Medicines used in childbirth

A special feature of pharmacotherapy in obstetrics is the participation of three specialties in it. According to rough estimates, during birth 32% of children born receive from the mother's body more than six drugs. One third of them are appointed in connection with the complications of taking other medications during pregnancy and childbirth. In this regard, it is necessary to list and give a description of the drugs used in childbirth (usually by obstetricians) from the positions of an anesthesiologist and a neonatologist.

[1], [2], [3], [4],

Drugs that stimulate delivery

[5], [6], [7], [8], [9]

Oxytocin

Increases the amplitude and frequency of contractions of the myometrium. With a bolus in / in the introduction of a dose exceeding 5-10 units, causes a decrease in OPSS by 50%, an increase in heart rate by 30%, a decrease in ADP. By 30%, which can aggravate the decrease in blood pressure, caused by the use of solutions MA, clonidine and other antihypertensive agents. Long-term administration of oxytocin should be performed with an infusomat, uncontrolled introduction of crystalloids as a solvent leads to an increase in preload on the myocardium and interstitial hyperhydration, which is often the main cause of maternal and fetal hypoxia. It should be noted that the introduction of exogenous oxytocin inhibits the production of endogenous hormone in the body of a woman. In this regard, after starting the infusion with medicines, it should not be interrupted, this leads to a complete cessation of labor. With / in the introduction of oxytocin, there is often a significant increase in the tone of the uterus, which leads to a deterioration of utero-placental blood flow, abnormal respiratory movements of the fetus due to hypoxia, inhibition of surfactant synthesis, an increase in the frequency of birth trauma, and a decrease in the pH of the cord blood of a newborn.

The change in fetal heart rate in response to a (standard stress) oxytocin test provides information on the reserves of the placental circulation.

[10], [11], [12], [13], [14], [15]

Methylergometrine

In small doses increases the strength and frequency of uterine contractions, accompanied by normal relaxation of the myometrium. As the dose increases, a prolonged tonic contraction of the myometrium develops. IV injection of metergergometrin can cause generalized vasospasm (increase in OPSS), a decrease in venous capacity and an increase in blood pressure, resulting in increased hydrostatic pressure in the capillaries (including in the pulmonary). These changes may provoke the development of eclampsia and pulmonary edema in patients with severe pre-eclampsia. In this regard, drugs are used only to stop postpartum hemorrhage.

Calcium preparations

Calcium chloride and calcium gluconate are uterotonic. In small doses (in / in 2-6 ml of 10% solution) they are used (in combination with propranolol) to eliminate DRE, in therapeutic doses - to accelerate uterine contraction and reduce the volume of blood loss during caesarean section (after fetal extraction) and in the postpartum period.

[16], [17], [18], [19], [20], [21], [22], [23]

Prostaglandins

Dinoprost (PG F2a) is prescribed to stimulate and stimulate the contractile activity of the myometrium in various periods of pregnancy (rhinoculation, artificial termination of pregnancy). Dinoprost can cause transient AH, severe bronchospasm, especially in pregnant women with concomitant bronchial asthma, increased motility of the gastrointestinal tract, nausea. Dinoprost increases the CB, increases the rhythm of the heart, increases the permeability of blood vessels. In Europe and North America, iv administration of dinoprost is used only for abortion.

Dinoprostone (PGE2) is used to stimulate labor. LS causes an increase in rhythmic contractions of the myometrium of the pregnant uterus, an increase in its tone and relaxation of the cervix. Dinoprostone reduces blood pressure due to a decrease in OPSS, which is accompanied by compensatory tachycardia. Unlike dinoprost, dinoproston dilates the pulmonary vessels and bronchi, but the permeability of capillaries, like dinoprost, increases. In 90% of pregnant women, the use of drugs is accompanied by hyperthermia, which lasts for 40-90 min after the infusion is stopped. With the introduction of dinoproston at a rate of 10 mcg / min or more, nausea, vomiting and tremor may develop.

The mechanism of action of misoprostol (PGE2) is similar to dinoproston.

PG is contraindicated in pregnant women with scar on the uterus, clinically narrow pelvis, glaucoma and severe somatic pathology: organic heart diseases, GB, peptic ulcer, diabetes, epilepsy, etc .; when they are / in the introduction of possible development of phlebitis.

[24], [25], [26], [27], [28], [29]

Tokolitiki

Beta2-adrenomimetiki (terbutaline, salbutamol, fenoterol, hexoprenaline). These

Medications are used to delay and stop preterm labor. Absolutely selective beta2-adrenomimetics is not present, all of them to some extent stimulate and beta2-receptors of a myocardium. Against the backdrop of an increase in SV by 25-50% to the III trimester of pregnancy, stimulation of beta-adrenoreceptors additionally increases CB up to 300%, which in 70% of cases leads to transient ECG changes in the form of ST segment depression and T wave inversion (signs of myocardial ischemia). When parenteral administration of tocolytics requires monitoring of pulse oximetry (absence of cyanosis due to a small amount of reduced hemoglobin).

