Hydroxyethyl Starch Preparations Research Articles

Adsorption of Malachite Green from Aqueous Solution Using Hydroxyethyl Starch Hydrogel Improved by Graphene Oxide

This study is the first report of the preparation of hydroxyethyl starch (HES) hydrogels rapidly crosslinked with divinyl sulfone in a single step and single pot. To develop the physical and chemical features of hydrogels, Graphene oxide (GO) nanoparticles were combined with the crosslinked HES. In addition to swelling studies, structural characterization of the samples was conducted with a scanning electron microscope (SEM) and transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), Brunauer–Emmett–Teller (BET) analysis and thermogravimetric analysis (TGA). For the removal of malachite green model dye by GO-HES, the effects of GO content, solution concentration, temperature, contact duration, dosage and pH on varying adsorption features were researched. Additionally, adsorption isotherms, kinetic and thermodynamic systematics were analyzed. The maximum adsorption capacity of GO-HES composite hydrogel was found to be 89.3 mg/g for Langmuir isotherm. The possible adsorption mechanism of the composite hydrogels for malachite green dye involved electrostatic, hydrogen bonding, and π–π interactions. In addition to reasonable cost and simple synthesis method, the prepared composite materials have potential use in wastewater treatment as adsorbents for the removal of dye from aqueous solutions due to efficient adsorption capacity.

Infusion therapy in the perioperative period

Background. Inadequate volume of perioperative infusion therapy (IT) is one of the predictors of postoperative complications. There are different types of infusion solutions on the pharmaceutical market: albumin, dextrans (Reopoliglukin), polyatomic alcohols (Reosorbilact, Sorbilact), hydroxyethyl starch preparations (Gekodez), modified gelatin (Volutenz), balanced colloid-hyperosmolar solution (Gekoton), etc (all listed solutions are produced by “Yuria-Pharm”).
 Objective. To describe the main features of perioperative IT.
 Materials and methods. Analysis of literature sources on this topic.
 Results and discussion. Inadequate IT can cause hypo- and hypervolemia, as well as slow the recovery after surgery, so the choice of infusion solution should be made very carefully. To eliminate endothelial dysfunction, which often accompanies the perioperative period, it is advisable to prescribe L-arginine (Tivortin, “Yuria-Pharm”), which acts as a substrate for the synthesis of nitric oxide. Tivortin has the following properties: membrane stabilizing, antioxidant, cytoprotective, detoxifying, endothelioprotective, anabolic, hepatoprotective, antihypoxic. L-arginine (Tivortin) also helps to correct acid-base balance, neutralizes and removes ammonia, promotes insulin synthesis and regulates blood glucose, reduces the activation and adhesion of leukocytes and platelets to the vascular endothelium. The position paper of the International Fluid Optimization Group (2015) states that in planned operations without blood loss, crystalloids can be prescribed (2 ml/kg/h for surgeries lasting >4 hours, up to 10 ml/kg/h for surgeries lasting up to 1 hour). However, the disadvantages of the most famous crystalloid (0.9 % saline) are the risk of hyperchloremic acidosis and the development of edema in case of overdose, so it is advisable to use ion-balanced solutions instead of 0.9 % NaCl. The ideal electrolyte solution should be isovolemic, isohydric, isooncotic, isoionic, and isotonic to the blood plasma. Elimination of the metabolic acidosis is an important task of perioperative IT. Soda-Bufer (“Yuria-Pharm”) can be used for this purpose, as the administration of sodium bicarbonate reduces mortality in patients with severe metabolic acidosis and acute kidney damage. To eliminate the intoxication syndrome, drugs of polyatomic alcohols (Reosorbilact) have been successfully used. Efficiency of Reosorbilact in the treatment of sepsis, peritonitis, pneumonia, burns, etc. was confirmed in the numerous studies. In addition to detoxification, Reosorbilact supports hemodynamics and microcirculation, corrects metabolic acidosis and water-electrolyte disorders, stimulates diuresis, normalizes the rheological properties of blood, which makes it the main drug for low-volume IT in the perioperative period. In turn, Xylate is the main solution in diabetes because it has antiketogenic and lipotropic properties, improves hemodynamics and microcirculation, corrects metabolic acidosis and has an osmodiuretic effect. In shock settings IT should be administered according to the ROSE concept (R (rescue) – aggressive IT; O (optimization) – support of tissue perfusion; S (stabilization) – supportive IT; E (evacuation) – deresuscitation, restoration of body functions).
 Conclusions. 1. Optimal IT improves the consequences of the surgery. 2. To eliminate endothelial dysfunction, it is advisable to prescribe L-arginine (Tivortin). 3. Reosorbilact is successfully used to eliminate the intoxication syndrome, which also supports hemodynamics and microcirculation, corrects metabolic acidosis and water-electrolyte disorders, which makes it the main drug for low-volume IT in the perioperative period. 4. Xylate is the main solution in diabetes because it has antiketogenic and lipotropic properties, improves hemodynamics and microcirculation. 5. In shock settings IT should be administered according to the ROSE concept (rescue, optimization, stabilization, evacuation).

