BACKGROUNDHypertonic hyperoncotic solutions (HHS), composed of 7.2 to 7.5% sodium chloride and 6 to 10% dextran or hydroxyethyl starch, are able to restore the disturbed macro- and microcirculation in hypovolemic states within a short period of time. Even small amounts of HHS induce a relevant fluid shift from the extravasal into the intravasal space, and the use of HHS has thus been recommended in acute hypovolemia and hypovolemic shock (principle of "small-volume resuscitation"). Recently, attention has also focused on the treatment of elevated intracranial pressure using HHS. Austria is the only European country where market authorization of HHS was already obtained several years ago and where HHS have been widely used in clinical routine for a comparatively long time. This offers the unique possibility of evaluating, for the first time, the safety profile of HHS solutions. In this study, we analyzed the reported adverse drug reactions of HHS in a large number of applications.METHODSMarketing and pharmacovigilance data as well as other relevant information obtained in Austria during the years 1991 to 2000, were used for analysis of safety aspects of HHS applications in routine clinical practice.RESULTSFrom 1991 to 2000, four adverse drug reactions related to HHS were reported, none of which was fatal. Out of these, 3 have to be regarded as anaphylactoid/anaphylactic reactions to hydroxyethyl starch. In one case an extreme overdose was infused resulting in a hyperosmolar syndrome. In the same time period approximately 56,000 HHS units were used in Austria in about 18,500 to 37,000 patients. With these numbers, the frequency of adverse drug reactions related to the prescribed application of HHS can be calculated: approximately 5 adverse drug reactions per 100,000 HHS units used; approximately 8-16 adverse drug reactions per 100,000 HHS-treated patients.CONCLUSIONAustrian experience with the use of a large number of HHS in clinical routine during nearly a decade indicates that the prescribed application of a combination of hydroxyethyl starch and hypertonic sodium chloride has a low potential for complications.

Objective: If or at which conditions hydroxyethyl starch (HES) is administerable in presence of reduced renal function, is a question still to be answered. The aim of this study was to give hints, whether a moderately reduced renal function (creatinine concentrations around 2,0 mg/dl) induces clinically relevant changes in pharmacokinetics of HES 200/0.5. Methods: Each of 8 test persons with elevated serum creatinine concentration (1.6-2.9 mg/dl - group H) and 6 test persons with normal serum creatinine concentration (0.7 - 1.1 mg/dl - group N) were infused with 500 ml of 10% HES 200/0.5 within 30 minutes. Concentrations of creatinine and HES were measured before starting the infusion, immediately after the end of the infusion as well as 30 minutes, 60 minutes, 3 hours, 6 hours and 24 hours I ater. Additionally in group H also the mean values of the intravital molecular mass of HES (weight average molecular weight Mw and number average molecular weight Mn) were assessed. HES concentrations were quantified by the hexokinase method. HES molecular mass spectrum was analyzed by an HPLC method. The mean dwelling time served as an indicator for HES pharmacokinetics. Results: The serum creatinine concentrations remained stable within the observation period. The HES serum concentrations were comparable between the two groups at any examination. Immediately after the end of the infusion, the HES serum concentration reached a maximum of 17.5 mg/ml (group H) and 17.4 mg/ml (group N), 24 hours later HES serum concentration ranged between 1.4 and 2.0 mg/ml (group H) respectively between 1.1 and 2.8 mg/ml (group N). The calculation for the mean dwelling time resulted in 5.0 hours for group H and 4.5 hours for group N (median values) without significant difference between the groups (p = 0.147). At the end of the observation period, the mean values of the molecular weight Mw and Mn measured in group H - reached the closest convergence (Mw: 71,000 Dalton; Mn: 58,000 Dalton; Mw/Mn: 1.32 - median values). Conclusion: Compensated renal failure with serum creatinine concentrations up to 2.9 mg/dl does not significantly delay the serum elimination of HES 200/0.5. All findings support the opinion that a peri-operative volume substitution with HES 200/0.5 can be applied in patients suffering from moderately reduced renal function in the same way as in patients without any renal impairment.

