Intravenous Hydroxocobalamin Versus Hextend Versus Control for Class III Hemorrhage Resuscitation in a Prehospital Swine Model.

Background: Hydroxyethyl starch (Hextend) has been used for hemorrhagic shock resuscitation, however, hydroxyethyl starch may be associated with adverse outcomes. Objective: To compare systolic blood pressure (sBP) in animals that had 30% of their blood volume removed and treated with intravenous hydroxocobalamin, hydroxyethyl starch, or no fluid. Methods: Twenty-eight swine (45-55 kg) were anesthetized and instrumented with continuous femoral and pulmonary artery pressure monitoring. Animals were hemorrhaged 20 mL/kg over 20 minutes and then administered 150 mg/kg IV hydroxocobalamin in 180 mL saline, 500 mL hydroxyethyl starch, or no fluid and monitored for 60 minutes. Data were modeled using repeated measures multivariate analysis of variance. Results: There were no significant differences before treatment. At 20 minutes after hemorrhage, there was no significant difference in mean sBP between treated groups, however, control animals displayed significantly lower mean sBP (p < 0.001). Mean arterial pressure and heart rate improved in the treated groups but not in the control group (p < 0.02). Prothrombin time was longer and platelet counts were lower in the Hextend group (p < 0.05). Moreover, thromboelastography analysis showed longer clotting (K) times (p < 0.05) for the hydroxyethyl starch-treated group. Conclusion: Hydroxocobalamin restored blood pressure more effectively than no treatment and as effectively as hydroxyethyl starch but did not adversely affect coagulation.

Should hydroxyethyl starch solutions be totally banned?

The choice of which intravenous solution to prescribe remains a matter of considerable debate in intensive care units around the world. Trends have been moving away from using hydroxyethyl starch solutions following concerns about safety. But are the available data sufficient to clearly assess the risk-benefit balance for all patients, and is there enough evidence of harm to justify removing these drugs completely from our hospitals?

Comparison of cryoprotectants in the preservation of Theileria parva sporozoites using an in vitro infectivity assay.

An in vitro infectivity assay was used to examine five cryoprotectants for their suitability for preserving Theileria parva sporozoites. All five were capable of preserving T. parva sporozoites through freezing, the optimal concentrations being 7.5% for glycerol, 5% for dimethyl sulphoxide (DMSO), poly (vinylpyrrolidone) (PVP) and poly(ethylene glycol) (PEG), and 2.5% for hydroxyethyl starch (HES). When the five cryoprotectants were compared at their optimal concentrations, using a modification of the standard method of stabilate preparation, glycerol was significantly better than the others (p < 0.05). Measurement of the effects of each cryoprotectant on the osmolality of the media revealed that glycerol and DMSO elevated the osmolality significantly (p < 0.05). Resuscitation of glycerol-preserved sporozoites required the presence of glycerol in the diluent to maintain infectivity. Studies on the effects of equilibration time in glycerol on the infectivity of sporozoites showed that those frozen immediately after mixing (2 min) were as infective as those frozen after 60 min of equilibration.

Efficacy and safety of deferoxamine conjugated to hydroxyethyl starch.

The efficacy and safety of deferoxamine conjugated to hydroxyethyl starch (HES-DFO) was evaluated in an in vitro rat cardiac membrane lipid peroxidation (CMLP) assay and in a swine model of regional myocardial ischemia/reperfusion injury in comparison to DFO. The rat CMLP results demonstrate that HES-DFO is at least as potent as DFO (IC50 = 10 and 13 microM, respectively). HES-DFO given intravenously (i.v.) at the equivalence of 25 mg/kg and 100 mg/kg DFO in a swine model of regional myocardial ischemia [20-min left anterior descending coronary artery (LAD) occlusion followed by 60-min reperfusion] showed no significant changes in hemodynamics as compared with DFO at 25 mg/kg i.v. In addition, HES-DFO was at least as potent as DFO with regard to recovery of regional segment shortening function (%SS). Furthermore, both HES-DFO and DFO significantly reduced tissue water content (edema) in the area at risk (AAR). We conclude that conjugation of DFO to HES improves the safety without any interference in the efficacy of DFO.

Hydroxyethyl starch.

HES products should be designated by both their number average of molecular weight (that determines colloidal activity) and molar substitution ratios. In addition to the original HES-70/70 developed in 1960, a rapidly excreted HES-50/50 has been available since 1977. HES-70/70 and human albumin are equivalent in both healthy and hypoalbuminemia subjects in regard to maximal and total effects on plasma volume, intravascular colloidal activity and plasma concentration of ingested colloid. Albumin and HES-70/70 are extravasated at nearly equal rates. Albumin elimination is predominantly monoexponential. HES-70/70 however, is partly metabolized and partly excreted in urine at rates that decrease progressively as the amount remaining in the body decreases. HES-50/50 has maximal effects on plasma volume and colloidal activity similar to those of dextran-40, but it is eliminated twice as rapidly and unlike dextran-40, does not accumulate on repeated ingestion of large doses. HES ingestion increases apparent serum activity of alpha amylase by slowing enzyme elimination. Anaphylactoid reactions have been infrequent and mild, even on repetitive ingestion in recurrent "Phoresis" donors. The effect of HES on coagulation in urine but does not slow urine flow by hyperviscosity. Hydroxyethylation of waxy starches yields safe colloids with the advantage of permitting selective control of drug effects by altering independently molecular size and rate of enzymatic hydrolysis, tailoring drug kinetics to specific uses.

[The effect of 6% hydroxyethyl starch, 45% dextran 60 and 5.5% oxy-poly-gelatine on blood volume and circulation in human volunteers (author's transl)]. / Wirkung von 6% iger Hydroxyäthylstärke, 4, 5% igem Dextran 60 und 5, 5% iger oxypolygelatine auf Blutvolumen und Kreislauf bei Versuchspersonen

Studies in 30 volunteers showed that the volume increasing effect of a 2.5% Oxypolygelatine-solution is rather short (90 to 240 min), whereas the volume effect of a 4.5% Dextran 60 solution remained stable over a period of 240 min hydroxethyl-starch solution 6% caused a distinct increase in blood volume after a period of 90 min and of 240 min in five volunteers, while the blood volume of the other volunteers remained rather constant. The parameters we measured provide no explanation for this effect.