Hydroxyethyl starch: trade name, composition of the drug, purpose and instructions for use

The use of hydroxyethyl starch solution in medicine has proven its effectiveness. For more than twenty years, the solution has been actively used to treat patients whose condition is accompanied by a decrease in circulating blood volume. A solution for infusion of hydroxyethyl starch 6% is also effective if the ratio of blood plasma and red blood cells, platelets, and leukocytes is disturbed for one reason or another. In some cases, a timely drip with the drug can save the patient’s life. Sometimes the drug is not administered by drip, but intravenously - it all depends on the conditions in which the patient is located and the clinical picture of his health.

Composition and release form

The drug is available in the form of a solution for infusion. The volume of each bottle is 250 ml or 500 ml. 1 liter of solution contains 60 g of hydroxyethyl starch. The trade names of the drug are different - there are many solutions that contain this particular component.

The composition is administered intravenously, by jet or drip. Hemodynamic impairment may be greater or lesser - accordingly, the dosage in each individual case will be different. As a rule, the duration of therapy and the required dosage are established based on the hematocrit value.

Pharmacological action of the drug

Hydroxyethyl starch infusion solution is a liquid based on specially processed starch. This is a high molecular weight compound that consists almost entirely of glucose residues obtained by polymerization.

The most important properties that affect the effectiveness of the drug and the duration of treatment are the average molecular weight and the degree of substitution of hydroxyethyl starch. Analogues of the drug have exactly the same structural formula. There are about 20 analogues on the pharmacological market, but only a few of them are widely used in medicine. The therapeutic effect is achieved due to the high similarity of the structural formula of hydroxyethyl starch with glycogen. This allows you to use the substance to improve the composition of the blood and restore it to acceptable values. The use of hydroxyethyl starch (trade name may differ) allows you to replace damaged cells and thereby restores impaired hemodynamics, improves microcirculation, rheological properties of blood (by reducing hematocrit), and reduces plasma viscosity. Since the structural formula of the substance is as close as possible to the natural formula, hydroxyethyl starch is tolerated relatively well, with minimal side effects.

The drug has long been used in medicine for a variety of diseases and conditions, but it has proven itself best when used as part of complex therapy for hypovolemic conditions and if the patient has lost a large amount of blood for one reason or another.

Pharmacological properties of the drug Hydroxyethyl starch

Hydroxyethylated starch is produced from waxy corn starch by partial hydrolysis of amylopectin followed by hydroxyethylation. A 6% solution of hydroxyethyl starch in an isotonic solution of sodium chloride is used as a colloidal plasma replacement agent. Infusion of such a weakly hyperoncotic solution leads to an increase in reduced colloid osmotic pressure and central venous pressure. Infusion of hydroxyethyl starch improves the rheological properties of blood. Hydroxyethylated starch does not accumulate in the body; some time after infusion is found in the cells of the reticuloendothelial system.

Indications for use of the drug

The instructions for use of hydroxyethyl starch provide for the use of the drug in the following cases:

• hemorrhagic, traumatic or septic shock and the resulting hypovolemic state;
• blood loss, including that resulting from surgery;
• violation of blood microcirculation;
• arterial hypotension due to surgery;
• acute arterial hypotension;
• when carrying out isovolemic hemodilution, the drug is also actively used;
• as part of complex (combined) therapy for venous thrombosis.

As a rule, hydroxyethyl starch preparations are used in hospital settings. At home, only a qualified specialist can install an IV and provide drip administration. Conditions that require therapy with hydroxyethyl starch require urgent medical attention.

Hypovolemia - symptoms, causes and therapy

Hypovolemic condition is one of the most common conditions for which therapy with hydroxyethyl starch is carried out. This is a persistent and progressive decrease in the volume of circulating blood in the patient's body. As a result of this condition (in the absence of qualified medical care), death can occur. For information: in a normal, healthy and non-pathological state, in adult women the total blood volume is 58–64 ml per 1 kg of body weight, in men – 65–75 ml/kg.

Reasons for the development of hypovolemia:

• blood loss caused by wounds, trauma, surgery, chronic diseases (some types of pathologies of the gastrointestinal tract can cause internal bleeding - this condition is a direct threat to the patient’s life);
• loss of a significant amount of fluid by the body (this condition can develop as a result of burns over a large area of ​​the body, polyuria, incessant diarrhea, severe vomiting in case of serious poisoning);
• sharp, sudden dilation of blood vessels with a change in the rhythm of circulating blood;
• various types of shock conditions provoked by injuries or chronic diseases of the cardiovascular system (heart attack, stroke, etc.);
• deficiency of incoming fluid (plain water) into the patient’s body against the background of the development of severe inflammatory and infectious processes; a similar condition can also arise due to the patient’s prolonged stay in a room with high air temperature).

Depending on a special medical indicator - hematocrit - several stages of hypovolemia are distinguished, while the instructions for hydroxyethyl starch warn that the drug is relatively more or less effective depending on the type of pathology:

• normocythemic is a general gradual decrease in the volume of circulating blood, while it should be taken into account that the ratio of plasma and formed elements remains almost completely preserved;
• oligocythemic - a decrease in the number of blood cells, i.e. we can say that the hematocrit value decreases;
• polycythemic - hematocrit is higher than normal, as the plasma volume indicator decreases.

Any stage of hypovolemia is very dangerous for the patient, for whatever reason it occurs. If you suspect such a condition, you should not self-medicate, even if it is possible to install a drip with hydroxyethyl starch at home. The patient needs long-term rehabilitation after serious blood loss; he needs constant high-quality monitoring of his condition, which can only be carried out by a professional.

Hydroxyethyl starch-Eskom

Hetastarch is used in the form of a 6% solution in a 0.9% NaCl solution (or with electrolytes), pentastarch - in the form of 6 and 10% solutions.

Administer intravenously by drip or stream. The dose and rate of administration are set individually depending on the severity of hemodynamic disorders and the severity of the patient’s condition. The first 10-20 ml should be administered slowly (possibility of developing anaphylactoid reactions).

The duration of therapy depends on the duration and severity of hypovolemia, the hemodynamic effect as a result of the therapy and the degree of hemodilution.

For HES with a molecular weight of 130 kDa and a concentration of 6%: the maximum daily dose in adults is 50 ml/kg (3500 ml/day with a body weight of 70 kg), in newborns and children under 2 years of age - 25 ml/kg; 2-10 years - 25 ml/kg; 10-18 years - 33 ml/kg; the maximum rate of administration is 20 ml/kg/h.

With developed shock - 0.5-1.5 l. For hemorrhagic shock, administer at a rate of up to 20 ml/kg/hour. In septic and burn shock, the infusion rate is slightly slower. In the absence of an emergency, the recommended infusion rate is 30 minutes per 500 ml of solution.

In situations requiring rapid compensation of hypovolemia and emergency replenishment of circulating blood volume, rapid administration of 500 ml of solution under pressure is permissible.

