Thiopental (Thiopental)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceThiopental sodiumThiopental sodium
Dosage form: & nbsppowder for solution for intravenous administration
Composition:
1 bottle contains
active substance: sodium thiopental 0.5 g or 1.0 g respectively
Description:
Yellowish white crystalline hygroscopic powder.

Pharmacotherapeutic group:means for non-induction general anesthesia
ATX: & nbsp

N.01.A.F   Barbiturates

N.01.A. F.03   Thiopental sodium

Pharmacodynamics:
The agent for non-induction general anesthesia of ultrashort action, a derivative of thiobarbituric acid, has a pronounced hypnotic, some miorelaxing and weak analgesic activity. Slows the opening time of GABA (gamma-amino-butyric acid) -dependent channels on the postsynaptic membrane of neurons of the brain, lengthens the time of entry of chloride ions into the interior of the nervous cells and causes hyperpolarization membrane.
Suppresses the stimulating effect of amino acids (aspartate and glutamate). In large doses, directly activating GABA receptors, exerts a GABA-stimulating effect.
Has anticonvulsant activity, increasing the threshold of excitability of neurons and blocking the conduction and spreading of convulsive impulse over the brain. Promotes muscle relaxation, suppressing polysynaptic reflexes and slowing down by intercalary neurons dorsal the brain.
Reduces the intensity of metabolic processes in the brain, the utilization of glucose and oxygen by the brain.
For the drug is also characterized by a decrease in intracranial pressure. Decrease in intracranial pressure, apparently, is mediated by a decrease in cerebral blood flow and volume against the background of increased resistance of cerebral vessels.
After intravenous injection, after 30-40 seconds a sleep state occurs, the depth of which can increase over the next 40 seconds. General anesthesia lasts 5-10 minutes. After that follows the period of postnarcotic sleep lasting 10-30 minutes. The useful duration of general anesthesia (the time of manipulation) is 5-8 minutes, characterized by short-term (after the introduction of a single dose, general anesthesia lasts 10-30 minutes) and awakening with some drowsiness and retrograde amnesia.
The surgical stage of general anesthesia is characterized by a decrease or disappearance of tendon and corneal reflexes, a slight narrowing (or normal size) of the pupils, a fixed or "floating" position of the eyeballs, a relaxation of the pharyngeal musculature with tongue deformity, a decrease in the depth of breathing, and a decrease in blood pressure (BP). When leaving the general anesthesia, the analgesic effect ceases simultaneously with the awakening of the patient. Upon repeated administration, the action is prolonged (cumulates).

Pharmacokinetics:
When administered intravenously, it quickly penetrates the brain, skeletal muscles, kidneys, liver and adipose tissue. The period of reaching the maximum concentration (TCmax) - for 30 seconds (brain), 15-30 minutes (muscle). In fat depots, the concentration of the drug is 6-12 times higher than plasma concentration. The volume of distribution - 1.7-2.5 l / kg, during pregnancy - 4.1 l / kg, in obese patients - 7.9 l / kg. The connection with plasma proteins is 76-86%.
First the drug enters the organs with intensive blood flow (brain, heart, liver, lungs), then quickly redistributed into muscle tissue. The balance between plasma concentration and concentration in muscle tissue is achieved within 15-30 minutes after injection.Due to the fact that the adipose tissue is poorly supplied with blood, a balance of plasma-fat concentrations is achieved after 1.5-2.5 hours. It penetrates the placental barrier and is secreted into breast milk. The maximum concentration of thiopental in the umbilical cord is achieved 2-3 minutes after intravenous administration. The concentration of thiopental in breast milk is low even when using high doses.
Metabolized mainly in the liver with the formation of inactive metabolites, 3-5% of the administered dose is desulfurized to pentobarbital, which is also an anesthetic; a small part of the drug is inactivated in the kidneys and brain. Leaching from adipose tissue limits the rate of elimination of thiopental. The half-life (T 1/2) of a single intravenous dose is 3-8 hours. T1 / 2 in the distribution phase - 5-9 minutes, in the elimination phase - 3-8 hours (lengthening up to 10-12 hours, during pregnancy - up to 26.1 hours, in obese patients - up to 27.85 hours), in children - 6.1 hours Clearance - 1.6-4.3 ml / kg / min, during pregnancy - 286 ml / min. It is excreted mainly by the kidneys by glomerular filtration. With repeated administration cumulates (associated with accumulation in adipose tissue).

