Clinical Outcomes and Medical Costs of Hydration Therapy with Hydroxyethyl Starch (130/0.4) or Acute Single Infarction.

OBJECTIVES: To investigate the effects of hydration with or without Hydroxyethyl Starch (HES) 130/0.4 on neurological outcomes and medical costs during hospitalisation in patients with a single infarction (SI) in the posterior lenticulostriate artery (LSA) territory. MATERIALS AND METHODS: In this retrospective, single-centre, non-blinded cohort study, SI in the posterior LSA was defined as an ischaemic lesion with a high-signal intensity area ≥20 mm. All patients received basic stroke care within 48 h of symptom onset between April 2015 and January 2019. Patients were divided into the following two groups by clinician's preference: 1) those administered HES 130/0.4 and 2) those receiving other infusion fluid. The relationships between hospital costs and hydration therapy type were examined. RESULTS: Eighteen (31%) of 58 patients received HES 130/0.4. The HES group had a significantly lower total cost than the control group (3.6 vs. 6.4 million yen, p=0.006). Moreover, the HES group had a significantly shorter hospital stay duration (79.5 vs. 141.0 days) and lower National Institutes of Health Stroke Scale score on day 7. Multivariate analysis found that HES 130/0.4 administration was an independent factor associated with high costs. CONCLUSIONS: Hydration therapy with HES 130/0.4 significantly decreased the total costs and hospitalisation duration of patients with SI in the posterior LSA territory.

An international comparison of the cost of fluid resuscitation therapies.

OBJECTIVE: Fluid resuscitation is a ubiquitous intervention in the management of patients treated in the intensive care unit, which has implications for intensive care unit resourcing and budgets. Our objective was to calculate the relative cost of resuscitation fluids in several countries to inform future economic evaluations. METHODS: We collected site-level data regarding the availability and cost of fluids as part of an international survey. We normalised costs to net present values using purchasing power parities and published inflation figures. Costs were also adjusted for equi-effective dosing based on intravascular volume expansion effectiveness and expressed as US dollars (USD) per 100 mL crystalloid equivalent. RESULTS: A total of 187 sites had access to cost data. Between countries, there was an approximate six fold variation in the cost of crystalloids and colloids overall. The average cost for crystalloids overall was less than 1 USD per 100 mL. In contrast, colloid fluids had higher average costs (59 USD per 100 mL). After adjusting for equi-effective dosing, saline was ∼27 times less costly than albumin (saline: 0.6 USD per 100 mL crystalloid equivalent; albumin 4-5%: 16.4 USD; albumin 20-25%: 15.8 USD) and ∼4 times less costly than hydroxyethyl starch solution (saline: 0.6 USD; hydroxyethyl starch solution: 2.5 USD). Buffered salt solutions, such as compound sodium acetate solutions (e.g., Plasmalyte®), had the highest average cost of crystalloid fluids, costing between 3 and 4 USD per 100 mL. CONCLUSION: The cost of fluid varies substantially between fluid types and between countries, although normal (0.9%) saline is consistently less costly than colloid preparations and some buffered salt solutions. These data can be used to inform future economic evaluations of fluid preparations.

Con: The Unclear Benefit of Albumin.

Many studies have shown that 20% human albumin solution infusions improve circulatory function in patients with advanced liver disease, and this treatment is widely recommended and used by all hepatologists. However, it is more expensive than other crystalloids or colloids, and several countries suffer shortages of supply. This article examines whether other fluids might be considered for these patients.

Hydroxyethyl starch versus saline for resuscitation of patients in intensive care: long-term outcomes and cost-effectiveness analysis of a cohort from CHEST.