Hemodilution: administration is carried out isovolemicly (with taking one’s own blood) or hypervolemicly (without taking one’s own blood) at small (250 ml), medium (500 ml) and high daily doses (2 times 500 ml). The criterion for effectiveness is the reduction in hematocrit determined for each patient. Infusion rate: 250 ml in 0.5-2 hours, 500 ml in 4-6 hours, 2 times 500 ml in 8-24 hours. Duration of administration - 10 days.

Acute normovolemic hemodilution to reduce the introduction of donor blood during surgical operations: the solution is administered immediately before surgery in a 1:1 ratio when the Ziehl hematocrit after acute normovolemic hemodilution is not lower than 30. Blood sampling - 2-3 times 500 ml of own blood, daily dose 2-3 times 500 ml of solution, blood sampling rate - 1 liter in 15-30 minutes, drug administration rate - 1 liter in 15-30 minutes. Typically, a single injection of the drug is used immediately before surgery. Repeated use is possible if the initial hematocrit is within normal limits.

For HES with a molecular weight of 130 kDa and a concentration of 10%: the maximum daily dose in adults is 30 ml/kg (2000 ml/day for a body weight of 70 kg), the maximum rate of administration is 20 ml/kg/h.

In situations requiring rapid compensation of hypovolemia and emergency replenishment of circulating blood volume, rapid administration of 500 ml of solution under pressure is permissible.

In the absence of an emergency, the recommended infusion rate is 30 minutes per 500 ml of solution.

For HES with a molecular weight of 200 kDa and a concentration of 6%:

The maximum daily dose in adults and children is 33 ml/kg, the maximum rate of administration is 20 ml/kg/h.

Average daily doses for children under 3 years of age are 10-15 ml/kg; 3-6 years - 15-20 ml/kg; 6-12 years - 15-20 ml/kg; 12-18 years - 33 ml/kg.

For the purpose of hemodilution, the daily dose is 500 ml over several days up to a total dose of 5 l, which can be exceeded in exceptional cases and distributed over a period of up to 4 weeks.

With developed shock - 0.5-1.5 l. For hemorrhagic shock, administer at a rate of up to 20 ml/h/kg. In septic and burn shock, the infusion rate is slightly slower.

In young patients without the risk of cardiovascular and pulmonary complications, the duration of therapy is determined by the hematocrit (should be at least 30%).

In the absence of an emergency, the recommended infusion rate is 30 minutes per 500 ml of solution.

Hemodilution: administration is carried out isovolemicly (with taking one’s own blood) or hypervolemicly (without taking one’s own blood) at small (250 ml), medium (500 ml) and high daily doses (2 times 500 ml). The criterion for effectiveness is the reduction in hematocrit determined for each patient. Infusion rate: 250 ml in 0.5-2 hours, 500 ml in 4-6 hours, 2 times 500 ml in 8-24 hours. Duration of administration - 10 days.

Acute normovolemic hemodilution to reduce the introduction of donor blood during surgical operations: the solution is administered immediately before surgery in a 1:1 ratio when the Ziehl hematocrit after acute normovolemic hemodilution is not lower than 30. Blood sampling - 2-3 times 500 ml of own blood, daily dose 2-3 times 500 ml of solution, blood sampling rate - 1 liter in 15-30 minutes, drug administration rate - 1 liter in 15-30 minutes. Typically, a single injection of the drug is used immediately before surgery. Repeated use is possible if the initial hematocrit is within normal limits.

For therapeutic hemodilution, multi-day or multi-week infusion regimens are used.

Multi-day regimen: daily infusion dose - 0.5-1 l of solution; in case of sudden deafness or intermittent claudication - 500-750 ml/day, in the acute phase of ischemic stroke - 750-1000 ml/day; rate of administration - 75-250 ml/h, course duration - 5-10 days. In the acute phase of ischemic stroke, at the beginning of therapy, an additional loading dose of 250-500 ml can be administered, while the rate of administration is carried out at an increased rate (250-500 ml/h).

Multi-week regimen: infusion is carried out 2-3 times a week, 250-500 ml at a rate of 125-250 ml/hour, lasting 3-6 weeks. In many cases, it is recommended to adapt the injected volume (if necessary, bloodletting) to hemodynamic and/or hemorheological parameters (CVP - 15 mm Hg, hematocrit - 38-42, etc.).

For HES with a NaCl content of 72 g: the maximum dose is 4 ml/kg IV bolus over 2-5 minutes (250 ml for a body weight of 60-70 kg), preferably administered into a central vein. The drug is administered once, repeated administrations are not recommended; after administration, standard plasma replacement therapy should be carried out. If subsequent standard plasma replacement therapy includes HES, then the total dose of HES received should include the HES contained in this drug.

For HES with a molecular weight of 200 kDa and a concentration of 10%: the maximum daily dose is 20 ml/kg per day. The maximum rate of administration is 20 ml/kg.

Average daily doses for children under 3 years of age are 8-10 ml/kg; 3-6 years - 10-15 ml/kg; 6-12 years - 10-15 ml/kg; 12-18 years - 20 ml/kg.

For the purpose of hemodilution, the daily dose is 500 ml over several days up to a total dose of 5 l, which can be exceeded in exceptional cases and distributed over a period of up to 4 weeks.

With developed shock - 0.5-1.5 l. For hemorrhagic shock, administer at a rate of up to 20 ml/h/kg. In septic and burn shock, the infusion rate is slightly slower.

In young patients without the risk of cardiovascular and pulmonary complications, the duration of therapy is determined by the hematocrit (should be at least 30%).

In the absence of an emergency, the recommended infusion rate is 30 minutes per 500 ml of solution.

Hemodilution: administration is carried out isovolemicly (with taking one’s own blood) or hypervolemicly (without taking one’s own blood) at small (250 ml), medium (500 ml) and high daily doses (2 times 500 ml). The criterion for effectiveness is the reduction in hematocrit determined for each patient. Infusion rate: 250 ml in 0.5-2 hours, 500 ml in 4-6 hours, 2 times 500 ml in 8-24 hours. Duration of administration - 10 days.

Acute normovolemic hemodilution to reduce the introduction of donor blood during surgical operations: administered immediately before surgery in a 1:1 ratio when the Ziehl hematocrit after acute normovolemic hemodilution is not lower than 30. Blood sampling - 2-3 times 500 ml of own blood, daily dose 2 -3 times 500 ml of solution, blood sampling rate - 1 liter in 15-30 minutes, drug administration rate - 1 liter in 15-30 minutes. Typically, a single injection of the drug is used immediately before surgery. Repeated use is possible if the initial hematocrit is within normal limits.

For therapeutic hemodilution, multi-day or multi-week infusion regimens are used.