Renal Morbidity of 6% Hydroxyethyl Starch 130/0.4 in 9000 Propensity Score Matched Pairs of Surgical Patients.

BACKGROUND:Several studies of critically ill patients reported that fluid resuscitation with hydroxyethyl starch (HES) solutions damages the kidneys, but their use for surgical patients is debated. Because different HES preparations have different safety profiles, we sought to determine whether 6% third-generation HES 130/0.4 was associated with renal morbidity when used for surgical patients.METHODS:We identified adults enrolled in a Japanese nationwide medical database who underwent surgery between 2014 and 2016, with HES 130/0.4 or without it (controls). These groups were balanced with propensity score matching in a 1:1 ratio without replacement by multivariable logistic regression with 36 covariates, including demographic characteristics, preoperative comorbidities, and anesthetic/surgical procedures. The primary outcome was the incidence of acute kidney injury (AKI) in patients receiving intraoperative HES and controls. Secondary outcomes were assessing whether HES was associated with worsening AKI stage, the incidence of renal-replacement therapy (RRT), hospital length-of-stay, and in-hospital 30-day mortality. Tertiary outcomes include the use of vasoactive agents and the fluid requirement on the day of surgery. Comparative analysis was made with χ2, Mann-Whitney U test, or the ordinal logistic regression analysis.RESULTS:Of 76,048 patients in the database, 58,425 were eligible: 9542 received HES and 48,883 controls. Propensity score matching identified 8823 matched pairs. The incidence of AKI was 6.2% (548/8823) in the HES group and 5.6% (492/8823) in controls (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.99–1.27; P = .07). Compared to controls, HES was not associated with worsening AKI stage (OR, 0.89; 95% CI, 0.79–1.01; P = .08). The incidence of RRT was lower in the HES group than that in controls (0.2% vs 0.4%, respectively; OR, 0.51; 95% CI, 0.29–0.91; P = .02). Median [interquartile range] hospital stay was 1 day longer in the HES group (12 [8–21] vs 11 [7–20] days; P < .001), but in-hospital 30-day mortality did not differ between groups (0.5% vs 0.6%, respectively: OR, 0.83; 95% CI, 0.56–1.24; P = .36). The use rate of vasoactive agents and the median net fluid requirement on the day of surgery were higher in the HES group (80.5% vs 70.0%: P < .001, 88.1 vs 73.6 mL/kg; P < .001, respectively) compared to controls.CONCLUSIONS:The present study did not demonstrate that 6% HES 130/0.4 increased the incidence and the severity of postoperative AKI. It was associated with a lower incidence of RRT when used for surgical patients.

