Thiopental Sodium

Class: Barbiturates
VA Class: CN202
Chemical Name: 5-Ethyl-dihydro-5-(1-methylbutyl)-2-thioxo-4,6(1H,5H)-pyrimidinedione monosodium salt
Molecular Formula: C11H17N2NaO2S
CAS Number: 71-73-8
Brands: Pentothal

Introduction

Barbiturate anesthetic.1 2 3 7 24

Uses for Thiopental Sodium

Induction and Maintenance of Anesthesia

Induction of general anesthesia prior to administration of other anesthetic agents or as the sole anesthetic agent for short (≤15 minutes) surgical procedures.1 2 3 4 7 12

Induction results in dose-related hypnotic effects (progressing from light sleep to unconsciousness) and anterograde amnesia, but not analgesia.1 2 12

Adjunct to regional anesthesia (also called block anesthesia or conduction anesthesia).1 2

As the hypnotic component of balanced anesthesia (e.g., IV hypnotic and/or inhalation anesthetic, analgesic, skeletal muscle relaxant).1 2 3 7 12

Seizures

Management of seizures occurring during or after administration of local or inhalation anesthetics and seizures attributed to various etiologies.1 2 3 6 7 12 23 47 78 110

Slideshow: Flashback: FDA Drug Approvals 2013

Control of generalized tonic-clonic status epilepticus refractory to conventional anticonvulsants in intubated and mechanically ventilated patients.3 6 47

Increased Intracranial Pressure

Management of increased intracranial pressure associated with neurosurgical procedures when adequate ventilation is maintained.1 2 3 7 12 13 58

Has been used to induce coma3 12 26 85 86 87 88 89 90 105 in the management of cerebral ischemia and increased intracranial pressure associated with head trauma injury/3 27 86 87 88 89 stroke,3 85 Reye’s syndrome,3 or hepatic encephalopathy;3 90 however, pentobarbital is the most commonly used barbiturate.26 89 Safety and efficacy for the management of increased intracranial pressure associated with neurotraumas are controversial 26 85 86 87 88 105 and are not established.26 85 88 105

Narcoanalysis

Hypnotic agent for narcoanalysis in psychiatric conditions; use historically misnomered as “truth serum.”1 2 104 106 123 124

Sedation in Children

To provide sedation when administered as extemporaneously prepared rectal suspensions, solutions, or suppositories prior to diagnostic procedures (e.g., computed tomography [CT scan], magnetic resonance imaging [MRI]).27 28 29 30 31 108

Thiopental Sodium Dosage and Administration

General

Test Dose

  • Prior to initiation of therapy, the manufacturers recommend administration of a 25- to 75-mg test dose (1–3 mL of a 2.5% solution) followed by observation of the patient for ≥60 seconds to detect unusual sensitivity and assess tolerance.1 2 12 Reduce dosage in particularly sensitive patients.12

  • If unexpectedly deep anesthesia or respiratory depression occurs, consider factors other than sensitivity (e.g., excessive premedication, unintended use of a more concentrated solution).1 2

Premedication

  • The manufacturers state that patients may receive premedication with other drugs (e.g., benzodiazepines [to relieve anxiety and produce anterograde amnesia], other barbiturates [to relieve anxiety and provide sedation]) prior to administration of thiopental for induction of anesthesia.1 2 12 Anticholinergic agents (e.g., atropine, scopolamine) also have been used (to suppress vagal reflexes and inhibit secretions).1 2 Peak effects of these drugs should be reached shortly before IV induction.1 2

Administration

IV Administration

For solution and drug compatibility, see Compatibility under Stability.

Administer by IV injection or continuous IV infusion.1 2 3

To decrease pain at the injection site, administer thiopental by slow injection into large veins (rather than into small hand veins); may also administer a local anesthetic or an opiate agonist prior to induction to minimize pain.12

Avoid extravasation and intra-arterial administration.1 2 (See Local Effects under Cautions.) Prior to IV infusion, check placement of the IV catheter to ensure that it is in the vein.1 2

Observe strict aseptic technique in preparing and handling thiopental solutions as commercially available thiopental sodium for injection contains no preservatives.1 2 Reconstituted solutions should not be sterilized by heat.1 2 Use promptly and discard any unused portion after 24 hours.1 2

Reconstitution for Intermittent IV Injection

For intermittent IV administration, reconstitute powder for injection with sterile water for injection, 0.9% sodium chloride injection, or 5% dextrose injection to a concentration of 2–5% (usually 2 or 2.5%).1 2

A 3.4% solution of thiopental sodium in sterile water for injection is isotonic.1 2 Do not use sterile water for injection for preparing solutions with concentrations <2%, since use of the resulting hypotonic solutions will cause hemolysis.1 2

Use 2.5- or 5-g vials when preparing solutions for several patients.1 2

Preparation of 2% Thiopental Sodium Solution12

Amount of Thiopental Sodium (g in vial)

Volume of Diluent

0.4 g

20 mL

1 g

50 mL

2.5 g

125 mL

5 g

250 mL

Preparation of 2.5% Thiopental Sodium Solution12

Amount of Thiopental Sodium (g in vial)

Volume of Diluent

0.25 g

10 mL

0.5 g

20 mL

1 g

40 mL

2.5 g

100 mL

5 g

200 mL

Preparation of 5% Thiopental Sodium Solution12

Amount of Thiopental Sodium (g in vial)

Volume of Diluent

1 g

20 mL

5 g

100 mL

Reconstitution for IV Infusion

For continuous IV infusion, reconstitute thiopental sodium powder for injection with 0.9% sodium chloride injection, 5% dextrose injection, or Normosol-R (pH 7.4) to a concentration of 0.2–0.4%.1 2

A 3.4% solution of thiopental sodium in sterile water for injection is isotonic.1 2 Do not use sterile water for injection for preparing solutions with concentrations <2%, since use of the resulting hypotonic solutions will cause hemolysis.1 2

Preparation of Thiopental for IV Infusion12

Desired Concentration of Final Solution

Amount of Thiopental Sodium (g in vial)

Volume of Diluent

0.2%

1 g

500 mL

0.4%

1 g

250 mL

0.4%

2 g

500 mL

Rate of Administration

IV injection: Administer slowly (see Dosage) to minimize respiratory depression and the possibility of overdosage.1 2 120

Depth of anesthesia is controlled by rate of IV infusion.1 2 Clinical assessment of the depth of anesthesia is based on responses to verbal commands and surgical stimulation, EEG changes, autonomic signs, eyelash reflex, and movement.4 7 12 119 120 121 122

Rectal Administration

Preparations for rectal use no longer commercially available in the US; extemporaneous rectal formulations have been prepared7 27 28 29 30 using commercially available thiopental sodium for injection.28 108