Indications:
  • General anesthesia for short-term surgical interventions;
  • introductory and basic general anesthesia (with the subsequent use of analgesics and muscle relaxants);
  • the arrest of convulsive conditions observed during or after inhalation anesthesia;
  • suppression of large epileptic seizures (grand mal), status epilepticus;
  • prevention of brain hypoxia (with artificial circulation, carotid endarterectomy and neurosurgical operations on the vessels of the brain);
  • drug analysis and drug smear in psychiatry.

Contraindications:
  • Hypersensitivity to thiopental and other barbiturates;
  • acute intoxication with alcohol, sleeping pills, narcotic analgesics and drugs for general anesthesia;
  • diseases that are a contraindication for general anesthesia, asthmatic status, shock. malignant hypertension;
  • porphyria, including acute intermittent (including in the anamnesis of the patient or his immediate family).

Carefully:
Hepatic and / or renal failure, diabetes mellitus, obesity, cachexia, adrenal insufficiency, myxedema, chronic obstructive pulmonary disease, bronchial asthma, severe cardiovascular failure,pronounced violations of the contractile function of the myocardium, cardiovascular diseases, arterial hypotension, collapse, hypovolemia, excessive
premedication, myasthenia gravis, myotonia, muscular dystrophy, sepsis, inflammatory diseases of the nasopharynx, febrile conditions, anemia, children's age.

Pregnancy and lactation:
The use of thiopental during pregnancy and lactation is possible if the intended benefit to the mother exceeds the potential risk to the fetus or baby. When using thiopental during lactation it is necessary to refrain from breastfeeding within 24 hours after the administration of the drug.

Dosing and Administration:
For intravenous administration only.
Enter the drug should be slow to avoid a sharp fall in blood pressure and the development of collapse.
The dose of Tiopental is selected individually, taking into account the patient's body weight, concomitant diseases. Before administration, premedication is carried out with atropine or methacin.
In adults, the dose for general anesthesia is usually 200-400 mg (50-100 mg at intervals of 30-40 seconds or once with 3-5 mg / kg of body weight).To assess the individual sensitivity to Thiopental, a test dose of 25 to 75 mg should be given before the administration of the main dose, followed by observation for 60 seconds. To maintain anesthesia, 50-100 mg. The average dose for short-term operations is 400-800 mg.
The maximum dose should not exceed 1 g (risk of cumulation).
To cure seizures, 75 to 125 mg of tyopental intravenously administered for 10 minutes; with secondary convulsions against the background of the introduction of local anesthetics - 125 - 250 mg. Drug analysis and drug smear: 100 mg intravenously for 1 minute. Patients should slowly count down, starting at 100. Stop the injection of Thiopental should be when the patient begins to fall asleep. Patients should be in a state of drowsiness and be able to answer questions.
For general anesthesia in children, Tyopental is administered once from the calculation of 3-5 mg / kg body weight (intravenously slowly, for 3-5 minutes); in children with a body weight of 30-50 kg - at a rate of 4-5 mg / kg. The maintenance dose is 25-50 mg.
Before the inhalation anesthesia without previous premedication, the drug is used in the following dosage: newborns 3-4 mg / kg, children from 1 to 12 months 5-8 mg / kg, 1 to 12 years 5-6 mg / kg.
Patients with impaired renal function (creatinine clearance less than 10 ml / min) are administered 75% of the average dose.
Preparation of solutions.
The drug is used as a 2.5-5% solution in water for injection, which is prepared immediately before use. Solutions should be absolutely transparent. When solutions with a concentration of less than 2% are used, hemolysis may develop (with rapid administration).