Hydroxyethyl starch stabilized polydopamine nanoparticles for cancer chemotherapy

Bio-inspired polydopamine (PDA) based nanomaterials, particularly nanoparticles (NPs), received tremendous attention and have been applied to various fields, including drug delivery. Nonetheless, bare PDA NPs will aggregate in physiological conditions and can be hardly applied for in vivo explorations. Herein, we present the preparation of novel hydroxyethyl starch coated PDA (HES-PDA) NPs for cancer chemotherapy. The frequently used PEG-modified PDA (PEG-PDA) NPs are also manufactured as a control and doxorubicin (DOX) is chosen as a model drug. The stability, drug loading capacity, lyophilization and rehydration property, biodistribution, in vitro and in vivo anti-tumor efficacy, and toxicity of DOX-loaded HES-PDA (DOX@HES-PDA NPs) are investigated. Collectively, DOX@HES-PDA NPs, similar to DOX@PEG-PDA NPs, show potent antitumor efficacy and dramatically mitigate toxicity associated with DOX. The HES-PDA NPs reported herein represent a novel biodegradable multifunctional nano-drug formulation, with significant translation potentials, for cancer chemotherapy against a wide spectrum of cancers.

Inflammatory Kidney and Liver Tissue Response to Different Hydroxyethylstarch (HES) Preparations in a Rat Model of Early Sepsis.

BackgroundTissue hypoperfusion and inflammation in sepsis can lead to organ failure including kidney and liver. In sepsis, mortality of acute kidney injury increases by more than 50%. Which type of volume replacement should be used is still an ongoing debate. We investigated the effect of different volume strategies on inflammatory mediators in kidney and liver in an early sepsis model.Material and MethodsAdult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) and assigned to three fluid replenishment groups. Animals received 30mL/kg of Ringer’s lactate (RL) for 2h, thereafter RL (75mL/kg), hydroxyethyl starch (HES) balanced (25mL/kg), containing malate and acetate, or HES saline (25mL/kg) for another 2h. Kidney and liver tissue was assessed for inflammation. In vitro rat endothelial cells were exposed to RL, HES balanced or HES saline for 2h, followed by stimulation with tumor necrosis factor-α (TNF-α) for another 4h. Alternatively, cells were exposed to malate, acetate or a mixture of malate and acetate, reflecting the according concentration of these substances in HES balanced. Pro-inflammatory cytokines were determined in cell supernatants.ResultsCytokine mRNA in kidney and liver was increased in CLP animals treated with HES balanced compared to RL, but not after application of HES saline. MCP-1 was 3.5fold (95% CI: 1.3, 5.6) (p<0.01) and TNF-α 2.3fold (95% CI: 1.2, 3.3) (p<0.001) upregulated in the kidney. Corresponding results were seen in liver tissue. TNF-α-stimulated endothelial cells co-exposed to RL expressed 3529±1040pg/mL MCP-1 and 59±23pg/mL CINC-1 protein. These cytokines increased by 2358pg/mL (95% CI: 1511, 3204) (p<0.001) and 29pg/ml (95% CI: 14, 45) (p<0.01) respectively when exposed to HES balanced instead. However, no further upregulation was observed with HES saline. PBS supplemented with acetate increased MCP-1 by 1325pg/mL (95% CI: 741, 1909) (p<0.001) and CINC-1 by 24pg/mL (95% CI: 9, 38) (p<0.01) compared to RL. Malate as well as HES saline did not affect cytokine expression.ConclusionWe identified HES balanced and specifically its component acetate as pro-inflammatory factor. How important this additional inflammatory burden on kidney and liver function is contributing to the sepsis-associated inflammatory burden in early sepsis needs further evaluation.

Update of use of hydroxyethyl starches in surgery and trauma

Update of use of hydroxyethyl starches in surgery and trauma

Fluid resuscitation in acute medicine: what is the current situation?

