Thiopental
Thiopental: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Thiopental Sodium
ATX code: N01AF03
Active ingredient: thiopental sodium (thiopental sodium)
Manufacturer: MedPro Inc. (Latvia)
Description and photo update: 2019-13-08
Thiopental is a drug for non-inhalation general anesthesia, has a pronounced hypnotic, weak analgesic and some muscle relaxant activity.
Release form and composition
The dosage form of Thiopental is a powder (lyophilisate) for preparing a solution for intravenous administration: yellowish-white, hygroscopic, crystalline (in bottles of 500 or 1000 mg, in a cardboard box of 1, 25 or 50 bottles).
The active substance in 1 bottle of lyophilized powder: sodium thiopental - 500 or 1000 mg.
Pharmacological properties
Pharmacodynamics
Thiopental is a thiobarbituric acid derivative, a drug intended for non-inhalation general anesthesia of ultrashort action, has a weak analgesic, pronounced hypnotic and some muscle relaxant activity.
Thiopental acts on the body as follows:
- suppresses the excitatory effect of amino acids (glutamate, aspartate);
- directly activates GABA receptors and has a GABA-stimulating effect (in large doses);
- slows down the opening time of GABA-dependent channels on the postsynaptic membrane of neurons in the brain;
- lengthens the time for chlorine ions to enter the nerve cell;
- causes membrane hyperpolarization;
- possesses anticonvulsant activity (by increasing the threshold of neuronal excitability and blocking the processes of conduction and propagation of a convulsive impulse through the brain);
- reduces the metabolic rate in the brain, the utilization of oxygen and glucose by the brain;
- promotes muscle relaxation (by suppressing polysynaptic reflexes and slowing down the conduction of an impulse through the intercalary neurons of the spinal cord);
- reduces intracranial pressure.
In 30–40 s after the intravenous administration of Thiopental, a state of sleep sets in, the depth of which can increase over the next 40 s. The duration of general anesthesia is from 5 to 10 minutes. This is followed by a period of post-drug sleep, which lasts from 10 to 30 minutes. The useful duration of general anesthesia (the period of manipulation) is from 5 to 8 minutes and is characterized by short duration (with the introduction of a single dose, general anesthesia can last from 10 to 30 minutes) and awakening with retrograde amnesia and some drowsiness.
At the surgical stage of general anesthesia, the disappearance or decrease of corneal and tendon reflexes, the maintenance of normal size or slight constriction of the pupils, the motionless or "floating" position of the eyeballs, relaxation of the pharyngeal muscles with retraction of the tongue, decrease in blood pressure and decrease in the depth of breathing are observed. Upon exiting general anesthesia, the analgesic effect ceases when the patient wakes up. With repeated administration, the effect of the drug is prolonged (cumulation takes place).
Pharmacokinetics
After intravenous administration, Thiopental rapidly penetrates into skeletal muscle, adipose tissue, liver, kidneys and brain. The maximum concentration in the tissues of the brain is reached within 30 s, in the muscles - 15–30 s. The concentration of the drug in fat depots exceeds the plasma concentration by 6–12 times. The volume of distribution is from 1.7 to 2.5 l / kg, in obese patients - 7.9 l / kg, in pregnant women - 4.1 l / kg. The connection with plasma proteins is 76–86%.
Thiopental enters the organs (brain, lungs, heart, liver) with intensive blood flow, after which it is quickly redistributed into muscle tissue. Equilibrium plasma-muscle concentrations occurs 15-30 minutes after injection. Due to poor blood supply to adipose tissue, an equilibrium between plasma-adipose tissue concentrations is observed after 1.5–2.5 hours.
Thiopental crosses the placental barrier and is excreted in breast milk. After intravenous administration, the maximum concentration of the drug in the umbilical cord is reached in 2-3 minutes. Even with high doses, the concentration of thiopental in breast milk is low.
The metabolism of the drug occurs mainly in the liver with the formation of inactive metabolites. 3 to 5% of the dose received is desulfurized to pentobarbital, which is also an anesthetic. A small part of the drug is inactivated in the brain and kidneys. The rate of thiopental elimination is limited by leaching from adipose tissue.