Multi-day regimen: daily infusion dose - 0.5-1 l of solution; in case of sudden deafness or intermittent claudication - 500-750 ml/day, in the acute phase of ischemic stroke - 750-1000 ml/day; rate of administration - 75-250 ml/h, course duration - 5-10 days. In the acute phase of ischemic stroke, at the beginning of therapy, an additional loading dose of 250-500 ml can be administered, while the rate of administration is carried out at an increased rate (250-500 ml/h).

Multi-week regimen: infusion is carried out 2-3 times a week, 250-500 ml at a rate of 125-250 ml/hour, lasting 3-6 weeks. In many cases, it is recommended to adapt the injected volume (if necessary, bloodletting) to hemodynamic and/or hemorheological parameters (CVP - 15 mm Hg, hematocrit - 38-42, etc.).

When taking blood in parallel, care must be taken to ensure that a hypovolemic state does not occur at any point in time (infusion is carried out either in parallel with or before bloodletting, and the amount administered must be greater than the amount of blood withdrawn). The daily dose is similar to that for replenishing blood volume.

For HES with a molecular weight of 450 kDa and a concentration of 6%: for hypovolemia, the average daily dose is 250-1000 ml, in exceptional cases - more than 20 ml/kg/day.

For the purpose of hemodilution, the daily dose is 500 ml over several days up to a total dose of 5 l, which can be exceeded in exceptional cases and distributed over a period of up to 4 weeks.

In the absence of an emergency, the recommended infusion rate is 30 minutes per 500 ml of solution.

List of contraindications for use

Instructions for use for hydroxyethyl starch (for all drugs that contain this active ingredient, it is almost completely similar) informs that there are the following contraindications for use:

• Individual high sensitivity to the active element.
• TBI, which is accompanied by increased intracranial pressure (ICP).
• If there is a suspicion of intracranial bleeding, as a rule, using the drug is strictly prohibited.
• Arterial hypertension (as opposed to hypotension, which is indicated in the list of indications for the use of drugs with hydroxyethyl starch as the main active ingredient).
• Chronic heart failure.
• Renal failure in both acute and chronic forms (accordingly, if the patient is on hemodialysis, the use of drugs containing hydroxyethyl starch is also prohibited).
• Acute left ventricular failure.
• Cardiogenic pulmonary edema.
• Thrombocytopenia.
• Allergy and intolerance to starch.
• Children's age up to 10 years.
• Overhydration, coagulopathy, hypocoagulation, dehydration.
• Hypofibrinogenemia.

There are also relative contraindications for use. Instructions for use for hydroxyethyl starch (this applies to all drugs that contain this active ingredient) indicate that the relative contraindications for use are as follows:

• chronic diseases of the liver, pancreas, kidneys;
• children under 10 years of age;
• von Willebrand disease;
• chronic diseases of the urinary system.

Side effects[edit]

HES may cause anaphylactoid reactions: hypersensitivity, mild flu-like symptoms, slow heartbeat, palpitations, airway spasms, and non-cardiogenic pulmonary edema. It is also associated with decreased hematocrit and blood clotting disorders. One liter of 6% solution (Hespan) reduces factor VIII levels by 50% and prolongs aPTT and also reduces vWF. [5] The coagulating effect of hetastarch administration is the direct transfer of fibrin into clots and a liquefying effect on the serum. Hetastarch can lead to platelet dysfunction by causing decreased availability of glycoprotein IIb-IIIa on platelets.

HES derivatives have been demonstrated to increase the incidence of acute renal failure and the need for renal replacement therapy, and to reduce long-term survival when used alone in cases of severe sepsis compared with lactated Ringer's solution. [6] The effects were tested on HES 130 kDa/0.42 in people with severe sepsis; analysis showed an increased incidence of renal failure and increased mortality compared with LR. [7] It has been recommended that because intermediate molecular weight HES solutions may be associated with harm, these solutions should not be routinely used in patients with septic shock. [8]

During 2010/11, a large number of research papers related to one author were retracted for ethical reasons, and this may affect clinical guidelines relating to HES products prepared before this date. [9]

Contraindications [edit]

The instructions for use indicate the following contraindications:

• This product should not be used by people with hypersensitivity or allergy to hydroxyethyl starch.
• Patients with renal failure not associated with low blood volume and patients on dialysis should avoid taking this product at high doses used for volume expansion.
• The use of hydroxyethyl starch with saline in its preparation is contraindicated in people with severely elevated blood sodium or chloride levels.
• Patients with intracranial bleeding should not use this product.

On November 25, 2013, following a public workshop to discuss new information about the risks and benefits of the GECA decision, [10] USFDA announced the addition of a black box warning to the prescriptive information that includes the following recommendations for health care professionals: [11]

• Do not use HES solutions in critically ill adult patients, including those with sepsis.
• Avoid use in patients with pre-existing renal dysfunction.
• Stop taking HES at the first sign of kidney damage.
• The need for renal replacement therapy has been reported for up to 90 days after HES administration. Continue to monitor renal function in all patients for at least 90 days.
• Avoid use in patients undergoing open heart surgery in combination with cardiopulmonary bypass due to excessive bleeding.
• Discontinue use of HES at the first sign of coagulopathy.
• Do not use HES products in patients with severe liver disease.
• Monitor liver function in patients receiving HES products.

Security issues[edit]

High molecular weight HES is associated with coagulopathy, pruritus, as well as nephrotoxicity, acute renal failure, and mortality. [7] [12] On the other hand, low molecular weight HES does not seem to exhibit such side effects. [2] However, some have suggested that small molecule HES poses a serious safety concern. They argue that studies that reach a different conclusion are unreliable for a number of reasons, including "inappropriate comparators, follow-up periods that are too short, low cumulative dose, and low-risk patients." (Hartog and Reinhart, 2009, p. 1340). [12] Recent results from the 6S study seem to confirm these concerns (see below).

In June 2012 in the New England Journal of Medicine

a 6S article was published raising concerns about the use of hydroxyethyl starch in sepsis. Specifically, the authors showed that resuscitation with hydroxyethyl starch (as opposed to Ringer's acetate) resulted in an increased risk of death or end-stage renal disease. [13] This study used Tetraspan (HES 130/0.42) from the pharmaceutical company B. Braun, but the original version of the publication contained the product specification HES 130/0.4. [13] The pharmaceutical company Fresenius Kabi, which produces a similar product but with the HES 130/0.4 specification, is threatening to take legal action against the author, Anders Perner, as they wanted to correct the misleading use of their product specification. [14] The academic community expressed concern about this type of corporate behavior, although Fresenius Kabi did not doubt the results of the study. [14]

The CHEST study compared Hes130/0.40 with saline in 7000 patients. The study was conducted on less sick people than six-year-olds; however, the increase in mortality was similar to the 6s. There has also been a significant increase in dialysis rates overall. The increase in creatinine confirmed the pathophysiological basis. In addition, patients required more blood products and had significantly more liver failure and pruritus. The study was published in NEJM

in October 2012 [15]