The administration of intravenous fluids for resuscitation is the most common intervention in acute medicine. There is increasing evidence that the type of fluid may directly affect patient-centred outcomes. There is a lack of evidence that colloids confer clinical benefit over crystalloids and they may be associated with harm. Hydroxyethyl starch preparations are associated with increased mortality and use of renal replacement therapy in critically ill patients, particularly those with sepsis; albumin is associated with increased mortality in patients with severe traumatic brain injury. Crystalloids, such as saline or balanced salt solutions, are increasingly recommended as first-line resuscitation fluids for the majority of patients with hypovolaemia. There is emerging evidence that saline may be associated with adverse outcomes due to the development of hyperchloraemic metabolic acidosis, although the safety of balanced salt solutions has not been established. Fluid requirements vary over the course of critical illness. The excessive use of fluids during the resuscitative period is associated with increased cumulative fluid balance and adverse outcomes in critically ill patients. The selection of fluid depends on the clinical context in which it is administered and requires careful consideration of the dose and potential for toxicity. There is an urgent need to conduct further high-quality randomized controlled trials of currently available fluid therapy in patients with critical illness.

Acute perioperative hemodilution without using hydroxyethyl starch : hemodynamic alterations under "controlled" hypovolemia

Up to now hydroxyethyl starch preparations have frequently been used to compensate for volume deficits accompanying blood withdrawal during acute normovolemic hemodilution. This approach was questioned with respect to the current limitations for use of hydroxyethyl starch solutions imposed by the European Medicines Agency. Because crystalloids distribute evenly across the whole extracellular compartment, 80 % of the infused solution will be "lost" to the interstitial space. Thus, a physiological adjustment of blood loss caused by hemodilution with crystalloids alone (1:5 ratio) seems hardly feasible and according to current data perhaps not even desirable. A 3:1 ratio (crystalloids versus blood loss) as applied in the current study can be regarded as a practical compromise between physiological needs and recommendations according to the literature (1.4:1) but will lead to moderate hypovolemia the hemodynamic consequences of which are not well described. The current study investigates the hemodynamic impact of a hemodilution with crystalloids under the precondition of a 3:1 substitution ratio compared to withdrawn blood. In the context of acute perioperative hemodilution 10 otherwise healthy women graded I and II on the American Society of Anesthesiologists (ASA) classification scheduled for open gynecological cancer surgery underwent an average blood withdrawal of 1097 ± 285ml which was substituted by an average of 3430 ± 806ml of Ringer's lactate. The resulting deficit in blood volume was exactly quantified by a double tracer technique. Hemodynamic changes were evaluated by a combination of thermodilution and pulse contour analysis (PiCCO system®). Subsequently, the remaining volume deficit was compensated by 245 ± 64ml of a 20 % albumin solution and hemodynamic parameters were again evaluated. When infusing Ringer's lactate in a 3:1 ratio compared to the actual blood loss, the blood volume decreased by 12 %. The volume effect of Ringer's lactate proved to be 17 %. While mean arterial pressure and heart rate remained constant, key hemodynamic parameters changed relevantly during the time course. A significant rise in cardiac output and myocardial contractility could be observed which was accompanied by a decrease in systemic vascular resistance. In contrast, cardiac preload and the parameters representing pulmonary vascular permeability remained unaltered. The infusion of 245 ± 64ml of a 20 % albumin solution nearly completely restituted blood volume and led to an insignificant rise in systemic vascular resistance but did not normalize cardiac output or myocardial contractility. In the study population, the loss of intravascular fluid during perioperative haemodilution could be compensated by an increase in cardiac performance. However, whether patients with a reduced cardiac capacity (i.e. older patients) are capable to improve their cardiac output sufficiently in order to compensate hypovolemia accompanying perioperative haemodilution with crystalloids remains questionable.

Molecular size and origin do not influence the harmful side effects of hydroxyethyl starch on human proximal tubule cells (HK-2) in vitro.