Concentrations for clinical use are calculated as follows:

Required concentration in%

Concentration in mg / ml

Required amount



Thiopental (g)

Water for injections (ml)

2,5

25

0,5

20

3,0

30

0,5

16,6

4,0

40

0,5

12,5

5,0

50

0,5

10

2,5

25

1,0

40

3,0

30

1,0

33,3

4,0

40

1,0

25

5,0

50

1,0

20



Side effects:
Allergic reactions: skin hyperemia, skin rashes and itching; rarely - anaphylactic shock, hemolytic anemia with impaired renal function (pain in the lower back, legs and stomach, nausea, vomiting, loss of appetite, unusual weakness, fever, pale skin).
From the side of the cardiovascular system: lowering blood pressure, tachycardia, arrhythmia, with rapid introduction, the development of collapse is possible.
On the part of the respiratory system: coughing, sneezing, hypersecretion of bronchial mucus, laryngospasm, bronchospasm, hypoventilation of the lungs; on the background of too rapid administration, it is possible to depress the respiratory center and apnea.
From the side of the nervous system: headache, muscle twitching, epileptic seizures, dizziness, inhibition, ataxia, anterograde amnesia, drowsiness in the postoperative period, anxiety (especially with pain in the postoperative period), increase in the tone of the vagus nerve; rarely - postoperative delirious psychosis (back pain, anxiety, confusion, agitation, hallucinations, restlessness, restless legs syndrome), paralysis of the radial nerve.
From the digestive system: hypersalivation, hiccough, nausea,
abdominal pain in the postoperative period; rarely vomiting.
Local reactions: with intravenous administration - soreness at the injection site, thrombophlebitis (administration of solutions with a high concentration of the drug), vasospasm and thrombosis at the injection site, irritation of the tissues at the injection site (congestion and flaking of the skin), necrosis.

Overdose:
Symptoms: oppression of the central nervous system, convulsions, muscle
hyperreactivity, respiratory depression up to apnea, laryngospasm, water electrolyte disturbances, marked decrease in arterial pressure, tachycardia; postnarcotic delirium.With a very high dose: pulmonary edema, circulatory collapse, cardiac arrest.
Treatment. Antidote - bemegrid. When breathing is stopped - artificial ventilation of lungs (IVL), 100% oxygen; with laryngospasm - muscle relaxants and 100% oxygen under pressure; at a collapse or the expressed depression of arterial pressure - plazmozameshchajushchie solutions, introduction vazopressornyh preparations and-or preparations with positive inotropic action. With convulsions - intravenous diazepam or phenytoin; with their ineffectiveness - mechanical ventilation and muscle relaxants.
The excretion of thiopental can be strengthened with the help of forced diuresis, peritoneal or hemodialysis.

Interaction:
Thiopental reduces the activity of glucocorticosteroids, hormonal contraceptives, indirect anticoagulants, griseofulvin, phenylbutazone, phenazone, phenytoin; increases the toxicity of methotrexate. It shows antagonism with the bemegrid.
Strengthens the effect of drugs that contribute to the development of hypothermia. Mutual enhancement of the effect is observed when combined with ethanol, tranquilizers, neuroleptics, antihistamines and other drugs that depress the function of the central nervous system.The action of Thiopental is enhanced and prolonged by valproic acid and MAO inhibitors.
Opioid analgesics reduce the strength of the analgesic action of Tiopental.
Ketamine increases the risk of lowering blood pressure and suppressing breathing. Diazoxide increases the risk of lowering blood pressure.
Simultaneous use with magnesium sulfate (for parenteral administration) is accompanied by an intensification of the inhibitory effect on the central nervous system; with antihypertensive drugs and diuretics - increased hypotensive effect.