Dosage

Available as thiopental sodium; dosage expressed in terms of the salt.1 2

Individual response to thiopental is variable; therefore, adjust dosage according to individual requirements and response, age, weight, gender, physical and clinical status, underlying pathologic conditions (e.g., shock, intestinal obstruction, malnutrition, anemia, burns, advanced malignancy, ulcerative colitis, uremia, alcoholism), and the type and amount of premedication or concomitant medication(s).1 2 7 12

Pediatric Patients

Pediatric patients require relatively larger doses than middle-aged and geriatric adults.1 2 11 12 120 121

Reduce dosage in neonates (because of decreased protein binding11 and reduced clearance).11 18

Induction and Maintenance of Anesthesia
IV

Induction of anesthesia in infants: 7–8 mg/kg administered over 20–30 seconds is recommended by some clinicians; however, this dosage is estimated for healthy individuals and should be titrated to clinical effect.4 12

Induction of anesthesia in children: 5–6 mg/kg administered over 20–30 seconds is recommended by some clinicians; however, this dosage is estimated for healthy individuals and should be titrated to clinical effect.4 12

Seizures
IV

Initial loading dose of 1 mg/kg followed by continuous IV infusion of 10–120 mcg/kg per minute has been used.6 A limited number of children receiving conventional anticonvulsants have received thiopental infusions for 3–5 days.7

Increased Intracranial Pressure
Increased Intracranial Pressure Associated with Trauma
IV

Children 3 months to 15 years of age: Initial dose of 5–10 mg/kg followed by continuous IV infusion of 1–4 mg/kg per hour.7 A more rapid IV infusion rate of up to 7–12 mg/kg per hour has been maintained for 8–10 days.7

Sedation
Rectal

25–50 mg/kg.27 28 29 31

In one study, dosage was based on both the child’s weight and age.29

Thiopental Sodium Dosage for Sedation Based on Child’s Weight and Age29

Age of Child

Dosage

<6 months

50 mg/kg

6 months to 1 year

35 mg/kg

>1 year

25 mg/kg (maximum 700 mg)

Adults

Younger patients require relatively larger doses than middle-aged and geriatric adults.1 2 11 12 120 121 Some clinicians estimate that dosage requirements decrease by 10% per decade over the age range of 20–80 years.7

Adult males usually require higher dosages than adult females.1 2 11 12 120 121

Induction and Maintenance of Anesthesia
IV

Moderately slow induction of anesthesia: Initially, 50–75 mg (2–3 mL of a 2.5% solution), usually administered at intervals of 20–40 seconds, based on patient response.1 2 Additional doses of 25–50 mg may be given as necessary when patient movements indicate lightening of anesthesia.1 2

Alternatively, some clinicians suggest induction doses administered over 20–30 seconds of 3–5 mg/kg in young adults or 2–4 mg/kg in older adults; however, these dosages are estimated for healthy individuals and should be titrated to clinical effect.4 12

Rapid induction as a component of balanced anesthesia: Initially, 210–280 mg (3–4 mg/kg) given in 2–4 divided doses in an average 70-kg adult.1 2

Maintenance of anesthesia: Intermittent injections or continuous IV infusion of a 0.2 or 0.4% solution may be used without additional anesthetic agents for short (≤15-minute) surgical procedures.1 2

Seizures
IV

75–125 mg (3–5 mL of a 2.5% solution) administered as soon as possible after seizures develop.1 2

Seizures following Administration of Local Anesthesia
IV

125–250 mg administered over 10 minutes;1 2 121 dosage depends on the amount of the local anesthetic used and its seizure characteristics.1 2

Generalized Tonic-Clonic Status Epilepticus
IV

Initial loading dose of 5 mg/kg followed in 30 minutes by continuous IV infusion of 1–3 mg/kg per hour for ≥12 hours after seizures abate is recommended by some clinicians.3 Alternatively, an initial loading dose of 250–1000 mg followed by continuous IV infusion of 80–120 mg per hour has been used for up to 13 days.47

Increased Intracranial Pressure
Increased Intracranial Pressure Associated with Neurosurgical Procedures
IV

1.5–3.5 mg/kg by intermittent IV infusion.1 2

Alternatively, an initial loading dose of 20 mg/kg administered over 1 hour, followed by a second loading dose of 10 mg/kg per hour over 6 hours and subsequently followed by a continuous IV maintenance infusion of 3 mg/kg per hour, has been used.117 118 120 Dosage was adjusted to maintain blood concentrations of 20–40 mcg/mL.117

Increased Intracranial Pressure Associated with Head Injury
IV

Low-dosage IV infusion (0.5–3 mg/kg per hour) administered in combination with other therapeutic agents (e.g., dihydroergotamine, metoprolol, clonidine) has been used.86 87

Narcoanalysis
IV

Patients usually receive an anticholinergic agent prior to a test dose of thiopental.1 2

Administer at a rate of 100 mg/minute (4 mL/minute of a 2.5% solution) while the patient counts backward from 100.1 2 Shortly after the counting becomes confused but before actual sleep occurs, discontinue thiopental, allowing the patient to return to a semidrowsy state under which conversation is coherent.1 2

Alternatively, administer as a 0.2% solution by continuous IV infusion at a rate ≤50 mL/minute (100 mg/minute).1 2

Some clinicians have used an initial IV loading dose of 25 mg followed by continuous IV infusion of 0.5 mg/kg per hour.104 123

Special Populations

Hepatic Impairment

Generally not recommended for use; however, if used, reduce dosage and rate of administration.1 2 96 121

Renal Impairment

Generally not recommended for use; however, if used, reduce dosage and rate of administration.1 2 96 121

Geriatric Patients

Reduce initial dosage.1 2 12 Some clinicians estimate that dosage requirements decrease by 10% per decade over the age range of 20–80 years.7

Obese Patients

Dosage requirements are proportional to body weight.1 2 Obese patients may require larger doses than relatively lean patients of the same weight;1 2 however, some clinicians suggest that dosage used in anesthesia7 should be based on lean body weight.7 12 120

Other Populations

Reduce dosage and administer slowly in patients with severe cardiovascular disease, hypotension or shock, status asthmaticus, and conditions that might prolong or intensify the hypnotic effect (e.g., excessive premedication, Addison’s disease, myxedema, increased blood urea concentrations, severe anemia, asthma, myasthenia gravis).1 2

Cautions for Thiopental Sodium

Contraindications

  • Known hypersensitivity to barbiturates.1 2

  • Patients in whom a suitable vein is not accessible for IV administration.1 2

  • History of acute intermittent porphyria or porphyria variegata,1 2 since thiopental interferes with porphyrin metabolism.12

  • Relative Contraindications (See Other Populations under Dosage and Administration):
  • Severe cardiovascular disease.1 2

