Efficacy and safety of 10% HES 130/0.4 versus 10% HES 200/0.5 for plasma volume expansion in cardiac surgery patients.

AIM: Hydroxyethyl starch (HES) solutions are frequently used for perioperative volume replacement. Whereas older HES specimen tended to accumulate in the plasma and to cause negative effects on hemostasis, more recent products, e.g., HES 130/0.4, are characterised by improved pharmacological properties. The present study was designed to compare the efficacy and safety of 10% HES 130/0.4 and 10% HES 200/0.5. METHODS: In this post-hoc analysis of a prospective, randomised, double-blind, multi-center therapeutic equivalence trial, 76 patients undergoing elective on-pump cardiac surgery received perioperative volume replacement using either 10% HES 130/0.4 (N.=37) or 10% HES 200/0.5 (N.=39) up to a maximum dose of 20 mL kg-1. RESULTS: Equivalent volumes of investigational medication were infused until 24 hours after the first administration (1577 vs. 1540 mL; treatment difference 37 [-150; 223] mL; P<0.0001 for equivalence). Whereas standard laboratory tests of coagulation were comparable between groups, von Willebrand factor activity on the first postoperative morning tended to be higher following treatment with 10% HES 130/0.4 as compared to 10% HES 200/0.5 (P=0.025) with this difference being statistically significant only in the per-protocol analysis (P=0.02). Treatment groups were comparable concerning other safety parameters and the incidence of adverse drug reactions. In particular, renal function was well preserved in both groups. CONCLUSION: Ten percent HES 130/0.4 was equally effective and safe as compared to 10% HES 200/0.5 for volume therapy in patients undergoing cardiovascular surgery. Postoperative coagulation and renal function, as measured by standard laboratory tests, were similar among groups.

Effect of 5 alpha-dihydrocorticoids on enzymes of gluconeogenesis in rat liver.

5 alpha-Dihydrocortisol (11 beta, 17, 21-trihydroxy-5 alpha-pregnane-3,20-dione), 5 alpha-dihydrocorticosterone (11 beta, 21-dihydroxy-5 alpha-pregnane-3,20-dione) as well as cortisol (11 beta, 17, 21-trihydroxy-4-pregnene-3,20-dione) and corticosterone (11 beta, 21-dihydroxy-4-pregnene-3,20-dione) were administered for seven days to male rats. Blood glucose increased in cortisol- and corticosterone-treated rats and blood insulin decreased after 5 alpha-dihydrocorticosteroid treatment. In the liver, total protein was elevated after cortisol, corticosterone and 5 alpha-dihydrocorticosterone application. Phosphoenolpyruvate carboxykinase and fructose-1,6-diphosphatase activities in liver were significantly lowered after treatment with 5 alpha-dihydrocortisol and 5 alpha-dihydrocorticosterone.

Pharmacokinetics and Tolerability of a New Hydroxyethyl Starch (HES) Specification [HES (130/0.4)] after Single-Dose Infusion of 6% or 10% Solutions in Healthy Volunteers.

OBJECTIVE: To investigate the pharmacokinetic profile and tolerability of a single-dose infusion of the new hydroxyethyl starch (HES) specification, HES (130/0.4), 6% and 10% solutions in healthy volunteers. STUDY DESIGN: In an open, randomised, single-dose, parallel-group study, 12 healthy volunteers (in each group) received intravenous infusions of 500ml of a new HES specification [HES (130/0.4)] of either 6% or 10% solution within 30 minutes. RESULTS: Plasma elimination initially occurred with an alpha half-life of approximately 0.5 to 0.75 hour. A half-life of approximately 12 hours was reported for the terminal phase. Between 60 to 70% of the total plasma elimination was due to renal excretion. The total plasma clearances of 31.4 ml/min and 26.0 ml/min for the 6 and 10% solutions, respectively, were higher than those reported for other HES specifications. The volume of distribution in the central compartment was approximately 5.9L, which roughly corresponded to the blood volume. Single doses of 6% and 10% HES (130/0.4) were well tolerated. CONCLUSION: The new HES specification demonstrated favourable pharmacokinetic properties compared with other HES specifications of medium or high molecular weight. No clinically relevant plasma accumulation and related undesired effects on haemostasis are expected to occur under multiple-dose conditions.