Thiopental is pharmaceutically incompatible (it should not be mixed in one syringe) with antibiotics (amikacin, benzylpenicillin, cephalosporins), narcotic analgesics (codeine, morphine), ephedrine, muscle relaxants (suxamethonium, tubocurarine), tranquilizers, phenothiazine, epinephrine, ascorbic acid, dipyridamole, chlorpromazine, ketamine, atropine, scopolamine and tubocurarine chloride.
Chemically incompatible with solutions having low pH, and with oxidants. Drugs that block tubular secretion (probenecid), and H1-histaminoblockers enhance the effect: aminophylline, analeptics, some antidepressants - weaken.
Diazoxide increases the risk of lowering blood pressure.

Special instructions:
To use only in the conditions of a specialized department of anesthetists-resuscitators, with the necessary means to maintain cardiac activity, ensure airway patency and the possibility of ventilation. It should be borne in mind that the achievement and maintenance of general anesthesia of the required depth and duration depend on the amount of the drug, and on the individual sensitivity to the patient.
Premedication should be carried out by any of the conventional means, with the exception of phenothiazine derivatives.
In inflammatory diseases of the upper respiratory tract, it is shown that the upper airways are passable, up to the intubation of the trachea.
It is necessary to reduce the dose in patients taking digoxin, diuretics, in patients who received as a premedication received morphine, and also after the administration of atropine, diazepam. In complete patients, as well as in patients who have already undergone general anesthesia within the last 36 hours, lower doses of thiopental may be sufficient to achieve the required depth of anesthesia.
With prolonged anesthesia, when the hypnotic effect caused by sodium thiopental is maintained by intravenous application of long-acting anesthetics and / or inhalational anesthetics, due to the danger of cumulative effect, the dose of thiopental sodium should not exceed 1 g.
In the case of intravenous jet infusion for children under 18 years of age, careful monitoring of the patient's condition is necessary in order to timely detect symptoms of respiratory depression, hemolysis, and lowering blood pressure.
It can be used in combination with muscle relaxants under condition of ventilation.
In patients with severe alcohol and drug dependence, it is difficult to achieve general anesthesia by the isolated use of thiopental and additional facilities for a common anesthesia.
Unintentional intraarterial (in / a) administration causes an instantaneous spasm of the vessel, accompanied by a circulatory disturbance distal to the injection site (possible thrombosis of the main vessel followed by the development of necrosis, gangrene). The first sign of it in patients who are conscious: complaints of a burning sensation that spreads along the course of the artery; in patients in a state of general anesthesia, the first symptoms are transient blanching, spotted cyanosis or dark skin coloration.Treatment: stop the injection, enter into / a at the site of the lesion a solution of heparin followed by anticoagulant therapy; solution of glucocorticosteroid followed by systemic therapy; conduct a sympathetic blockade or blockade of the brachial plexus (in / a introduction procaine).
When chemical irritation of the tissues is associated with a high pH value of the solution (10-11), if a solution falls under the skin, a local anesthetic is administered to quickly dissolve the infiltrate and the warmth is activated (activation of the local circulation) .The sign of extravasation is subcutaneous swelling.

Effect on the ability to drive transp. cf. and fur:
After outpatient use, patients should go out with accompanying persons only and, within 24 hours, exercise caution when driving vehicles and engage in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:
0.5 g or 1.0 g powder for the preparation of a solution for intravenous administration in vials;
Packaging:
25 or 50 bottles with instructions for medical use in a pack of cardboard (packaging for hospitals).

Storage conditions:
In the dark place at a temperature below 25 ° C.
Keep out of the reach of children.

Shelf life:
4 years.
Do not use after the expiration date.

Terms of leave from pharmacies:For hospitals
Registration number:П N012389 / 01
Date of registration:09.07.2007
The owner of the registration certificate:Sandoz GmbHSandoz GmbH Austria
Manufacturer: & nbsp
Information update date: & nbsp09.09.2015
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