Medicines must be administered with the aid of an infusomat (the accuracy of dosing and the reduction in volume, often unrecorded, pourable solutions). Antidiuretic effect leads to the reabsorption of sodium and water (to limit the intake of sodium), decreases CODpl. (at CODpll "12 mm Hg the probability of developing pulmonary edema is high). By the third hour of infusion of tocolitics, the glucose and insulin level is maximally increased, which leads to hypokalemia and ketonemia. Accumulation of these metabolites can result in the development of hyperosmolar syndrome. Babies born need glycemic control during the day. The frequency of pulmonary edema with beta-adrenomimetic therapy is up to 4%. The combined use of beta-adrenomimetics and GCS significantly increases the risk of its development.

Prophylaxis of the listed complications:

• the appointment of beta-adrenomimetics according to strict indications;
• restriction (the whole!) of the injected liquid to 1.5-2.5 l / day;
• introduction of drugs through infusomat;
• begin the infusion or oral administration of drugs with minimal doses, if possible in combination with calcium antagonists, MgS04 and progesterone, to reduce their dose.

A good therapeutic effect is the introduction of a blocking agent for the oxidation of fatty acids of trimethylhydrazinium propionate dihydrate. LS is administered immediately before tocolysis. Due to its sensitizing effect on beta-adrenergic receptors, their affinity with the beta- adrenomimetics injected increases. This allows to reduce the dose of beta-adrenomimetics by 2 times in order to achieve the necessary tocolytic effect, which eliminates the development of their side effects: trimethylhydrazinium propionate dihydrate, 10% rr, iv 5 ml, once; to perform anesthesia 2 hours after stopping the infusion or 12 hours after the last dose of the tablet form of drugs, give preference to regional methods.

Magnesium sulfate

LS is most often used to treat preeclampsia and eclampsia, it is also very effective as a tocolytic. Magnesium ions when magnesium sulfate is administered in large doses are antagonists of calcium ions, which contributes to a decrease in their intracellular aggression. LS has anticonvulsant and sedative effect, hypotensive effect is insignificant. Magnesium sulfate causes broncho- and vasodilation, increases blood flow in the uterus and kidneys, increases the synthesis of prostacyclin by endothelium, reduces the plasma renin activity and the level of angiotensin-converting enzyme, reduces the aggregation of platelets. The drug can reduce uterine activity, the variability of the basal fetal heart rate (cardiac tomogram), cause neuromuscular and respiratory depression in the newborn (premature).

[30], [31], [32], [33], [34], [35], [36], [37], [38]

Indomethacin

Has tocolytic activity, because inhibits the synthesis of PG, stimulating the contractile activity of the uterus and the production of progesterone.

Vasopressor drugs

The ideal obstetric vasopressor should increase the BP of the woman giving birth without decreasing the uterine-placental blood flow, providing mainly beta-adrenostimulating and limited alpha-adrenostimulating action.

Ephedrine is the drug of choice in arterial hypotension in pregnant women.

Alpha-adrenomimetiki (phenylephrine) and agents stimulating a- and beta-adrenoreceptors (epinephrine and norepinephrine) increase the blood pressure of the parturient woman at the expense of the utero-placental blood flow. However, there is evidence that phenylephrine, used in small doses, does not worsen utero-placental blood flow. It is used when ephedrine is ineffective or contraindicated. Dopamine is prescribed according to strict indications when a beneficial effect on the mother exceeds the potential risk to the fetus.

Contraindications: idiopathic hypertrophic subaortic stenosis; in this case there is no improvement in the parameters of hemodynamics due to the presence of an obstruction to the filling of the ventricles and / or outflow from them.

Infusion-transfusion therapy

In uncomplicated cesarean section before the incision of the uterus, the infusion volume is not less than 400-600 ml, the total volume is 1200-2000 ml (colloids and crystalloids).

Below is a protocol of infusion-transfusion therapy for bleeding in obstetrics, in which its qualitative composition is determined (Table 23.3). In connection with the fact that hemorrhagic shock is SPON, which develops due to timely not replenished blood loss, the time of onset and the speed of infusion should be optimal: stably maintain hemodynamic parameters and a minute diuresis at a safe level.

Transfusion of FFP can be replaced by the introduction of plasma coagulation factors. If the bleeding leads to the development / exacerbation of DIC syndrome and the situation allowed assessing the coagulation, anticoagulation and fibrinolytic potentials of the blood, revealing normal (subnormal) coagulation, decreasing physiological anticoagulants and fibrinolysis, transfusion of the supernatant fraction of FFP (FFP, from which the cryoprecipitate ). When treating DVS-syndrome, the effective dose of FFP is 15-30 ml / kg. If it is necessary to activate AT III (I and II degrees of the syndrome), heparin is added to the tank with thawed plasmas:

Fresh-frozen plasma in / in 15-30 ml / kg, the frequency of administration is determined by clinical expediency.

