Pentothal (Thiopental Sodium)



Thiopental Sodium

I.V. Anesthetic

Indications And Clinical Uses: As the sole anesthetic agent for brief (15-minute) procedures; for induction of anesthesia prior to administration of other anesthetic agents; to supplement regional anesthesia; to provide hypnosis during balanced anesthesia with other agents for analgesia or muscle relaxation; for the control of convulsive states during or following inhalation anesthesia, local anesthesia, or other causes; in neurosurgical patients with increased intracranial pressure, if adequate ventilation is provided; and for narcoanalysis and narcosynthesis in psychiatric disorders.

Contra-Indications: Absolute Contraindications: Absence of suitable veins for i.v. administration; hypersensitivity (allergy) to barbiturates; variegate porphyria (South African) or acute intermittent porphyria; patients with severe respiratory embarrassment; status asthmaticus and; inflammatory conditions of the mouth, jaw, and neck.

Relative Contraindications: Severe cardiovascular disease; hypotension or shock; and conditions in which the hypnotic effect may be prolonged or potentiated-excessive premedication, Addison’s disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma and myasthenia gravis.

Diluents in Pentothal Ready-to-Mix syringes should not be used for fluid replacement. Do not use unless diluent is clear and the syringe package is undamaged.

Manufacturers’ Warnings In Clinical States: Keep resuscitative and endotracheal intubation equipment and oxygen readily available. Maintain patency of the airway at all times.

This drug should be administered only by persons qualified in the use of i.v. anesthetics.

Avoid extravasation or intra-arterial injection.

May be habit forming.

I.V. administration of Sterile Water for Injection USP, without a solute, may result in hemolysis.

Use aseptic technique for preparing thiopental solutions.

Administer only clear, reconstituted solutions.

Use within 24 hours after reconstitution. Discard unused portions.

Precautions: General: A person competent in anesthesia management should be in constant attendance and adequate facilities for support of respiration and circulation should be available when thiopental for injection is being used.

Observe aseptic precautions at all times in preparation and handling of thiopental solutions.

If used in conditions involving relative contraindications, reduce dosage and administer slowly.

Thiopental should be administered with caution to patients with pre-existing hypotension or in conditions where the hypnotic effect may be prolonged or intensified, such as in the presence of liver disease and renal disease.

Care should be taken in administering the drug to patients with advanced cardiac disease, increased intracranial pressure, ophtalmoplegia plus, asthma, myasthenia gravis and endocrine insufficiency (pituitary, thyroid, adrenal, pancreas).

Drug Interactions: The following drug interactions have been reported with thiopental.

Pregnancy: It is not known whether thiopental can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Thiopental should be given to a pregnant woman only if clearly needed.

Lactation : Thiopental readily crosses the placenta barrier and small amounts may appear in the milk of nursing mothers following administration of large doses.

Adverse Reactions: Adverse reactions include respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, hypotension, tachycardia, sneezing, coughing, bronchospasm, laryngospam and shivering. Anaphylactic and anaphylactoid reactions to thiopental have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema should be managed by conventional means.

Hypersensitivity reactions to barbiturates, including thiopental have been reported.

Rarely, immune hemolytic anemia with renal failure and radial nerve palsy have been reported.

Reactions which may occur because of the diluents, technique of preparation or mixing, or administration of reconstituted solutions of thiopental include febrile response or infection at site of injection, venous thrombosis or phlebitis extending from the site of injection and extravasation.

If an adverse reaction does occur, discontinue the injection, evaluate the patient, institute appropriate therapeutic counter measures and save the remainder of unused solution (or the used container or syringe) for examination if deemed necessary.

Symptoms And Treatment Of Overdose: Symptoms: Overdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the drug should be discontinued, a patent airway established (intubate if necessary) or maintained, and oxygen should be administered, with assisted ventilation if necessary. The lethal dose of barbiturates varies and cannot be stated with certainty. Lethal blood level may be as low as 1 mg/100 mL for short-acting barbiturates; less if other depressant drugs or alcohol are also present.

Cardiovascular collapse may also follow too rapid injection or overdosage. Treatment should be directed toward supporting the blood pressure and using volume expansion and/or vasopressor agents as appropriate.

Treatment: It is generally agreed that respiratory depression or arrest, due to unusual sensitivity to thiopental or overdosage, is easily managed if there is no concomitant respiratory obstruction. If the airway is patent, any method of ventilating the lungs (that prevents hypoxia) should be successful in maintaining other vital functions. Since depression of respiratory activity is one of the characteristic actions of the drug, it is important to observe respiration closely.