The half-life of a single intravenous dose is from 3 to 8 hours. The half-life in the distribution phase is from 5 to 9 minutes, in the elimination phase - from 3 to 8 hours (it can be extended to 10–12 hours, in obese patients - up to 27, 85 hours, in pregnant women - up to 26.1 hours), in children - 6.1 hours. Clearance - from 1.6 to 4.3 ml / kg / min, in pregnant women - 286 ml / min. The drug is excreted mainly by the kidneys by glomerular filtration. Re-introduction leads to cumulation (associated with accumulation in adipose tissue).
Indications for use
- general anesthesia for short surgical interventions;
- basic general and induction anesthesia (before the use of muscle relaxants and analgesics);
- drug synthesis / drug analysis in psychiatry;
- large epileptic seizures (for relief), status epilepticus;
- convulsive conditions observed during / after inhalation anesthesia (for relief);
- hypoxia of the brain against the background of artificial circulation, carotid endarterectomy and neurosurgical operations on the vessels of the brain (with a preventive purpose).
Contraindications
Absolute:
- acute intoxication caused by drugs for general anesthesia, alcohol, narcotic analgesics and hypnotics;
- porphyria, including acute intermittent (including a burdened personal or family history);
- asthmatic status;
- diseases that are contraindicated for general anesthesia;
- malignant hypertension;
- shock;
- individual intolerance to the components of the drug.
Relative (the use of Thiopental requires caution in the presence of the following diseases / conditions):
- diabetes;
- renal / hepatic impairment;
- obesity;
- cachexia;
- adrenal insufficiency;
- chronic obstructive pulmonary disease;
- bronchial asthma;
- myxedema;
- severe cardiovascular insufficiency;
- hypovolemia;
- severe violations of the contractile function of the myocardium;
- arterial hypotension;
- diseases of the cardiovascular system;
- collapse;
- myasthenia gravis;
- excessive premedication;
- muscular dystrophy;
- myotonia;
- inflammatory diseases of the nasopharynx;
- sepsis;
- anemia;
- feverish conditions;
- childhood;
- pregnancy and lactation (the use of Thiopental is possible in cases where the intended benefits are higher than the possible harm; women during lactation after using the drug are recommended to refrain from breastfeeding for 24 hours).
Instructions for the use of Thiopental: method and dosage
Thiopental is intended exclusively for intravenous administration.
To avoid a sharp drop in blood pressure and the occurrence of collapse, it is recommended to inject the solution slowly.
The dosage regimen is selected individually, taking into account the patient's weight and the presence of concomitant diseases. Before the introduction of Thiopental, premedication with metacin or atropine is performed.
The average adult dose for administration to general anesthesia is 200–400 mg (50–100 mg at intervals of 30–40 seconds or a single dose at the rate of 3–5 mg / kg of body weight). To assess individual sensitivity, before the main dose of Thiopental is administered, a trial dose of 25–75 mg should be administered, followed by monitoring the patient's condition for 1 minute. To maintain anesthesia, 50–100 mg of the solution is injected. For short-term operations, the average dose is 400-800 mg.
Due to the risk of cumulation, the maximum dose of 1000 mg should not be exceeded.
The use of Thiopental for other indications:
- relief of seizures: 75–125 mg for 10 minutes;
- Secondary convulsions during administration of local anesthetics: 125–250 mg;
- narcosis / drug analysis: 100 mg for 1 minute. The patient should slowly count down, starting from 100, the introduction is stopped when he begins to fall asleep. Patients should be asleep and able to answer questions.
For children, for general anesthesia, the solution is injected once at the rate of 3-5 mg / kg of body weight (for 3-5 minutes), with a body weight of 30-50 kg - 4-5 mg / kg. The maintenance dose is 25-50 mg.
Before carrying out inhalation anesthesia without prior premedication, Thiopental is used in the following doses:
- newborns: 3-4 mg / kg;
- 1–12 months: 5–8 mg / kg;
- 1–12 years: 5–6 mg / kg.