Recently, clinical trials revealed renal impairment induced by hydroxyethyl starch (HES) in septic patients. In prior studies, we managed to demonstrate that HES accumulated in renal proximal tubule cells (PTCs). The related pathomechanism has not yet been discovered. To validate our hypothesis that the HES molecule itself is harmful, regardless of its molecule size or origin, we conducted a comprehensive study to elucidate the influences of different HES preparations on PTC viability in vitro. Cell viability of human PTC was measured with a cytotoxicity assay, quantifying the reduction of tetrazolium salt to colored formazan. Experiments were performed by assessing the influence of different carrier solutions of HES (balanced, nonbalanced, culture medium), different average molecular weights (70, 130, 200 kDa), different origins (potato or corn derived), and various durations of incubation (2-21 hours). Furthermore, HES 130/0.4 was fractionated by ultrafiltration, and the impact on cell viability of average single-size fractions with <3, 3 to 10, 10 to 30, 30 to 50, 50 to 100, and >100 kDa was investigated. We also tested the possible synergistic effects of inflammation induced by tumor necrosis factor-α. All tested HES solutions, regardless of origin or carrier matrix, decreased cell viability in an equivalent, dose-dependent manner. Coincubation with tumor necrosis factor-α did not reduce HES-induced reduction of cell viability. Minor differences were detected comparing 70, 130, and 200 kDa preparations. Analysis of fractionated HES revealed that each fraction decreased cell viability. Even small HES molecules (10-30 kDa) were significantly deleterious. For the first time, we were able to show that only the total mass of HES molecules applied is responsible for the harmful impact on renal PTC in vitro. Neither molecular size nor their origin showed any relevance.

Контроль качества молекулярно-массового распределения полисахаридов с помощью эксклюзионной хроматографии с детектором многоуглового лазерного светорассеяния

Показано, что контроль качества лекарственных средств на основе гидроксиэтилированного крахмала можно проводить с помощью абсолютного метода анализа молекулярно-массового распределения — эксклюзионной хроматографии с детектором многоуглового лазерного светорассеяния. В работе приведены результаты, необходимые для обоснования включения описанной методики в отечественные нормативные документы на гидроксиэтилированный крахмал.

The ideal fluid.

The characteristics of an ideal intravenous fluid in the critically ill patient are discussed. Intravenous fluids are the most frequent drug administered to patients. Questioning the use of commonly administered intravenous fluids has resulted in an increased focus on their efficacy and safety. Discrimination between fluids currently in use has been the central theme of many recent large studies, and emerging from these findings is an understanding of characteristics that would make for an ideal fluid for critically ill patients. There is increased morbidity and mortality with high chloride-containing crystalloid solutions and hydroxyethyl starch preparations, with resultant international governmental agency warnings regarding hydroxyethyl starch . The ideal fluid is one which achieves the aim of administration while minimizing or negating adverse effects, is inexpensive, and sufficiently stable when stored to be used in a wide range of clinical settings. The ideal fluid currently does not exist. Of existing options, use of hydroxyethyl starches and high chloride-containing crystalloid solutions should be discouraged. There is a lack of direct evidence that a balanced crystalloid solution confers benefit, however, the trend of recent data would support future investigation into the advantage of balanced solution over 0.9% saline.

Fluid resuscitation in trauma and critical care : Current guidelines

Outcome data on fluid therapy in trauma and critically ill patients suggests a direct correlation between positive fluid balance and increased mortality. Randomised-controlled trials over the past decade comparing the effects of hydroxyethyl starch (HES) preparations and crystalloids for fluid resuscitation in critically illpatients have demonstrated an increased mortality and use of renal replacement therapy (RRT) associated with HES solutions. Balanced salt solutions have shown promise as initial resuscitation fluids, though there is not enough clinical data regarding their comparative safety and efficacy.

New insights into fluid resuscitation

Recent high-quality randomised-controlled trials comparing the effects of hydroxyethyl starch (HES) preparations and crystalloids for fluid resuscitation in critically ill patients have demonstrated an increased risk of death and use of renal replacement therapy (RRT). Consequently, a number of systematic reviews incorporating these new results have been published that have consistently demonstrated an increased risk of death and use of RRT associated with HES solutions, regardless of type of HES and dose administered, both in general intensive care patients and in those with severe sepsis. These effects become apparent in the post-resuscitation period and may relate to increased tissue accumulation associated with HES. These results question the clinical role of semi-synthetic colloids for fluid resuscitation and mandate a reappraisal about how these fluids are administered to critically ill patients, specifically considering the potential for toxicity.

