Effects of different plasma expanders on rats subjected to severe acute normovolemic hemodilution.

BACKGROUND: Plasma expanders are widely used for acute normovolemic hemodilution (ANH). However, existing studies have not focused on large-volume infusion with colloidal plasma expanders, and there is a lack of studies that compare the effects of different plasma expanders. METHODS: The viscosity, hydrodynamic radius (Rh) and colloid osmotic pressure (COP) of plasma expanders were determined by a cone-plate viscometer, Zetasizer and cut-off membrane, respectively. Sixty male rats were randomized into five groups with Gelofusine (Gel), Hydroxyethyl Starch 200/0.5 (HES200), Hydroxyethyl Starch 130/0.4 (HES130), Hydroxyethyl Starch 40 (HES40), and Dextran40 (Dex40), with 12 rats used in each group to build the ANH model. ANH was performed by the withdrawal of blood and simultaneous infusion of plasma expanders. Acid-base, lactate, blood gas and physiological parameters were detected. RESULTS: Gel had a lower intrinsic viscosity than HES200 and HES130 (P < 0.01), but at a low shear rate in a mixture of colloids, red cells and plasma, Gel had a higher viscosity (P < 0.05 or P < 0.01, respectively). For hydroxyethyl starch plasma expanders, the COP at a certain concentration decreases from 11.1 mmHg to 6.1 mmHg with the increase of Rh from 10.7 nm to 20.2 nm. A severe ANH model, with the hematocrit of 40% of the baseline level, was established and accompanied by disturbances in acid-base, lactate and blood gas parameters. At the end of ANH and 60 min afterward, the Dex40 group showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) decreased significantly in all groups at the end of ANH. The DBP and MAP in the Dex40 group further decreased 60 min after the end of ANH. During the process of ANH, the Dex40 group showed a drop and recovery in SBP, DBP and MAP. The DBP and MAP in the HES200 group were significantly higher than those in the other groups at some time points (P < 0.05 or P < 0.01). CONCLUSION: Gel had a low intrinsic viscosity but may increase the whole blood viscosity at low shear rates. Rh and COP showed a strong correlation among hydroxyethyl starch plasma expanders. Dex40 showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other plasma expanders. During the process of ANH, Dex40 displayed a V-shaped recovery pattern for blood pressure, and HES200 had the advantage in sustaining the DBP and MAP at some time points.

Capillary refill time variation induced by passive leg raising predicts capillary refill time response to volume expansion.

BACKGROUND: A peripheral perfusion-targeted resuscitation during early septic shock has shown encouraging results. Capillary refill time, which has a prognostic value, was used. Adding accuracy and predictability on capillary refill time (CRT) measurement, if feasible, would benefit to peripheral perfusion-targeted resuscitation. We assessed whether a reduction of capillary refill time during passive leg raising (ΔCRT-PLR) predicted volume-induced peripheral perfusion improvement defined as a significant decrease of capillary refill time following volume expansion. METHODS: Thirty-four patients with acute circulatory failure were selected. Haemodynamic variables, metabolic variables (PCO2gap), and four capillary refill time measurements were recorded before and during a passive leg raising test and after a 500-mL volume expansion over 20 min. Receiver operating characteristic curves were built, and areas under the curves were calculated (ROCAUC). Confidence intervals (CI) were performed using a bootstrap analysis. We recorded mortality at day 90. RESULTS: The least significant change in the capillary refill time was 25% [95% CI, 18-30]. We defined CRT responders as patients showing a reduction of at least 25% of capillary refill time after volume expansion. A decrease of 27% in ΔCRT-PLR predicted peripheral perfusion improvement with a sensitivity of 87% [95% CI, 73-100] and a specificity of 100% [95% CI, 74-100]. The ROCAUC of ΔCRT-PLR was 0.94 [95% CI, 0.87-1.0]. The ROCAUC of baseline capillary refill time was 0.73 [95% CI, 0.54-0.90] and of baseline PCO2gap was 0.79 [0.61-0.93]. Capillary refill time was significantly longer in non-survivors than in survivors at day 90. CONCLUSION: ΔCRT-PLR predicted peripheral perfusion response following volume expansion. This simple low-cost and non-invasive diagnostic method could be used in peripheral perfusion-targeted resuscitation protocols. TRIAL REGISTRATION: CPP Lyon Sud-Est II ANSM: 2014-A01034-43 Clinicaltrial.gov, NCT02248025 , registered 13th of September 2014.

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?

[Problems of development, production and clinical use of highly effective blood substitutes]. / Problemy razrabotki, proizvodstva i klinicheskogo primeneniia vysokoéffektivnykh krovezamenitelei.

An analysis of biological properties of blood substitutes has shown the expedience of wider clinical use instead of polyglucin of such substitutes as polyglucol, polifer, rondex, neorondex, polyoxidin, volecam; instead of rheopolyglucin--the rheopolyglucin with glucose, rheogluman and rheoglusol prepared for clinical tests; instead of haemodesin--haemodesin-H, neohaemodesin, gluconeodesin; instead of protein hydrolysates--polyamine and purified from peptides infusamine, hydromine, amicin; instead of 0.9% solution of sodium chloride--disol, quintasol, lactasol, mafusol. They have polyfunctional properties and considerably increase the effectiveness of the infusion--transfusion therapy.

Quality control of hemoglobin solutions. I. The purity of hemoglobin before modification.