Should laryngospasm occur, it may be relieved by one of the usual methods, such as the use of a relaxant drug or positive pressure oxygen. Endotracheal intubation may be indicated in difficult cases.

Dosage And Administration: Thiopental is administered by i.v. route only. Individual response to the drug is so varied that there can be no fixed dosage. The drug should be titrated against patient requirements as governed by age, sex and body weight. Younger patients require relatively larger doses than middle-aged and elderly persons: the latter metabolize the drug more slowly. Prepuberty requirements are the same for both sexes, but adult females require less than adult males. Dose is usually proportional to body weight and obese patients require a larger dose than relatively lean persons of the same weight.

Reconstituted solutions of thiopental should be inspected visually for particular matter and discoloration, whenever solution and container permit.

Premedication: Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. In addition, a barbiturate or an opiate is often given. Sodium pentobarbital injection is suggested because it provides a preliminary indication of how the patient will react to barbiturate anesthesia. Ideally, the peak effect of these medications should be reached shortly before the time of induction.

Test Dose: It is advisable to inject a small “test” dose of 25 to 75 mg: (1 to 3 mL of a 2.5% solution) of thiopental to assess tolerance or unusual sensitivity to thiopental, and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: the patient may be unusually sensitive to thiopental, the solution may be more concentrated than had been assumed, or the patient may have received too much premedication.

Anesthesia: Moderately slow induction can usually be accomplished in the “average” adult by injection of 50 to 75 mg (2 to 3 mL of a 2.5% solution) at intervals of 20 to 40 seconds, depending on the reaction of the patient. Once anesthesia is established, additional injections of 25 to 50 mg can be given whenever the patient moves.

Slow injection is recommended to minimize respiratory depression and the possibility of overdosage. The smallest dose consistent with attaining the surgical objective is the desired goal. Momentary apnea following each injection is typical, and progressive decrease in the amplitude of respiration appears with increasing dosage. Pulse remains normal or increases slightly and returns to normal. Blood pressure usually falls slightly and returns toward normal. Muscles usually relax about 30 seconds after unconsciousness is attained, but this may be masked if a skeletal muscle relaxant is used. The tone of jaw muscles is a fairly reliable index. The pupils may dilate but later contract: sensitivity to light is not usually lost until a level of anesthesia deep enough to permit surgery is attained. Nystagmus and divergent strabismus are characteristic during early stages, but at the level of surgical anesthesia, the eyes are central and fixed. Corneal and conjunctival reflexes disappear during surgical anesthesia.

When thiopental is used for induction in balanced anesthesia with a skeletal muscle relaxant and an inhalation agent, the total dose of thiopental can be estimated and then injected in 2 to 4 fractional doses. With this technique, brief periods of apnea may occur which may require assisted or controlled pulmonary ventilation. As an initial dose, 210 to 280 mg (3 to 4 mg/kg) is usually required for rapid induction in the average adult (70 kg).

When thiopental is used as the sole anesthetic agent, the desired level of anesthesia can be maintained by injection of small, repeated doses as needed or by using a continuous i.v. drip in a 0.2 or 0.4% concentration. (Sterile Water should not be used as the diluent in these concentrations, since hemolysis will occur. Solutions may be prepared with Dextrose 5% in water, Sodium Chloride Injection or Normosol-R.) With continuous drip, the depth of anesthesia is controlled by adjusting the rate of infusion.

Convulsive States: For the control of convulsive states following anesthesia (inhalation or local) or other causes, 75 to 125 mg (3 to 5 mL of a 2.5% solution) should be given as soon as possible after the convulsion begins. Convulsions following the use of a local anesthetic may require 125 to 250 mg of thiopental, given over a 10-minute period. If the convulsion is caused by a local anesthetic, the required dose of thiopental will depend upon the amount of local anesthetic given and its convulsant properties.

Neurosurgical Patients with Increased Intracranial Pressure: In neurosurgical patients, intermittent bolus injections of 1.5 to 3.5 mg/kg of body weight may be given to reduce intraoperative elevations of intracranial pressure, if adequate ventilation is provided.

