Medications used in labor

A special feature of pharmacotherapy in obstetrics is the participation of doctors of three specialties. According to rough estimates, during childbirth, 32% of newborns receive more than six drugs from the mother's body. One third of them are prescribed due to complications of the pregnant woman taking other drugs during pregnancy and childbirth. In this regard, it is necessary to list and characterize the drugs used in childbirth (usually by obstetricians) from the standpoint of an anesthesiologist and neonatologist.

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Drugs that induce labor

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Oxytocin

Increases the amplitude and frequency of myometrial contractions. When administered intravenously by bolus in a dose exceeding 5-10 U, it causes a decrease in total peripheral vascular resistance by 50%, an increase in heart rate by 30%, and a decrease in average blood pressure by 30%, which may aggravate the decrease in blood pressure caused by the use of MA solutions, clonidine, and other antihypertensive agents. Long-term administration of oxytocin should be carried out using an infusion pump, since uncontrolled administration of crystalloids as a solvent leads to an increase in the preload on the myocardium and interstitial hyperhydration, which is often the main cause of hypoxia in the mother and fetus. It should be noted that the administration of exogenous oxytocin suppresses the production of endogenous hormone in the woman's body. In this regard, having started the infusion of drugs, it should not be interrupted, since this leads to a complete cessation of labor. With intravenous administration of oxytocin, a significant increase in uterine tone is often observed, which leads to a deterioration in uteroplacental blood flow, pathological respiratory movements of the fetus due to hypoxia, inhibition of surfactant synthesis, an increase in the incidence of birth trauma, and a decrease in the pH of the umbilical cord blood of the newborn.

Changes in fetal heart rate in response to the (standard stress) oxytocin test provide information on placental circulatory reserves.

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Methylergometrine

In small doses, it increases the strength and frequency of uterine contractions, accompanied by normal relaxation of the myometrium. With an increase in the dose, a prolonged tonic contraction of the myometrium develops. Intravenous administration of methylergometrine can cause generalized vascular spasm (increase in OPSS), decrease in venous capacity and increase in blood pressure, resulting in increased hydrostatic pressure in the capillaries (including pulmonary capillaries). The above changes can provoke the development of eclampsia and pulmonary edema in patients with severe preeclampsia. In this regard, the drugs are used only to stop postpartum hemorrhage.

Calcium supplements

Calcium chloride and calcium gluconate are uterotonics. In small doses (IV 2-6 ml of 10% solution) they are used (in combination with propranolol) to eliminate DRD, in therapeutic doses - to accelerate uterine contractions and reduce the volume of blood loss during cesarean section (after extraction of the fetus) and in the postpartum period.

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Prostaglandins

Dinoprost (PG F2a) is prescribed to excite and stimulate contractile activity of the myometrium at various stages of pregnancy (labor acceleration, artificial termination of pregnancy). Dinoprost can cause transient hypertension, severe bronchospasm, especially in pregnant women with concomitant bronchial asthma, increased gastrointestinal motility, nausea. Dinoprost increases cardiac output, accelerates heart rate, and increases vascular permeability. In Europe and North America, intravenous administration of dinoprost is used only for termination of pregnancy.

Dinoprostone (PGE2) is used to stimulate labor. The drug causes increased rhythmic contractions of the myometrium of the pregnant uterus, increased tone, and relaxation of the cervix. Dinoprostone reduces blood pressure due to a decrease in total peripheral vascular resistance, which is accompanied by compensatory tachycardia. Unlike dinoprost, dinoprostone dilates pulmonary vessels and bronchi, but increases capillary permeability, like dinoprost. In 90% of pregnant women, the use of drugs is accompanied by hyperthermia, which persists for 40-90 minutes after the infusion is stopped. When dinoprostone is administered 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 dinoprostone.

PGs are contraindicated for pregnant women with a scar on the uterus, clinically narrow pelvis, glaucoma and severe somatic pathology: organic heart disease, hypertension, peptic ulcer, diabetes mellitus, epilepsy, etc.; with their intravenous administration, phlebitis may develop.