  • Hypotension or shock.1 2

  • Status asthmaticus.1 2

  • Conditions that might prolong or intensify the hypnotic effect (e.g., excessive premedication, Addison’s disease, hepatic or renal impairment, myxedema, increased blood urea concentrations, severe anemia, asthma, myasthenia gravis).1 2

Warnings/Precautions

Warnings

Respiratory and Cardiovascular Effects

Possible respiratory depression.1 2 3 4 7 12 13 14 May depress ventilatory response to carbon dioxide stimulation12 or cause decreases in tidal volume.12 Apnea and hypoventilation may result from unusual responsiveness or overdosage.1 2

Laryngospasm may occur during light anesthesia at intubation or, in the absence of intubation, it may be associated with irritation caused by foreign matter or secretions in the respiratory tract.1 2 7 Laryngospasm or bronchospasm is more likely caused by premature insertion of oral airways or endotracheal tubes in inadequately anesthetized patients by airway reactivity.12 Manufacturers state that laryngeal and bronchial vagal reflexes may be suppressed and secretions minimized by premedication with an anticholinergic agent (e.g., atropine, scopolamine) and administration of a barbiturate or an opiate agonist.1 2 121

Possible myocardial depression (proportional to the amount of drug that is in direct contact with the heart),1 2 33 36 38 cardiac arrhythmias (occurring rarely in patients with adequate ventilation),1 2 increased heart rate,12 circulatory depression,7 vasodilation,12 and hypotension (especially in hypovolemic patients).3 7 38 These effects may be particularly severe in patients with impaired vascular homeostatic mechanisms.1 2 7 12 13 120

Appropriate resuscitative equipment for prevention and treatment of anesthetic emergencies must be readily available.1 2 Facilities for intubation, assisted respiration, and administration of oxygen must be available whenever the drug is used.1 2

Supervised Administration

Should be administered only by individuals qualified in the use of IV anesthetics.1 2

Local Effects

Local reactions at the injection site reported; 12 33 36 38 IV administration has caused pain,12 36 38 venous thrombosis,33 phlebitis,33 and thrombophlebitis.33

Extravasation can cause chemical irritation of perivascular tissues (possibly associated with high alkalinity [pH 10–11] of the injection);120 121 local reactions can vary from slight tenderness to venospasm, extensive necrosis, and sloughing.1 2

Inadvertent intra-arterial injection may cause arteriospasm and severe pain along the affected artery; the resulting necrosis can progress to gangrene.1 2 Increased risk of intra-arterial administration if aberrant arteries are present (especially at the medial aspect of the antecubital fossa).1 2

Decrease pain at the injection site by slow injection into large veins (rather than into small hand veins) and by administration of a local anesthetic or an opiate agonist prior to induction.12

IV solutions in concentrations >2.5% appear to be associated with an increased incidence of local adverse effects;33 severe tissue injury may occur when solutions of these concentrations are injected sub-Q or intra-arterially.12

In a conscious patient, the first manifestation of intra-arterial injection may be a complaint of fiery burning that roughly follows the distribution path of the injected artery with blanching of the arm and fingers; stop the injection immediately and assess the situation.1 2

Treatment of extravasation or inadvertent intra-arterial injection includes application of moist heat and administration of a 1% procaine injection at the affected site.1 2 120 The most appropriate therapy for inadvertent intra-arterial injection has not been fully established; efforts aimed at prevention are important; consult the manufacturers’ labeling for suggested therapies that may be beneficial.1 2

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic or anaphylactoid and other serious hypersensitivity reactions (e.g., urticaria,1 2 flushing and/or rash [on the face, neck, and/or upper chest],12 33 42 bronchospasm,1 2 42 45 61 vasodilation,1 2 hypotension,42 44 edema,1 2 44 angioedema,42 cardiovascular collapse,45 shock,12 death1 2 3 12 33 34 40 41 42 43 44 61 ) reported rarely.1 2

Allergic reactions often appear to be immediate type I IgE-mediated hypersensitivity reactions,33 34 40 41 42 43 44 45 although some reactions may result from direct histamine release.33 34 42 43 46 Hypersensitivity reactions are most likely to occur in patients with asthma33 34 61 or urticaria42 and in those with a history of atopy34 40 42 43 61 or allergies to other drugs and/or food.33 40 42 43 44 45

General Precautions

Postoperative Shivering

Postoperative shivering (manifested by facial muscle twitching and occasionally by tremor of arms, head, shoulder, and body) reported in up to 65% of patients receiving general anesthesia.1 2 56 57 120 Shivering may lead to increased oxygen demand with increases in minute ventilation and cardiac output.56 57

Management includes administration of chlorpromazine or methylphenidate, raising room temperature to 22°C, and covering patient with blankets.1 2

Concomitant Medical Conditions

Use with caution in patients with advanced cardiac disease, increased intracranial pressure, ophthalmoplegia plus, asthma, myasthenia gravis, and endocrine disorders (e.g., pituitary, thyroid, adrenal, pancreas).1 2

Specific Populations

Pregnancy

Category C.1

Usual anesthesia induction doses have been used safely in women undergoing cesarean section.12 Use in pregnant women only when clearly needed.1 2

Lactation

Distributed into colostrum7 20 50 and milk.1 2 50

Many clinicians state that nursing women undergoing surgery may receive usual anesthetic induction doses of thiopental;12 51 52 however, since trace amounts of the drug may be present in milk, drowsiness of nursing infants may occur on the day of the procedure.12

Pediatric Use

Safety and efficacy not established in children.1 2 120 121

Pharmacology of thiopental in infants and children is similar to that in adults; however, pharmacokinetics may be different in neonates and young infants because of their immature organs of elimination (see Distribution and also Elimination, under Pharmacokinetics).7 12 Induction doses tend to be higher (relative to weight) in children.12 (See Pediatric Patients under Dosage and Administration.)

Used rectally to provide sedation.27 28 29 30 31 108 However, 1 manufacturer does not recommend such use, because the high alkalinity of thiopental may result in local irritation.121

Geriatric Use

Possible reduced clearance and prolonged drug-associated effects.12 120 121 (See Special Populations under Dosage and Administration.)