Objective: Hydroxyethyl starch (HES) is mainly eliminated via the kidneys. Any information about extrarenal elimination obtained so far has been either incomplete or contradictory. The objective of this study was to quantify the intestinal excretion of infused HES with a mean molecular weight of 200,000 and a molar substitution of 0.5 (HES 200/0.5) and to compare the reappearance/recovery rate in urine and plasma.Design: Prospective clinical study without control group.Setting: The study was conducted at the Institute of Hypertension of the Society of Clinical Pharmacology, Vienna, Austria, which is an establishment for research in volunteers.Participants: The results of six out of seven healthy male volunteers were appropriate for analysis. One trial subject had to be excluded from the study because of severe protocol violation (mixing of stool and urine samples).Interventions and methods: Each volunteer was administered 500 ml of 10 % HES 200/0.5 in a 0.9 % NaCl solution intravenously within 1 h. A gut lavage with 6 l of a polysaccharide free solution was continuously administered from 3 h prior to until 2 h after the HES infusion to facilitate the collection of the samples and to exclude any source of error at analysis. HES was quantified with the hexokinase method.Measurements and results: Right from the beginning of the infusion until 10 h after its completion, the cumulative HES excretion with feces (principle parameter) and urine as well as selective plasma volume and HES plasma level were measured. Six and 14 h after the infusion had been completed, the recovery rates of HES in urine were about 30 % and 40 %, respectively, and in plasma about 23 % and 8 %, respectively. By contrast, not more than a kind of “background noise amount” of HES (about 0.2 %) could be recovered in feces ( mean value in % of the infused amount of the substance). Six and 14 h after the infusion had been completed, the total recovery rates of HES were 53 % and 49 %, respectively.Conclusion: In a physiologically unimpaired gut HES 200/0.5 is not, or only to an infinitesimal extent, eliminated via the intestine. The question if there is any alternative path to renal excretion for HES still remains to be answered. As the calculated reappearance/recovery rate of HES is only about 50 % of the administered dose, further investigations as to the final fate of HES appear necessary.

Hypertonic-hyperoncotic solutions are a supplementary possibility in the acute treatment of hypovolemia. The main mechanism of action of this solution is, induced by the tonicity of the infusion (approximately 2400 mOsm/l), the transcapillary fluid shift from the intracellular and interstitial to the intravascular compartment. Additionally the fluidity of blood is improved (due to an increase in the diameter of the capillaries), the adherence of leucocytes to the endothelial wall is reduced, and the arteriolar vasomotion is restarted. Due to the available prehospital and clinical results it can be concluded, that hypertonic-hyperoncotic solutions offer advantages compared to conventional fluid therapy regimes: rapid stabilization of hemodynamics, reduction of posttraumatic volume deficiency, of posttraumatic edema and of posttraumatic complications and an improvement of the outcome of the patients. If the therapeutic recommendations are followed, such as a dose of 4 ml/kg body weight, infusion time of about 3-5 minutes and after the end of the infusion application of colloids or crystalloids in an amount as needed, no side effects will occur. Only immediately after the end of infusion sodium, chloride and osmolarity will slightly increase, however these parameters will normalize within the first posttraumatic day. Hypertonic-hyperoncotic solutions are trigger-solutions, as with the infusion of these types of solution it is possible to restore hemodynamics adequately and to prevent shock-induced complications.

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Die Erste Hilfe, Notfall- und Katastrophenmedizin ist ein relativ junges interdisziplinäres Fachgebiet. Es ist nur Teilgebiet verschiedener Fächer und war bislang getrennt in Notfallmedizin (= Notarztwesen) und Erste Hilfe (= Laienhilfe, Sanitäter). Nachdem aber eine gute notfallmedizinische Versorgung ohne Erste-Hilfe-Basismaßnahmen nicht zielführend ist, versucht die Universitätsklinik für Anästhesiologie, den Medizinstudenten der Karl-Franzens-Universität Graz eine umfangreiche Ausbildung in der Primärversorgung von Notfallpatienten anzubieten. Je nach Wissensstand und Studienfortschritt der Kollegen werden Vorlesungen und Praktika über alle Gebiete der Ersten Hilfe, Notfall- und Katastrophenmedizin angeboten. Die Akzeptanz ist trotz dieser kurzen Laufzeit von drei Jahren schon sehr gut und wir erwarten uns eine Zunahme der Hörerzahl in den nächsten Jahren.