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Tocolytics

Beta2-adrenergic agonists (terbutaline, salbutamol, fenoterol, hexoprenaline). These

Medicines are used to delay and stop premature labor. There are no absolutely selective beta2-adrenergic agonists, all of them stimulate beta2-receptors of the myocardium to varying degrees. Against the background of an increase in cardiac output by 25-50% by the third trimester of pregnancy, stimulation of beta-adrenergic receptors additionally increases cardiac output by 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). With parenteral administration of tocolytics, pulse oximetry monitoring is necessary (absence of cyanosis due to a small amount of restored hemoglobin).

Medicines should be administered using an infusion pump (accuracy of dosing and reduction of the volume of frequently unaccounted for solutions being transfused). The antidiuretic effect leads to reabsorption of sodium and water (limit sodium intake), and the COPpl decreases (with a COPpl of <12 mm Hg, there is a high probability of developing pulmonary edema). By the third hour of tocolytic infusion, the glucose and insulin levels reach their maximum, leading to hypokalemia and ketonemia. Accumulation of the above metabolites may result in the development of hyperosmolar syndrome. In newborns, glycemia must be monitored for 24 hours. The incidence of pulmonary edema during beta-adrenergic therapy is up to 4%. The combined use of beta-adrenergic agents and GCS significantly increases the risk of its development.

Prevention of the listed complications:

• prescribing beta-adrenergic agonists according to strict indications;
• limitation (of all!) administered fluid to 1.5-2.5 l/day;
• administration of drugs through an infusion pump;
• start infusion or oral administration of drugs with minimal doses, if possible in combination with calcium antagonists, MgSO4 and progesterone, which allow reducing their dose.

A good therapeutic effect is provided by intravenous administration of the fatty acid oxidation blocker trimethylhydrazinium propionate dihydrate. The drug is administered immediately before tocolysis. Due to its sensitizing effect on beta-adrenergic receptors, their affinity with the administered beta-adrenergic agonists increases. This allows for a 2-fold reduction in the dose of beta-adrenergic agonists to achieve the required tocolytic effect, which eliminates the development of their side effects: trimethylhydrazinium propionate dihydrate, 10% solution, intravenous 5 ml, once; perform anesthesia 2 hours after the infusion is stopped or 12 hours after the last dose of the drug in tablet form; give preference to regional methods.

Magnesium sulfate

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

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Indomethacin

It has tocolytic activity, as it inhibits the synthesis of progesterone, which stimulates contractile activity of the uterus and the production of progesterone.

Vasopressor drugs

The ideal obstetric vasopressor should increase the mother's blood pressure without reducing uteroplacental blood flow, and have a predominantly beta-adrenergic and limited alpha-adrenergic effect.

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

Alpha-adrenergic agonists (phenylephrine) and agents stimulating a- and beta-adrenergic receptors (epinephrine and norepinephrine) increase the mother's blood pressure to the detriment of uteroplacental blood flow. However, there is evidence that phenylephrine, used in small doses, does not worsen uteroplacental blood flow. It is used when ephedrine is ineffective or contraindicated. Dopamine is prescribed according to strict indications, when the beneficial effect for the mother outweighs the potential risk to the fetus.

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

Infusion-transfusion therapy

In case of uncomplicated cesarean section before uterine incision, the infusion volume is at least 400-600 ml, the total volume is 1200-2000 ml (colloids and crystalloids).

Below is a protocol for infusion-transfusion therapy for bleeding in obstetrics, which defines its qualitative composition (Table 23.3). Since hemorrhagic shock is a multisystem syndrome that develops as a result of blood loss that is not replenished in a timely manner, the start time and rate of infusion should be optimal: stably maintaining hemodynamic parameters and minute diuresis at a safe level.

Transfusion of FFP can be replaced by the introduction of plasma coagulation factors. If bleeding leads to the development/exacerbation of DIC syndrome and the situation allowed to evaluate the coagulation, anticoagulation and fibrinolytic potentials of the blood, revealing normal (subnormal) coagulation, a decrease in the indicators of physiological anticoagulants and fibrinolysis, transfusion of the supernatal fraction of FFP (FFP from which cryoprecipitate has been removed) is indicated. In the treatment of DIC 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 container with defrosted plasma:

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

Heparin in fresh frozen plasma 0.1-0.25 U/ml plasma, the frequency of administration is determined by clinical feasibility. Transfusion of red blood cells is carried out when hemoglobin decreases to < 80 g/l and Ht < 25% (objective assessment is possible only taking into account infusion and physiological hemodilution, as a rule, this is the end of the first day after bleeding). In this regard, to resolve the issue of the volume, rate and qualitative composition of infusion-transfusion therapy during and in the first hours after bleeding, comprehensive monitoring of hemoglobin, hematocrit and FSC, blood loss volume, minute diuresis, Sa02 and auscultatory picture over the lungs is necessary.