Hepatic Impairment

Hypnotic effect may be prolonged.1 2 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Hypnotic effect may be prolonged.1 2 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, sneezing, coughing, bronchospasm, laryngospasm, shivering.1 2

Interactions for Thiopental Sodium

Protein-bound Drugs

Potential for thiopental to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs.3 7 67

Specific Drugs

Drug

Interaction

Comments

Aminophylline

Administration of low-dose (e.g., 2 mg/kg) IV aminophylline after surgery may partially reverse thiopental-induced sedation in the early phase of recovery1 2 82 83

Aspirin

Thiopental theoretically could be displaced from binding sites by, or could displace from binding sites, aspirin3 7 67

Potentiation of hypnotic effect reported3

Clonidine

IV administration of clonidine 2.5 or 5 mg prior to induction of anesthesia with thiopental reduced thiopental dosage requirements by about 25 or 37%, respectively12 94

Some clinicians recommend reduction of thiopental dosage when clonidine is administered as an adjunct to anesthesia94

CNS depressants (e.g., sedatives, hypnotics, opiates, nitrous oxide, alcohol)

Thiopental may be additive with or potentiate the effects of other CNS depressants;1 2 3 71 65 75 92 premedication with other CNS depressants may potentiate hypnotic effect of thiopental3 71

Possible reduction of antinociceptive effect of opiate analgesics1 2 71

Adjustment of thiopental dosage may be required with concomitant use3 71

Chronic use of CNS depressants (e.g., alcohol) may increase thiopental dosage required to achieve the desired anesthetic effect3 75

Diazoxide

Hypotension reported during induction of anesthesia with thiopental in patients undergoing surgery for insulinoma who were receiving oral diazoxide (a highly protein-bound drug) for several days prior to surgery1 2 84

Ketamine

Additive anesthetic effects reported in 1 study;70 76 in another study, increased thiopental doses required to achieve unconsciousness70 76

Meprobamate

Thiopental theoretically could be displaced from binding sites by, or could displace from binding sites, meprobamate3 7 67

Possible potentiation of hypnotic effects7

Metoclopramide

Administration of metoclopramide prior to induction of anesthesia with thiopental can reduce thiopental dosage requirements64

Midazolam

Possible potentiation of hypnotic effect3 71

Reduce thiopental dosages for induction of anesthesia by about 15% in patients receiving premedication with IM midazolam69

Phenothiazines (e.g., chlorpromazine, promethazine)

Possible potentiation of hypnotic effects;68 concomitant use of thiopental in patients receiving chlorpromazine reported to prolong sleep time and reduce thiopental dosage requirements by 60%68

Possible increased excitatory effects of thiopental3 72

Possible increased hypotension3 72

Probenecid

Thiopental theoretically could be displaced from binding sites by, or could displace from binding sites, probenecid3 7 67

Possible prolongation of hypnotic effects (possibly through competition for protein-binding sites)3 67 81

Reduction of thiopental dosage may be necessary73 81

Sulfisoxazole

Thiopental theoretically could be displaced from binding sites by, or could displace from binding sites, sulfisoxazole3 7 67

Potentiation of hypnotic effects reported7

Thiopental Sodium Pharmacokinetics

Absorption

Bioavailability

Rectal absorption may be unpredictable when using a suspension rather than a solution of the drug.3

Onset

Following IV administration of usual induction doses (2.5–5 mg/kg) in adults, hypnosis1 2 or unconsciousness3 4 7 occurs within 10–40 seconds,1 2 3 4 7 11 16 with maximal effects occurring in about 1 minute.7 16

Following rectal administration in children, onset of sedation generally occurs within 3–15 minutes.27 28 29 30 31

Duration

Following IV administration of usual induction doses (2.5–5 mg/kg) in adults, duration of anesthesia persists for 5–8 minutes.1 2 3 4 7 11 13 16

Duration of action is variable;7 13 16 the duration of single doses usually is determined by redistribution of the drug from the CNS rather than by the rate of elimination.7 13 16 However, the anesthesia effect is prolonged following repeated injections or continuous infusion because of drug accumulation in adipose tissue.1 2 4 7 16

Following rectal administration in children, sedation generally persists for about 0.5–5 hours.27 28 29 30 31

Distribution

Extent

Following IV administration, thiopental is rapidly distributed to all tissues and fluids, with high concentrations in brain and liver.4 7

Penetrates the blood-brain barrier rapidly; rate of entry into the brain is limited only by the rate of cerebral blood flow.7 16 24

Readily crosses the placenta1 2 4 7 19 20 49 53 55 and is distributed into fetal blood and umbilical vein blood at delivery.1 2 7 19 20 49 53

Distributed into milk;7 20 50 colostrum-to-plasma ratios of 0.67–0.68 reported at 4 and 9 hours after induction of anesthesia.7 20

Plasma Protein Binding

Approximately 80%1 2 3 7 11 (mainly albumin).7 11

Special Populations

Plasma protein binding may be decreased in neonates.11

Elimination

Metabolism

Metabolized mainly in the liver by the CYP enzyme system and to a lesser extent in other organs and tissues (e.g., kidneys, brain).1 2 3 4 7

Undergoes desulfuration to form pentobarbital, an active metabolite.7 13 Both thiopental and pentobarbital undergo oxidation and hydroxylation to form the corresponding carboxylic acid metabolites and alcohols, respectively;7 all detected metabolites are pharmacologically inactive.1 2 7

Elimination Route

Excreted mainly in urine as inactive metabolites,1 2 7 with small amounts as unchanged drug.7

Half-life

Following small IV doses, concentrations appear to decline in a monoexponential (first-order) fashion, with an elimination half-life of about 3–22 hours.1 2 7 11 14

Following rapid IV (“bolus”) injection, pharmacokinetics described by a triexponential equation;3 24 the drug appears to undergo rapid and slow distribution phases followed by a terminal elimination phase.24 In the rapid distribution phase, thiopental rapidly distributes into highly perfused organs (CNS, viscera);7 16 in the slow distribution phase, the drug equilibrates between highly perfused organs and adipose tissue.7 16 In adults, the mean plasma half-lives in the initial distribution phase and slow distribution phase are about 1.7–13.2 and 39.5–161.4 minutes, respectively.7

At high therapeutic concentrations, pharmacokinetics characterized by Michaelis-Menten kinetics,7 11 with a first-order elimination half-life of 9.7–49.4 hours.7

Special Populations

In pediatric patients 5 months to 13 years of age, elimination half-life is about one-half the elimination half-life in adults (about 6 hours).7 11 59

In neonates, elimination half-life is increased by 2-fold compared with their mothers’ (about 15 hours).7 11 59

Stability

Storage

Parenteral

Powder for Injection

15–30°C.1 2

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Incompatible with acidic solutions or drugs.1 2 12

Solution CompatibilityHID

Compatible

Alcohol 5%, dextrose 5%

Dextran 6% in dextrose 5%

Dextran 6% in sodium chloride 0.9%

Dextrose 2.5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in sodium chloride 0.225 or 0.45%

Dextrose 2.5 or 5% in water

Multielectrolyte solution

Normosol R

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Incompatible

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose 5% in Ringer’s injection, lactated

Dextrose 10% in sodium chloride 0.9%

Dextrose 10% in water

Fructose 10% in sodium chloride 0.9%

Fructose 10% solutions

Fructose 10% in water

Invert sugar 5 and 10% in sodium chloride 0.9%

Invert sugar 5 and 10% in water

Ionosol products

Normosol solutions (except R)