BACKGROUND: Hydroxyethyl starch for fluid resuscitation in critically ill patients is not associated with improved short-term patient-centred outcomes compared with crystalloid fluid solutions. However, its effect on longer term health economic outcomes has not been reported. METHODS: We did a prespecified cost-effectiveness analysis of a cohort of patients from New South Wales enrolled in the Crystalloid versus Hydroxyethyl Starch Trial (CHEST), who were randomised to treatment with either 6% hydroxyethyl starch with a molecular weight of 130 kD and a molar substitution ratio of 0·4 or 0·9% sodium chloride (saline) for fluid resuscitation. Clinical outcomes were mortality and life-years gained at 6 months and 24 months, health-related quality of life at 6 months, and quality-adjusted life-years gained at 6 months. Health economic outcomes were hospital and intensive-care unit (ICU) resource use and costs at 24 months and cost-effectiveness, which we defined as the probability of reaching a willingness-to-pay threshold of less than A$50 000 per quality-adjusted life-year gained at 6 months and $100 000 per life-year gained at 24 months. CHEST is registered with ClinicalTrials.gov, number NCT00935168. FINDINGS: 3537 (51%) of 7000 patients were enrolled into CHEST from New South Wales, of whom 3450 (98%) were included in our cost-effectiveness analysis. Mortality at both 6 months and 24 months did not differ between the hydroxyethyl starch and saline groups (6 months: 397/1684 [24%] vs 382/1706 [22%]; relative risk [RR] 1·05, 95% CI 0·93-1·19; p=0·41; 24 months: 586/1687 [35%] vs 594/1708 [35%]; RR 1·00, 95% CI 0·91-1·10; p=0·89). The mean number of life-years gained at 6 months and 24 months was similar between the hydroxyethyl starch and saline groups (6 months: 0·41 days [SD 0·18] vs 0·41 days [0·17]; p=0·25; 24 months: 1·46 years [SD 0·80] vs 1·47 years [0·79]; p=0·72). At 6 months, the mean health-related quality of life score was 0·67 (SD 0·34) with hydroxyethyl starch versus 0·69 (0·35) with saline (p=0·33). The mean number of quality-adjusted life-years gained did not differ between the hydroxyethyl starch and saline groups at 6 months (0·26 days [SD 0·18] vs 0·26 days [0·18]; p=0·33). Total hospital costs (including ICU costs) at 24 months were similar between the hydroxyethyl starch and saline groups (A$62 196 [55 935] vs $62 617 [56 452]; p=0·83). The probability that hydroxyethyl starch was cost effective was 11% at 6 months and 29% at 24 months. INTERPRETATION: Although longer term clinical outcomes did not differ between patients resuscitated with hydroxyethyl starch or saline in the ICU, from a health-care payer's perspective, the probability that hydroxyethyl starch is cost effective in these patients is low. FUNDING: Division of Critical Care and Trauma, George Institute for Global Health.

Cost-minimization analysis of two fluid products for resuscitation of critically injured trauma patients.

PURPOSE: Results of a study to determine potential cost benefits of substituting an alternative electrolyte solution for 0.9% sodium chloride injection for the initial fluid resuscitation of trauma patients are presented. METHODS: Using data from a randomized clinical trial that compared 24-hour fluid resuscitation outcomes in critically injured trauma patients treated with 0.9% sodium chloride injection and those who received a balanced electrolyte solution (Plasma-Lyte A, Baxter Healthcare), a cost-minimization analysis was performed at a large medical center. The outcomes evaluated included fluid and drug acquisition costs, materials and nurse labor costs, and costs associated with electrolyte replacement. RESULTS: The use of Plasma-Lyte A was associated with a relatively higher fluid acquisition cost but a reduced need for magnesium replacement. During the first 24 hours of hospitalization, 4 of 24 patients (17%) treated with 0.9% sodium chloride injection and none of the patients who received the comparator product (n = 22) required supplemental magnesium. Patients treated with 0.9% sodium chloride injection received a median of 4 g of magnesium (interquartile range [IQR], 2.5-4.0 g), compared with a median of 0 g (IQR 0-2 g) in the comparator group. Taking into account the costs of consumable supplies and nursing labor, the cost-minimization analysis indicated a 24-hour cost differential of $12.35 in favor of Plasma-Lyte A. CONCLUSION: Substitution of Plasma-Lyte A for 0.9% sodium chloride injection for fluid resuscitation during the first 24 hours after traumatic injury was associated with decreased magnesium replacement requirements and a net cost benefit to the institution.

Hydroxyethyl starch reduces coagulation competence and increases blood loss during major surgery: results from a randomized controlled trial.