The indication for platelet transfusion is a decrease in the platelet count to < 70 x 103/ml.

The ratio of colloids and crystalloids should be no less than 2:1, the volume of dextrans should not exceed 20 ml/kg.

The main goal of correction of colloid osmotic state in hemorrhagic shock is to prevent a decrease in the colloid osmotic state below 15 mm Hg and an increase in the osmolality discriminant above 40 mOsm/kg.

Massive blood loss dictates the need for prolonged mechanical ventilation.

Dextrose solutions are used intraoperatively only after the delivery of the fetus or in pregnant women at 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

Preeclampsia is a generalized endothelial injury (GEI) accompanied by MODS, which is based on increased vascular permeability, hemodynamic disturbances and related disorders. According to the classification of the World Health Organization, preeclampsia is a condition in which hypertension, edema and proteinuria develop after 20 weeks of pregnancy. Hypertension that occurs before 20 weeks of pregnancy and earlier is considered chronic (usually it is hypertension). Hypertension that develops later is a manifestation of gestosis and is characterized by generalized endothelial injury. Proteinuria and/or edema that appear before 20 weeks of pregnancy are more often a consequence of chronic hypertension or kidney disease. However, about 20% of women with preeclampsia and eclampsia have SBP < 140 mm Hg and DBP < 90 mm Hg.

Eclampsia is a multisystem disorder characterized by single or multiple 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. Cerebral edema in pregnant women with eclampsia is rarely detected, more often it is of iatrogenic (irrational infusion-transfusion therapy) or secondary (anoxia during seizures) origin.

In order for the diagnosis of hypertension to be objective and treatment to be optimal, it is necessary to strictly follow the rules for measuring blood pressure. Blood pressure should be measured at rest three times with an interval of 1 min (the average figure is close to the true one) on the upper and lower extremities (diagnosis of ACC) in the left lateral position. It is necessary to select the cuff correctly and record the DBP.

Proteinuria is defined as a 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 ACC syndrome (therefore, a comprehensive assessment is necessary).

Obstetricians are well aware of the edematous form of preeclampsia, which has an extremely unfavorable prognosis. In this regard, it is necessary to evaluate additional criteria, which include thrombocytopenia, visual impairment, renal function (reduced filtration, prerenal oliguria), and the appearance of neurological symptoms.

A decrease in the platelet count to 150 x 103/ml or less is detected in 30% of pregnant women with preeclampsia. 15% of pregnant women with severe preeclampsia (often with the development of HELLP syndrome) have severe thrombocytopenia - 100 x 103/ml or less.

Impaired autoregulation and cerebral vascular patency (dysfunction of the SAS and endothelial damage) leads to its ischemia, which causes visual disturbances (diplopia, photophobia, etc.) and the appearance of neurological symptoms. In 80% of pregnant women with eclampsia, headache preceded the development of eclampsia. Neurological symptoms may be a manifestation of hypoglycemia, which often complicates preeclampsia.

HELLP syndrome is a form of severe preeclampsia and a variant of MODS (with frequent development of DIC), developing mainly in multiparous women, characterized by high maternal (up to 75%) and perinatal (79: 1000) mortality. Early signs of the syndrome are nausea, vomiting, pain in the epigastrium and right hypochondrium, severe edema. 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 AST in HELLP syndrome is about 0.55. It should be noted that, unlike severe preeclampsia, in HELLP syndrome the main laboratory changes reach a maximum 24-48 hours after delivery. The development of the syndrome can be accompanied by serious complications: DIC (21%), placental abruption (16%), acute renal failure (7.5%), pulmonary edema (6%), formation of subcapsular hematomas and liver rupture, retinal detachment (0.9%).

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