Glycocalyx Degradation Causes Microvascular Perfusion Failure in the Ex Vivo Perfused Mouse Lung

The endothelial glycocalyx (GLX) is pivotal to vascular barrier function. We investigated the consequences of GLX degradation on pulmonary microvascular perfusion and, prompted by evidence that hydroxyethyl starch (HES) improves microcirculation, studied the effects of two HES preparations during GLX diminution. C57 BL/6 black mice lungs were explanted and perfused with 1-mL/min buffer solution containing autologous erythrocytes (red blood cells) at a hematocrit of 5%. Microvessel perfusion was quantified by video fluorescence microscopy at 0 and 90 min. To register interstitial edema, alveolar septal width was quantified. Pulmonary artery pressure (PAP), airway pressure, and left atrial pressure were recorded continuously. Lungs were randomly assigned to four groups (each n = 5): (i) control: no treatment, (ii) HEP1: heparinase I (1 mU/mL) was injected for GLX degradation, (iii) HES 130, and (iv) HES 200: one third of perfusion fluid was exchanged for 6% HES 130/0.4 or 10% HES 200/0.5 before GLX degradation. Analysis of variance on ranks and pairwise multiple comparisons were used for statistics, P < 0.05. Compared with control, GLX degradation effected perfusion failure in microvessels, increased PAP, and facilitated interstitial edema formation after a 90-min period of perfusion. In contrast to HES 200/0.5, pretreatment with HES 130/0.4 attenuated all of these consequences. Sequelae of GLX degradation in lung include perfusion failure in microvessels, interstitial edema formation, and increase in PAP. We assume that these effects are a consequence of vascular barrier dysfunction. Beneficial effects of HES 130/0.4 are presumably a result of its lower red blood cell bridging capacity compared with HES 200/0.5.

Safety of Modern Starches Used During Surgery

Various hydroxyethyl starch (HES) preparations have been used for decades to augment blood volume. There has been concern recently regarding possible adverse outcomes when using HES in the intensive care setting, especially in patients with septic shock. However, the pharmacokinetic and pharmacodynamic properties of HES preparations depend on their chemical composition and source material. Thus, different clinical conditions could result in differing effectiveness and safety for these preparations. Consequently, we assessed the safety of tetrastarches when used during surgery, using a formal search, that yielded 59 primary full publications of studies that met a priori inclusion criteria and randomly allocated 4529 patients with 2139 patients treated with tetrastarch compared with 2390 patients treated with a comparator. There were no indications that the use of tetrastarches during surgery induces adverse renal effects as assessed by change or absolute concentrations of serum creatinine or need for renal replacement therapy (39 trials, 3389 patients), increased blood loss (38 trials, 3280 patients), allogeneic erythrocyte transfusion (20 trials, 2151 patients; odds ratio for HES transfusion 0.73 [95% confidence interval = 0.61-0.87], P = 0.0005), or increased mortality (odds ratio for HES mortality = 0.51 [0.24-1.05], P = 0.079).

Inflammatory Response to Colloids Compared to Crystalloid Priming in Cardiac Surgery Patients with Cardiopulmonary Bypass

"Cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response syndrome that may contribute to postoperative morbidity and mortality. We investigated the in-flammatory responses to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass. Thirty patients undergoing coronary artery bypass grafting (CABG) preparing for CPB were randomized into Ringer's solution (RS), 10% hydroxyethyl starch (HES) or 25% human albumin (HA) group. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β ), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured before CPB, at the end of CPB and 1, 6 and 12 h after CPB. Serum C-reactive protein (CRP) was determined pre-operatively and then daily for 2 days. Body-weight gain was significantly decreased on the day after surgery in the HES group than in the RS group. Volume priming in CPB for CABG patients using HA or HES preparation had less tendency for intense inflammatory response with lower levels of TNF-α, IL-1 β , IL-6 and higher levels of IL-10 compared to patients treated with RS. HES prime had lower levels of circulating CRP than in patients treated with HA or Ringer prime on the second post-operative day. Our data indicate that volume priming using colloid during CPB in CABG patients might exert beneficial effects on inflammatory responses."

