in 46% in the Ringer group (p = .029). Postoperative infections were more frequently observed in the Ringer group (17%) compared to the HES group (0), p = .037. There were no significant differences between groups in mortality, hospital length of stay and clinical complications other than infection. CONCLUSIONS: During hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated Ringer.

Effect of resuscitation with hypertonic sodium chloride hydroxyethyl starch 40 injection mixed with suberoylanilide hydroxamic acid on oxidative stress responses and histone acetylation in lung tissues in a rat model of lethal hemorrhagic shock after entering high altitude for the first time / 中华麻醉学杂志

Objective To evaluate the effect of resuscitation with hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH40) mixed with suberoylanilide hydroxamic acid (SAHA) on oxidative stress responses of lung tissues and histone acetylation in a rat model of lethal hemorrhagic shock after entering high altitude for the first time.Methods Forty-five healthy male Wistar rats,aged 3-4 months,weighing 250-300 g,were transported from the breeding area at altitude 1500 m to the experimental area at altitude 3 780 m.The rats were divided into 3 groups (n=15 each) using a random number table:sham operation group (group Sham),hemorrhagic shock group (group HS),and resuscitation with HSH40 mixed with SAHA group (group HSH/SAHA).Lethal hemorrhagic shock was induced by removing 40％ of blood volume from the left femoral artery at a constant speed within 10 min,followed by removing 15％ of blood volume from the right femoral vein at a constant speed within 50 min.Only cannulation was performed,and the rats received no blood letting or resuscitation in group Sham.The animals were resuscitated via the right femoral artery after successful establishment of the model,SAHA 7.5/Kg dissolved in HSH40 4 ml/kg was infused within 5 min in group HSH+SAHA.Immediately before blood letting,immediately after blood letting and at 3 h after resuscitation (at the time of death for the rats survived less than 3 h),arterial blood samples were obtained for blood gas analysis,and pH value,partial pressure of arterial carbon dioxide (PaCO2),partial pressure of arterial oxygen (PaO2) and arterial oxygen saturation (SaO2) were recorded.The rats were sacrificed after blood samples were collected from the abdominal aorta at 3 h after resuscitation (at the time of death for the rats died within 3 h after resuscitation),and lungs were removed for examination of the pathologic changes which were scored (with a light microscope) and for determination of wet to dry weight ratio (W/D ratio),activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) and expression of histone H3 acetylation at lysine 9 (Ac-H3K9) in lung tissues (by Western blot).Results Compared with group Sham,the lung injury score,W/D ratio and content of MDA were significantly increased,and the activity of SOD was decreased in HS and HSH+SAHA groups,pH value and PaCO2 were significantly decreased and PaO2 and SaO2 were increased immediately after blood letting and at 3 h after resuscitation in group HS,and PaO2 and SaO2 were significantly increased immediately after blood letting and at 3 h after resuscitation,pH value and PaCO2 were decreased immediately after blood letting,and the expression of Ac-H3K9 was up-regulated in group HSH+SAHA (P＜0.05).Compared with group HS,pH value,PaCO2,PaO2 and SaO2 were significantly increased at 3 h after resuscitation,the lung injury score,W/D ratio and content of MDA were decreased,the activity of SOD was increased,and the expression of Ac-H3K9 was up-regulated in group HSH+SAHA (P＜0.05).Conclusion The mechanism by which resuscitation with HSH40 mixed with SAHA exerts lung protection may be related to inhibiting oxidative stress responses and histone acetylation in lung tissues in a rat model of lethal hemorrhagic shock after entering high altitude for the first time.

Development of extravascular leakage of 6％ hydroxyethyl starch 130/0.4 when used for acute hemodilution in pediatric patients undergoing open heart surgery / 中华麻醉学杂志

Objective To evaluate the development of extravascular leakage of 6％ hydroxyethyl starch (HES) 130/0.4 when used for acute hemodilution in the pediatric patients undergoing open heart surgery.Methods Forty-eight American Society of Anesthesiologists physical status Ⅰ or Ⅱ pediatric patients,aged 2-12 yr,weighing 12-53 kg,scheduled for elective surgical repair of ventricular or atrial septal defect,were divided into 2 groups (n =24 each) according to age:preschool group (2 yr ≤ age ≤ 6 yr) and school-age group (6 yr＜age ≤ 12yr).After anesthesia induction and endotracheal intubation,a volume of 6％ HES 130/0.4 equivalent to 10％ of the blood volume was infused via the central veins at 0.5 ml · kg-1 · min-1 in two groups.Immediately before infusion of HES (T0) and at 15 and 30 min after the end of infusion (T1,2),blood samples were collected fron the central vein for determination of plasma colloid osmotic pressure (COP) and hemnoglobin (Hb) concentrations.The concentrations of 6％ HES 130/ 0.4 in plasma at T1 and T2 and in urine at T2 were measured by the anthranone colorimetric method.Results Compared with the baseline value at T0,the concentrations of Hh in plasma were significantly decreased at T1,2 in preschool group,and the concentrations of Hb in plasma were significantly decreased and plasma COP was increased at T1,2 in school-age group (P＜0.05).There were no significant differences in plasma Hb concentrations or COP at each time point between two groups (P＞0.05).The plasma 6％ HES 130/0.4 concentrations were significantly lower at T2 than at T1 in two groups (P＞0.05).Compared with school-age group,the plasma 6％ HES 130/0.4 concentrations were significantly decreased at T1,2 in preschool group (P＜0.05).There was no significant difference in 6％ HES 130/0.4 concentrations in urine between the two groups (P＞0.05).Conclusion When 6％ HES 130/0.4 is used for acute hemodilution,extravascular leakage happens after acute hemodilution and is more obvious in the preschool pediatric patients undergoing open heart surgery.