OBJECTIVE: This study evaluated whether administration of hydroxyethyl starch (HES) 130/0.4 affects coagulation competence and influences the perioperative blood loss. BACKGROUND: Artificial colloids substitute blood volume during surgery; with the administration of HES 130/0.4 (Voluven, Fresenius Kabi, Uppsala, Sweden) only a minor effect on coagulation competence is expected. METHODS: Eighty patients were scanned for enrollment in the study, and 40 patients fulfilled the inclusion criteria. Two patients withdrew their consent to participate in the study, and 5 patients were excluded. Thus, 16 patients were randomized to receive lactated Ringer's solution and 17 to receive HES 130/0.4. RESULTS: Among the patients receiving HES 130/0.4, thrombelastography indicated reduced clot strength (P < 0.001) and blinded evaluation of the perioperative blood loss was 2.2 (range 0.5 to 5.0) versus 1.4 (range 0.5 to 2.4) L in the patients who received HES 130/0.4 or lactated Ringer, respectively (P < 0.038). The patients in the lactated Ringer's group, however, received more fluid (P < 0.0001) than those in the HES 130/0.4 group. There was no significant difference between the 2 groups with regard to frequency of reoperations or the length of hospital stay, but use of HES 130/0.4 was both more expensive and less efficacious than the use of lactated Ringer. CONCLUSIONS: Administration of HES 130/0.4 reduced clot strength and perioperative hemorrhage increased by more than 50%, while administration of lactated Ringer's solution provoked an approximately 2.5 times greater positive volume balance at the end of surgery.

[Guidelines on therapy with blood components and plasma derivatives: human albumin. Recommendations of the scientific advisory board of the Medical Council]. / Querschnittleitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten: Humanalbumin. Empfehlungen des wissenschaftlichen Beirats der Bundesärztekammer.

Human albumin (HA) is by far the most expensive option for volume replacement and correction of hypoalbuminemia but is still widely used. The value of HA in the clinical setting continues to be controversial and it remains unclear whether there is still a place for using such a high-priced substance in the present cost-consciousness climate. Thus the Medical Council has presented some recommendations with regard to blood and plasma products including HA. There appear to be no indications for HA to correct hypovolemia either perioperatively or in the intensive care setting including children and patients undergoing cardiac or liver surgery. For maintaining colloid oncotic pressure (COP) cheaper modern synthetic colloids can be alternatively given and the value of HA for correcting hypoalbuminemia is also not clearly justified. Some small uncontrolled studies have shown that only patients with liver cirrhosis, spontaneous bacterial peritonitis and massive ascites drainage may profit from HA. Theoretical benefits such as oxygen radical scavenging or binding of toxic substances are no indications for using HA as beneficial clinical consequences have not yet been demonstrated. Experimental data from cell lines or animals must be viewed with skepticism because they do not mimic the clinical setting. According to the recommendations of the scientific advisory board of the Medical Council the use of HA should be considered very cautiously.

Hydroxyethyl starch 130/0.4 versus modified fluid gelatin for volume expansion in cardiac surgery patients: the effects on perioperative bleeding and transfusion needs.

In this prospective, randomized, open controlled study we compared the effects on net red blood cell loss of 6% hydroxyethyl starch 130/0.4 (HES: n = 64) and 3% modified fluid gelatin (GEL: n = 68) administered for intravascular volume management in patients undergoing coronary surgery. Blood losses were calculated from determination of circulating blood volume and measurement of preoperative and postoperative hematocrit. Amount of colloids that could be administered was limited to 50 mL/kg. If additional fluids were required, balanced crystalloid solution was used. Anesthetic and surgical techniques were standardized. Both groups were similar with regard to demographic and intraoperative variables. Total study drug was 48.9 +/- 17.2 mL/kg in the HES group and 48.9 +/- 14.6 mL/kg in the GEL group. Total red blood cell loss was 544 +/- 305 mL in the HES group and 504 +/- 327 mL the GEL group. Measured blood losses were also similar in both groups (HES, 19.4 +/- 12.3 mL/kg; GEL, 19.2 +/- 14.5 mL/kg). Exposure to allogeneic blood product was comparable in both groups. In the conditions of the present study, HES 130/0.4 up to 50 mL/kg is a valuable alternative to modified fluid gelatin for plasma volume expansion during and after cardiac surgery.

