Contraindications
Absolute:
- Intracranial bleeding or acute cerebrovascular accidents of the hemorrhagic type;
- Overhydration;
- Hypokalemia;
- Hypervolemia;
- Hyperchloremia;
- Pulmonary edema;
- Hypernatremia;
- Dehydration;
- Burns;
- Sepsis;
- Kidney failure;
- Decompensated chronic heart failure;
- Severe bleeding disorders;
- Hemodialysis;
- Critical conditions (usually patients who are in the intensive care unit/resuscitation unit);
- Conditions after organ transplantation and open heart surgery under artificial circulation;
- Severe liver failure;
- Intracranial hypertension;
- Pregnancy (first trimester);
- Age under 18 years (due to the lack of necessary clinical data for patients in this age group);
- Hypersensitivity to the components of the drug.
Relative (Refortan HES 10% is prescribed with caution in the presence of the following diseases/conditions):
- Compensated chronic heart failure;
- Liver failure (mild/moderate severity);
- Blood clotting disorders, hemorrhagic diathesis;
- Conditions after surgical interventions;
- Injuries;
- Age from 65 years;
- Pregnancy (II-III trimesters; use is possible only for health reasons after assessing the benefit/risk ratio due to the likelihood of developing anaphylactic reactions and damage to the fetal brain).
Directions for use and dosage
Refortan HES 10% is used as an intravenous infusion.
Unless otherwise prescribed, the solution should be administered intravenously in doses necessary to replace the volume of circulating plasma.
The daily dose and rate of administration are calculated depending on blood loss, hematocrit and hemoglobin concentration. It is recommended to use the lowest effective dose whenever possible.
The start of administration must be limited to the initial stage of restoration of circulating blood volume (CBV). Duration of administration is up to 24 hours.
The first 10-20 ml of Refortan HES 10%, due to the likelihood of developing anaphylactic reactions, should be administered slowly, carefully monitoring the patient's condition. If the dose is too high/rapidly administered, the risk of overloading the circulatory system must be taken into account. Therapy is carried out under constant hemodynamic monitoring (to make it possible to interrupt the infusion immediately after achieving the appropriate target level of hemodynamic parameters).
In young patients without the risk of pulmonary complications, the limit for the use of a volume-replacing colloidal drug is considered to be a hematocrit of up to 30%. The maximum infusion rate for adults averages 18 ml/kg/hour (determined by baseline hemodynamic parameters).
The maximum daily dose is 18 ml/kg (1.8 g HES/kg). For patients weighing 75 kg, this corresponds to 1350 ml of Refortan HES 10%.
Indications for use
Refortan is indicated for:
- Treatment and prevention of hypovolemic conditions and shock (including septic) in infectious diseases, wounds, burns, intoxications, traumatic lesions, surgical interventions and other conditions requiring replacement of circulating blood volume (CBV);
- Hemodilution (therapeutic blood dilution);
- Acute normovolemic hemodilution during surgical interventions (in order to reduce the need for donor blood).
Side effects
Possible adverse reactions (>1/10 – very common; >1/100, <1/10 – often; >1/1000, <1/100 – uncommon; >1/10,000, <1/1000 – rare; < 1/10,000 - very rare; with unknown frequency - if it is impossible to estimate the frequency of occurrence from the available data):
- Immune system: very rarely - anaphylactoid reactions (most often in the form of chills, slight fever, vomiting, urticaria, itching), flu-like syndrome (including muscle/headache, swelling of the lower extremities), enlargement of the parotid and submandibular salivary glands, severe intolerance reactions , occurring with shock and life-threatening symptoms (sometimes up to respiratory/cardiac arrest). In cases of intolerance reactions, the infusion should be immediately interrupted and, at the same time, standard emergency measures should be started;
- Lymphatic and hematopoietic system: very often - decreased hematocrit/plasma protein concentration due to hemodilution; often (depending on the dose administered) - a decrease in the concentration of blood coagulation factors at relatively high doses of HES (a transient increase in bleeding/clotting time is possible);
- Skin and subcutaneous fat: infrequently (with long-term daily administration of the drug in medium/high doses) - itching that is difficult to relieve (it may appear several weeks after the end of treatment and persist for a long time);
- Kidneys and urinary tract: rarely – pain in the kidney area (it is recommended to interrupt the infusion, ensure sufficient fluid intake into the body, and frequently monitor serum creatinine levels); with unknown frequency - impaired renal function;
- Liver and biliary tract: with unknown frequency - liver damage;
- Laboratory indicators: very often - increased serum amylase activity (due to the formation of the HES-amylase complex, which is slowly excreted by the kidneys; not associated with the clinical manifestation of pancreatitis). It is possible to change such laboratory parameters as the concentrations of fatty acids, protein, glucose, sorbitol dehydrogenase in the blood plasma, cholesterol, biuret test, ESR, specific gravity of urine.