Plasma Substitutes Therapy in Pediatrics

Hypovolemia is the most common cause of circulatory failure in children and may lead to critical tissue perfusion and eventually multiple-organ failure. Administration of fluids to maintain or restore intravascular volume represents a common intervention after hemorrhagic shock occurring during surgical procedures or in patients with trauma. Notwithstanding, there is uncertainty whether the type of fluid may significantly influence the outcome, especially in pediatrics. Both human albumin and crystalloids are usually administered: the advantages of crystalloids include low cost, lack of effect on coagulation, no risk of anaphylactic reaction or transmission of infectious agents. However, large amount of crystalloid infusion has been correlated with pulmonary oedema, bilateral pleural effusions, intestinal intussusception, excessive bowel edema, impairing closure of surgical wounds and peripheral edema. Moreover, intravascular volume expansion obtained by crystalloids is known to be significantly shorter and less efficacious than colloids. Among synthetic colloids, gelatins have been used for many years in children, also in early infancy, to treat intravascular fluid deficits. Hydroxyethylstarch (HES) preparations have been introduced recently, becoming very popular for vascular loading both in adults and children. However, the number of pediatric studies aimed at evaluating HES efficacy and tolerance is limited. Given the ongoing controversies on the use of colloids in childhood, this review will focus on the pharmacodynamics of synthetic and non synthetic colloids for the treatment of critical blood loss in pediatrics.

Retractions Lead to Revision of Review Article “Contemporary Fluid Management in Cardiac Anesthesia”