As a consequence, in November 2012, the European Regulatory Agency (EMA) launched a Formal Safety Assessment Procedure for all HES products. The FDA held a public workshop in September 2012 to address the safety concerns of HES [10], which most participants agreed should be addressed by regulators. The Surviving Sepsis Campaign has decided to ban HES from treating patients with sepsis. [16]

On 14 June 2013, PRAC, which is the safety committee of the EMA, the European regulatory agency, published on its official website a recommendation to suspend the registration of all HES products in Europe. The risk-benefit ratio is negative based on the results of 3 megatrials (VISEP, 6S, CHEST). Clinical benefit could not be demonstrated in any patient population, and there was sufficient evidence of harm, particularly renal failure due to long-term storage of the product in vital organs, which severely limited its potential indications. [3] The FDA followed on June 24. On June 27, the MHRA recalled HES products because the risks outweigh the potential benefits and safer, cheaper alternatives are available. [11] [17]

The EMA held a special expert meeting on 18 December 2021 to help inform its further consideration of this issue. Some additional long-term data have been published, although some trials have not yet been completed. On 12 January 2018, PRAC [Pharmacovigilance Risk Assessment Committee] recommended that the European Medicines Agency revoke the marketing authorization for medicinal products containing hydroxyethyl starch. The problem was that some uses were outside the scope of the limited license, perhaps in areas of practice where there was evidence of harm. This may be a global problem, as there is evidence that in practice areas such as postpartum haemorrhage, use of the drug continues outside of WHO recommendations. The recommendation was adopted by the Coordination Group for Mutual Recognition and Decentralized Procedures (CMDh) on 26 January 2021[18] In April 2021, the European Commission asked the PRAC and CMDh to continue to consider any possible unmet medical needs that may arise as a result of the suspension, and the appropriateness and likely effectiveness of additional risk mitigation measures. Having considered these specific aspects, in May 2018 the PRAC confirmed its previous recommendation for suspension and sent a revised recommendation to the CMDh. The CMDh concluded that HES infusion solutions should remain on the market provided that a combination of additional measures are implemented to protect patients. The European Commission adopted a decision on 17 July 2021 that is legally binding throughout the EU. [19]

What side effects does the drug cause?

The drug has exactly the same side effects, regardless of what its trade name is. Analogues of “Hydroxyethyl starch” are represented by more than a dozen drugs, however, when using them, the possibility of developing the following side effects should be taken into account:

• tachycardia (if the patient complains about the speed and quality of the heart rhythm, administration should be stopped immediately);
• allergic reactions are possible: urticaria, skin itching, nausea, dermatitis;
• from the digestive system, diarrhea and nausea may develop;
• increased plasma amylase levels (not associated with manifestations of pancreatitis);
• a relatively rare side effect is the appearance of skin itching, which is not accompanied by rashes and dermatitis;
• when using high doses, bleeding time may be prolonged.

Interaction with other medicinal substances

Before starting administration, you should make sure that it is possible in parallel with medications already taken - the instructions for using hydroxyethyl starch warn about this. The active substance may antagonize the components of other drugs. If for some reason they are not combined, many serious side effects may develop. The name “Hydroxyethyl starch INN” is one of the most common, but it should be noted that doctors often use its analogues - these are “Volekam”, “Hemohes”, “Voluven”, “Hydroxyethyl starch-Eskom”.

The drug cannot be mixed in the same dropper bottle with any other solutions and compositions.

When used in parallel with heparin, the risk of increased bleeding increases. Therefore, such a combination is undesirable.

When taken in parallel with beta-blockers and vasodilators, it should be taken into account that changes in blood pressure can be diagnosed, and the heart rate may change.

The use of drugs containing hydroxyethyl starch can have a significant impact on various blood test parameters - in particular, the amount of fatty acids, the amount of protein, and ESR. The specific gravity of urine may also change with regular use.

Trade names of hydroxyethyl starch

Preparations containing hydroxyethyl starch may have the following names:

• "N-hydroxyethyl starch";
• "Hydroxyethyl starch";
• “Hydroxyethyl starch 200/0.5”;
• "Hemohes 10%";
• "Venofundin";
• "Hydroxyethyl starch 130/0.4";
• "Hydroxyethyl starch-Eskom";
• "Hydrael 130";
• "Volekam";
• "Volekam" GEK-200;
• "Voluven";
• "HyperHAES Infucol";
• "Hemohes GETA-SORB";
• "Tetraspan";
• "Stabizol GES";
• "Refortan HES";
• "Plasmastabil 200";
• "Plasmaline";
• "Infucol";
• "Hesplasma."

The name, as a rule, does not reflect the composition or percentage of the substance used, so you should carefully study the instructions. As mentioned above, the drug is usually used in hospital settings. There, drugs with the following trade names of hydroxyethyl starch are most often used:

• "Volekam";
• "Plasmaline";
• "Hemohes."

Links[edit]