Ringer’s injection

Ringer’s injection, lactated

Variable

Dextrose 5% in sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Chloramphenicol sodium succinate

Hydrocortisone sodium succinate

Oxytocin

Pentobarbital sodium

Phenobarbital sodium

Potassium chloride

Sodium bicarbonate

Incompatible

Amikacin sulfate

Dimenhydrinate

Diphenhydramine HCl

Hydromorphone HCl

Insulin, regular

Meperidine HCl

Metaraminol bitartrate

Morphine sulfate

Norepinephrine bitartrate

Penicillin G potassium

Prochlorperazine edisylate

Promethazine HCl

Succinylcholine chloride

Variable

Ephedrine sulfate

Y-Site CompatibilityHID

Compatible

Bivalirudin

Fentanyl citrate

Furosemide

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Milrinone lactate

Mivacurium chloride

Nitroglycerin

Propofol

Ranitidine HCl

Remifentanil HCl

Incompatible

Alfentanil HCl

Ascorbic acid injection

Atracurium besylate

Atropine sulfate

Diltiazem HCl

Dobutamine HCl

Dopamine HCl

Ephedrine sulfate

Epinephrine HCl

Fenoldopam mesylate

Hydromorphone HCl

Labetalol HCl

Lidocaine HCl

Midazolam HCl

Nicardipine HCl

Norepinephrine bitartrate

Pancuronium bromide

Phenylephrine HCl

Succinylcholine chloride

Sufentanil citrate

Vecuronium bromide

Variable

Lorazepam

Morphine sulfate

Actions

  • CNS effects appear to be related, at least partially, to thiopental’s ability to enhance the activity of GABA by altering inhibitory synaptic transmissions that are mediated by GABAA receptors.10 13 14

  • Capable of producing all levels of CNS depression—from mild sedation to hypnosis to deep coma to death.12

  • Is a poor skeletal muscle relaxant, has no analgesic activity, and may increase the reaction to painful stimuli at subanesthetic doses.4 7 13

  • Exhibits anticonvulsant activity.1 2 3 6 7 12 23 47 78 110

  • May reduce cerebral metabolic rate (measured by cerebral metabolic rate for oxygen; CMRO2) in a dose-dependent manner;13 26 105 decreases in CMRO2 may result in decreased cerebral blood flow and intracranial pressure.13

Advice to Patients

  • Importance of informing patients that their ability to perform activities requiring mental alertness (e.g., driving, operating machinery) may be impaired for some time after undergoing general anesthesia or sedation.b

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 2

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2

  • Importance of informing patients of other important precautionary information.1 2 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule III (C-III) drug.1 2

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Thiopental Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

250 mg

Pentothal ( C-III; with 10 mL sterile water for injection or sodium chloride 0.9% injection; available with a disposable syringe and needle)

Hospira

400 mg

Pentothal ( C-III; with 20 mL sterile water for injection or sodium chloride 0.9% injection; available with a disposable syringe and needle)

Hospira

500 mg*

Pentothal ( C-III; with 20 mL sterile water for injection or sodium chloride 0.9% injection; available with or without a disposable syringe and needle)

Hospira

Thiopental Sodium ( C-III; with 20 mL sodium chloride 0.9% injection; available with a disposable syringe and needle)

Baxter Anesthesia

1 g*

Penthothal ( C-III; with 40 or 50 mL sterile water for injection)

Hospira

Thiopental Sodium ( C-III; with 40 mL sodium chloride 0.9% injection; available with transfer spikes)

Baxter

2.5 g*

Pentothal ( C-III; with 100 or 150 mL sterile water for injection)

Hospira

Thiopental Sodium ( C-III; with 100 mL sterile water for injection; available with transfer spikes)

Baxter

5 g*

Pentothal ( C-III; with 200 or 250 mL sterile water for injection)

Hospira

Thiopental Sodium ( C-III; with 200 mL sterile water for injection; available with transfer spikes)

Baxter

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Abbott. Pentothal thiopental sodium for injection prescribing information. North Chicago, IL; 1993 Nov.

2. Baxter. Thiopental Sodium for injection prescribing information. Deerfield, IL; 1998 Sep.

3. Martindale: the complete drug reference. 32nd ed. Parfitt K, ed. London: Pharmaceutical Press, 1999:1233-4.

4. Carmichael FJ, Haas DA. General Anesthetics. In: Kalant H and Roschlau WHE, eds. Principles of Medical Pharmacology. 6th edition. New York: Oxford University Press; 1998:278-92.

5. Budavari S ed. The Merck Index. 12th ed. Whitehouse Station, NJ: Merck & CO., Inc. 1996:1595.

6. Lohr A Jr, Werneck LC. [Comparative non-randomized study with midazolam versus thiopental in children with refractory status epilepticus.] (Portuguese; with English abstract.) Arq Neuropsiquiatr. 2000; 58:282-7.

7. Russo H, Bressolle F. Pharmacodynamics and pharmacokinetics of thiopental. Clin Pharmacokinet. 1998; 35:95-134. [PubMed 9739479]

8. Newton DW. Introduction: physiochemical determinants of incompatibility and instability drugs for injection and infusion. In: Trissel LA. Handbook on injectable drugs. 3rd ed. Bethesda, MD: American Society of Hospital Pharmacists, Inc; 1983:xi-xxi.

9. (unused reference number)

10. Hales TG, Olsen RW. Basic pharmacology of intravenous induction agents. In: Bowdle TA, Horita A, Kharasch ED, eds. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:295-306.

11. Henthorn TK. Pharmacokinetics of intravenous induction agents. In: Bowdle TA, Horita A, Kharasch ED, eds. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:307-18.

12. Fragen RJ. Clinical pharmacology and applications of intravenous anesthetic induction agents. In: Bowdle TA, Horita A, Kharasch ED. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:319-36.

13. Witzum JL. Evers AS, Crowder CM. General Anesthetics. In: Hardman JG, Gilman AG, Limbird LE, eds. Goodman and Gilman’s The pharmacological basis of therapeutics. 10th ed. McGraw-Hill; 2001: 337-44.

14. Donnelly AJ, Shafer AL. Perioperative care. In: Young LL, Koda- Kimble MA, eds. Applied Therapeutics: The clinical use of drugs. 6th ed. Vancouver WA: Applied Therapeutics, Inc.; 1995:8-1-8-24.