Plasma substitution effects of a new hydroxyethyl starch HES 130/0.4 compared with HES 200/0.5 during and after extended acute normovolaemic haemodilution.

BACKGROUND: The volume expansion effect of a recently introduced hydroxyethyl starch, HES 130/0.4, was compared with the commonly used HES 200/0.5 after rapid infusion of a single large dose (up to 2 litres) administered during acute normovolaemic haemodilution (ANH). METHODS: This prospective, randomized, double-blind study included 40 patients scheduled for major abdominal surgery with no contraindication to ANH. Patients were randomized to undergo ANH with either HES 130/0.4 (n=20) or HES 200/0.5 (n=20). Blood was collected to reach a target haemoglobin level of about 8.0 g dl(-1) and simultaneously replaced by the same volume of colloid (HES 130: 1825 [SD 245] ml; HES 200: 1925 [183] ml). Heart rate, mean arterial pressure, cardiac filling pressure, and cardiac output were measured before induction of anaesthesia (baseline), 10 min after completion of ANH, before surgery, at the end of surgery and on the following morning (postoperative day 1; POD1). ANH blood was systematically retransfused during surgery or before POD1. RESULTS: Exchange of about 40% of blood volume resulted in similar haemodynamic changes in both groups. Filling pressures increased significantly, while cardiac index remained unchanged (HES 130: from 3.3 [0.4] to 3.2 [0.7] litre min(-1) m(-2); HES 200: from 3.0 [0.6] to 3.1 [0.7] litre min(-1) m(-2)). Need for crystalloids and colloids was similar between the groups during surgery and on POD1. Total blood loss (HES 130: median 2165 ml, range 660-2970 ml; HES 200: median 2464 ml, range 640-19 380 ml) and amount of allogeneic red blood cells transfused (HES 130: median 0, range 0-4 units; HES 200: median 0, range 0-18 units) were comparable in the two groups. CONCLUSIONS: This study demonstrates a good immediate and medium-term plasma volume substitution effect of HES 130 compared with HES 200. HES 130 could represent a suitable synthetic colloid for plasma volume substitution during extensive ANH.

A novel hydroxyethyl starch (Voluven) for effective perioperative plasma volume substitution in cardiac surgery.

PURPOSE: To compare the new hydroxyethyl starch HES 130/0.4 (Voluven) and the standard HES 200/0.5 (pentastarch) regarding effectiveness for plasma volume substitution and safety of large volumes in heart surgery. METHODS: Fifty-nine patients scheduled for coronary artery bypass grafting were enrolled in a prospective, randomised, double-blind, parallel-group, multicentre, clinical, phase III study. Hydroxyethyl starch was used as the exclusive artificial colloid for acute normovolemic hemodilution, priming of the heart lung machine, and for intra- and postoperative plasma volume substitution from induction of anesthesia until 16 hr after the end of surgery. Efficacy was evaluated by comparing the amount of colloid infused, hemodynamics, and colloid osmotic pressure (COP). Safety endpoints were blood loss, the use of allogeneic blood products, coagulation variables, and adverse events. RESULTS: Effectiveness, as assessed by the total amount of infused HES volumes within the treatment period, was similar between HES 130/0.4 and HES 200/0.5 (2,550 mL +/- 561 mL vs 2,466 mL +/- 516 mL). Also, no differences were found for the use of other colloids (pasteurised plasma), hemodynamics, and COP In HES 130/0.4 patients, the postoperative increase of von-Willebrand factor (vWF) was higher (P < 0.01), blood loss was lower, and less packed red blood cells were transfused. CONCLUSION: Hydroxyethyl starch 130/0.4 is an effective plasma volume expander in heart surgery and may be used as the sole artificial colloid to cover the perioperative period. We found a reduced influence of HES 130/0.4 on the physiologic postoperative increase of vWF.