In case of impaired renal function with creatinine clearance up to 10 ml / min, the dose is reduced by 25%.
Thiopental is used in the form of a 2.5–5% solution in water for injection, which is prepared immediately before administration. The prepared solutions must be absolutely transparent. If solutions with a concentration of up to 2% are used, hemolysis may develop (with rapid administration).
Side effects
- cardiovascular system: lowering blood pressure, arrhythmia, tachycardia, collapse (with rapid administration of the solution);
- nervous system: muscle twitching, headache, epileptic seizures, dizziness, lethargy, anterograde amnesia, ataxia, drowsiness in the postoperative period, anxiety (especially with pain in the postoperative period), increased vagus nerve tone; rarely - radial nerve paralysis, postoperative delirious psychosis (in the form of anxiety, back pain, anxiety, hallucinations, confusion, agitation, restless legs syndrome);
- digestive system: hiccups, hypersalivation, nausea, abdominal pain (in the postoperative period); rarely - vomiting;
- respiratory system: cough, hypersecretion of bronchial mucus, sneezing, laryngospasm, bronchospasm, hypoventilation of the lungs, apnea and oppression of the respiratory center (if administered too quickly);
- local reactions: with intravenous administration - soreness at the injection site, thrombophlebitis (with the introduction of high concentrations), vascular spasm and thrombosis at the injection site, necrosis, tissue irritation at the injection site (in the form of hyperemia and peeling of the skin);
- allergic reactions: skin rashes, skin flushing, itching; rarely - anaphylactic shock, hemolytic anemia with impaired renal function (in the form of pain in the stomach, legs, lumbar region, nausea, vomiting, loss of appetite, unusual weakness, fever, pallor of the skin).
Overdose
In case of an overdose of Thiopental, the following symptoms are observed:
hyperreactivity, convulsions, depression of the central nervous system, laryngospasm, respiratory depression up to apnea, tachycardia, marked decrease in blood pressure, water-electrolyte disturbances, post-anesthetic delirium. When using very large doses, it is possible to develop pulmonary edema, circulatory collapse, cardiac arrest.
The antidote is bemegrid. Recommended treatment:
- respiratory arrest - 100% oxygen, artificial ventilation;
- laryngospasm - 100% oxygen under pressure, muscle relaxants;
- collapse with a pronounced decrease in blood pressure - the introduction of drugs with a positive inotropic effect and / or vasopressor drugs, plasma-substituting solutions;
- convulsions - intravenous administration of phenytoin or diazepam, if they are ineffective - muscle relaxants and artificial ventilation.
Forced diuresis, peritoneal or hemodialysis increase the excretion of thiopental.
special instructions
Thiopental should be used only by anesthesiologists-resuscitators in a specialized department, if there are funds required to maintain cardiac activity, ensure airway patency and provide mechanical ventilation. It should be taken into account that in order to achieve and maintain general anesthesia of the required duration and depth, it is necessary to take into account the patient's individual sensitivity to the action of the drug.
Premedication can be carried out by any of the conventional means, except for phenothiazine derivatives.
In inflammatory diseases of the upper respiratory tract, the patency of the upper respiratory tract should be ensured, up to tracheal intubation.
The dose of Thiopental is reduced in the following cases:
- combined use with digoxin, diuretics;
- premedication with morphine;
- previous administration of diazepam, atropine.
For obese patients, as well as for patients who have already undergone general anesthesia over the past 36 hours, the use of lower doses may be sufficient to achieve the desired depth of anesthesia.
With prolonged anesthesia, when the hypnotic effect caused by Thiopental is supported by intravenous use of inhalation anesthetics / long-acting anesthetics, it is not recommended to exceed the dose of 1000 mg (due to the existing probability of a cumulative effect).
In order to timely detect signs of respiratory depression, hemolysis, lowering blood pressure in children under 18 years of age with intravenous jet injection, careful monitoring of the condition is required.
Provided that artificial ventilation of the lungs is carried out, combined use with muscle relaxants is possible.
