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.

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.

Choice of Fluids in Severe Septic Patients - A Cost-effectiveness Analysis Informed by Recent Clinical Trials.

Fluid resuscitation with colloids is an established second line therapy for septic patients. Evidence of relative efficacy outcomes is tempered by considerations of the relative costs of the individual fluids. An assessment of recent large clinical trials was performed, resulting in a ranking in the efficacy of these therapies. Probabilities for mortality and the need for renal replacement therapy (RRT) were derived and used to inform a decision analysis model comparing the effect of crystalloid, albumin and hydroxyethyl starch solutions in severe septic patients followed from hospital admission to 90 days in intensive care. The US payer perspective was used. Model inputs for costs and efficacy were derived from the peer-reviewed literature, assuming that that all fluid preparations are bio-equivalent within each class of these therapies. Probabilities for mortality and the need for renal replacement therapy (RRT) data were synthesized using a Bayesian meta-analysis. Relative to crystalloid therapy, 0.21 life years were gained with albumin and 0.85 life years were lost with hydroxyethyl starch. One-way sensitivity analysis showed that the model's outcomes were sensitive to the cost of RRT but not to the costs of the actual fluids or any other costs. We conclude that albumin may be the most cost-effective treatment in these patients when the total medical costs and iatrogenic morbidities involved in treating sepsis with fluids are considered. These results should assist and inform decision making in the choice of these drugs.

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.

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.

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.

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.

Replacement fluids in plasmapheresis: cross-over comparative study.

OBJECTIVE: To compare the tolerance and the cost of three replacement fluids in plasmapheresis: albumin 4% alone, albumin 4% + dextran 40, or albumin 4% + hydroxyethylstarch 6%. DESIGN: A one center randomized, cross-over, comparative study designed to explore the tolerance and the colloid oncotic pressure in patients undergoing plasmapheresis. PATIENTS: 225 plasmapheresis procedures were performed in 27 patients. MEASUREMENTS AND RESULTS: Hemodynamic tolerance was good in the three treatment groups. Serum protein concentration after plasmapheresis was significantly lower in the albumin + hydroxyethylstarch group, followed by albumin + dextran 40, versus albumin alone. Colloid oncotic pressure before and after exchange was similar in the three groups. CONCLUSIONS: The clinical use of 25-30% of hydroxyethylstarch 6% or dextran 40 with albumin 4% was clinically well tolerated and associated with a 12% decrease of the cost of substitution solutions.

[Economic impact of a prescription protocol in an intensive care unit]. / Impact économique d'un protocole de prescription en réanimation.

OBJECTIVE: To assess the economic impact of a prescribing protocol for i.v. fluid therapy and artificial nutrition. STUDY DESIGN: Comparative study, before and during use of the protocol. PATIENTS: The study included 555 ICU patients allocated into two groups, before and after starting with the protocol. The groups were comparable for number, pathologies, age, severity score, duration of ICU stay, incidence of nosocomial infections, mortality rate. METHOD: In February 1995, a written literature-based prescribing protocol for fluid therapy (hydroxyethylstarch and albumin), and artificial nutrition (enteral nutrition as first-line therapy) was devised. A cost analysis was made for two 6-month periods: before (August 1994 to January 1995) and after start of protocol (February to July 1995). RESULTS: The prescription of albumin and hydroxyethylstarch decreased (by 33 and 58% respectively), whereas administration of Ringer lactate and gelatine solutes increased simultaneously. This induced a cost saving of 15,000 FF (a 20% decrease in cost). The reduction of parenteral nutrition in favour of early enteral nutrition induced a cost saving of 56,000 FF (31% decrease in cost). CONCLUSION: Our prescribing protocol generated a cost saving of 9% of the pharmaceutical budget and decreased the cost-benefit ratio of our ICU.