Sodium thiopental

General characteristics. Structure:

Active agent: sodium thiopental - 0,5 g, 1 g.

Pharmacological properties:

Pharmacodynamics. Means for not inhalation general anesthesia of ultrashort action, derivative thiobarbituric acid. Has the expressed somnolent, some myorelaxation and weak analgeziruyushchy activity. Slows down time of opening of channels GAMK-zavisimykh on a postsynaptic membrane of neurons of a brain, extends time of an entrance of ions of chlorine in a nervous cell and causes hyperpolarization of a membrane. Suppresses exciting effect of amino acids (aspartate and a glutamate). In high doses, directly activating GAMK-receptors, has the GAMK-promoting effect. Has anticonvulsant activity, raising an excitation threshold of neurons and blocking carrying out and distribution of a convulsive impulse on a brain. Promotes muscle relaxation, suppressing polisinaptichesky reflexes and slowing down carrying out on internuncial neurons of a spinal cord. Reduces intensity of metabolic processes in a brain, utilization by a brain of glucose and oxygen. Has somnolent effect which is shown by acceleration of process of backfilling and change of structure of a dream. Oppresses (дозозависимо) a respiratory center and reduces its sensitivity to carbon dioxide. Has (дозозависимо) cardiodepressive effect: reduces a stroke output of blood, minute volume of blood, arterial pressure. Increases the capacity of venous system, reduces a hepatic blood stream and a glomerular filtration rate. Exerts exciting impact on n.vagus and can cause a laryngospasm, plentiful secretion of slime. After intravenous administration the general anesthesia develops in 30-40 sec.; after rectal - in 8-10 min., it is characterized by short duration (after introduction of a single dose the general anesthesia proceeds 10-30 min.) and awakening with some drowsiness and retrograde amnesia. At an exit from the general anesthesia analgeziruyushchy action stops along with awakening of the patient.

Pharmacokinetics. At intravenous administration quickly gets into a brain, skeletal muscles, kidneys, a liver and fatty tissue. Time of approach of the maximum concentration - during 30 sec. (brain), 15-30 min. (muscle). In fat depos concentration of drug is 6-12 times higher, than in a blood plasma. Distribution volume - 1.7-2.5 l/kg, during pregnancy - 4.1 l/kg, at patients with obesity is 7.9 l/kg. Communication with proteins of plasma - 76-86%. Gets through a placental barrier and it is allocated with breast milk. It is metabolized generally in a liver, with formation of inactive metabolites, 3-5% of a dose are desulphurized to pentobarbital, an insignificant part is inactivated in kidneys and a brain. An elimination half-life in a distribution phase - 5-9 min., in an elimination phase - 3-8 h (lengthening to 10-12 h is possible; during pregnancy - to 26.1 h, patients with obesity - to 27.5 h), at children have 6.1 h. Clearance - 1.6-4.3 ml/kg/min., during pregnancy - 286 ml/min. It is removed preferential by kidneys by glomerular filtering. At repeated introduction it kumulirutsya (it is connected with accumulation in fatty tissue).

Indications to use:

The general anesthesia at short-term surgical interventions, introduction and basic general anesthesia (with the subsequent use of analgetics and muscle relaxants).
Big epileptic seizures (grand mal), the epileptic status, increase in intracranial pressure, prevention of a hypoxia of a brain (at artificial circulation, carotid endarterectomy, neurosurgical operations on brain vessels), the narcoanalysis and a narcosynthesis in psychiatry.

Route of administration and doses:

Intravenously slowly (in order to avoid a collapse), at adults solutions use 2-2.5% (more rare than 5% solution - is used a technique of fractional introduction); to children and the weakened patients of advanced age - 1% solution.
Solutions are prepared just before the use on sterile water for injections. The prepared solution has to be absolutely transparent. At bystry administration of solutions with concentration less than 2% are possible hemolysis development. Before introduction carry out premedication by atropine or Methacinum.
The adult for introduction to the general anesthesia: a trial dose - 25-75 mg, with the subsequent observation during 60 sec. before introduction of the main dose. Introduction general anesthesia - 200-400 mg (on 50-100 mg with an interval 30-40 sec. before achievement of desirable effect or once at the rate of 3-5 mg/kg). For anesthesia maintenance - 50-100 mg.
For stopping of spasms - 75-125 mg intravenously within 10 min.; development of spasms at local anesthesia - 125-250 mg within 10 min.
At a brain hypoxia in 1 min. enter 1.5-3.5 mg/kg to a temporary stop of blood circulation.
The narcoanalysis - 100 mg within 1 min. To suggest the patient to consider slowly from 100 to 1. To interrupt administration of thiopental just before backfilling. The patient has to be in semi-wakefulness and keep ability to answer questions.
At a renal failure (clearance of creatinine less than 10 ml/min.) - 75% of an average dose.
The highest single dose of drug for adults intravenously - 1 g (50 ml of 2% of solution).
It is necessary to enter solution intravenously slowly, with a speed no more than 1 ml/min. In the beginning usually enter 1-2 ml, and in 20-30 sec. - other quantity.
To children - intravenously struyno, slowly within 3-5 min., once at the rate of 3-5 mg/kg. Before carrying out inhalation anesthesia without the previous premedication at newborns - 3-4 mg/kg, 1-12 months - 5-8 mg/kg, 1-12 years - 5 - 6 mg/kg; for the general anesthesia at children with the body weight of 30-50 kg - 4-5 mg/kg. A maintenance dose - 25-50 mg. At children with depression of function of kidneys (clearance of creatinine less than 10 ml/min.) - 75% of an average dose.

Features of use:

To apply only in the conditions of specialized department intensivists, in the presence of means to maintenance of cordial activity and ensuring passability of respiratory tracts, artificial ventilation of the lungs. It is necessary to consider that achievement and maintenance of the general anesthesia of required depth and duration depends also on amount of drug, and on individual sensitivity of the patient to it.
At inflammatory diseases of upper respiratory tracts ensuring passability of upper respiratory tracts is shown, up to a trachea intubation.
Inadvertent intra arterial introduction causes the instant spasm of a vessel which is followed by blood circulation disturbance distalny places of an injection (thrombosis of the main vessel with the subsequent development of a necrosis, gangrene is possible). Its first sign at the patients who are in consciousness: complaints to the burning sensation extending on the artery course; patients in a condition of the general anesthesia have first symptoms - tranzitorny blanching, spotty cyanosis or dark coloring of skin.
Treatment: to stop introduction, to enter vnutriarterialno into the place of defeat heparin solution with the subsequent anticoagulating therapy; glucocorticosteroid solution with the subsequent system therapy; to carry out sympathetic blockade or blockade of humeral neuroplex (intra arterial introduction of Procainum).
At chemical irritation of fabrics (it is connected with high PH value of solution (10-11) in case of hit of solution under skin, for the purpose of a bystry rassasyvaniye of infiltrate enter local anesthetic and carry out warming (activation of local blood circulation).
Ekstravazation sign - hypodermic swelling.
In case of intravenous jet administration to children 18 years are younger careful control of a condition of the patient for the purpose of early detection of symptoms of respiratory depression, hemolysis, a lowering of arterial pressure, an ekstravazation is necessary.
The anesthetizing effect is unreliable at the persons abusing ethanol.
It is necessary to reduce a dose at the patients accepting digoxin, diuretics; at patients who in premedication received morphine, and also after administration of atropine, diazepam.
Premedication - any of the standard medicines, except for derivatives of a fenotiazin.
At long anesthesia when the somnolent effect caused by sodium thiopental is supported by intravenous use of anesthetics of long action and/or inhalation anesthetics, in connection with danger of cumulative effect the dose of thiopental of sodium should not exceed 1 g.
It is possible to apply in combination with muscle relaxants on condition of carrying out artificial ventilation of the lungs.
Raises n.vagus tone therefore before use it is necessary to enter an adequate dose of atropine. Right after approach of the general anesthesia it is necessary to provide passability of respiratory tracts. Accustoming can develop.
Thiopental does not influence a tone of a pregnant uterus. After intravenous administration the maximum concentration in an umbilical cord is noted in 2-3 min. The most admissible dose - 250 mg. When using in obstetric and gynecologic surgery can cause oppression of the central nervous system in newborns.