It is not yet clear whether the toxicity of hemoglobin solutions is due to hemoglobin per se, contaminants, or both. To elucidate the problem, it is first necessary to prepare "pure hemoglobin," i.e., hemoglobin completely free of (a) bacterial endotoxins, (b) phospholipids of the red cell membrane, and (c) other proteins and/or peptides. The methods found most sensitive in the determination of such purity are here presented. Consensus on the adoption of these methods and on the meaning of the term "purity" would help to achieve (a) a better understanding of the toxicity problem, (b) a more meaningful exchange of information among investigators and (c) the ultimate development of nontoxic solutions.

[The content of calcium and magnesium in official Soviet solutions used in extracorporeal circulation, anesthesia and resuscitation]. / Soderzhanie kal'tsiia i magniia v ofitsinal'nykh otechestvennykh rastvorakh, primeniaemykh pri iskusstvennom krovoobrashchenii, anestezii i reanimatsii.

Total calcium (CaT) and total magnesium (MgT) levels have been determined in 21 solutions used in cardiopulmonary bypass surgery and manufactured in the USSR. It has been found that a great number of solutions differ in CaT content from human plasma. Some solutions contain Ca, which is not required by the prescription. Even in one and the same lot solutions vary greatly in Ca content (gelatinol). A large number of the solutions tested does not correspond to blood in MgT content, either. Like Ca, this parameter is quite unstable. Such differences in CaT and MgT levels practically in all standard Soviet-made solutions make it impossible to determine accurately precise amount of the solution required. The optimal way of hypercalcemia and hypermagnesiuemia prevention is the elaboration of the solutions identical to blood in their Ca and Mg content, or the use of colloids, practically free of electrolytes (hexaethyl starch).

Virus safe plasma exchange medium containing essential human plasma proteins.

CFFP (Coagulation Factor Free Plasma from Biotest) is manufactured under standardized conditions from pooled human plasma of more than 1000 donors per lot. It is sterilized by beta-PL/UV and has not the risks of FFP to transmit viral diseases. CFFP offers desirable advantages as a plasma exchange solution over albumin and FFP as it avoids serious depletions or deviation of normal plasma constituents.

Blood substitutes: where are we?

Plasma volume expanders exist and are available. Balance salt solutions are preferred for initial resuscitation. Albumin should be avoided. Synthetic coagulation factors are not available. They exist because proper component therapy creates them to be stored for selective use. A substitute for the prime function of blood--oxygen delivery by the red cell--does not yet exist. Its clear that one is needed; the form is not yet identified. Fluorocarbon emulsions have a certain chemical cleanliness that makes them appealing, yet there are many unanswered questions, especially as to oxygen-carrying capacity and toxicity. Fluorocarbons have been pushed to clinical testing before their time. Chemically modified stroma-free hemoglobin continues to evolve and develop as a useful blood substitute. Most of the early problems seem to have been resolved and a third generation of molecules, the second set of modifications, is promising.

[Comparison of effects of hydroxyethylstarch (HES 200/0.5) administered pre- and postoperatively in vascular surgery with dextran 40 (60) (author's transl)]. / Vergleich der Wirkung von prä- und intraoperativ verabreichter mittelmolekularer Hydroxyäthylstärke (HAS 200/0,5) bzw. von Dextran 40 (6) bei gefässchirurgischen Eingriffen.

In a randomised study comprising 16 patients undergoing vascular surgery of the lower extremities blood replacement was performed after preinfusion of either 500 ml 10% hydroxyethylstarch (LMW-HES) or 10% dextran 40 (followed by dextran 60 intraoperatively). After infusion of 500 ml within 30 min preoperatively there was a significant rise in PCWP, PAP, RAP and CI accompanied by an increase in blood volume and colloid osmotic pressure, whereas hematocrit fell. No difference between the two plasmasubstitutres was found, prolonged infusion of HES, however, caused a lesser rise in cardiac pressures and blood volume. Overloading of the circulation could be ruled out by ECG, Frank-Starling curves, blood gases, observation of total pulmonary vascular resistance and vascular filtration pressure. The modified haemodilution technique suggested, using preoperative priming without blood drainage and subsequent dilution by blood replacement up to a total amount of 1,500 ml by HES or dextran thus seems to be free of risks and may be recommended. For monitoring purposes during prolonged operations not only filling pressures should serve as a guideline, determination of blood volume and fluid balance being imperative.

Prekallikrein activator levels and side effects with human albumin preparations.

Recently the question has been raised whether the presence of prekallikrein activator (PKA) in human blood products for i.v. application could possibly cause adverse reactions in the recipient as observed now and then. Up to now a correlation between both properties is far from being established, even though in the U.S. there has been extensive discussion over some PPL batches containing elevated amounts of PKA, presumed to be causally related to an increased frequency of side reactions. As has been demonstrated in the past through wide clinical experience, human albumin is an exceptionally safe blood product. If at all, side effects sometimes seem to occur related to certain individual lots, the reason for which is still unrevealed. In the pursuit of eventually finding some association between PKA levels in and side reactions with albumin, we performed PKA measurements on a panel of commercial human albumin batches, a few of which had been reported occasionally to cause adverse reactions. The assay procedure was essentially that published (3). BOB PKA reference No 1 was included as a standard. PKA was detected in moderate amounts in huge series of albumin batches without any reported side reactions. We conclude, therefore, that PKA levels in the range of trace amounts cannot be related to side reactions with human albumin preparations.