1. ^ a b Zarychansky, R; Abu-Setta, A.M.; Turgeon, A.F.; Houston, BL; McIntyre, L; Marshall, J.C.; Fergusson, D.A. (February 20, 2013). "Association of hydroxyethyl starch use with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis". JAMA: Journal of the American Medical Association
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2. ^ ab Westphal, M.; James, M.; Kozek-Langenecker, S.; Stocker, R.; Guidet, B.; Van Aken, H. (2009). “Hydroxyethyl starches: different products, different effects. [Review] [140 links]". Anesthesiology
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3. ^ ab "Hydroxyethyl starch (HES) solutions should no longer be used in patients with sepsis, burn injuries, or in critically ill patients" (press release). European Medicines Agency. 2013-10-23.
4. Lewis, Sharon R.; Pritchard, Michael W.; Evans, David Joo; Butler, Andrew R.; Alderson, Phil; Smith, Andrew F.; Roberts, Ian (8 March 2018). "Colloids versus crystalloids for fluid resuscitation in the critically ill". Cochrane Database of Systematic Reviews
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5. Miller: Anesthesia, 6th ed., pp. 1787
6. Brunkhorst FM, Engel C, Bloos F, et al (January 2008). "Intensive insulin therapy and pentastarch resuscitation in severe sepsis". N.Engl.
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7. ^ a b Perner, A.; Haase, N.; Wetterslev, J.; Åneman, A.; Tenhunen, J.; Guttormsen, A. B.; Klemenzson, G.; and others. (2011). "Comparison of the effect of hydroxyethyl starch 130/0.4 with a balanced crystalloid solution on mortality and renal failure in patients with severe sepsis (study 6S - Scandinavian starch for severe sepsis/septic shock): study protocol, double-blind study design and rationale, randomized clinical trial ". Tests
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10. ^ b "Public Seminar: Risks and Benefits of Hydroxylethyl Starch Solutions", Vaccines, Blood and Biologics
    , US Food and Drug Administration
11. ^ ab "FDA Safety Communication: Boxed Warning of Increased Mortality and Severe Kidney Damage, and Additional Warning of Risk of Bleeding with the Use of Hydroxyethyl Starch Solutions in Certain Conditions", Vaccines, Blood & Biologics
    , US Food and Drug Administration, November 25 , 2013
12. ^ a b Hartog, S.; Reinhart, K. (2009). "CONTROL: Hydroxyethyl starch solutions are unsafe for seriously ill patients." Reanimatology
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13. ^ a b Perner A., ​​Haase N., Guttormsen A.B., Tenhunen J., Klemencson G., Ohneman A., Madsen K.R., Møller M.H., Elkjær J.M., Poulsen L. M., Bendtsen A., Winding R., Stensen M., Berezovich P., Sø-Jensen P., Bestl M., Strand K., Wiis J., White J. O., Thornberg K. J., Quist L., Nielsen J., Andersen L.H., Holst L.B., Tormar K., Kjeldgaard A.L., Fabricius M.L., Mondrup F, FK Pott, Möller T.P., Winkel P. , Wetterslev J. , 6C Trial, Group; Scandinavian Critical Care Trials, Group (July 12, 2012). "Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis". New England Journal of Medicine
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14. ^ ab Wojcik, Jepp (July 24, 2012). "Pharmaceutical giant threatens Danish scientist". ScienceNordic
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16. Dellinger, R. Phillip; Levy, Mitchell M.; Rhodes, Andrew M.B.; Annane, Jillali; Gerlach, Herwig; Opal, Stephen M.; Sevransky, Jonathan E.; Sprung, Charles L.; Douglas, Ivor S.; Jaeschke, Roman; Osborne, Tiffany M.; Nunnally, Mark E.; Townsend, Sean R.; Reinhart, Conrad; Kleinpell, Ruth M.; Angus, Derek S.; Deutschman, Clifford S.; Machado, Flavia R.; Rubenfeld, Gordon D.; Webb, Stephen A.; Beale, Richard J.; Vincent, Jean-Louis; Moreno, Rui; Sepsis Campaign Guidelines Committee, including a pediatric subgroup (February 2013). "Surviving Sepsis Campaign: International Guidelines for the Management of Severe Sepsis and Septic Shock: 2012." Critical Care Medicine
    .
    41
    (2):580–637. DOI: 10.1097/CCM.0b013e31827e83af.PMID 23353941. S2CID 34855187.
17. Press release: MHRA suspends use of hydroxyethyl starch (HES) drops, Medicines and Healthcare Products Regulatory Agency, 27 June 2013, archived from the original on 1 July 2013.
18. "European Medicines Agency - Medicines for human use - medicinal products containing hydroxyethyl starch (HES)". www.ema.europa.eu
    . Retrieved January 27, 2021.
19. "Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients". European Medicines Agency
    . July 17, 2021.
20. ↑
    Bork, K. (January 2005).
    "Itch precipitated by hydroxyethyl starch: a review." British Journal of Dermatology
    .
    152
    (1):3–12. DOI: 10.1111/j.1365-2133.2004.06272.x. PMID 15656795. S2CID 13483776.
21. “PRAC confirms that hydroxyethyl starch (HES) solutions should no longer be used in patients with sepsis, burn injuries or in critically ill patients” (press release). Pharmacovigilance Risk Assessment Committee, European Medicines Agency. October 11, 2013

"Volecam" - an analogue of hydroxyethyl starch

Hydroxyethylated starch is used as the main active ingredient in the manufacture of this drug.

Pharmacological action: increases the rheological properties of blood composition by reducing hematocrit, reduces plasma viscosity. When administered regularly through a dropper, it restores microcirculation.

Widely used in modern medicine for bleeding and hypovolemic conditions. It has contraindications and side effects that were described above. A number of drugs that have hydroxyethyl starch as the main active ingredient have them in common. The use of the drug should not be carried out by the patient independently, without prior examination by a doctor and a prescription with the recommended dosage.