Side effects:

From cardiovascular system: lowering of arterial pressure, arrhythmia, tachycardia, collapse.
From respiratory system: cough, sneezing, hypersecretion of bronchial slime, laryngospasm, bronchospasm, hypoventilation of lungs, диспноэ, oppression of a respiratory center, apnoea.
From a nervous system: a headache, muscular twitchings, epileptic seizures, increase in a tone n.vagus, dizziness, block, an ataxy, an ecmnesia, drowsiness in the postoperative period, uneasiness, especially at pains in the postoperative period, is rare - postoperative delirious psychosis (a dorsodynia, uneasiness, confusion of consciousness, excitement, hallucinations, concern, a syndrome of uneasy legs), paralysis of a beam nerve.
From the alimentary system: hypersalivation, nausea, vomiting, an abdominal pain in the postoperative period.
Allergic reactions: a dermahemia, rash, a skin itch, a small tortoiseshell, rhinitis, an acute anaphylaxis, it is rare - hemolitic anemia with a renal failure (a back pain, legs and a stomach, nausea, vomiting, appetite loss, unusual weakness, heat, pallor of integuments).
Others: hiccups.
Local reactions: at intravenous administration - morbidity in an injection site, thrombophlebitis (administration of solutions with high concentration of drug), a spasm of a vessel and fibrinferments in the place of an injection, irritation of fabrics in the place of an injection (a hyperemia and a peeling of skin), a necrosis; damage of the nerves suitable to the place of an injection.

Interaction with other medicines:

Symptoms: oppression of the central nervous system, a spasm, muscular hyperreactivity, respiratory depression up to an apnoea, a laryngospasm, water and electrolytic disturbances, the expressed lowering of arterial pressure, decrease in the general peripheric vascular resistance (toxic action at overdose begins with the first seconds), tachycardia; post-narcotic delirium. At very high dose: fluid lungs, circulator collapse, cardiac standstill.
Treatment: an antidote - Bemegridum. At an apnoea - artificial ventilation of the lungs, 100% oxygen; at a laryngospasm - muscle relaxants and 100% oxygen under pressure; at a collapse or the expressed lowering of arterial pressure - plasma substituting solutions, administration of angiotonic medicines and/or drugs with positive inotropic action. At spasms - intravenous administration of diazepam; at their inefficiency - artificial ventilation of the lungs and muscle relaxants.

Contraindications:

Hypersensitivity to drug components; a porphyria, including acute alternating (including in the anamnesis at the patient or his immediate family); the diseases which are a contraindication for the general anesthesia; intoxication ethanol, narcotic analgetics, hypnotic drugs and medicines for the general anesthesia; shock, asthmatic status, malignant hypertension, pregnancy, lactation period. 
Use at pregnancy Use at pregnancy is possible only in that case when the estimated advantage for mother exceeds potential risk for a fruit.
It is recommended to stop breastfeeding in need of purpose of drug.

Overdose:

Symptoms: oppression of the central nervous system, a spasm, muscular hyperreactivity, respiratory depression up to an apnoea, a laryngospasm, water and electrolytic disturbances, the expressed lowering of arterial pressure, decrease in the general peripheric vascular resistance (toxic action at overdose begins with the first seconds), tachycardia; post-narcotic delirium. At very high dose: fluid lungs, circulator collapse, cardiac standstill.
Treatment: an antidote - Bemegridum. At an apnoea - artificial ventilation of the lungs, 100% oxygen; at a laryngospasm - muscle relaxants and 100% oxygen under pressure; at a collapse or the expressed lowering of arterial pressure - plasma substituting solutions, administration of angiotonic medicines and/or drugs with positive inotropic action. At spasms - intravenous administration of diazepam; at their inefficiency - artificial ventilation of the lungs and muscle relaxants.

Storage conditions:

List No. 1 SDV. In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children. Drug belongs to the list No. 1 of strong substances of Standing committee on control of MZ Russian Federation drugs. 
Period of validity 2 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for пригот. solution for in/in introductions of 500 mg: фл. 1, 5, 10 or 50 pieces.