Numerous articles authored by Dr Joachim Boldt were retracted from international journals on anesthesia and intensive care medicine because of missing institutional review board approvals. Therefore, we believe our recent publication1Habicher M. Perrino Jr, A. Spies C.D. et al.Contemporary fluid management in cardiac anesthesia.J Cardiothorac Vasc Anesth. 2011; 25: 1141-1153Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar needed to be updated to re-evaluate conclusions that might have been influenced by the retracted data. Our review cited 5 articles by Dr Boldt.2Boldt J. Lenz M. Kumle B. et al.Volume replacement strategies on intensive care units: Results from a postal survey.Intensive Care Med. 1998; 24: 147-151Crossref PubMed Scopus (118) Google Scholar, 3Boldt J. Haisch G. Suttner S. et al.Effects of a new modified, balanced hydroxyethyl starch preparation (Hextend) on measures of coagulation.Br J Anaesth. 2002; 89: 722-728Crossref PubMed Scopus (99) Google Scholar, 4Boldt J. PRO: Hydroxyethyl starch can be safely used in the intensive care patient—The renal debate.Intensive Care Med. 2009; 35: 1331-1336Crossref PubMed Scopus (27) Google Scholar, 5Boldt J. Brenner T. Lehmann A. et al.Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: Comparison of a new starch preparation with gelatin.Intensive Care Med. 2003; 29: 763-769Crossref PubMed Scopus (91) Google Scholar, 6Boldt J. Brosch Ch. Röhm K. et al.Comparison of the effects of gelatin and a modern hydroxyethyl starch solution on renal function and inflammatory response in elderly cardiac surgery patients.Br J Anaesth. 2008; 100: 457-464Crossref PubMed Scopus (76) Google Scholar Three of these 5 publications are among the articles that were retracted.3Boldt J. Haisch G. Suttner S. et al.Effects of a new modified, balanced hydroxyethyl starch preparation (Hextend) on measures of coagulation.Br J Anaesth. 2002; 89: 722-728Crossref PubMed Scopus (99) Google Scholar, 5Boldt J. Brenner T. Lehmann A. et al.Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: Comparison of a new starch preparation with gelatin.Intensive Care Med. 2003; 29: 763-769Crossref PubMed Scopus (91) Google Scholar, 6Boldt J. Brosch Ch. Röhm K. et al.Comparison of the effects of gelatin and a modern hydroxyethyl starch solution on renal function and inflammatory response in elderly cardiac surgery patients.Br J Anaesth. 2008; 100: 457-464Crossref PubMed Scopus (76) Google Scholar After discussion within our group, we decided to remove all sentences and paragraphs discussing these publications by Dr Boldt to counter the argument that any conclusion drawn in this review article could have been influenced by possibly fraudulent data. In particular, the section “Colloids and Renal Function in Cardiac Surgery” is a concern because the 2 prospective randomized trials addressing this issue were authored by Dr Boldt and are among the retracted articles. We removed the discussion of the articles by Dr Boldt and discussed data from related surgical specialties because, to the best of our knowledge, no other studies investigating the effect of colloids on renal function in cardiac surgery are available. The conclusions drawn are different from the original article because no recommendations on the safe use of starch solutions regarding renal function in cardiac surgical patients, regardless of the generation of starches used, can be made. The entire discussion of the issue concerning Dr Boldt emphasizes that the gap of knowledge regarding the safety of colloid solutions and especially the impact on renal function in cardiac surgery needs to be addressed by sufficiently powered, prospective, randomized trials. Contemporary Fluid Management in Cardiac AnesthesiaJournal of Cardiothoracic and Vascular AnesthesiaVol. 25Issue 6PreviewTHE PRESCRIPTION OF perioperative fluids has been a persistent controversy among anesthesiologists, surgeons, and intensivists. Interestingly, disagreements within each specialty as to the appropriate types and amounts of fluids required are just as intense as that seen among the specialties. The challenge in navigating these waters is demanding because the safe harbor of optimal fluid administration is bounded by hypovolemia and end-organ hypoperfusion (resulting from inadequate fluids) and congestive heart failure and the negative effects of edema formation on respiration and wound healing (resulting from excessive fluids). Full-Text PDF

What is the optimal type of fluid to be used for peri‐operative fluid optimisation directed by oesophageal Doppler monitoring?

The objective of this review was to determine the optimal type or class of intravenous fluid to be used during peri-operative patient optimisation guided by oesophageal Doppler monitoring and to identify future directions for research. We undertook a literature review of patients undergoing major (general, colorectal, orthopaedic and urological) surgery, whose fluid therapy was managed using peri-operative oesophageal Doppler monitoring. We identified 10 studies that included 891 randomised patients. A variety of regimens and types of fluid were used in association with oesophageal Doppler monitoring, including crystalloid, gelatin and hydroxyethyl starch. A wide variety of hydroxyethyl starch preparations were used, including high molecular weight and highly substituted hetastarches, and lower molecular weight tetrastarches. Most studies were of high quality, associated with reduced hospital stay, but underpowered to evaluate other outcomes. In units with established enhanced recovery facilities, the benefits of colloid based on oesophageal Doppler monitoring were not reproduced. There is little evidence to support preferential use of any particular type of fluid during oesophageal Doppler guided optimisation; however, routine use of colloids is associated with significantly higher costs and may increase hospital stay. Furthermore, many of these fluids have not been evaluated in patient populations in whom optimisation is being applied or proposed, and the potential for harm cannot be excluded. Recommendations for future studies are provided, including adequate power for primary end points beyond hospital stay and adequate follow-up, and inclusion of a crystalloid comparison group.

Balanced hydroxyethylstarch preparations: are they all the same? In-vitro thrombelastometry and whole blood aggregometry: Retraction

Balanced hydroxyethylstarch preparations: are they all the same? In-vitro thrombelastometry and whole blood aggregometry: Retraction