Objective To study Hemoglobin glutamer-200 bovine (Hb-200), 6% hetastarch (HES) and shed whole blood (WB) resuscitation in canine hemorrhagic shock.Study design Prospective laboratory investigation.Animals Twelve adult dogs [29 ± 1 kg (mean ± SD)].Methods Anesthetized dogs were instrumented for recording systemic and mesenteric hemodynamic parameters and withdrawal of arterial, mixed and mesenteric venous blood, in which hematological, oxygenation, blood gas and acid–bases variables were determined. Recordings were made before [baseline (BL)], after 1 hour of hypovolemia and immediately and 3 hours post-resuscitation with 30 mL kg−1 of either Hb-200, HES, or WB.Results Blood withdrawal (average 34 ± 2 mL kg−1) caused significant hemodynamic changes, metabolic acidosis and hyperlactatemia characteristic for hemorrhagic shock. Only WB transfusion restored all variables. Hemoglobin glutamer-200 bovine infusion returned most hemodynamic parameters including cardiac output and mesenteric arterial blood flow to BL but increased mean arterial pressure above BL (p < 0.05). However, Hb-200 failed to restore total Hb and arterial oxygen content (CaO2), leaving systemic (DO2I) and mesenteric O2 delivery (DO2Im) below BL (p < 0.05). Nevertheless, acid–base variables recovered completely after Hb-200 resuscitation, and met-hemoglobin (Met-Hb) levels increased (p < 0.05). Hetastarch resuscitation returned hemodynamic variables to or above BL but further decreased total Hb and CaO2, preventing recovery of sDO2I and mDO2I (p < 0.05). Thus, systemic and mesenteric O2 extraction stayed above BL (p < 0.05) while acid–base variables recovered to BL, although slower than in Hb-200 and WB groups (p < 0.05).Conclusions and clinical relevance Resuscitation with Hb-200 seemed to resolve metabolic acidosis and lactatemia more rapidly than HES, but not WB; yet it is not superior to HES in improving DO2I and DO2Im. The hyperoncotic property of solutions like Hb-200 that results in rapid volume expansion with more homogenous microvascular perfusion and the ability to facilitate diffusive O2 transfer accelerating metabolic recovery may be the key mechanisms underlying their beneficial effects as resuscitants.

In Austria emergency and disaster medicine is a young interdisciplinary subject. It is only a borderline discipline encompassing different medical subjects and was subdivided into emergency medicine for medical doctors only and first-aid for lay people and emergency technicians. In fact, since emergency medicine without first-aid can't be successful, the Department of Anaesthesiology at the University of Graz let all students of the medical faculty have a comprehensive education in the treatment of injured of acutely ill patients. According to the three steps of the study lectures and practices, all parts of first-aid, emergency and disaster medicine were offered. In spite of the short time since this has been running, we found a good acceptance and we hope to increase the interest evinced by medical students in our training programme.

Hypertonic-hyperoncotic solutions are a supplementation to conventional fluid regimens in the management of hypovolemia due to trauma, hemorrhage and shock. In this review the possible modes of action of these solutions are discussed and their efficacy both in experimental and clinical settings is presented. Possible side effects, such as hypernatremia and possible problems in the presence of increased intracranial pressure, following administration of hypertonic-hyperoncotic solutions are discussed, as well as the reaction of normovolemic patients to such infusions.