Colloid or crystalloid for resuscitation of major burns.

There is continuing debate over the merits of colloid versus crystalloids for the resuscitation of major burns. This article reviews fluids used in burn resuscitation and discusses potential advantages and disadvantages of colloid and crystalloid.

New light on intravascular volume replacement regimens: what did we learn from the past three years?

UNLABELLED: Definition of the "ideal" intravascular fluid volume replacement strategy still remains a critical problem. This article analyzes studies on volume replacement by using a MEDLINE search of the past 3 years (from January 1, 2000, to December 12, 2002). Forty original studies in humans with a total of 2454 subjects were identified. Five studies were performed in volunteers (n = 113); the other 35 studies (n = 2341) were performed in a variety of patients (e.g., cardiac surgery, trauma patients, children, and intensive care unit patients). The influence of different volume replacement regimens on coagulation was one of the major topics of interest (16 studies with 1183 subjects), and other studies focused on metabolic state, alterations in macro- and microcirculation, volume distribution, and organ function (e.g., kidney function and splanchnic perfusion). Among all synthetic colloids, hydroxyethyl starch (HES) was the solution most often studied. Two new HES preparations have been approved (Hextend), a balanced hetastarch solution, and a new third-generation HES [130/0.4]). Only two studies used albumin, and no superiority of albumin was found over less expensive synthetic colloids. In almost all studies, the outcome either was no end-point or was not reported. Volume replacement has often been hitherto based on dogma and personal beliefs. Future well performed studies in this area will hopefully help to shed new light on the ideal volume replacement strategy. IMPLICATIONS: By using a MEDLINE search covering the last 3 yr, the present knowledge on volume replacement regimens was analyzed. Forty studies in humans were identified. New hydroxyethyl starch preparations have shed light on this topic, whereas no additional data supporting the use of albumin have been presented.

Albumin versus crystalloid therapy in the management of hepatorenal syndrome: a model for using meta analysis in cost effectiveness studies and the design of clinical trials.

We applied traditional methods of gathering, integrating and summarizing findings of current literature, with new approaches for assessing the cost effectiveness of two treatments for hepatorenal syndrome (HRS). Findings of this cost effectiveness study are used to form a proposal for a multi-center prospective clinical trial, to assess the economic and clinical benefits of albumen versus crystalloid therapy in the care of these patients. Our initial findings suggest that albumin therapy is superior to standard crystalloid therapy, in the treatment of HRS patients. The number of survival days appears to increase with this form of therapy per dollar cost, while patients await liver transplantation.

A prospective randomized study comparing two techniques of perioperative blood conservation: isovolemic hemodilution and hypervolemic hemodilution.

UNLABELLED: We compared hypervolemic hemodilution (HVH) and isovolemic hemodilution (IVH) as means of perioperative blood conservation under standardized conditions. Thirty ASA status I/II adults slated for orthopedic, ear-nose-throat, or general surgery with expected blood loss of >500 mL underwent either IVH (n = 15) or HVH (n = 15). They were hemodiluted to a hematocrit (Hct) of 25% by blood withdrawal and simultaneous polygeline (Hemaccel((R))) infusion (IVH) or by infusing polygeline without blood withdrawal, thus creating hypervolemia (HVH). Further blood loss to a Hct of 20% was allowed before autologous/allogeneic blood transfusion to aim for a 24-h postoperative Hct of > or =25%. Systolic blood pressure (P = 0.0107) and central venous pressure (P = 0.0281) were significantly higher during HVH. The mean difference (MD) between the target postdilution Hct of 25% and the Hct achieved was not statistically significant in either group (MD [95% confidence interval; CI], 0% [-0.7% to 0.7%] for IVH and 0.6% [-0.1% to 1.3%] for HVH). The actual amount of allogeneic blood used was similar in the two groups, with an MD (95% CI) of -7 (-326 to 312), and was significantly less than the corresponding projected amount (MD [95% CI], -581 mL [-753 to -409 mL] in IVH; -376 mL [-531 to -221] in HVH). The two techniques were similar in time taken (MD [95% CI] = 7 min [-0.5 to 14.5 min]), cost incurred (MD [95% CI] = $1.7 (-$4.10 to $7.50]), and volumes of polygeline used (MD [95% CI] = -6 mL/kg body weight [-16 to 4 mL/kg body weight]). This study found IVH and HVH comparable in significantly reducing perioperative allogeneic blood requirements, time needed, and cost incurred. The formula used for achieving the desired HVH appears promising. IMPLICATIONS: Both hypervolemic hemodilution (HVH) and isovolemic hemodilution (IVH) claim to reduce red blood cell loss during surgery by diluting the patient's blood. This study found both comparable in significantly reducing the exposure to bank blood in the perioperative period, the time needed, and the cost incurred. HVH, being simpler, because it does not involve blood withdrawal, appeared superior to IVH in the healthy adults studied. Larger studies are needed to substantiate the results.

