Gestosis - Treatment

In case of edema, treatment can be carried out in antenatal clinics. Pregnant women with gestosis, preeclampsia and eclampsia should be hospitalized in obstetric hospitals located in multidisciplinary hospitals with an intensive care unit and a department for nursing premature babies, or in perinatal centers.

Therapy for pregnant women is based on the treatment of symptoms and signs of secondary manifestations of gestosis, with the goal of reducing the incidence of complications for the mother and fetus.

The principles of gestosis therapy consist of creating a therapeutic and protective regimen; restoring the function of vital organs; and rapid and gentle delivery.

The creation of a therapeutic and protective regime is carried out by normalizing the function of the central nervous system.

Restoration of the function of vital organs, along with hypotensive, infusion-transfusion (ITT) and detoxification therapy, normalization of water-salt metabolism, rheological and coagulation properties of the blood, improvement of uteroplacental blood flow, includes normalization of the structural and functional properties of cell membranes.

Treatment of gestosis currently needs to be carried out under the control of:

• CVP (within 3–4 cm H2O);
• diuresis (at least 35 ml/h);
• blood concentration indicators (hemoglobin not less than 70 g/l, hematocrit not less than 0.25 l/l, number of erythrocytes not less than 2.5×10 ¹² /l and platelets not less than 100×10 ⁹ /l);
• biochemical blood parameters (total protein not less than 60 g/l, alkaline phosphatase, AST, ALT, total bilirubin, creatinine within the physiological norm depending on the determination method);
• electrolytes (K ⁺ no more than 5.5 mmol/l, Na ⁺ no more than 130–159 mmol/l). Normalization of the central nervous system function is achieved by sedative and psychotropic therapy.

In patients with mild to moderate gestosis without extragenital pathology, preference is given to sedatives of plant origin (valerian rhizomes with roots or valerian rhizome tincture 3 times a day; motherwort herb - liquid extract - 20 drops 3-4 times; peony rooting herb, rhizomes and roots - tincture - 1 teaspoon 3 times) in combination with sleeping pills (nitrazepam 1 tablet at night) or tranquilizers (diazepam, oxazepam) in doses depending on the condition.

In case of moderate gestosis and preeclampsia, all initial manipulations are carried out against the background of neuroleptoanalgesia using benzodiazepine tranquilizers, neuroleptics, analgesics, antihistamines, barbiturates as indicated.

Intubation and artificial ventilation are indicated in eclampsia and its complications. In the postoperative or postpartum periods, the mother can be transferred to independent breathing no earlier than 2 hours after delivery and only with stabilization of systolic blood pressure (no higher than 140–150 mm Hg), normalization of central venous pressure, heart rate, and diuresis rate (more than 35 ml/h) against the background of consciousness recovery.

The use of gamma-hydroxybutyric acid, calcium salt, is contraindicated due to its ability to cause arterial hypertension and psychomotor agitation.

Antihypertensive therapy is carried out when the systolic blood pressure level exceeds the initial pre-pregnancy level by 30 mm Hg, and the diastolic blood pressure by 15 mm Hg. Currently, the following is recommended:

• calcium antagonists (magnesium sulfate up to 12 g/day, verapamil 80 mg 3 times a day, amlodipine 5 mg 1 time per day);
• adrenergic receptor blockers and stimulants (clonidine 150 mg 3 times a day, betaxolol 20 mg 1 time per day, nebivolol 2.5 mg 2 times a day);
• vasodilators (hydralazine 10–25 mg 3 times a day, sodium nitroprusside 50–100 mcg, prazosin 1 mg 1–2 times a day);
• ganglion blockers (azamethonium bromide 5% 0.2–0.75 ml, hexamethonium benzosulfonate 2.5% 1–1.5 ml).

In mild gestosis, monotherapy is used (calcium antagonists, antispasmodics); in moderate gestosis, complex therapy is used for 5–7 days, followed by a transition to monotherapy if there is an effect.

The following combinations are most effective:

• calcium antagonists + clonidine (85%);
• vasodilators + clonidine (82%).

In severe forms of gestosis, including preeclampsia and eclampsia, complex hypotensive therapy is performed. At low CVP values (less than 3 cm H2O), hypotensive therapy should be preceded by ITT. Magnesium sulfate is recognized as the drug of choice. The initial dose is 2.5 g of dry matter. The total daily dose of magnesium sulfate is at least 12 g intravenously under the control of respiratory rate, hourly diuresis and knee reflex activity. Calcium antagonists can be used simultaneously with magnesium sulfate: verapamil at 80 mg/day or amlodipine 5-10 mg/day. Calcium antagonists can be combined with clonidine in an individual dose. If there is no effect from hypotensive therapy, short-acting ganglion blockers (azamethonium bromide) or nitrate derivatives (sodium nitroprusside) are used.