Hydroxyethylstarch (HES) is today one of the most frequently used artificial plasma substitutes in prehospital, as well as in clinical settings. However, there are no studies comparing the volume effect of different HES solutions. The goals of the present study therefore were to compare the volume effect of three HES solutions, which are similar with regard to mean molecular weight but different in concentration and degree of substitution. The obtained results enable guidelines for fluid resuscitation in hypovolemia to be laid down. In 30 patients fulfilling the ASA physical status classification I and II 500 ml of either 10% HES 200/0.5, 6% HES 200/0.5 or 6% HES 200/0.6-0.66 were infused within 30 min. The effect of each solution was evaluated using the mechanical oscillator technique (MOT). This technique measures precisely density changes of blood and plasma and allows-using standard formulae-calculation of blood and plasma volume changes. All 3 HES solutions showed similar effects in increasing plasma volume. Immediately after the end of infusion plasma volume was increased by about 800 ml with 10% HES and by about 650 ml with 6% HES 200/0.5. The volume expanding effect of 6% HES 200/0.6-0.66 amounted to 700 ml. The volume expanding effect of all starches decreased only slightly during the following two hours; an interesting detail observed was a second volume effect of HES (about 20% of the volume infused). We conclude that for the correlation of fluid deficits due to trauma, hemorrhage and shock HES solutions seem to be most effective artificial plasma substitutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertonic-hyperoncotic solutions are a supplementation to conventional fluid regimens in the management of hypovolemia due to trauma, hemorrhage and shock. In this review the possible modes of action of these solutions are discussed and their efficacy both in experimental and clinical settings is presented. Possible side effects, such as hypernatremia and possible problems in the presence of increased intracranial pressure, following administration of hypertonic-hyperoncotic solutions are discussed, as well as the reaction of normovolemic patients to such infusions.

Goals of the present study were to compare the volume effect of different artificial plasma substitutes. Due to the obtained results guidelines for fluid resuscitation in hypovolemia will be given.In 70 patients according to ASA physical status classification I and II 500 ml of different synthetic colloids (gelatine, dextrans, hydroxyethylstarches) were applicated within 30 minutes. As control group lacteted Ringer's solution was given. The effect of each solution was evaluated using the mechanical oszillator technique (MOT). This technique measures precisely density changes of blood and plasma and allows - using standard formulas - to calculate blood and plasma volume changes.10% Dextran 40 has the largest volume expanding effect. Immediately after the end of infusion plasma volume increase was 1100 ml. This expansion decreased only slightly during the following 2 hours and was about 900 ml 2 hours after the end of dextran application. The increase in plasma volume due to 6% dextran 60 was about 600 ml; this changes in intravascular volume remained unchanged too. Gelatine increased plasma volume by about 550 ml; however this effect lasted only for a short period (30 min); two hours after the end of infusion the increase in plasma volume was about 50 ml. All used hydroxyethylstarches (10% HES 200/0.5, 6% HES 200/0.5, 6% HES 200/0.6-0.66) showed similar effects in increasing plasma volume. The value after the end of infusion was about 800 ml and decreased only slightly during the following 2 hours; an interesting detail observed was a second volume effect of hydroxyethylstarch (about 20% of the volume infused). Crystalloids increased plasma volume about 380 ml immediately after the end of infusion; two hours later about 100 ml remained within the intravascular space.We conclude that to correct fluid deficits due to trauma, hemorrhage and shock hydroxyethylstarches seem to be the most effective artificial plasma substitutes. Due to studies concerning with the pattern of substitution we recommed 10% HES 200/0.5 as substitute of the first choice in hypovolemia.

Synthetic colloids especially dextrans given in amounts greater than 1.5 g/kg BW/day tend to interact with coagulation. 6% hydroxyethylstarch 200/0.6-0.66 is a new artificial colloid which offers a lot of advantages in contrast to dextrans and/or gelatine; these advantages are due to a large volume expanding effect. However it has not been clarified whether this new colloid has any influence on hemostasis. The present study deals with the effect of 6% HES 200/0.6-0.55 on coagulation parameters. 12 patients undergoing minor surgical interventions were given 500 ml of HES immediately before starting anaesthesia and on the 1.-3. postoperative day. All evaluated coagulation parameters (partial thrombin time, thrombin time, fibrinogen, antithrombine III, factor VIII-activity, thrombocytes and platelet aggregation) were within the normal range throughout the evaluated period. We conclude theat 6% HES 200/0.6-0.66 has no influence on coagulation except the dilutional one and can be recommended for patients in surgical settings as an excellent and safe artificial colloid.

