Refortan

Refortan is a plasma substitute containing the active substance HES, dissolved in an isotonic liquid NaCl.

The medication is practically an iso-oncotic liquid, with the introduction of which volumes can be achieved, on average corresponding to 100% or slightly higher than 100% of the applied amount of drugs. The therapeutic agent can be used in clinical procedures as an isovolemic fluid for administration of infusions. [1]

Indications Refortan

It is used for hypovolemia associated with severe blood loss - in situations where the use of crystalloids alone will not be enough.

Release form

The release of the drug substance is made in the form of an infusion liquid - inside glass or polyethylene bottles with a volume of 0.25 or 0.5 liters; inside a pack - 10 such bottles.

Pharmacodynamics

HES is a synthetic foreign colloid obtained from waxy corn starch through partial hydrolysis of amylopectin followed by hydroxyethylation.

Taking into account the volumes of the injected drug, the indicators of central intravenous pressure, as well as colloid-osmotic pressure, increase significantly; in the case of their reduced level, they increase to normal values. 

Pharmacokinetics

On average, Refortan stays inside the blood plasma for a period of 5-6 hours (in the case of a 4-hour infusion of 0.5 l of 10% liquid) in people with normal renal function. After the specified 5-6 hours from the moment of completion of the procedure, the plasma Cmax of HES is halved.

The well-controlled effect of short-term volume acquisition (about 3 hours), and in addition, favorable rheological characteristics (stabilization of enhanced platelet aggregation and a decrease in hematocrit and blood viscosity indicators) allow the drug to be used to replenish the volume for a short and medium-term period. The use of HES is limited to the initial stage of volume recovery, with a maximum time interval of 24 hours. [2]

HES, which is compatible with other plasma substitutes, is deposited for a short period inside tissues (mainly inside the RGS). Despite the fact that after several months the presence of deposited vacuoles inside the cells of the CGV was noted, there is no information that the function of the CGC is impaired.

The drug undergoes continuous cleavage by blood serum amylase and is excreted by the kidneys. After 24 hours, approximately 70% of the HES used is excreted in the urine; approximately 10% of the substance is registered inside the blood serum. Only a small amount of the drug is excreted during the dialysis process, and the significance of hemofiltration cannot be reliably determined.

Dosing and administration

It is necessary to use HES only at the initial stage of volume recovery, with a maximum allowable time interval of 24 hours.

The initial 10-20 ml of fluid is injected at a low speed, carefully monitoring the patient's condition (to avoid the appearance of anaphylactic signs).

Refortan is used in the minimum effective portions over a short period of time. During therapy, it is necessary to constantly monitor hemodynamics, and immediately after reaching its necessary values, stop treatment. Do not use portions in excess of the maximum permissible daily dosage.

Per day, it is allowed to inject no more than 30 mg / kg of the drug (corresponding to 1.8 g / kg). Thus, a person weighing 75 kg requires the introduction of 2250 ml of the drug.

Taking into account the state of cardiac blood flow, the infusion rate should be no more than 20 ml / kg per hour.

The medication should be injected in / in the way.

• Application for children

Information regarding the prescription of the medication in pediatrics is limited, which is why HES medications are not used for children.

Use Refortan during pregnancy

There is no information regarding the safety of administration of HES to pregnant women. Animal tests on the effects of HES on reproductiveness have not shown that it adversely affects the fetus, but there is too little evidence to establish the safety of drugs in relation to embryo / fetal development, pregnancy, peri- and postnatal development. It is prohibited to administer HES in the 1st trimester, and during the 2nd and 3rd trimester it is allowed to use only under strict indications. When Refortan is administered to pregnant women, it is necessary to take into account the likelihood of anaphylactic signs that can cause cerebral damage in the fetus.

There is no information regarding the use of the drug for HB, which is why it must be administered very carefully during the indicated period.

Contraindications

The main contraindications:

• increased intolerance to the active ingredient or to any of the other elements of the drug;
• burns or sepsis;
• hypervolemia;
• failure of the kidneys or renal replacement treatment;
• hemorrhage of cerebral or intracranial nature;
• appointment to critically ill persons;
• severe coagulopathy;
• lack of fibrinogen (in such situations, the medication can be used only if the patient's life is threatened and it is impossible to receive donor blood);
• use in people with transplanted organs;
• CHF;
• hypokalemia, as well as hypernatasia or -chloremia, proceeding in a severe form;
• severe hepatic dysfunction;
• hyperhydria (also pulmonary edema);
• dehydration, in which it is necessary to adjust the level of EBV.