Pharmacological properties of the drug Refortan
Plasma-substituting colloidal preparation, solution of 6% hydroxyethyl starch in isotonic solution of sodium chloride. Hydroxyethyl starch is obtained from waxy corn starch by partial hydrolysis of amylopectin followed by hydroxyethylation. Refortan is an almost iso-oncotic/weak hyperoncotic solution. Infusion of the drug leads to an increase in reduced colloid osmotic and central venous pressure. Improves the rheological properties of blood. The half-life of hydroxyethyl starch after a 4-hour infusion of 500 ml of the drug is about 5–6 hours. It does not accumulate in the body; some time after infusion is detected in the cells of the reticuloendothelial system.
special instructions
Refortan HES 10% has no effect on the determination of blood group.
It must be taken into account that if administered too quickly and when high doses are used, hemodynamics may be disrupted.
During therapy, it is necessary to monitor the electrolyte composition of the blood serum, ensure sufficient intake of fluid into the body (at least 2-3 liters per day), and also monitor the functional state of the kidneys. To prevent the occurrence of overhydration, which can lead to decompensation of heart failure in the presence of a history of heart disease, blood volume and cardiac activity should be monitored.
If there is a lack of fibrinogen, Refortan HES 10% can be used only in emergency cases when the patient’s life is in danger in the absence of donor blood components.
Due to the existing likelihood of anaphylactoid (allergic) reactions, careful monitoring of the patient's condition and establishment of a low rate of drug administration are indicated. Symptoms of anaphylaxis can develop within minutes. Main symptoms: redness of the skin (sudden rush of blood to the neck, face), severe itching, suffocation (in the form of a feeling of “coma in the throat”). The next stage is characterized by the appearance of nausea, abdominal cramps, tachycardia, arterial hypotension, which can in some cases lead to loss of consciousness, including cessation of cardiac activity and respiratory arrest.
If intolerance reactions develop, it is necessary to immediately interrupt the administration of Refortan HES 10% and take emergency measures.
In case of renal failure, as well as in patients receiving renal replacement therapy, the use of the drug is contraindicated. At the beginning of treatment, serum creatinine levels should be monitored. When the first signs indicating the development of kidney disorders appear, therapy is canceled. There are reports of an increased need for renal replacement therapy after administration of the drug (up to 90 days; during this period it is recommended to monitor the state of renal function).
There is a relationship between the dose and the frequency of development of itching in otoneurological diseases (tinnitus, severe hearing loss, sound trauma). Against the background of these diseases, it is recommended to limit the daily dose of Refortan HES 10% to 250 ml.
In case of severe liver failure, the drug is not prescribed. Patients with mild/moderate severity or bleeding disorders should use Refortan HES 10% with caution. Severe hemodilution should be avoided when treating hypovolemia. In cases of re-prescribing the drug, careful monitoring of blood clotting parameters is necessary. The reason for discontinuation of the drug is the appearance of the first signs of coagulopathy.
Before prescribing Refortan HES 10% to patients after trauma or surgery, the balance of benefit with uncertain long-term safety should be assessed, since long-term data confirming the safety and effectiveness of the drug in this group of patients are lacking. It is recommended to consider the use of other available therapeutic measures.