Infusion-transfusion therapy (ITT) is used to normalize the volume of circulating blood, colloid osmotic pressure of plasma, rheological and coagulation properties of blood, and macro- and microhemodynamic parameters.

• In addition to crystalloids (Mafusol - potassium chloride + magnesium chloride + sodium chloride + sodium fumarate, Khlosol - sodium acetate + sodium chloride + potassium chloride), the ITT also includes infucol.
• The ratio of colloids and crystalloids, the volume of ITT depend on the hematocrit value (not lower than 0.27 l/l and not higher than 0.35 l/l), diuresis (50–100 ml/h), central venous pressure (not less than 3–4 cm H2O), hemostasis parameters (antithrombin III level not less than 70%, endogenous heparin not lower than 0.07 U/ml), arterial pressure, and plasma protein content (not less than 50 g/l).

If colloids predominate in the ITT composition, complications such as colloid nephrosis and worsening hypertension are possible; with an overdose of crystalloids, hyperhydration develops.

When performing ITT, the rate of fluid administration and its ratio to diuresis are important. At the beginning of the infusion, the rate of administration of solutions is 2-3 times higher than that of diuresis, subsequently, during or at the end of fluid administration, the amount of urine in 1 hour should exceed the volume of fluid administered by 1.5-2 times.

To normalize diuresis in mild to moderate gestosis, if bed rest is ineffective, use diuretic herbal infusions (juniper berries, 1 tablespoon 3 times a day, bearberry leaves, 30 ml 3 times a day, horsetail herb, orthosiphon stamineus leaves, lingonberry leaves, blue cornflower flowers, birch buds) and herbal diuretics (lespedeza capitata tincture, lespedeza bicolor shoots) 1–2 teaspoons a day.

If the latter are ineffective, potassium-sparing diuretics are prescribed (hydrochlorothiazide + triamterene, 1 tablet for 2-3 days).

Saluretics (furosemide) are administered for moderate and severe gestosis with restoration of central venous pressure to 3–4 cm H2O, total protein content in the blood of at least 50 g/l, hyperhydration, and diuresis of less than 30 ml/h.

If there is no effect from the administration of furosemide at the maximum dose (500 mg/day in divided doses), isolated ultrafiltration is used for the purpose of dehydration.

In case of acute renal failure, the patient is transferred to a specialized nephrology department for hemodialysis. Normalization of rheological and coagulation properties of blood should include one of the disaggregants. Dipyridamole (2 tablets 3 times) or pentoxifylline (1 tablet 3 times), or xanthinol nicotinate (1 tablet 3 times) or acetylsalicylic acid are prescribed. Dipyridamole is one of the most effective drugs, it corrects placental blood flow, prevents placental dystrophy, eliminates fetal hypoxia. It is possible to use anticoagulants - low molecular weight heparins (calcium nadroparin, sodium enoxaparin, sodium dalteparin). Disaggregants are initially used in the form of intravenous solutions, then - tablets, for at least 1 month.

Indications for the use of low-molecular-weight heparins (calcium nadroparin, sodium enoxaparin, sodium dalteparin) are a decrease in the level of endogenous heparin to 0.07–0.04 U/ml and below, antithrombin III to 85.0–60.0% and below, chronometric and structural hypercirculation according to thromboelastogram data, an increase in platelet aggregation to 60% and above. Low-molecular-weight heparins are used when dynamic laboratory monitoring of the coagulation properties of the blood is possible. They should not be used in thrombocytopenia, severe hypertension (BP 160/100 mm Hg and above), since there is a risk of hemorrhage.

Normalization of the structural and functional properties of cell membranes and cellular metabolism is carried out by antioxidants (vitamin E, actovegin, solcoseryl), membrane stabilizers containing polyunsaturated fatty acids (phospholipids, soybean oil + triglycerides, omega-3 triglycerides [20%]).

Correction of structural and functional disorders of cell membranes in pregnant women with mild gestosis is achieved by including tablets (vitamin E up to 600 mg/day) in the treatment complex, as well as phospholipids (2 drops 3 times a day).