15. Tanelian DL, Kosek P, Mody I et al. The role of the GABAA receptor/chloride channel complex in anesthesia. Anesthesiology. 1993; 78:757-76. [IDIS 316350] [PubMed 8385426]

16. Duvaldestin P. Pharmacokinetics in intravenous anesthetic practice. Clin Pharmacokinet. 1981; 6:61-82. [IDIS 165380] [PubMed 6113908]

17. Vozeh S, Schmidlin O, Taeschner W. Pharmacokinetic drug data. Clin Pharmacokinet.1988; 15:254-282 [IDIS 247363] [PubMed 3191648]

18. Henthorn TK Avram MJ, Krejcie TC. Intravascular mixing and drug distribution: the concurrent disposition of thiopental and indocyanine green. Clin Pharmacol Ther. 1989; 45:56-65. [IDIS 249962] [PubMed 2910638]

19. Bach V, Carl P, Ravlo O et al. A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia. Anesth Analg. 1989; 68:238-42. [IDIS 252263] [PubMed 2919760]

20. Esener Z, Sarihasan B, Güven H et al. Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum. Br J Anaesth. 1992; 69:586-8. [IDIS 307347] [PubMed 1467101]

21. Burch PG, Stanski DR. Pharmacokinetics of thiopental in renal failure. Anesthesiology. 1981; 55(Suppl): A176.

22. Henthorn TK. Emerging concepts in pharmacokinetics. In: Bowdle TA, Horita A, Kharasch ED. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:741-54.

23. Young GB, Blume WT, Bolton CF et al. Anesthetic barbiturates in refractory status epilepticus. Can J Neurol Sci. 1980; 7:291-2. [PubMed 7214243]

24. Burch PG, Stanski DR. The role of metabolism and protein binding in thiopental anesthesia. Anesthesiology. 1983; 58:146-52. [IDIS 165879] [PubMed 6824168]

25. Morgan DJ, Blackman GL, Paull JD et al. Pharmacokinetics and plasma binding of thiopental. I: studies in surgical patients. Anesthesiology. 1981; 54:468-73. [IDIS 133050] [PubMed 7235274]

26. Anon. The use of barbiturates in the control of intracranial hypertension. J Neurotrauma. 1996; 13:711-4. [PubMed 8941890]

27. De Boer AG, De Leede LGJ, Breimer DD. Drug absorption by sublingual and rectal routes. Br J Anaesth. 1984; 56:69-82. [IDIS 182485] [PubMed 6140933]

28. Nahata MC. Sedation in pediatric patients undergoing diagnostic procedures. Drug Intell Clin Pharm. 1988; 22:711-5. [IDIS 245367] [PubMed 3063482]

29. Alp H, Güler I, Orbak Z et al. Efficacy and safety of rectal thiopental: sedation for children undergoing computed tomography and magnetic resonance imaging. Pediatrics Int. 1999; 41:538-41.

30. De Boer AG, Moolenaar F, De Leede LGJ et al. Rectal drug administration: clinical pharmacokinetic considerations. Clin Pharmacokinet. 1982; 7:285-311. [IDIS 160658] [PubMed 6126289]

31. Burckart GJ, White TJ III, Siegle RL et al. Rectal thiopental versus an intramuscular cocktail for sedating children before computerized tomography. Am J Hosp Pharm. 1980; 37:222-4. [PubMed 7361794]

32. Boucher BA, Hanes SD. Pharmacokinetic alterations after severe head injury. Clin Pharmacokinet. 1998; 35:209-21. [PubMed 9784934]

33. Clarke RSJ. Adverse effects of intravenously administered drug used in anaesthetic practice. Drugs. 1981; 22:26-41. [IDIS 164821] [PubMed 7021121]

34. Bird AG. Severe drug reactions during anesthesia. Adv Drug React Ac Pois Rev. 1987; 3:117-140.

35. Korttila K, Nuotto EJ, Lichtor JL et al. Clinical recovery and psychomotor function after brief anesthesia with propofol or thiopental. Anesthesiology. 1992; 76:676-81. [IDIS 296072] [PubMed 1575333]

36. Baudoin Z, Vrhovac B. Thiopental sodium. In: Dukes MNG. Meyler’s side effects of drugs. 13th ed. Amsterdam: Elsevier; 1996:276.

37. Habibi B, Basty R, Chodez S et al. Thiopental-related immune hemolytic anemia and renal failure. N Engl J Med. 1985; 312:353-5. [IDIS 198132] [PubMed 3969087]

38. Sear JW. Toxicity of IV anaesthetics. Br J Anaesth. 1987; 59:24-45. [IDIS 242934] [PubMed 3548787]

39. Jensen NF, Fiddler DS, Striepe V. Anesthetic considerations in porphyrias. Anesth Analg. 1995; 80:591-9. [IDIS 343295] [PubMed 7864431]

40. Binkley K, Cheema A, Sussman G. Generalized allergic reactions during anesthesia. J Allergy Clin Immunol. 1992; 89:768-74. [IDIS 292816] [PubMed 1545098]

41. Fisher MM, Baldo BA, Silbert BS. Anaphylaxis during anesthesia: use of radioimmunoassays to determine etiology and drugs responsible in fatal cases. Anesthesiology. 1991; 75:1112-5. [IDIS 2295232] [PubMed 1741501]

42. Moscicki RA, Sockin SM, Corsello BF. Anaphylaxis during induction of general anesthesia: subsequent evaluation and management. J Allergy Clin Immunol. 1990; 86:325-32. [IDIS 274725] [PubMed 2212407]

43. Moudgil GC. Anaesthesia and allergic drug reactions. Can Anaesth Soc J. 1986; 33:400-14. [IDIS 216200] [PubMed 3521800]

44. Dolovich J, Evans S, Rosenbloom D et al. Anaphylaxis due to thiopental sodium anesthesia. Can Med Assoc J. 1980; 123:292-4. [PubMed 6167340]

45. Moneret-Vautrin DA, Widmer S, Gueant JL et al. Simultaneous anaphylaxis to thiopentone and a neuromuscular blocker: a study of two cases. Br J Anesth. 1990; 64:743-5.

46. Levy JH. Anaphylactic reaction to thiopental. JAMA. 1993; 270:2503.

47. Modica PA, Tempelhoff R, White PF. Pro- and anticonvulsant effects of anesthetics (Part II). Anesth Analg. 1990; 70:433-44. [IDIS 267841] [PubMed 2180345]

48. Leach AA. An unusual complication of thiopentone administration. Anaesthesia. 1986; 46:762.

49. Jorgensen NP, Walstad RA, Molne K. The concentrations of ceftazidime and thiopental in maternal plasma, placental tissue and amniotic fluid in early pregnancy. Acta Obstet Gynecol Scand. 1987; 66:29-33. [PubMed 3300134]

50. Andersen LW, Qvist T, Hertz J et al. Concentrations of thiopentone in mature breast milk and colostrum following an induction dose. Acta Anaesthesiol Scand. 1987; 31:30-2. [PubMed 3825473]

51. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics. 2001; 108:776-89. [IDIS 468574] [PubMed 11533352]

52. Anderson PO. Drug use during breast-feeding. Clin Pharm. 1991; 10:594-624. [IDIS 283187] [PubMed 1934918]

53. Datta S, Alper MH. Anesthesia for cesarean section. Anesthesiology. 1980; 53:142-60. [IDIS 118575] [PubMed 6998326]

54. Ong BY, Cohen MM. Anesthesia for cesarean section—Effects on neonates. Anesth Analg. 1989; 68:270-5. [IDIS 252266] [PubMed 2919765]

55. Clark RB. Anesthesia in obstetrics. Postgrad Med. 1973; 53:158-62. [PubMed 4571934]

56. Singh P, Harwood R, Cartwright DP et al. A comparison of thiopentone and propofol with respect to the incidence of postoperative shivering. Anaesthesia. 199; 49:996-8.