The status of hemoglobin-based red cell substitutes.

Red cell substitutes are currently under development for use in a variety of surgery and trauma-related clinical conditions. The need for artificial oxygen-carrying fluids continues to be driven by the shortage of donor blood, the complex logistics of blood banking, the risk of virally transmitted diseases, current transfusion practices, and the projected increased demand for blood products in the future. The effort to develop a replacement for the red cell component has evolved over the last century and has presented a number of significant challenges including safety and efficacy concerns. Recent progress in understanding the fundamental interactions of hemoglobin with the body at the molecular, cellular and tissue levels has led to the production of improved red cell substitutes suitable for clinical testing. Currently, seven products are being tested for a variety of applications including trauma, surgery, sepsis, cancer and anemia. Although some of these trials were unsuccessful, the majority of the available products exert no toxicity or only low level side effects. Encouraging results in early clinical trials with oxygen-carrying fluids support further development of these products and have increased the hope that a usable oxygen-carrying fluid will soon be available in the clinic. The purpose of this review is to provide up-to-date information on the status of these products with special emphasis on pre-clinical and clinical experience.

[Plasma substitutes: strategies for use in intensive therapy to maintain a correct ratio between therapeutic efficacy and costs]. / I sostituti di volume plasmatico: strategie di impiego in terapia intensiva per il mantenimento di un corretto rapporto tra efficacia terapeutica e costi.

BACKGROUND: The coice of one product rather than another in clinical practice is based on two main criteria: therapeutic efficacy and the cost of the product in question. However, if therapeutic efficacy is equal, the choice of a less expensive product is not necessarily the right option. We compared the costs and therapeutic efficacy of two products used in plasma replacement therapy in order to identify which would be the most advantageous. METHODS: A total of 126 patients due to undergo major abdominal surgery were recruited and, having been duly informed, they were divided into two random groups. One group was treated with a solution of hydroxyethylamide 6% with an intermediate molecular weight (MW 200 kDa SD 0.5), and the other was treated with a solution of modified fluid gelatine (MFG) at 4% (MW 30 kDa). The solutions were administered to patients at the start of surgery until the morning of the first postoperative day in order to maintain mean arterial pressure (MAP) greater than 60 mmHg and central venous pressure (CVP) between 10 and 14 mmHg. Moreover, the costs of the two products and their additional charges were taken into consideration, taken from the supply lists provided by the pharmacy in the hospital where the study was carried out. RESULTS: No significant differences were found between the two groups in terms of therapeutic efficacy. In economic terms, the cost of the entire infusion treatment was comparable between the two groups in spite of the higher cost of hydroxyethylamide. CONCLUSIONS: The higher cost of hydroxyethylamide was compensated by the fact that a smaller amount of the solution is required to obtain the same hemodynamic parameters guaranteed by gelatine. Moreover, no adverse reactions were reported in this study to either compound. In the international literature, gelatine is associated with adverse reactions in a greater number of cases than hydroxyethylamide. This study shows that when proposing strategies of use, a simple cost analysis of the products used is not sufficient for a correct decision.

Role of replacement fluids in the immediate complications of plasma exchange. French Registry Cooperative Group.