In case of moderate and severe gestosis, membrane-active substances are administered intramuscularly and intravenously until the effect is achieved, followed by a transition to tablets, the course lasts up to 3–4 weeks.

In patients with moderate gestosis and intrauterine growth retardation of the fetus at a gestation period of up to 30–32 weeks or less, soybean oil + triglycerides are administered at 100 ml every 2–3 days and Solcoseryl at 1 ml for 15–20 days.

The complex therapy of gestosis is aimed at normalizing the uteroplacental circulation. Additionally, beta-adrenomimetics (hexoprenaline) are used for this purpose.

Immunotherapy with allogeneic lymphocytes of the husband (immunocytotherapy) and immunoglobulin. The mechanism of the therapeutic effect of immunocytotherapy with allogeneic lymphocytes is associated with the normalization of the processes of immune recognition of fetal alloantigens by the mother's body and the enhancement of suppressor mechanisms [34]. Immunization of the mother with allogeneic lymphocytes of the husband, reactivating the weakened local immune response, activates the synthesis of interleukins and growth factors, the secretion of placental proteins, which ensure the normal development of pregnancy. Immunocytotherapy is carried out once a month. The optimal periods of pregnancy for immunocytotherapy are 15-20, 20-24, 25-29 and 30-33 weeks.

Monitoring is carried out by weekly general clinical examination for 1 month. The frequency of lymphocyte administration depends on the clinical effect, proteinuria, hemodynamic parameters, body weight and the level of placental proteins in the blood serum.

Extracorporeal methods of detoxification and dehydration - plasmapheresis and ultrafiltration - are used in the treatment of severe forms of gestosis.

Indications for plasmapheresis:

• severe gestosis with gestation periods up to 34 weeks and no effect from ITT for the purpose of prolonging pregnancy;
• complicated forms of gestosis (HELLP syndrome and acute gastrointestinal tract disease) to stop hemolysis, disseminated intravascular coagulation, and eliminate hyperbilirubinemia. Indications for ultrafiltration:
• posteclamptic coma;
• cerebral edema;
• intractable pulmonary edema;
• anasarca.

Discrete plasmapheresis and ultrafiltration are performed by a specialist who has undergone training in the department of extracorporeal detoxification methods.

Recent studies have shown that calcium supplements can reduce the incidence of hypertension, preeclampsia, and premature birth. It is interesting to note that pregnant women with a transplanted kidney did not develop gestosis while receiving glucocorticoid (methylprednisolone) and immunosuppressive therapy with cytostatics (cyclosporine), and the existing dropsy did not progress to a more severe form. In addition, when preventing distress syndrome with glucocorticoids in women with severe gestosis, an improvement in their condition and the possibility of prolonging their pregnancy by more than 2 weeks were noted.

In the treatment of gestosis, the duration of therapy in pregnant women is of great importance. In mild gestosis, inpatient treatment is advisable to be carried out for 14 days, in moderate - 14-20 days. Subsequently, measures are taken to prevent recurrence of gestosis in the conditions of a women's consultation. In severe gestosis, inpatient treatment is carried out until delivery.

Management and treatment of pregnant women with HELLP syndrome and AFGB:

• intensive preoperative preparation (IPT);
• emergency abdominal delivery;
• replacement and hepatoprotective therapy;
• prevention of massive blood loss during surgery and in the postpartum period;
• antibacterial therapy.

Treatment of pregnant women and women in labor with the above complications is carried out with additional monitoring every 6 hours:

• the number of red blood cells and platelets;
• total protein;
• bilirubin;
• prothrombin index;
• APTT;
• Lee-White blood clotting time;
• liver transaminase levels.

Urgent abdominal delivery is performed against the background of complex intensive therapy.

Infusion-transfusion therapy is supplemented with hepatoprotectors (10% glucose solution in combination with macrodoses of ascorbic acid - up to 10 g / day), replacement therapy [fresh frozen plasma at least 20 ml / (kg x day), transfusion of platelet concentrate (at least 2 doses) if the platelet level is less than 50x10 ⁹ /l]. In the absence of platelet concentrate, it is permissible to administer at least 4 doses of platelet-rich plasma, which can be prepared from reserve donors on various types of centrifuges in a soft sedimentation mode. If systolic blood pressure increases above 140 mm Hg, relative controlled hypotension is indicated.

The specified complex therapy is carried out against the background of the administration of glucocorticoids (prednisolone at least 500 mg/day intravenously).