Side effects Refortan

Among the side symptoms:

• disorders of blood and lymphatic activity: often there is a decrease in blood proteins and hematocrit due to hemodilution. Quite often (depending on the volume of the injected portion), relatively large doses of HES cause a dilution of the concentration of clotting factors, which may change blood clotting. It is possible to lengthen the periods of bleeding;
• problems with digestive function: possible liver damage;
• lesions of subcutaneous tissues and epidermis: sometimes with prolonged use of HES, persistent itching appears, causing extremely uncomfortable sensations, which can develop after completion of therapy and last for several months;
• data from additional analyzes: often after the drug infusion procedure, the blood amylase index significantly increases, but this should not be considered as a symptom of pancreatic disease;
• disorders in the work of the urethra and kidneys: occasionally pain in the lumbar region appears. With such violations, it is necessary to stop the infusion, carefully monitor the blood creatinine index and ensure the flow of fluid in sufficient volumes into the patient's body. When dehydrated, the use of drugs can cause anuria. Development of renal damage is possible;
• immune manifestations: single anaphylactic signs with varying degrees of severity are observed.

Anaphylactic manifestations. There is some information about the appearance of anaphylactic signs associated with HES. They are mainly in the form of vomiting, a slight increase in temperature, itching, a feeling of coldness and hives. There is an increase in the size of the parotid and submandibular salivary glands, the appearance of swelling on the legs and mild flu-like symptoms (headaches and muscle pains). Severe manifestations of intolerance, in which a state of shock and life-threatening signs (cessation of respiration and heart function) develop, are only occasionally noted. If allergies are observed, the infusion should be stopped immediately and the standard ambulance procedures should be carried out at the same time.

Signs of anaphylaxis. Violations can occur after a few minutes. Among the manifestations that can cause anxiety, sudden redness of the epidermis and severe itching. Sometimes there is a feeling of suffocation and a lump in the throat. More intense manifestations are abdominal cramps, nausea, tachycardia and a strong decrease in blood pressure, which can cause loss of consciousness, as well as respiratory arrest and cardiac arrest.

Treatment for anaphylaxis. With the development of the first symptoms (nausea, epidermal manifestations), it is necessary to stop the infusion (while leaving the cannula inside the vein or providing free access to the vein), seat the patient with his head down and release the respiratory ducts. It is also necessary to immediately inject him with adrenaline (dissolve 1 ml of adrenaline liquid in 10 ml; proportion 1k 1000). First, 1 ml of liquid is injected (contains 0.1 mg of adrenaline), with monitoring of blood pressure and pulse.

To increase the volume, 5% human albumin is injected through an IV injection. In addition, prednisolone (0.25-1 g) or the corresponding volume of another GCS can be administered in the same way. Prednisolone can be administered several times. For children, portions of prednisone with adrenaline are reduced, taking into account weight and age.

Other procedures are also carried out - for example, the use of oxygen, mechanical ventilation, the use of antihistamines. Patients need to be treated in intensive care.

Overdose

With acute intoxication, hypervolemia may develop. With such a violation, you must immediately stop the infusion and administer a diuretic drug (the latter is at the discretion of the doctor).

Interactions with other drugs

In the case of mixing with infusion fluids, concentrate for the manufacture of infusion fluid, injection solution and lyophilisates or dry components for the preparation of injection fluids, it is necessary to carefully visually inspect them for miscibility / compatibility of substances.

Use in combination with aminoglycosides can lead to potentiation of their nephrotoxicity.

Storage conditions

Refortan must be kept in a place closed from the penetration of children. Glass vials should be kept at temperatures no more than 25 ° C.

Shelf life

Refortan can be applied within a 5-year term from the date of marketing of the pharmaceutical substance.

Analogs

The analogs of the drug are the drugs Tenziton, Perftoran, Albumin with Promit-infusion, Chetasorb and Biocerulin, and besides this Refordez and Gestar with Gek-infusion.