OBJECTIVE: Comparison of side effects (fever shivering and/or allergic reactions, collapse, symptomatic hypocalcaemia) of the different substitution fluids used during therapeutical plasmapheresis. DESIGN: Multicentric retrospective comparative study designed to explore the side effects due to the replacements fluids (albumin alone or associated with dextran 40, modified fluid gelatin, hydroxyethyl starch), and to determine the best combination in patients undergoing plasmapheresis. PATIENTS: 46,895 procedures were performed on 5,167 patients between 1990 and 1994. The analysis concerns 33,962 sessions, divided into two groups (group 1: 21,079 sessions from 1990 to 1992 comparing albumin alone versus combined albumin-macromolecules and the different combinations among these, group 2: 12,883 sessions in 1993-1994 comparing albumin alone versus albumin-hydroxyethyl starch). Because of the diversity of the products used, 13,029 sessions were not studied because groups of small sample sizes were formed. MEASUREMENTS AND RESULTS: In group 1, the comparison of albumin + macromolecules with albumin alone, shows the best haemodynamic tolerance, lower frequency of fever shivering and/or allergic reactions in the albumin alone subgroup. On the other hand, hypocalcaemia is significantly higher in this subgroup. The combinations albumin + dextran 40 (but after hapten inhibition) and albumin + hydroxyethyl starch are equivalent. Albumin + modified fluid gelatin is the combination presenting the highest incidence in terms of allergic manifestations. In group 2, albumin + hydroxyethyl starch versus albumin alone, the former is preferable in terms of the three side effects studied. CONCLUSION: The results of this study show a combination of albumin 4% hydroxyethyl starch to replace plasma during plasma exchange to be the method presenting the lowest morbidity and the best cost/effectiveness ratio.

The epidemiology of hemorrhage related to cardiothoracic operations.

OBJECTIVE: To define the epidemiology, risk factors, and unadjusted cost of hemorrhages related to cardiothoracic operations. STUDY DESIGN: We conducted two case-control studies to evaluate the risk of hemorrhage following cardiothoracic operations. The definition of hemorrhage required one of the following: reoperation for bleeding, postoperative loss of greater than 800 mL of blood over 4 hours, or surgeon-diagnosed excessive intraoperative bleeding. SETTING: The cardiothoracic surgery service of a university hospital. RESULTS: Of 511 patients undergoing cardiothoracic operations, 93 (18%) met the definition of hemorrhage. In the first case-control study, 3 (14%) of 21 cases and 0 of 42 controls died (odds ratio [OR], 15.0; 95% confidence interval [CI95], 1.18-191.55). Compared with controls, cases received significantly more packed red blood cells intraoperatively (OR, 1.18/100 mL; CI95, 1.01-1.38), and significantly more platelets (OR, 3.26/100 mL; CI95, 1.47-7.26) and fresh frozen plasma (OR, 1.73/100 mL; CI95, 1.05-.84) in the intensive-care unit. Cases were more likely than controls to receive protamine postoperatively (OR, 3.74; CI95, 1.27-11.02). Previous sternotomy, preoperative aspirin or heparin, and preoperative laboratory values did not predict bleeding. The median unadjusted hospital cost was $3,458 higher for patients who suffered hemorrhage than for controls. To decrease costs, hetastarch (acquisition cost $45/500 mL) was substituted for albumin (acquisition cost $76/100 mL) in the pump priming solution (estimated possible cost savings, $7,000-$53,000/year). Because hemorrhage rates increased subsequently, we conducted a second case-control study that identified patient age (P=.02) and use of greater than 5 mL/kg of hetastarch (OR, 1.82) as risk factors for hemorrhage. The cost of treating hemorrhages exceeded all estimates of possible cost savings ($7,000-$53,000 per year). CONCLUSIONS: Our definition of hemorrhage identified patients who required increased volumes of blood products and who had an increased crude mortality rate and a higher unadjusted cost of hospitalization. Patient age and hetastarch use were risk factors for hemorrhage. Efforts to save money by substituting less expensive products inadvertently may increase costs by increasing the probability of perioperative adverse events.