In the postoperative period, against the background of careful clinical and laboratory monitoring, replenishment of plasma coagulation factors [fresh frozen plasma 12–15 ml/(kg x day)], hepatoprotective therapy (glutamic acid) against the background of massive antibacterial therapy are continued; plasmapheresis and ultrafiltration are performed as indicated.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ]

Tactics of pregnancy and childbirth management

If the treatment for gestosis is effective, pregnancy continues until the time that guarantees the birth of a viable fetus, or until labor occurs.

Currently, in severe forms of gestosis, more active pregnancy management tactics are used. Indications for early delivery include not only eclampsia and its complications, but also severe gestosis and preeclampsia with no effect from therapy within 3-12 hours, as well as moderate gestosis with no effect from therapy within 5-6 days.

Currently, indications for caesarean section have been expanded:

• eclampsia and its complications;
• complications of gestosis: coma, cerebral hemorrhage, acute renal failure, HELLP syndrome, acute renal failure, retinal detachment and hemorrhage into it, premature detachment of a normally located placenta, etc.;
• severe gestosis and preeclampsia with an unprepared cervix and indications for early delivery;
• combination of gestosis with other obstetric pathology;
• long-term gestosis (more than 3 weeks).

Caesarean section in gestosis is performed under epidural anesthesia. After the fetus is extracted, to prevent bleeding, it is advisable to administer 20,000 IU of aprotinin intravenously by bolus followed by 5 IU of oxytocin. Intraoperative blood loss is compensated with fresh frozen plasma, hydroxyethyl starch solution (6 or 10%) and crystalloids.

If it is possible to deliver the baby through the natural birth canal, a prostaglandin gel is first introduced into the cervical canal or into the posterior vaginal fornix to improve the functional state of the uterus and prepare the cervix. With the cervix prepared, an amniotomy is performed with subsequent labor induction.

During vaginal delivery in the first stage of labor, along with the use of classical methods (early rupture of the amniotic sac, adequate hypotensive therapy, ITT no more than 500 ml), staged long-term analgesia is administered, including epidural anesthesia.

In the second stage of labor, continuation of epidural anesthesia is most optimal.

When managing labor in pregnant women with gestosis, it is necessary to prevent bleeding in the second period and adequately replenish blood loss in the third and early postpartum periods.

In the postpartum period, ITT is carried out in full for at least 3–5 days, depending on the regression of symptoms of the pathological process under the control of clinical and laboratory data.

The most common mistakes in the treatment of severe forms of gestosis:

• underestimation of the severity of the condition;
• inadequate therapy and/or its untimely implementation;
• uncontrolled ITT, which promotes hyperhydration;
• incorrect delivery tactics - delivery through the natural birth canal in severe forms of gestosis and their complications;
• inadequate prevention of bleeding.

Obstetric tactics. If the treatment of gestosis is effective, pregnancy continues until the period that guarantees the birth of a viable fetus or until labor begins.

Currently, active pregnancy management tactics are used for moderate and severe forms of gestosis. Indications for early delivery include not only eclampsia and its complications, but also severe forms (with no effect from therapy within 3-6 hours) and moderate (with no effect from therapy within 5-6 days) forms of gestosis.

Indications for cesarean section in gestosis are:

1. Eclampsia and its complications.
2. Complications of gestosis (coma, cerebral hemorrhage, acute renal failure, HELLP syndrome, acute uterine insufficiency, retinal detachment, retinal hemorrhage, premature detachment of a normally located placenta, fetoplacental insufficiency).
3. Severe gestosis, preeclampsia with an unprepared cervix.
4. Combination of gestosis with other obstetric pathology.

In severe forms of gestosis, cesarean section is performed only under endotracheal anesthesia. The use of epidural anesthesia is permissible only in mild and moderate forms of gestosis.

If it is possible to deliver the baby through the natural birth canal, prostaglandin-containing gels (cerviprost) should be used to prepare the cervix. With the cervix prepared, amniotomy is performed with subsequent labor induction.

During vaginal delivery, gradual long-term analgesia is administered, including epidural anesthesia.

The most common mistakes in the treatment of gestosis are:

• underestimation of anamnesis data and clinical research methods;
• incorrect interpretation of laboratory and instrumental research methods;
• inadequate therapy and its untimely initiation;
• uncontrolled ITT, which promotes hyperhydration;
• incorrect delivery tactics;
• inadequate prevention of bleeding.