57. Cheong KF, Chen FG, Yau GHM. Postanaesthetic shivering—A comparison of thiopentone and propofol. Ann Acad Med Singapore. 1998; 27:729-32. [PubMed 9919351]

58. Shapiro BA, Warren J, Egol AB et al. Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Crit Care Med. 1995; 23:1596-1600. [IDIS 354085] [PubMed 7664563]

59. Gaspari F, Marraro G, Penna GF et al. Elimination kinetics of thiopentone in mothers and their newborn infants. Eur J Clin Pharmacol. 1985; 28:321-25. [IDIS 201405] [PubMed 4007037]

60. Backer RC, Caplan YH, Duncan CE. Thiopental suicide – case report. Clin Toxicol. 1975; 8:283-7. [PubMed 1175345]

61. Dundee JW, Assem ESK, Gaston JM et al. Sensitivity to intravenous anaesthetics: a report of three cases. Br Med J. 1974; 1:63-5. [PubMed 4272996]

62. Sulfisoxazole (Gantrisin) interactions: thiopental (pentothal). In: Hansten PD, Horn JR. Hansten and Horn’s drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997:466-7.

63. Probenecid (Benemid) interactions: thiopental (pentothal). In: Hansten PD, Horn JR. Hansten and Horn’s drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997:444-5.

64. Mehta D, Bradley EL, Kissin I. Metoclopramide decreases thiopental hypnotic requirements. Anesth Analg. 1993; 77:784-7. [IDIS 321297] [PubMed 8214666]

65. Lichtor JL, Zacny JP, Coalson DW et al. The interaction between alcohol and the residual effects of thiopental anesthesia. Anesthesiology. 1993; 79:28-35. [IDIS 317760] [PubMed 8342825]

66. Fassoulaki A, Sarantopoulos C, Papilas K. Flumazenil reduces the duration of thiopentone but not propofol anaesthesia in humans. Can J Anaesth. 1993; 40:10-12. [IDIS 308606] [PubMed 8425236]

67. Wood M. Plasma drug binding: implications for anesthesiologists. Anesth Analg. 1986; 65:786-804. [IDIS 217629] [PubMed 3087239]

68. Janowsky EC, Risch C, Janowsky DS. Effects of anesthesia on patients taking psychotropic drugs. J Clin Psychopharmacol. 1981; 1:14-20. [PubMed 6117578]

69. Roche Laboratories. Versed (midazolam hydrochloride) injection prescribing information (dated 2000 Jun). In: Physicians’ desk reference. 56th ed. Montvale, NJ: Medical Economics Company Inc; 2002:3027-33.

70. Barbiturate Anesthetics/Ketamine. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St Louis: JB Lippincott Co; 1999(Jul):111c.

71. Barbiturate Anesthetics/Narcotic Analgesics. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St Louis: JB Lippincott Co; 1996(Apr):112.

72. Barbiturate Anesthetics/Phenothiazines. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St Louis: JB Lippincott Co; 1990(Jan):113.

73. Barbiturate Anesthetics/Probenecid. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St Louis: JB Lippincott Co; 1990(Jan):114.

74. Barbiturate Anesthetics/Sufonamides. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St Louis: JB Lippincott Co; 1990(Jan):115.

75. Ethanol/Barbiturates. In: Tatro DS, Olin BR, Hebel SK eds. Drug interaction facts. St Louis: JB Lippincott Co; 1994(Apr):324.

76. G, Valenti S, Vincenti E et al. Interaction between thiopentone and subhypnotic doses of ketamine. Eur J Anesthesiol. 1992; 9:43-7.

77. Roytblat L, Katz J, Rozentsveig V et al. Anaesthetic interaction between thiopentone and ketamine. Eur J Anaesthesiol. 1992; 9:307-12. [PubMed 1628634]

78. Pourrat X, Serekian JM, Antier D et al. [Generalized tonic-clonic status epilepticus: therapeutic strategy.] (French; with English abstract.) Presse Med.2001; 30:1031-6.

79. (unused reference number)

80. Roelofse JA. Anaesthesia and diazoxide. S Afr Med J. 1984; 137:794.

81. Kaukinen S, Eerola M, Ylitalo P. Prolongation of thiopentone anaesthesia by probenecid. Br J Anaesth. 1980; 52:603-6. [IDIS 115978] [PubMed 7000105]

82. Chen YC, Chan KH, Tsou MY et al. The reversal effect of low dose aminophylline on thiopental-induced sedation. Chung Hua I Hsueh Tsa Chih (Taipei). 1993; 52:145-8.

83. Krintel JJ, Wegmann F. Aminophylline reduces the depth and duration of sedation with barbiturates. Acta Anaesthesiol Scand. 1987; 31:352-4. [PubMed 3296607]

84. Burch PG, McLeskey CH. Anesthesia for patients with insulinoma treatment with oral diazoxide. Anesthesiology. 1981; 55:472-475. [IDIS 166391] [PubMed 6271026]

85. Schwab S, Spranger M, Schwartz S et al. Barbiturate coma in severe hemispheric stroke: useful or obsolete? Neurology. 1997; 48:1608-13.

86. Naredi S, Edén E, Zäll S et al. A standardized neurosurgical/neurointensive therapy directed toward vasogenic edema after severe traumatic brain injury: clinical results. Intensive Care Med. 1998; 24:446-51. [IDIS 409134] [PubMed 9660259]

87. Eker C, Ásgeirsson B, Grande PO et al. Improved outcome after severe head injury with a new therapy based on principles for brain volume regulation and preserved microcirculation. Crit Care Med. 1998; 26:1881-6. [IDIS 418847] [PubMed 9824083]

88. Stover JF, Stocker R. Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury. Eur J Pharmacol. 1998; 54:529-34.

89. Boucher BA, Phelps SJ. Acute management of the head injury patient. In: DiPiro JT, Talbert RL, Yee GC, eds. Pharmacotherapy: a pathophysiologic approach. 4th ed. Stamford, CT: Appleton & Lange; 1999:991-7.