Solutions of hydroxyethyl starch in infusion therapy of acute blood loss

Blood loss is the most common and evolutionarily oldest damage to the human body, occurring in response to significant loss of blood from the vessels and characterized by the development of a number of compensatory and pathological reactions. Blood loss of more than 30% of the circulating blood volume (CBV) in less than 2 hours is considered massive [7,8]. As a result of blood loss, pathological phenomena develop in the body, the most important of which are a decrease in blood volume, changes in vascular tone and a decrease in cardiac performance with the subsequent development of hypotension, hypoxemia and hypoxia, organ hypoperfusion and metabolic acidosis, which causes the most severe manifestations of hemorrhagic shock [6,7] . Activation of all coagulation links makes it possible to develop disseminated intravascular coagulation (DIC syndrome). As a physiological defense, the body responds to its most frequent damage with hemodilution, which improves blood fluidity and reduces its viscosity, mobilization from the red blood cell depot, a sharp decrease in the need for both blood volume and oxygen delivery, an increase in respiratory rate, cardiac output, oxygen return and utilization in tissues. Acute blood loss leads to the release of catecholamines by the adrenal glands, causing spasm of peripheral vessels and, accordingly, a decrease in the volume of the vascular bed, which partially compensates for the resulting deficit of bcc [5,10]. Redistribution of organ blood flow (centralization of blood circulation) makes it possible to temporarily preserve blood flow in vital organs and ensure the maintenance of life in critical conditions. However, subsequently this compensatory mechanism can cause the development of severe complications of acute blood loss [6,7]. The strategic principles of transfusion therapy for acute blood loss, based on its pathogenesis, are the restoration of organ blood flow (perfusion) by achieving the required volume of blood volume. Maintaining the level of coagulation factors in quantities sufficient for hemostasis, on the one hand, and to counteract excessive disseminated coagulation, on the other. Replenishing the number of circulating red blood cells (oxygen carriers) to a level that ensures a minimum sufficient oxygen consumption in the tissues. The question of prioritizing among these principles remains open. However, most experts consider hypovolemia to be the most acute problem of blood loss, and accordingly, the first place in treatment regimens is given to the replenishment of blood volume, which is a critical factor for maintaining stable hemodynamics. The pathogenetic role of a decrease in blood volume in the development of severe disorders of homeostasis determines the importance of timely and adequate correction of volumetric disorders on treatment outcomes in patients with acute massive blood loss [8,10]. In this regard, infusion and transfusion therapy plays a leading role in restoring and maintaining bcc adequate to hemodynamic demands, normalizing the rheological properties of blood and water and electrolyte balance. At the same time, the effectiveness of infusion-transfusion therapy largely depends on the targeted justification of its program, the characteristics of infusion solutions, their pharmacological properties and pharmacokinetics [7,17]. As is known, there are three types of infusion media for intravenous administration: crystalloids, colloids and blood components. Crystalloid solutions contain water and electrolytes. They are balanced, hypertonic and hypotonic. The main advantages of crystalloid solutions are low reactogenicity, no effect on renal function and the immune system, and no significant effect on the hemostatic system. Crystalloid solutions, especially balanced salt solutions (K, Mg aspartate, Ringer's solution, Hartmann's solution, mafusol), correct electrolyte balance [17]. The main disadvantage of crystalloids is their rapid redistribution from the vascular bed into the intercellular space: 75–80% of the administered drug ends up in the interstitium 1–2 hours after infusion. Due to such a short-lived volemic effect, maintaining bcc with the isolated use of saline solutions requires the administration of a large volume of solutions, which is fraught with the risk of hypervolemia and the development of edematous syndrome [13,14]. Blood components include fresh frozen plasma (FFP) and albumin solution. In terms of its effect on the hemostatic system, FFP is an optimal transfusion medium. However, a number of properties significantly limit its use. First of all, there is a high risk of transmitting viral infections. In addition, donor plasma contains antibodies and leukocytes, which are a powerful factor in the development of leukoaglutination and systemic inflammatory response. This leads to generalized damage to the endothelium, primarily to the vessels of the pulmonary circulation [1,12]. Today, it is generally accepted that FFP transfusion in clinical practice is carried out only for the purpose of preventing or restoring hemostatic disorders associated with a deficiency of blood coagulation factors [3]. Many clinical studies have led to the conclusion that albumin solutions cannot serve as a first-line treatment for correcting hypovolemia. Albumin should currently be considered as a drug that has its own “niche”; indications for albumin transfusions today can be reduced only to the need to correct severe hypoalbuminemia [1,3]. In addition, the use of albumin and FFP is limited by their high cost, which is an order of magnitude or more higher than the cost of modern synthetic colloidal plasma substitutes [10]. Artificial colloidal solutions include dextrans, gelatin derivatives and hydroxyethyl starches. Dextran is a water-soluble high-molecular polysaccharide. Plasma replacement agents based on dextran are divided into two main groups: low molecular weight dextrans and medium molecular dextrans. Medium molecular dextrans cause a volumetric effect of up to 130% lasting 4–6 hours. Low molecular weight dextrans cause a volumetric effect of up to 175% lasting 3–4 hours. The main problem when used as volume-substituting agents based on dextran, in addition to the relatively high reactogenicity, is their narrow therapeutic "window". The use of large volumes of dextran solutions helps to prolong the hypocoagulation state due to their heparin-like action, and can lead to blockade of the RES and the occurrence of a “dextran kidney burn.” An overdose of dextran-based solutions can lead to various pathological changes in the lungs, tissue dehydration, renal failure, and pathological intra- and postoperative bleeding [4,5,9]. Gelatins are polypeptides derived from bovine collagen and are classified according to the difference in solution preparation (oxygelatins, urea-bound gelatin solutions and liquid modified gelatin solutions). Gelatin-based solutions are the least toxic and can be used in patients with kidney pathology. Gelatin derivatives increase plasma volume by 100%, but this effect is short-lived and lasts 3–4 hours [2,5]. Over the past decade, in many countries around the world, the class of colloidal plasma replacement agents based on hydroxyethyl starch (HES) has taken a leading position. The targeted development and introduction into medical practice of colloidal solutions of hydroxyethyl starch (HES) has opened up new opportunities for solving existing problems in practice. HES is a high molecular weight substance consisting of polymerized glucose residues. The starting materials for the production of HES are starch from potato tubers, as well as grains of various varieties of corn, wheat and rice. HES from potatoes, as well as from waxy corn grains, along with linear amylose chains, contains a fraction of branched amylopectin. The high content of amylopectin in potato starch (75–80%), as well as in waxy corn starch (over 95%), allows them to be used after hydroxyethylation as raw materials for the preparation of plasma-substituting drugs. When compared with colloidal plasma-substituting solutions produced from raw materials of other origin (albumin, dextran, gelatin), the features and advantages of colloidal solutions based on HES are revealed [15]. First of all, this concerns the safety of use and the extremely low frequency of adverse reactions. The low risk of adverse reactions when using HES solutions is due to the structural similarity of the HES and glycogen molecules. HES solutions are much less likely than gelatin and dextran solutions to cause allergic reactions. When using HES solutions, other undesirable reactions that occur when using other means of infusion therapy were not registered: there was no increase in the level of histamine that occurs with the direct administration of gelatin solutions, and the appearance of antigen-antibody reactions characteristic of dextran solutions was not detected [2,6, eleven]. The main parameters reflecting the physicochemical properties of HES-based drugs are: MW – molecular weight; MS – molecular substitution; DS – degree of substitution. Solutions of hydroxyethylated starch are polydisperse and contain molecules of varying masses. The higher the molecular weight, for example 200,000–450,000, and the degree of substitution (from 0.5 to 0.7), the longer the drug will remain in the lumen of the vessel. Drugs with an average molecular weight of 200,000 D and a degree of substitution of 0.5 are assigned to the pharmacological group “Pentastarch”, and drugs with a high molecular weight of 450,000 D and a degree of substitution of 0.7 are assigned to the pharmacological group “Hetastarch”, in which Stabizol should be distinguished. This circumstance should be taken into account when choosing a specific HES-based drug for targeted infusion therapy. The weight average molecular weight (Mw) is calculated from the weight fraction of individual molecular species and their molecular weights. Mw of Stabizol = 450,000 D. The lower the molecular weight and the more low molecular weight fractions in the polydisperse preparation, the higher the colloid-oncotic pressure (COP). Stabizol CODE = 18 mm Hg. It is very important that at effective COD values, Stabizol has a high molecular weight, which determines the advantages of its use over albumin, plasma and dextrans in conditions of increased endothelial permeability. HES solutions are capable of “sealing” pores in the endothelium that appear in various forms of damage [2,6]. HES solutions usually affect the volume of intravascular fluid within 24 hours, Stabizol - within 30 hours. The main route of elimination is renal excretion. HES polymers with a molecular weight of less than 59 CD are almost immediately removed from the blood by glomerular filtration. Renal elimination by filtration continues after hydrolysis of larger fragments into smaller ones. The oncotic pressure created by HES solutions does not affect the current through large pores, but mainly affects the current through small pores, which are the majority in capillaries.[4,5,12]. Clinical observations suggest that, in addition to the properties of ideal volume replenishment, Stabizol also has pharmacological properties [6]: 1. in contrast to fresh frozen plasma and crystalloid solutions, it can reduce “capillary leakage” and tissue edema; 2. in conditions of ischemia-reperfusion injury, Stabizol reduces the degree of damage to the lungs and other internal organs, as well as the release of xanthine oxidase. In case of hypovolemic shock, infusion therapy with the use of Stabizol reduces the incidence of pulmonary edema compared with the use of albumin and saline sodium chloride solution; 3. Stabizol reduces the concentration of circulating factor VIII and inhibits the release of von Willebrand factor from endothelial cells. This suggests that Stabizol is able to inhibit the expression of P-selectin and the activation of endothelial cells. Because leukocyte-endothelial interactions determine transendothelial output and tissue infiltration by leukocytes, influencing this pathogenetic mechanism may reduce the severity of tissue damage in many critical conditions. This appears to play an important role in patients with initially low concentrations of coagulation factors, where reliable hemostasis is absolutely necessary [6,7]. A thorough clinical analysis of the use of Stabizol in intensive care has shown its following qualities: highly effective for hypovolemia and shock due to the normalization of hemodynamics, microcirculation, improvement of oxygen delivery and consumption by organs and tissues, restoration of porous capillary walls; effectively and sufficiently improves the rheological properties of blood: reduces hematocrit, reduces plasma viscosity, reduces platelet aggregation, prevents erythrocyte aggregation; due to the permitted high doses (up to 20 ml/kg body weight per day for a 6% solution), it allows you to refuse to use other colloids; in the dosages used does not affect the hemocoagulation system; allows you to completely abandon and/or sharply reduce the use of donor blood products and concomitant drug therapy; practically does not cause adverse or allergic reactions and is well tolerated [6,11]. The first 10–20 ml of solution should be administered slowly and with strict monitoring of the patient's condition. The daily dose and rate of infusion depend on the amount of blood loss and hematocrit value. The duration and extent of therapy depend on the duration and extent of hypovolemia. When replacing blood volume, the average daily dose is usually 500–1000 ml. In the absence of an acute emergency situation, the recommended duration of infusion is at least 30 minutes per 500 ml of Stabizol. In the vast majority of cases, Stabizol is able to provide a more economical treatment for acute critical conditions. Accumulating clinical experience indicates that in some pathological conditions the use of HES solutions is preferable to the administration of other colloidal solutions [5,11,15]. Extensive clinical domestic and foreign experience has shown that when providing care to patients in intensive care units, the daily use of HES solutions ensures high efficiency and predictability of infusion-transfusion therapy, reduction in the use of infusion-transfusion media, limiting the use of blood products, multiple reductions in administered volumes of FFP and red blood cell mass and, as a consequence, a significant reduction in the cost of treatment per patient [10,15]. The data obtained suggest that Stabizol can be used to replenish blood loss and is a highly effective remedy. The hemodilution caused by its administration persists during the first day after surgery, without leading to a significant decrease in hemocoagulation potential and an increase in the risk of hemorrhagic complications, and a decrease in platelet aggregation helps eliminate their relative deficiency and normalize the aggregation properties of erythrocytes. In addition, it is hemodilution that has a preventive effect in terms of postoperative anemia and hypoproteinemia, both direct and indirect through improving microcirculation and reducing interstitial tissue edema. For the same reasons, when replacing blood loss with Stabizol, a more favorable course of the postoperative period is noted [7,16]. Thus, the main positive properties of Stabizol can be presented as follows: [11] J rapid replenishment of lost blood volume due to the intravascular distribution space (absence of edema with large doses of administration); J persistent volemic effect; J 100% achieved volume relative to the injected volume of liquid; J high stability of iso-oncotic colloid-osmotic pressure; J the rheological effect is comparable in action to the administration of pentoxifylline; J duration of action – more than 30 hours; J does not cause direct histamine release; J low incidence of anaphylactoid reactions and severe incompatibility reactions; J does not affect organ functions; J long shelf life. Extensive clinical experience accumulated in recent years allows us to conclude that in critical conditions, which are accompanied by generalized endothelial damage and a decrease in plasma oncotic pressure, HES solutions of various concentrations and molecular weights are optimal in the infusion therapy program. The model for optimization of infusion -transfusion therapy with acute blood loss, we have chosen operations of total endoprosthetics of the hip joint. Endoprosthetics of the hip joint are almost always associated with trauma and significant blood loss. Infusion -transfusion therapy for endoprosthetics until recently was not a subject of special study. Along with the traditional general requirement of the patient’s absolute safety, the problems of replenishing the volume of circulating blood, and the restoration of systemic hemodynamics are made to the fore. We conducted a study in a group of patients who underwent the endopusthesis of the hip joint for deforming coksartorosis, including 24 people (14 men, 10 women). The age of the patients was from 50 to 78 years (average age - 64 years). Patients were comparable in the degree of anesthesiological risk (II - III in ASA) and related pathology. The endoprosthetics operation of the hip joint was carried out in spinal anesthesia with a 0.5 solution of bupivacaine. Preinfusion in both groups carried out 800.0 ml of crystalloids (physiological solution). Indications for the use of plasma substitute drugs (reform n = 10 and stabisol n = 6) was the maintenance of the BCC and plasma for intraoperative blood loss, which was an average of 800 ml. Such blood loss is characteristic of this type of operation. In 8 patients with blood loss, it amounted to more than 1000 ml, which was an indication for the additional administration of 200-300 ml of erythrocyte mass and SZP, stabizol was used to stabilize hemodynamics. In addition to these plasma substitutions, all the operated solutions were infused with crystalloid solutions (isotonic sodium chloride solution, trisol solution, 5% glucose solution) in an amount of 2000 ml. We controlled the following parameters. 