Psychiatric Disorders: For narcoanalysis and narcosynthesis in psychiatric disorders, premedication with an anticholinergic agent may precede administration of thiopental. After a test dose, thiopental is injected at a slow rate of 100 mg/min (4 mL/min of a 2.5% solution) with the patient counting backwards from 100. Shortly after counting, the patient becomes confused but before actual sleep is produced, the injection is discontinued. Allow the patient to return to a semidrowsy state where conversation is coherent. Alternatively, thiopental may be administered by rapid i.v. drip using a 0.2% concentration in 5 % dextrose and water. At this concentration, the rate of administration should not exceed 50 mL/min.

Management of Some Complications: Respiratory depression (hypoventilation, apnea), which may result from either unusual responsiveness to thiopental or overdosage, is managed as stated above. Thiopental should be considered to have the same potential for producing respiratory depression as an inhalation agent, and patency of the airway must be protected at all times.

Laryngospasm may occur with light thiopental narcosis at intubation, or in the absence of intubation if foreign matter or secretions in the respiratory tract create irritation. Laryngeal and bronchial vagal reflexes can be suppressed, and secretions minimized by giving atropine or scopolamine premedication and a barbiturate or opiate. Use of a skeletal muscle relaxant or positive pressure oxygen will usually relieve laryngospasm. Tracheotomy may be indicated in difficult cases.

Myocardial depression, proportional to the amount of drug in direct contact with the heart, can occur and may cause hypotension, particularly in patients with an unhealthy myocardium. Arrhythmias may appear if Pco2 is elevated, but they are uncommon with adequate ventilation. Management of myocardial depression is the same as for overdosage. Thiopental does not sensitize the heart to epinephrine or other sympathomimetic amines.

Extravascular infiltration should be a avoided. Care should be taken to insure that the needle is within the lumen of the vein before injection of thiopental. Extravascular injection may cause chemical irritation of the tissues varying from slight tenderness to venospasm, extensive necrosis and sloughing. This is due primarily to the high alkalinity (pH 10 to 11) of clinical concentrations of the drug. If extravasation occurs, the local irritant effects can be reduced by injection of 1 % procaine locally to relieve pain and enhance vasodilatation. Local application of heat also may help to increase local circulation and removal of the infiltrate.

Intra-arterial injection can occur inadvertently, especially if an aberrant superficial artery is present at the medial aspect of the antecubital fossa. The area selected for i.v. injection of the drug should be palpated for detection of an underlying pulsating vessel. Accidental intra-arterial injection can cause arteriospasm and severe pain along the course of the artery with blanching of the arm and fingers. Appropriate corrective measures should be instituted promptly to avoid possible development of gangrene. Any patient complaint of pain warrants stopping the injection. Methods suggested for dealing with this complication vary with the severity of symptoms. The following have been suggested: Dilute the injected thiopental by removing the tourniquet and any restrictive garments; leave the needle in place, if possible; inject the artery with a dilute solution of papaverine, 40 to 80 mg, or 10 mL of 1% procaine, to inhibit smooth muscle spasm; if necessary, perform sympathetic block of the brachial plexus and/or stellate ganglion to relieve pain and assist in opening collateral circulation (papaverine can be injected into subclavian artery, if desired); unless otherwise contraindicated, institute immediate heparinization to prevent thrombus formation; consider local infiltration of an alpha-adrenergic blocking agent such as phentolamine into the vasospastic area; and provide additional symptomatic treatment as required.

Shivering after thiopental anesthesia, manifested by twitching face muscles and occasional progression to tremors of the arms, head, shoulders and body, is a thermal reaction due to increased sensitivity to cold. Shivering appears if the room environment is cold and if a large ventilatory heat loss has been sustained with balanced inhalation anesthesia employing nitrous oxide. Treatment consists of warming the patient with blankets, maintaining room temperature near 22°C, and administration of chlorpromazine or methylphenidate.

Reconstitution of Solutions: Thiopental is supplied as a sterile, yellowish, hygroscopic powder stabilized with anhydrous sodium carbonate as a buffer.

The diluent (Sterile Water for Injection USP) in Pentothal Ready-to-Mix Syringes is supplied in a separate container to allow for mixing with the thiopental in the powder vial to permit immediate i.v. injection of reconstituted solution into a vein or attachment to a standard stopcock assembly.

Since thiopental contains no added bacteriostatic agent, extreme care in preparation and handling should be exercised at all times to prevent the introduction of microbial contaminants. Solutions should be freshly prepared and used promptly. Reconstituted solutions of thiopental may be kept, tightly stoppered, under refrigeration up to 24 hours, unused portions should be discarded after 24 hours. Sterilization by heating should not be attempted.