90. Forbes A, Alexander GJ, O’Grady JG et al. Thiopental infusion in the treatment of intracranial hypertension complicating fulminant hepatic failure. Hepatology. 1989; 10:306-10. [PubMed 2759548]

91. Bullock R, Chestnut RM, Clifton G et al. Guidelines for the management of severe head injury. Eur J Emerg Med. 1996; 2:109-27.

92. Wilder-Smith OH, Ravussin PA, Decosterd LA et al. Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points. Br J Anaesth. 1999; 83:590-5. [IDIS 435322] [PubMed 10673875]

93. Kissin I. A concept for assessing interactions of general anesthetics. Anesth Analg. 1997; 85:204-10. [IDIS 389617] [PubMed 9212148]

94. Leslie K, Mooney PH, Silbert BS. Effect of intravenous clonidine on the dose of thiopental required to induce anesthesia. Anesth Analg. 1992; 75:530-5. [IDIS 302489] [PubMed 1530166]

95. Bass NM, Williams RL. Guide to drug dosage in hepatic disease. Clin Pharmacokinet. 1988; 15:396-420. [IDIS 249947] [PubMed 3072141]

96. Bennet WM. Guide to drug dosage in renal failure. Clin Pharmacokinet. 1988; 15:326-54. [IDIS 250553] [PubMed 3060292]

97. Wada DR, Björkman S, Ebling WF et al. Computer simulation of the effects of alterations in blood flows and body composition on thiopental pharmacokinetics in humans. Anesthesiology. 1997; 87:884-99. [IDIS 396580] [PubMed 9357892]

98. Lzar ER, Jolly DT, Tam YK. Propofol and thiopental in a 1:1 volume mixture is chemically stable. Anesth Analg. 1998; 86:422-6. [IDIS 400789] [PubMed 9459260]

99. Pankerd RJ, Jones RD. Physiochemical compatibility of propofol with thiopental sodium. Am J Health-Syst Pharm. 1996; 53:2606-10. [IDIS 374425] [PubMed 8913389]

100. Chernin EL, Stewar JT, Smiler B. Stability of thiopental sodium and propofol in polypropylene syringes at 23 and 4&#x02DA;C. Am J Health-Syst Pharm. 1996; 53:1576-9. [IDIS 367724] [PubMed 8809279]

101. Crowther J, Hrazdil J, Jolly DT. Growth of microorganisms in propofol, thiopental, and a 1:1 mixture of propofol and thiopental. Anesth Analg. 1996; 82:475-8. [IDIS 361758] [PubMed 8623946]

102. Cernin EL, Smiler B. Propofol-thiopental combination: implications for cost savings and clinical use. Am J Anesthesiology. 1997; 24:251-3.

103. Trissel LA. Handbook on injectable drugs. 11th ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc; 1998:1219-26.

104. Simon EP, Dahl LF. The sodium penthotal hypnosis interview with follow-up treatment for complex regional pain syndrome. J Pain Symptom Management. 1999; 18:132-6.

105. Stover JF, Pleines UE, Morganti-Kossmann MC et al. Thiopental attenuates energetic impairment but fails to normalize cerebrospinal fluid glutamate in brain-injured patients. Crit Care Med. 1999; 27:1351-7. [IDIS 432495] [PubMed 10446831]

106. Smith JW, Lemere F, Dunn RB. Pentothal interviews in the treatment of alcoholism. Psychosomatics. 1971; 12:330-1. [PubMed 5172949]

107. (unused reference number)

108. Nguyen MT, Greenberg SB, Fitzhugh KR et al. Pediatric Imaging: Sedation with an injection formulation modified for rectal administration. Radiology. 2001; 221:760-2. [IDIS 473792] [PubMed 11719673]

109. Neville BGR. Epilepsy in childhood. Br Med J. 1997; 315:924-30.

110. Chapman MG, Smith M, Hirsch NP. Status epilepticus. Anaesthesia. 2001; 56:648-59. [IDIS 467143] [PubMed 11437765]

111. Rantala H, Saukkonen AL, Remes M et al. Efficacy of five days’ barbiturate anesthesia in the treatment of intractable epilepsies in children. Epilepsia. 1999; 40:1775-79. [IDIS 440993] [PubMed 10612343]

112. Mayersohn M, Calkins JM, Perrier DG et al. Thiopental kinetics in obese surgical patients. Anesthesiology. 1981; 55(Suppl): A178.

113. Jung D, Mayersohn M, Perrier D et al. Thiopental disposition in lean and obese patients undergoing surgery. Anesthesiology. 1982; 56:269-74. [IDIS 149322] [PubMed 7065435]

114. Potyk DK, Raudaskoski P. Overview of anesthesia for primary care physicians. West J Med. 1998; 168:517-21. [PubMed 9655993]

115. Beattie C. History and principles of anesthesiology. In: Hardman JG, Gilman AG, Limbird LE, eds Goodman and Gilman’s The pharmacological basis of therapeutics. 10th ed. McGraw-Hill; 2001: 321-35.

116. Cordato DJ, Mather LE, Gross AS et al. Pharmacokinetics of thiopental enantiomers during and following prolonged high-dose therapy. Anesthesiology.1999: 91:1693-1702.

117. Quandt C, de los Reyes RA, Diaz FG. Barbiturate-induced coma for the treatment of cerebral ischemia: review of outcome. Clin Pharm. 1982; 1:549-50. [IDIS 161403] [PubMed 7185542]

118. Quandt CM, De Los Reyes RA. Pharmacologic management of acute intracranial hypertension. Drug Intell Clin Pharm. 1984; 18:105-12. [IDIS 181290] [PubMed 6697873]

119. Glass PS, Bloom M, Kearse L et al. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology. 1997; 86:836-47. [IDIS 384520] [PubMed 9105228]

120. Reviewers’ comments (personal observations).

121. Abbott Laboratories, Abbott Park, IL: Personal communication.

122. Reviewers’ comments (personal observations) on Propofol 28:04.

123. Russo MB, Brooks FR, Fontenot JP et al. Sodium pentothal hypnosis: a procedure for evaluating medical patients with suspected psychiatric co-morbidity. Military Medicine. 1997; 162:215-8. [IDIS 383920] [PubMed 9121671]

124. Taher Y, Fakhr-El-Islam M, El-Sherif A et al. The effect of pentothal as a “truth serum”: a controlled study. J Egypt Med Assoc. 1969; 52:75-81. [PubMed 5350189]

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1541-8.

b. AHFS Drug Information 2004. McEvoy GK, ed. Barbiturate General Statement . Bethesda, MD: American Society of Health-System Pharmacists; 2004:2363-6.

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