リフォルタン

Refortan is a plasma substitute containing the active substance HEC dissolved in isotonic liquid NaCl.

The drug is a virtually iso-oncotic fluid, the introduction of which can achieve volumes that on average correspond to 100% or slightly higher than 100% of the applied amount of the drug. The therapeutic agent can be used in clinical procedures as an isovolemic fluid for the introduction of infusions. [ 1 ]

適応症 リフォルタン

It is used in cases of hypovolemia associated with severe blood loss – in situations where the use of crystalloids alone will not be sufficient.

リリースフォーム

The medicinal substance is released in the form of an infusion liquid - inside glass or polyethylene bottles with a volume of 0.25 or 0.5 l; there are 10 such bottles inside a pack.

薬力学

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

Taking into account the volumes of the administered drug, the central intravenous pressure and colloid osmotic pressure values increase significantly; if their level is reduced, they increase to normal values.

薬物動態

On average, Refortan remains in the blood plasma for 5-6 hours (in 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 HEC decreases by half.

Well-controlled effect of short-term volume acquisition (about 3 hours), and in addition, favorable rheological characteristics (stabilization of increased platelet aggregation and reduction of hematocrit and blood viscosity) allow the use of the drug for volume replenishment for a short and medium period of time. The use of HEC is limited to the initial stage of volume restoration, with a maximum time interval equal to 24 hours. [ 2 ]

HEC, which is compatible with other plasma substitutes, is deposited within tissues for a short period (mainly within the RGS). Although after several months the presence of deposited vacuoles within the RGS cells was noted, there is no information that the RGS function is impaired.

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

投薬および投与

HEC should be used exclusively at the initial stage of volume restoration, with a maximum allowable time interval of 24 hours.

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

Refortan is used in minimal effective doses for a short period of time. During therapy, hemodynamics should be constantly monitored, and treatment should be stopped immediately upon reaching the required values. Doses exceeding the maximum permissible daily dosage should not be used.

No more than 30 mg/kg of the drug (corresponding to 1.8 g/kg) can be administered per day. Thus, a person weighing 75 kg requires the administration of 2250 ml of the drug.

Taking into account the state of cardiac blood flow, the rate of infusion should not exceed 20 ml/kg per hour.

The medication must be administered intravenously.

• Application for children

Information regarding the use of the drug in pediatrics is limited, which is why HEC medications are not used in children.

妊娠中に使用する リフォルタン

There is no information regarding the safety of administering HEC to pregnant women. Animal testing of the effects of HEC on reproduction has not shown that it has a negative effect on the fetus, but the data obtained are too insufficient to establish the safety of the drug in terms of embryo/fetus development, pregnancy, peri- and postnatal development. HEC is prohibited in the first trimester, and during the second and third trimesters it is allowed to be used only for strict indications. When administering Refortan to pregnant women, the likelihood of anaphylactic symptoms that can cause brain damage to the fetus should be taken into account.

There is no information regarding the use of the drug during breastfeeding, which is why it should be administered very carefully during this period.

禁忌

Main contraindications:

• increased intolerance to the active component or any of the other elements of the drug;
• burns or sepsis;
• hypervolemia;
• renal failure or renal replacement therapy;
• hemorrhage of a cerebral or intracranial nature;
• appointment to persons in critical condition;
• severe coagulopathy;
• fibrinogen deficiency (in such situations, the medication can only be used if the patient’s life is at risk and it is impossible to obtain donor blood);
• use in people with organ transplants;
• ZSN;
• hypokalemia, as well as hypernatemia or -chloremia, occurring in severe form;
• severe liver dysfunction;
• hyperhydria (also pulmonary edema);
• dehydration, in which case it is necessary to correct the EBV level.

副作用 リフォルタン

Side effects include:

• disorders of blood and lymphatic activity: often there is a decrease in blood protein levels and hematocrit due to hemodilution. Quite often (depending on the volume of the administered portion), relatively large doses of HEC cause dilution of the concentration of coagulation factors, which can change blood clotting. Prolongation of bleeding periods is possible;
• problems with digestive function: liver damage is possible;
• lesions of subcutaneous tissues and epidermis: sometimes with prolonged use of HEC, persistent itching appears, causing extremely uncomfortable sensations, which can develop after the end of therapy and last for several months;
• additional analysis data: often after the drug infusion procedure, the blood amylase level increases significantly, but this should not be considered a symptom of pancreatic disease;
• disorders of the urinary tract and kidneys: pain in the lumbar region occasionally appears. In such cases, it is necessary to stop the infusion, carefully monitor the blood creatinine level and ensure the patient receives sufficient amounts of fluid. In case of dehydration, the use of drugs can cause anuria. Renal damage may develop;
• immune manifestations: anaphylactic symptoms of varying severity are observed occasionally.

Anaphylactic manifestations. There are isolated reports of anaphylactic symptoms associated with HEC. They mainly take the form of vomiting, a slight increase in temperature, itching, a feeling of cold and urticaria. An increase in the size of the parotid and submandibular salivary glands, swelling of the legs and mild flu-like symptoms (headaches and muscle pain) are noted. Only isolated cases of severe manifestations of intolerance are noted, in which a state of shock and life-threatening symptoms (respiratory and cardiac arrest) develop. If an allergy is observed, the infusion should be stopped immediately and standard emergency procedures should be carried out at the same time.

Signs of anaphylaxis. Violations may occur within a few minutes. Symptoms that may cause anxiety include sudden reddening of the epidermis and severe itching. Sometimes there is a feeling of suffocation and a lump in the throat. More intense symptoms include abdominal cramps, nausea, tachycardia, and a sharp drop in blood pressure that may cause loss of consciousness, as well as respiratory and cardiac arrest.

Treatment of anaphylaxis. When the first symptoms develop (nausea, epidermal manifestations), stop the infusion (leaving the cannula inside the vein or providing free access to the vein), seat the patient, lowering his head down, and free the respiratory ducts. It is also necessary to immediately administer adrenaline (dissolve 1 ml of adrenaline liquid in 10 ml; proportion 1 to 1000). First, administer 1 ml of liquid (contains 0.1 mg of adrenaline), monitoring the blood pressure and pulse.

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

Other procedures are also carried out, such as the use of oxygen, artificial ventilation, and the use of antihistamines. Patients must be treated in intensive care.

過剰摂取

In acute intoxication, hypervolemia may develop. In such a disorder, the infusion should be stopped immediately and a diuretic drug should be administered (the latter at the doctor's discretion).

他の薬との相互作用

In case of mixing with infusion fluids, concentrate for the preparation of infusion fluid, injection solution and lyophilisates or dry components for the preparation of injection fluids, they must be carefully visually inspected for miscibility/compatibility of substances.

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

保管条件

Refortan must be stored in a place closed to children. Glass bottles must be kept at a temperature of no more than 25°C.

賞味期限

Refortan can be used within a 5-year period from the date of sale of the pharmaceutical substance.

Analogues

Analogues of the drug are Tensiton, Perftoran, Albumin with Promit infusion, Hetasorb and Biocerulin, as well as Refordez and Gestar with Gek infusion.