Pentothal (Thiopental Sodium) - Indications and Dosage

INDICATIONS AND USAGE

Pentothal (Thiopental Sodium for Injection) is indicated (1) as the sole anesthetic agent for brief (15 minute) procedures, (2) for induction of anesthesia prior to administration of other anesthetic agents, (3) to supplement regional anesthesia, (4) to provide hypnosis during balanced anesthesia with other agents for analgesia or muscle relaxation, (5) for the control of convulsive states during or following inhalation anesthesia, local anesthesia, or other causes, (6) in neurosurgical patients with increased intracranial pressure, if adequate ventilation is provided, and (7) for narcoanalysis and narcosynthesis in psychiatric disorders.

DOSAGE AND ADMINISTRATION

Pentothal is administered by the intravenous 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. Pre-puberty 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.

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 (Nembutal^®) 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 Pentothal (Thiopental Sodium for Injection) to assess tolerance or unusual sensitivity to Pentothal, and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: (1) the patient may be unusually sensitive to Pentothal, (2) the solution may be more concentrated than had been assumed, or (3) the patient may have received too much premedication.

Use in 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 but 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 Pentothal (Thiopental Sodium for Injection) is used for induction in balanced anesthesia with a skeletal muscle relaxant and an inhalation agent, the total dose of Pentothal can be estimated and then injected in two to four 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) of Pentothal is usually required for rapid induction in the average adult (70 kg).

When Pentothal (Thiopental Sodium for Injection) 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 intravenous 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.) With continuous drip, the depth of anesthesia is controlled by adjusting the rate of infusion.

Use in 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 Pentothal given over a ten minute period. If the convulsion is caused by a local anesthetic, the required dose of Pentothal will depend upon the amount of local anesthetic given and its convulsant properties.

Use in 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.

Use in Psychiatric Disorders

For narcoanalysis and narcosynthesis in psychiatric disorders, premedication with an anticholinergic agent may precede administration of Pentothal. After a test dose, Pentothal (Thiopental Sodium for Injection) 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 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, Pentothal 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 Pentothal or overdosage, is managed as stated above. Pentothal 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 Pentothal 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. Tracheostomy 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. Pentothal (Thiopental Sodium for Injection) does not sensitize the heart to epinephrine or other sympathomimetic amines.

Extravascular infiltration should be avoided. Care should be taken to insure that the needle is within the lumen of the vein before injection of Pentothal. 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 alkaline 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 intravenous 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:

1. Dilute the injected Pentothal (Thiopental Sodium for Injection) by removing the tourniquet and any restrictive garments.
2. Leave the needle in place, if possible.
3. Inject the artery with a dilute solution of papaverine, 40 to 80 mg, or 10 mL of 1% procaine, to inhibit smooth muscle spasm.
4. 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 the subclavian artery, if desired.
5. Unless otherwise contraindicated, institute immediate heparinization to prevent thrombus formation.
6. Consider local infiltration of an alpha-adrenergic blocking agent such as phentolamine into the vasospastic area.
7. Provide additional symptomatic treatment as required.

Shivering after Pentothal anesthesia, manifested by twitching face muscles and occasional progression to tremors of the arms, head, shoulder 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 (72° F), and administration of chlorpromazine or methylphenidate.

DOSAGE AND ADMINISTRATION

Pentothal solutions should be administered only by intravenous injection and by individuals experienced in the conduct of intravenous anesthesia.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Keep reconstituted solution in a cool place. 

NDC No.	Pentothal	Pentothal Container	Diluent (mL)*	Theoretical Reconstituted Conc.
0409-3158-10	500 mg	Vial	W  (20)	2.5% (25 mg/mL)
0409-6431-10	1 g	Vial	W  (20)	5% (50 mg/mL)

Revised: April, 2010

Made in Italy                           K156946A

Hospira, Inc., Lake Forest, IL 60045 USA

COMPATIBILITY

Any solution of Pentothal (Thiopental Sodium for Injection) with a visible precipitate should not be administered. The stability of Pentothal 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 (increase acidity) of Pentothal 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 Pentothal solutions. The most stable solutions are those reconstituted in water or isotonic saline, kept under refrigeration and tightly stoppered. The presence or absence of a visible precipitate offers a practical guide to the physical compatibility of prepared solutions of Pentothal.

CALCULATIONS FOR VARIOUS CONCENTRATIONS
Concentration Desired		Amount to Use
Percent	mg/mL	Pentothal g	Diluent mL
0.2	2	1	500
0.4	4	{1	250
		2	500
2.0	20	{5	250
		10	500
2.5	25	{1	40
		5	200
5	50	{1	20
		5	100

Reconstituted solutions of Pentothal (Thiopental Sodium for Injection) should be inspected visually for particulate matter and discoloration, whenever solution and container permit.

HOW SUPPLIED

Pentothal is available as shown.