To reduce the likelihood of developing renal and cardiovascular complications associated with hypervolemia, elderly patients, who are most likely to have heart/renal failure, need to carefully select the dose and monitor the condition during treatment.
Refortan HES 10% (Refortan HES 10%)
Release form, composition and packaging
Solution for infusion 10% transparent, slightly opalescent.
100 ml hydroxyethyl starch 200/0.5 10 g
- osmolarity about 300 mOsm/l
- colloid osmotic pressure (COP) about 85 mbar = approx. 65 mmHg
- pH 4.0-7.0
Excipients: sodium chloride, water for injection.
Clinical and pharmacological group
Plasma replacement drug.
pharmachologic effect
Plasma replacement drug. It is a 10% isotonic solution of hydroxyethyl starch (HES) (a hydroxyl derivative of the acid hydrolysis product of corn starch) with an average molecular weight of 200,000 daltons and a degree of substitution of 0.5, which means that for every 10 glucose residues of amylopectin there are 5 hydroxyethyl groups.
HES, due to its ability to bind and retain water, has the ability to increase the bcc by 85-100% of the administered volume (the plasma-substituting effect is stable for 4-6 hours). Restores impaired hemodynamics, improves microcirculation, rheological properties of blood (by reducing hematocrit), reduces blood viscosity, reduces platelet aggregation and prevents erythrocyte aggregation.
The similarity of the structure of hydroxyethyl starch with the structure of glycogen explains the good tolerability of the drug; it does not have a locally irritating or immunotoxic effect. Accumulating in RES cells, it does not have a toxic effect on the liver, lungs, spleen, or lymph nodes.
Indications for use of the drug
- replenishment of blood volume in vessels in conditions of insufficient circulating blood volume;
- prevention and treatment of hypovolemic shock due to burns, injuries, surgeries;
- hemodilution (eg, isovolemic hemodilution).
Dosage regimen
Mode of application
Long-term intravenous infusion using a dropper.
The first 10-20 ml should be administered slowly and with strict monitoring of the patient's condition, due to the impossibility of completely eliminating anaphylactoid reactions. The daily dose and rate of infusion depend on the amount of blood loss and the hematocrit value. The duration and extent of therapy depend on the duration and extent of hypovolemia. When using the drug for hemodilution purposes, they usually follow multi-day therapy regimens.
Daily dose
When replacing blood volume, the average daily dose is usually 250 - 1000 ml. Only in exceptional cases is it allowed to exceed the value of 20 ml/kg body weight. When using the drug for hemodilution for several days in a row, the daily dose is usually 250 - 500 ml. The total dosage of 5 l can only be exceeded in exceptional cases, and the dose can be distributed over a treatment period of up to 4 weeks.
Infusion rate
In the absence of an acute emergency situation, the recommended duration of infusion is at least 30 minutes per 500 ml of Refortan HES 200/0.5.
Use only transparent to slightly opalescent and colorless to no more intensely colored solutions than slightly yellow ones.
For one-time use only.
Use only solutions in undamaged containers!
The use of solutions after the expiration date is not permitted!
Refortan HES 200/0.5 from the started container should be used up as soon as possible.
Side effect
Anaphylactoid reactions to hydroxyethyl starch (incidence - in terms of the administered number of units of infusion solution - about 0.085%). Such reactions manifest themselves in the form of vomiting, slight fever, chills, itching and nettle fever. Enlargement of the superior submandibular and parotid salivary glands and flu-like symptoms (headache, muscle pain and peripheral edema of the lower extremities) were observed.
Intolerance reactions, accompanied by shock and life-threatening symptoms (sometimes up to the cessation of cardiac circulation and respiratory arrest) are extremely rare (incidence - in terms of the given number of units of infusion solution - about 0.006%).
If an intolerance reaction occurs, the infusion should be stopped immediately, and all necessary emergency measures should be taken at the same time (see section Special instructions).