In the presence of severe alcohol and drug addiction, the isolated use of Thiopental is difficult to achieve general anesthesia, therefore, the use of additional agents for general anesthesia may be required.
Unintentional intra-arterial injection of the drug can lead to instant vasospasm, accompanied by impaired circulation distal to the injection site (thrombosis of the main vessel may develop, followed by gangrene and necrosis). The first signs of this disorder: complaints of a burning sensation that spreads along the artery (in patients who are conscious), transient blanching, dark skin color / spotted cyanosis (in patients under general anesthesia). Therapeutic measures: termination of the administration of Thiopental, intra-arterial injection of a heparin solution into the site of injury, followed by anticoagulant therapy; introduction of a glucocorticosteroid solution followed by systemic therapy;carrying out sympathetic blockade or blockade of the brachial plexus (intra-arterial injection of procaine).
With subcutaneous administration, chemical irritation of tissues develops, which is associated with a high pH value of the solution (10–11), for rapid resorption of the infiltrate, a local anesthetic is injected and warming is performed (to activate local circulation). Subcutaneous swelling is a sign of extravasation.
After the outpatient use of Thiopental, the patient can go outside only with an accompanying person; for 24 hours, care must be taken when driving and performing other potentially dangerous types of work.
Application during pregnancy and lactation
The appointment of Thiopental during pregnancy is possible only after a careful assessment of the possible benefits to the mother and potential harm to the fetus. When using the drug during lactation after a dose, it is necessary to stop breastfeeding for 24 hours.
Pediatric use
In childhood, thiopental is used as a means for basic anesthesia, mainly with increased nervous excitability.
With impaired renal function
It is forbidden to use the drug for organic kidney disease.
For violations of liver function
According to the instructions, Thiopental is forbidden to use for organic liver diseases.
Drug interactions
With the combined use of Thiopental with certain drugs / substances, the following effects may develop:
- glucocorticosteroids, hormonal contraceptives, indirect anticoagulants, griseofulvin, phenylbutazone, phenazone, phenytoin: a decrease in their activity;
- methotrexate: increasing its toxicity;
- bemegrid: development of antagonism;
- drugs that contribute to the appearance of hypothermia: increasing their effect;
- ethanol, tranquilizers, antipsychotics, antihistamines and other drugs that inhibit the function of the central nervous system: mutual enhancement of action;
- valproic acid, monoamine oxidase inhibitors: enhancement and prolongation of action;
- diuretics, drugs with antihypertensive effect: increased antihypertensive effect;
- drugs blocking tubular secretion (probenecid), H 1 -histaminoblokatov: strengthening the effect of Thiopental;
- diazoxide: increasing the likelihood of lowering blood pressure;
- ketamine: an increase in the likelihood of lowering blood pressure and suppressing breathing;
- magnesium sulfate (parenteral administration): increased inhibitory effect on the central nervous system;
- opioid analgesics: decrease in the severity of the analgesic action of Thiopental;
- solutions with a low pH value, oxidizing agents: chemical incompatibility;
- antibiotics (benzylpenicillin, amikacin, cephalosporins), narcotic analgesics (codeine, morphine), atropine, phenothiazine, epinephrine, ephedrine, muscle relaxants (suxamethonium, tubocurarine), tranquilizers, dipyridamole, chloropromocinic acid, non-corrosive acid (you cannot mix drugs in one syringe);
- analeptics, aminophylline, some antidepressants: weakening of the effect of Thiopental;
- diazoxide: possibly lowering blood pressure.
Analogs
The analogue of Thiopental is Thiopental sodium.
Terms and conditions of storage
Store in a dark place at temperatures up to 25 ° C. Keep out of the reach of children.
Shelf life is 4 years.
Terms of dispensing from pharmacies
Released for hospitals.
Reviews about Thiopental
Reviews of Thiopental indicate that with the correct dosage and compliance with the instructions, the use of the drug does not cause the development of postoperative complications.
The price of Thiopental in pharmacies
The approximate price for Thiopental is 250 rubles per 10 ml bottle.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