Ziel der vorliegenden Untersuchung war die Beurteilung der Plasmavolumenveränderungen nach Applikation von 500 ml 6% HES 200/0.6-0.66 innerhalb von 30 min an 12 Patienten der ASA-Klassifikationen I und II. In einer Kontrollgruppe an ebenfalls 12 Personen wurden 500 ml Ringerlaktat innerhalb desselben Zeitraumes verabreicht. Eine weitere Fragestellung dieser Untersuchung war die mögliche Be-einflussung des hämostaseologischen Potentials bei Mehrfachapplikation von 6% Hydroxyäthylstärke während des folgenden postoperativen Zeitraums (1.-3. post-operativer Tag). 6% HES 200/0.6-0.66 führte zu einer Volumenaugmentation, gemessen mit der Biegeschwingermethode, von zusätzlich 200 ml (40% der infundierten Menge) unmittelbar nach Ende der Volumenzufuhr sowie zu einem weiteren Flüssigkeitseinstrom von 100 ml (20% der Infusionsmenge) innerhalb der folgenden Stunde. Die Beeinflussung des Gerinnungspotentials ging mit Ausnahme der Faktor-VIII-Konzentration nicht über den dilutionsbedingten Effekt hinaus. Die Faktor-VIII-Aktivität sank bis auf 50% des Ausgangswertes ab, zeigte jedoch in der weiteren Folge eine Tendenz zur Normalisierung. 6% HES 200/0.6-0.66 zeigt eine effektive Volumenexpansion von bis zu 60% der infundierten Menge und übt auf die Gerinnung keine nachteiligen Wirkungen aus.

The main goal of the recent study was to evaluate changes in plasma volume due the application of 6% HES 200/0/6-0.66. 12 patients according to the ASA physical status classification (I,II) undergoing minor surgical interventions received 500 ml of this artificial plasma substitute within 30 min. In a control group (n = 12), 500 ml of lactated Ringer's solution was given within the same period. A further question of the present investigation was the possible influence of 6% HES on coagulation during the following period (1st - 3rd postoperative days). 6% HES 200/0/6-0.66 led to an additional augmentation of plasma volume measured via the mechanical oscillator technique of 200 ml (40% of the volume given) immediately at the end of infusion. A second increase in plasma volume of 100 ml(20% of the volume infused) could be observed 1 h later. With exception of the activity of factor VIII, the coagulation parameters had not been altered by infusion of 6% HES. The activity of factor VIII decreased to about 50% of the control level but showed a tendency to normalization within the following observation period. 6% HES 200/0.6-0.66 has a marked volume-expanding effect and exerts no influence on coagulation except a temporary decrease of factor VIII activity.

The main goal of the recent study was to evaluate changes in plasma volume due to the application of 6% HES 200/0.6-0.66. 12 patients according to the ASA physical status classification (I, II) undergoing minor surgical interventions received 500 ml of this artificial plasma substitute within 30 min. In a control group (n = 12), 500 ml of lactated Ringer's solution was given within the same period. A further question of the present investigation was the possible influence of 6% HES on coagulation during the following period (1st-3rd postoperative days). 6% HES 200/0.6-0.66 led to an additional augmentation of plasma volume measured via the mechanical oscillator technique of 200 ml (40% of the volume given) immediately at the end of infusion. A second increase in plasma volume of 100 ml (20% of the volume infused) could be observed 1 h later. With exception of the activity of factor VIII, the coagulation parameters had not been altered by infusion of 6% HES. The activity of factor VIII decreased to about 50% of the control level but showed a tendency to normalization within the following observation period. 6% HES 200/0.6-0.66 has a marked volume-expanding effect and exerts no influence on coagulation except a temporary decrease of factor VIII activity.

Based on the controversy >>crystalloids vs. colloids<< in fluid resuscitation of hypovolemia the pathophysiological background of shock is discussed. Due to listing the goals of shock therapy pharmacodynamic and pharmacocinetic properties of all available, but of newer preparations of blood substitutes too, are defined. Finally special points for a rationale basis of fluid therapy in hypovolemia are explored. Recommendations for administering colloids and crystalloids in hypovolemic shock are: synthetic colloids should be given in therapy of hypovolemia, in disorders of blood fluidity and in situations when oxygen transport capacity of blood has to be improved. Crystalloids should be administered if intracellular and/or interstitial volume deficits have to be replaced.