Acute hypervolemic hemodilution with hydroxyethyl starch 130/0.4-electrolyte injection versus hydroxyethyl starch 130/0.4-sodium chloride injection for blood-saving effect / 中华麻醉学杂志

Objective To compare the blood-saving effect when acute hypervolemic hemodilution (AHH) was performed with hydroxyethyl starch (HES) 130/0.4 dissolved in electrolyte injection (HES-E) and HES 130/0.4 in sodium chloride injection (HES-NaCl).Methods Thirty patients of both sexes,aged 18-60 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,with body mass index of 18-25 kg/m2,hemoglobin (Hb) ＞100 g/L,hematocrit (Hct) ＞ 35％,scheduled for elective abdominal operations under general anesthesia,were randomly divided into HES-E group and HES-NaCl group using a random number table,with 15 patients in each group.AHH was performed after induction of anesthesia.In HES-E and HES-NaCl groups,HES-E and HES-NaCl 15 ml/kg were intravenously infused over 30 min,respectively,and the infusion was conpleted before skin incision.Immediately after onset of AHH (T1),at 2 h after the end of AHH (T2),and at the end of operation (T3),arterial blood samples were collected for blood gas analysis and blood routine test,and pH value,base excess,HCO3-,K+,Na+,Cl-,Ca2+,Hb and Hct were recorded.Venous blood samples were collected at T1 and T2 for measurement of blood coagulation parameters including prothrombin time,activated partial thromboplastin time and fibrinogen and thrombelastography parameters.The volume of liquid intake and output and requirement for allogeneic blood transfusion were recorded,and the blood volume expansion rate was calculated.Results Compared with group HES-NaCl,no significant changes were found in the total volume of liquid infused,requirement for allogeneic blood transfusion,blood volume expansion rate,blood coagulation parameters at each time point,Hb and Hct (P＞0.05),pH value,base excess,HCO3 and K+ were significantly increased,and Na+ and Cl-were significantly decreased in group HES-E (P＜0.01).Conclusion There is no significant difference in the blood-saving effect between AHH with HES-E and HES-NaCl clinically,but HES-E can maintain homeostasis better.

Effect of 6%hydroxyethyl starch 130∕0.4 on acute kidney injury in elderly patients：a prospective, multicenter, randomized, double-blind, controlled clinical trial / 中华麻醉学杂志

Objective To evaluate the effect of 6% hydroxyethyl starch 130∕0. 4 on acute kidney injury in elderly patients in a prospective, multicenter, randomized, double?blind, controlled clinical tri?al. Methods A total of 120 patients of both sexes, aged 65-82 yr, weighing 56-83 kg, of American So?ciety of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective orthopaedics and hernia surgery, were divided into either hydroxyethyl starch group ( group HES) or lactated Ringer′s solution group ( group LR) , with 60 patients in each group. Hydroxyethyl starch and lactated Ringer′s solution were infused intra?venously at a rate of 7. 5 ml∕kg during 1st hour of surgery in HES and LR groups, respectively. Lactated Ringer′s solution was then infused at a rate of 5 ml∕kg starting from 2nd hour of surgery until the end of sur?gery in both groups. Before surgery, at the end of surgery and at 1, 3 and 5 days after surgery, blood sam?ples and urine specimens were collected for determination of the concentrations of neutrophil gelatinase?asso?ciated lipocalin, interleukin?18 (IL?18), plasma creatinine, urine β2 microglobulin and urine albumin. The estimated glomerular filtration rate was calculated. Results The level of urine IL?18 was significantly higher at each time point after surgery than before surgery and immediately after the end of surgery ( P0.05) . Conclusion Compared with lactated Ringer′s solution, 6% hydroxyethyl starch 130∕0.4 does not aggravate acute kidney injury in elderly patients.