Both during and at the end of high-dose long-term hemodilution therapy using HES infusion solutions, a transient appearance of itching was observed.
The level of amylase in the serum after infusion of the drug Refortan HES 200/0.5 increases noticeably, however, after 3-5 days it returns to normal. No diagnostic or therapeutic measures are required.
When high doses of Refortan HES 200/0.5 are administered, the possibility of increased bleeding cannot be ruled out (a dilution effect, and sometimes, possibly, a specific effect of the drug). Therefore, increasing the dosage to a value exceeding the maximum recommended should only be done in exceptional cases.
Contraindications to the use of the drug
- hypervolemia;
- states of hyperhydration;
- severe congestive heart failure;
- kidney failure in combination with oliguria or anuria, as well as with a serum creatinine level of 2.0 mg/dl;
- severe hemorrhagic diathesis;
- known patient hypersensitivity to hydroxyethyl starch (HES).
Particular caution is recommended in patients with pulmonary edema, decompensated heart failure, impaired renal function, chronic liver disease, bleeding diathesis or dehydration with narrowing of the extracellular space, in which case it is recommended to first replace fluid (using crystalloid solutions). Given the research results, it is also recommended to exercise caution in fibrinogen deficiency. There are no data available for use in children under 10 years of age.
Pregnancy and lactation
There is also no experience with the use of the drug during pregnancy and lactation, so it is recommended to carefully weigh the benefit-risk ratio when using the drug Refortan GES 200/0.5.
Use for liver dysfunction
Particular caution is recommended in patients with chronic liver diseases.
Use for renal impairment
Particular caution is recommended in patients with impaired renal function.
special instructions
The first 10-20 ml should be administered slowly, carefully monitoring the patient's condition, due to the impossibility of completely eliminating anaphylactoid reactions. The risk of circulatory overload if the dose is too high and the infusion rate is too high must be taken into account.
During treatment with Refortan HES 200/0.5, it is necessary to ensure sufficient fluid supply to the body. Monitoring of serum electrolytes (including sodium, potassium and chloride) is recommended.
In shock conditions caused mainly by loss of water and electrolytes (severe vomiting, diarrhea, burns), after initial treatment with Refortan HES 200/0.5, further treatment with a balanced solution of electrolytes is recommended.
Increased doses of Refortan HES 200/0.5 cause a liquefaction effect and lead to a decrease in hematocrit, as well as a decrease in the concentration of hemoglobin and plasma protein. Hemoglobin values below 10 g% and hematocrit below 27 are considered critical. Starting with total protein levels <5.0 g%, albumin administration is indicated. If blood loss exceeds 20-25% of the circulating blood volume, additional administration of red blood cells is necessarily indicated.
Drug interactions
When used simultaneously with aminoglycoside antibiotics, HES can potentiate their nephrotoxicity.
HES may affect clinical and chemical parameters (glucose, protein, ROE, biuret, fatty acid, cholesterol, sorbitol dehydrogenase, urine specific gravity, urine electrophoresis in the form of pseudo-paraproteinuria).
When using infusion solutions in combination (concentrates for the preparation of infusion solutions, injection solutions and powders for injection purposes, or dry matter for the preparation of injection solutions), it is recommended each time to carefully (at least visually) check the compatibility (miscibility) of the drugs (however, it is still possible chemical or therapeutic incompatibilities invisible to the eye).
Storage conditions and periods
Keep the medicine out of the reach of children!
Store at a temperature no higher than 25°C! Shelf life: 5 years.
Use before the date indicated on the package.
Drug interactions
When mixing Refortan HES 10% with other drugs/substances in the same container/system, pharmaceutical incompatibility may develop.
Before each administration, it is necessary to carefully (at least visually) monitor the compatibility of drugs, however, this does not exclude cases of pharmacological/chemical interactions that are not visually determined.
With the combined use of Refortan HES 10% with aminoglycoside antibiotics, the nephrotoxicity of the latter may be potentiated.