1. Hemodynamic profile - heart rate, blood pressure during the entire periodical period, BCC, cardiac index, general peripheral resistance, stroke volume. These indicators were recorded in the following stages: initially, at the time of the greatest blood loss, after the start of the infusion of colloidal drugs, 6 hours after the start of infusion therapy. 2. The number of red blood cells, hemoglobin, hematocrit - initially, immediately after surgery, 1 and 3 days after surgery. 3. Indicators of the hemostasis system (platelets, ACTV, PI, fibrinogen) - initially, immediately after surgery, 1 and 3 days after surgery. 4. Biochemical indicators of blood (O. White, urea, bilirubin, AST, ALT, amylase) - initially, on 1 and 3 days after the operation. BCC predictably reduced at the time of the greatest blood loss in all patients. After the introduction of stabisol and reform, the BCC increased by 13.4% and 12.6%, respectively. The stabilization of the BCC took place by the end of 1 day, a slightly slow recovery was noted in a group of patients with blood loss of more than 1000 ml, but by the third day in all groups of the OCC was recorded in the strip of physiological values. The dynamics of hemodynamic indicators when using reform and stabisol in 16 patients without single -moraine blood loss shows that after 8-10 minutes. After the start of infusion, a clear improvement in hemodynamics indicators is noted: the pulse frequency is reduced by 15%, blood pressure increases by an average of 10%. In 8 patients with greater blood loss, before the start of the drug infusion (stabisol was used), unstable hemodynamics were observed: a decrease in systolic blood pressure to 90 mm Hg and diastolic blood pressure to 60 mm Hg, an increase in the pulse frequency to 120. Stabilization of these indicators was observed within 115 minutes from the beginning of the infusion: an increase in blood pressure by 10-15%, a decrease in the pulse frequency by an average of 20%. At the time of the greatest blood loss in all groups, the maximum decrease in SI, UO, an increase in the OPSS was noted. The greatest changes were expressed in patients with blood losses of more than 1000 ml. After the start of infusion therapy with reform and stabizol, an increase in SI by 20% and 15.8%, respectively, UO - by 24.6% and 30%, respectively. The decrease in the OPSS amounted to 24% and 32%, respectively, in patients with predicted blood loss. In patients with blood loss, more than 1000 ml of dynamics of changes in the test indicators were on average 10% lower. 6 hours after the start of infusion therapy of blood loss, a certain decrease in SI, UO and an increase in the OPSS in patients of all groups were noted, but not one of the indicators went beyond physiological values. The greatest decrease in hemoglobin, hematocrit and the number of red blood cells was recorded after surgery. By the end of the first day, the stabilization of the indicators of “red blood” was noted at almost the same level in all groups, given the transfusion of the red blood cell and SZP in a group where blood loss was more than 1000 ml. By the third day, the amount of hemoglobin, red blood cells and hematocrit were returned to a strip of physiological values. According to the indicators of the blood coagulation system (PI, fibrinogen, ACTV) a day after infusion therapy, all patients had a shift in the direction of hypocoagulation, which was associated with hemodulation and directly blood loss. In the stabizole group, changes in hemocoagulograms were more pronounced compared to reform: PI - 14.9% to 2.9%; ACTVT - 6.3% to 2.7%; Fibrinogen - 24.7% to 21.9%. Normalization of hemocoagulogram indicators occurred on the 2nd day after surgery, and in no case a hemorrhagic syndrome was observed in the postoperative period. The shifts of metabolic indicators were within physiological values. A moderate (by 10-15% of the upper boundary of the norm) an increase in the level of amylase was noted, which is naturally associated with metabolism of hydroxyethyl starch. By the 3rd day, the level of amylase in the blood returned to the strip of physiological values. In no case, there were no side and allergic reactions to the introduction of colloidal drugs. Conclusion 1. The inclusion of hydroxyethyl starch preparations 200/0.5 and 450/0.7 (reform plus, stabisol) in the therapy of blood loss allows you to quickly and effectively stabilize systemic hemodynamics, while maintaining the normovolemic type of blood circulation, maintaining the volume effect is maintained within 4–6 hours. 2. The use of HEC solutions in combination with crystalloid solutions is effective and safe as perioperative infusion therapy for surgical interventions, accompanied by blood loss of no more than10–25% of BCC, without the use of blood components. A decrease in hemoglobin, hematocrit and the amount of red blood cells is a consequence of blood loss and hemodilization and is reversible. 3. In the recommended doses of 15–20 ml/kg of body weight, hydroxyethyl starch preparations (stabisol and reform plus) do not have a clinically significant effect on the coagulating system of blood and do not cause shifts of biochemical indicators of blood. 4. GEC 200/0.5 and 450/0.7 drugs do not cause anaphylactic reactions and are mostly compatible with many drugs. Literature 1. Gelfand B. R., Protsenko D. N., Mamontova O.A., Ignatenko O.V., Gelfand E. B., Shipilova O. S. Role and the effectiveness of albumin drugs in intensive care: state of issue in 2006. Bulletin of intensive therapy, 2006, N1 2. Molchanov I.V., Bulanov A.Yu., Shulutko E.M. Some aspects of infusion therapy. Wedge. Anesthesiol. And resuscitate. 2004; 13). 3. Rudnov V.A. Infusion -transfusion therapy as a component of intensive therapy of Sepsis Surgery/Appendix, No. 1, 2005. 4. Bulanov S.A., Gorodetsky V.M., Shulutko E.M. Colloidal volumetric solutions and hemostasis. Ross. magazine Anesthesiol. And intensively. ter. 1999. 5. Shilova N.L., Borisov A.Yu., Butrov A.V. Optimization of infusion therapy in the operations of total endoprosthetics of the hip joint. News anesthesiol. And resuscitate. (Critical cell medicine). 2005; 1. 6. V. N. Serov, I. I. Baranov solutions of hydroxyethylated starch in the obstetric and gynecological practice of RMG volume 14, No. 1, 2006 7. V.N. Serov, N.I. Afonin, S.A. Shapovalenko, O.A. Goldina, Yu.V. Gorbachevsky basic infusion -transfusion prevention and therapy of bleeding in obstetric and gynecological practice based on hydroxyethylized starch solutions. Bulletin of the Blood Service of Russia, No. 2, .2000) 8. A.E. Shestopalov, R.F. Bakeev Modern aspects of volumetric -substituting therapy of acute blood loss in wounded. Actual issues of intensive therapy. No. 8–9, 2001 9. Kondratyev A.N., Novikov V. Yu. The reaction of the hemostasis system on neurosurgical surgery and the effect of infusion therapy clinical anesthesiology and resuscitation of volume 1. No. 1, 2004. 10. Butrov A.V., Borisov A.Yu. Modern synthetic colloidal plasma substitute solutions in intensive care of acute blood loss. Consilium Medicom (gastroenterology/surgery) volume 7, No. 6, 2005. 11. Rudenko M.I. Replacing operating blood loss with reform and stabizol. News anesthesiol. And resuscitate. (Critical cell medicine). 2005; 4. 12. V.A. Inglish, R.E. Inglish, I.G. Wilson infusion therapy in the periodic period Update in anaestesia, No. 12, 2006. 13. Hwang G., Marota Ja Anesthesia for Abdominal Surgery. In: Hurford We, Bailin MT, Dawison JK, Haspel KL, Rosow C., EdS. Clinical anesthesia Procedures of the Massachusetts General Hospital. Philadelphia: Lippincott - Raven, 1997. 14. Tonnesen As Crystalloids and Colloids. In: Miller RD, ed. Anesthesia, 3rd edn. New York: Churchill LivingStone, 1990. 15. Boldt J. Fluid Management of Patients Underhing Abdominal Surgery - More Questions European Journal of anaestheles 2006. 16. . Mjr ragaller, H. Theilen, T. Koch. Volume Replaceement in Critically Ill Pathents with Acute Renal Failure Journal of the American Social of Nephrology, 2001. Volume 12 17. Lobo DN, Dube MG, Neal KR, Allison SP, Rowlandlandland S BJ Perioperative Fluid and Electrolyte Management: A Survey of Consultant Surgeons in the UK. Ann R Coil Surg Engl 2002.

"Hemohes" - principle of action and indications for use

"Hemohes" is another analogue with hydroxyethyl starch in its composition. Able to reduce hematocrit, reduces plasma viscosity. Like the analogues listed above, it is used in medicine as an independent remedy or as part of a combined course of treatment for conditions during which the composition of the blood is disrupted, after heavy bleeding, loss of a large amount of fluid by the body, with serious dehydration and disturbances in the composition of the blood resulting from it.

Since the main active ingredient of the drug is hydroxyethyl starch, the instructions for use for “Hemohes” are almost completely similar to such drugs as “N-hydroxyethyl starch”, “Hydroxyethyl Starch 200” and the like. It is not recommended to use the drug on your own. As a rule, it is used in a hospital setting for heavy blood loss, dehydration, etc.