Heparin in fresh frozen plasma 0.1-0.25 U / ml plasma, the frequency of administration is determined by clinical feasibility. Transfusion of erythrocyte mass is carried out with a decrease in hemoglobin <80 g / l and Ht <25% (an objective assessment is possible only when taking into account infusion and physiological hemodilution, usually the end of the first day after bleeding). In this regard, to address the issue of the volume, speed and quality of the infusion-transfusion therapy during and during the first hours after bleeding, comprehensive monitoring of hemoglobin, hematocrit and VSC parameters, blood loss, minute diuresis, Sa02 and auscultatory pattern over the lungs is required.

The indication for transfusion of platelet mass is a decrease in the number of platelets <70 x 103 / ml.

The ratio of colloids to crystalloids should not be lower than 2: 1, the volume of dextrans should not exceed 20 ml / kg.

The main goal of correction of the colloid osmotic state in hemorrhagic shock is to prevent a decrease in CODpl. Below 15 mm Hg. Art. And an increase in the osmolality tolerance of more than 40 mosm / kg.

Massive blood loss dictates the need for prolonged ventilation.

Dextrose solutions are intraoperatively applied only after fetal extraction or in pregnant women with a risk of developing hypoglycemia (risk of developing hypoglycemia in the fetus / newborn).

The presence of concomitant diseases of the cardiovascular system and respiratory organs requires an individual approach to both anesthesia and infusion therapy.

Correction of disorders: preeclampsia, eclampsia and HELLP-syndrome

Pre-eclampsia is a generalized endothelial damage (SSR), accompanied by SPON, which is based on increased vascular wall permeability, hemodynamic disorders and related disorders. According to the World Health Organization classification, pre-eclampsia is a condition in which hypertension, edema and proteinuria develop after 20 weeks of pregnancy. Hypertension, which occurred before 20 weeks of pregnancy and earlier, is considered chronic (more often it is GB). Hypertension, developed later, is a manifestation of gestosis and is characterized by generalized damage to the endothelium. Proteinuria and / or swelling that appear before the 20th week of pregnancy are more likely to result from chronic hypertension or kidney disease. However, about 20% of women with preeclampsia and eclampsia have SBP <140 mmHg. Art. And DBP <90 mm Hg. Art.

Eclampsia is a SPON, characterized by a single or multiple occurrence of seizures (not related to other brain diseases) in patients with preeclampsia during pregnancy, childbirth or within 7 days of the postpartum period. The main cause of seizures is cerebral ischemia, caused by dysfunction of the vascular wall. Edema of the brain in pregnant women with eclampsia is rarely detected, more often it is yatogenic (irrational infusion-transfusion therapy) or secondary (anoxia during convulsions) origin.

To ensure that diagnosis of hypertension is objective, and treatment is optimal, strict adherence to BP measurement rules is necessary. BP should be measured at rest in triplicate with an interval of 1 min (the average figure is close to the true one) on the upper and lower extremities (ACC diagnosis) in the position on the left side. It is necessary to select the correct cuff and register the DBP.

Proteinuria is the loss of 300 mg of protein in daily urine or more than 1 g / L in any portion.

Edema occurs in 80% of healthy pregnant women and is often due to the syndrome of ACC (therefore, a comprehensive assessment is needed).

Obstetricians are well aware of the leaky form of preeclampsia, extremely unfavorable in the prognostic plan. In this regard, it is necessary to evaluate additional criteria, which include thrombocytopenia, visual impairment and renal function (reduced filtration, prerenal oliguria), the appearance of neurologic symptoms.

Reducing the number of platelets up to 150x103 / ml less reveal in 30% of pregnant women with preeclampsia. 15% of pregnant women with severe preeclampsia (often with the development of HELLP-syndrome) have expressed thrombocytopenia - 100 x 103 / ml or less.

Disturbance of autoregulation and patency of cerebral vessels (dysfunction of SAS and damage to the endothelium) leads to its ischemia, which causes visual disorders (diplopia, photophobia, etc.) and the appearance of neurologic symptoms. In 80% of pregnant women with eclampsia, the headache preceded the development of eclampsia. Neurological symptoms may be a manifestation of hypoglycemia, often complicating preeclampsia.

HELLP-syndrome is a form of severe preeclampsia and a variant of SPON (with frequent development of ICE), which develops mainly in multicentric women, characterized by high maternal mortality (up to 75%) and perinatal (79: 1000) lethality. Early signs of the syndrome - nausea, vomiting, epigastric pain and right hypochondrium, marked swelling. Laboratory changes appear long before the described complaints. It is important to determine the activity of LDH, reflecting the degree of damage to hepatocytes and the severity of hemolysis. The ratio of ALT and ACT in HELLP-syndrome is about 0.55. It should be noted that, in contrast to severe preeclampsia in HELLP-syndrome, the basic laboratory changes reach a maximum in 24-48 hours after birth. The development of the syndrome can be accompanied by terrible complications: DVS (21%), placental abruption (16%), arthritis (7.5%), pulmonary edema (6%), subcapsular hematomas and liver rupture, retinal detachment (0.9%) .

[39], [40], [41], [42], [43], [44]