Directions for Preparing the Pentothal Solutions, Excluding Ready-to-Mix Syringes. Solutions should be prepared aseptically with 1 of the 3 following diluents: Sterile Water for Injection, USP, sodium chloride injection, USP, or 5% dextrose injection, USP. Clinical concentrations used for intermittent i.v. administration vary between 2 and 5%. A 2 or 2.5% solution is most commonly used. A 3.4% concentration in sterile water for injection is isotonic; concentrations less than 2% in this diluent are not used because they cause hemolysis. For continuous i.v. drip administration, concentrations of 0.2 or 0.4% are used. Solutions may be prepared by adding Pentothal to 5% dextrose injection, USP, sodium chloride injection, USP, or Normosol-R pH 7.4.

Directions for Preparing the Pentothal Ready-to-Mix Syringe: Use aseptic technique: Do not assemble until ready to use.

1. Remove caps from powder vial and injector.

2. Insert powder vial into injector and rotate clockwise approximately 3 turns.

3. Remove fliptop from diluent vial. Swab stopper. Remove needle cover. Insert needle into target area of diluent vial stopper.

4. Position syringe upright, depress powder vial to transfer air into diluent vial. Release pressure on powder vial and allow diluent to fill powder vial. Repeat until air in powder vial has been displaced.

5. Transfer remaining diluent by slowly pulling back on powder vial.

6. Remove and discard empty diluent vial. Replace needle cover. Shake until powder is completely dissolved.

7. Use reconstituted solution only if it is clear, free from precipitate and not discolored.

Medication, fluid path and needle are sterile if caps and protective covers are undisturbed and package is intact. Component exteriors are not sterile. Single dose unit. Discard unused portion. For i.v. use.

Compatibility: Any solution of thiopental with a visible precipitate should be discarded. The stability of thiopental solutions depends upon several factors, including the diluent, temperature of storage and the amount of carbon dioxide from room air that gains access to the solution. Any factor or condition which tends to lower pH (increased acidity) of thiopental solutions will increase the likelihood of precipitation of thiopental acid. Such factors include the use of diluents which are too acidic and the absorption of carbon dioxide, which can combine with water to form carbonic acid.

Solutions of succinylcholine, tubocurarine or other drugs which have an acid pH should not be mixed with thiopental solutions. The most stable solutions are those reconstituted in water or isotonic saline, kept under refrigeration and tightly stoppered.

Availability And Storage: Combination Kits: 2.5 g/vial: Each kit contains: one 2.5 g thiopental sodium vial and one 100 mL bottle of water for injection to provide a 2.5% solution after reconstitution. Packages of 25 kits. Protect from freezing and high temperatures, above 38°C.

1 g/vial: Each kit contains: one 1 g thiopental sodium vial and one 50 mL vial of water for injection to provide a 2% solution after reconstitution. To obtain a 2.5% solution after reconstitution, use only 40 mL of water for injection. Packages of 25 kits. Protect from freezing and high temperatures, above 38°C.

5 g/vial: Each kit contains: one 5 g thiopental sodium vial and one 200 mL bottle of water for injection to provide a 2.5% solution after reconstitution. Packages of 25 kits. Protect from freezing and high temperatures, above 38°C.

Vials: 500 mg: Each vial of sterile, yellowish, hydroscopic powder for injection, stabilized with anydrous sodium carbonate as a buffer, contains: thiopental sodium 500 mg. Packages of 25 vials. Protect from freezing and high temperatures, above 38°C.

1 g: Each vial of sterile, yellowish, hydroscopic powder for injection, stabilized with anydrous sodium carbonate as buffer, contains: thiopental sodium 1 g. Packages of 25 vials. Protect from freezing and high temperatures, above 38°C.

Ready to Mix Syringes: 250 mg: Each single dose unit contains: thiopental sodium powder 250 mg accompanied with 10 mL of diluent, providing a reconstituted concentration of 2.5%. Store at controlled room temperature (15 to 30°C).

500 mg: Each single dose unit contains: thiopental sodium powder 500 mg accompanied with 20 mL of diluent, providing a reconstituted concentration of 2.5%. Store at controlled room temperature (15 to 30°C).

PENTOTHAL® Abbott Thiopental Sodium I.V. Anesthetic

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