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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 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 Reyes 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
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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 (13 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 Interm ittent IV Injection
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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 25% (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 1g 2.5 g 5g 20 mL 50 mL 125 mL 250 mL

Preparation of 2.5% Thiopental Sodium Solution12 Amount of Thiopental Sodium (g in vial) Volume of Diluent 0.25 g 0.5 g 1g 2.5 g 5g 10 mL 20 mL 40 mL 100 mL 200 mL

Preparation of 5% Thiopental Sodium Solution12 Amount of Thiopental Sodium (g in vial) Volume of Diluent 1g 5g 20 mL 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 0.20.4%.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
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0.2% 0.4% 0.4%

1g 1g 2g

500 mL 250 mL 500 mL

Rate of Adm inistration

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: 78 mg/kg administered over 2030 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: 56 mg/kg administered over 2030 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 10120 mcg/kg per minute has been used.6 A limited number of children receiving conventional anticonvulsants have received thiopental infusions for 35 days.7

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Increased Intracranial Pressure


Increased Intracranial Pressure Associated with Trauma

IV Children 3 months to 15 years of age: Initial dose of 510 mg/kg followed by continuous IV infusion of 14 mg/kg per hour.7 A more rapid IV infusion rate of up to 712 mg/kg per hour has been maintained for 810 days.7
Sedation
Rectal

2550 mg/kg.27 28 29 31 In one study, dosage was based on both the childs weight and age.29 Thiopental Sodium Dosage for Sedation Based on Childs 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 2080 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, 5075 mg (23 mL of a 2.5% solution), usually administered at intervals of 2040 seconds, based on patient response.1 2 Additional doses of 2550 mg may be given as necessary when patient movements indicate lightening of anesthesia.1 2 Alternatively, some clinicians suggest induction doses administered over 2030 seconds of 35 mg/kg in young adults or 24 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, 210280 mg (34 mg/kg) given in 24 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
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IV

Thiopental Sodium - Print Version

75125 mg (35 mL of a 2.5% solution) administered as soon as possible after seizures develop.1 2
Seizures following Administration of Local Anesthesia

IV 125250 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 13 mg/kg per hour for 12 hours after seizures abate is recommended by some clinicians.3 Alternatively, an initial loading dose of 2501000 mg followed by continuous IV infusion of 80120 mg per hour has been used for up to 13 days.47
Increased Intracranial Pressure
Increased Intracranial Pressure Associated with Neurosurgical Procedures

IV 1.53.5 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 2040 mcg/mL.117
Increased Intracranial Pressure Associated with Head Injury

IV Low-dosage IV infusion (0.53 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

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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 2080 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, Addisons 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, Addisons 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
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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 Adm inistration

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 1011] 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
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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 atopy 34 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 22C, and covering patient with blankets.1 2
Concom itant 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.)
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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 Im pairm ent

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

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 Administration of low-dose (e.g., 2 mg/kg) IV aminophylline after surgery may partially reverse thiopental-induced sedation in the early phase of recovery 1 2 82 83 Thiopental theoretically could be displaced from binding sites by, or could displace from binding sites, aspirin3 7 67 Potentiation of hypnotic effect reported3 Some clinicians recommend IV administration of clonidine 2.5 or 5 mg prior to induction reduction of thiopental dosage when of anesthesia with thiopental reduced thiopental dosage clonidine is administered as an requirements by about 25 or 37%, respectively 12 94 adjunct to anesthesia94 Adjustment of thiopental dosage may be required with concomitant use3 71 Comments

Aminophylline

Aspirin

Clonidine

CNS depressants (e.g., sedatives, hypnotics, opiates,

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 Chronic use of CNS depressants thiopental3 71

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nitrous oxide, alcohol)

Possible reduction of antinociceptive effect of opiate analgesics 1 2 71

(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 surgery 1 2 84 Additive anesthetic effects reported in 1 study;70 76 in another study, increased thiopental doses required to achieve unconsciousness 70 76 Thiopental theoretically could be displaced from binding sites by, or could displace from binding sites, meprobamate3 7 67 Possible potentiation of hypnotic effects 7 Administration of metoclopramide prior to induction of anesthesia with thiopental can reduce thiopental dosage requirements 64 Reduce thiopental dosages for induction of anesthesia by about 15% in patients receiving premedication with IM midazolam69

Ketamine

Meprobamate

Metoclopramide

Midazolam

Possible potentiation of hypnotic effect3 71

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

Probenecid

7 67

Reduction of thiopental dosage may be necessary 73 81

Possible prolongation of hypnotic effects (possibly through competition for protein-binding sites)3 67 81 Thiopental theoretically could be displaced from binding sites by, or could displace from binding sites, sulfisoxazole3 7 67 Potentiation of hypnotic effects reported7

Sulfisoxazole

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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 (2.55 mg/kg) in adults, hypnosis 1 2 or unconsciousness 3 4 7 occurs within 1040 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 315 minutes.27 28 29 30 31 Duration Following IV administration of usual induction doses (2.55 mg/kg) in adults, duration of anesthesia persists for 58 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 0.55 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 0.670.68 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
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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 322 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 1.713.2 and 39.5161.4 minutes, respectively.7 At high therapeutic concentrations, pharmacokinetics characterized by Michaelis-Menten kinetics,7 11 with a first-order elimination half-life of 9.749.4 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
Pow der for Injection

1530C.1 2

Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Incompatible with acidic solutions or drugs.1 2 12
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Solution Com patibilityHID

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 DextroseRingers injection combinations DextroseRingers injection, lactated, combinations Dextrose 5% in Ringers 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)
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Ringers injection Ringers 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


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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

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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 thiopentals 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 depressionfrom 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
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May reduce cerebral metabolic rate (measured by cerebral metabolic rate for oxygen; CMRO2) in a dosedependent 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 Pentothal (C-III; with 10 mL sterile water for injection or sodium chloride 0.9% injection; available with a disposable syringe and needle) Pentothal (C-III; with 20 mL sterile water for injection or sodium chloride 0.9% injection; available with a disposable syringe and needle) 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) Manufacturer

For Parenteral injection, for IV use

250 mg

Hospira

400 mg

Hospira

500 mg*

Hospira

Thiopental Sodium (C-III; with 20 mL sodium chloride 0.9% injection; Baxter available with a disposable syringe and needle) 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; Baxter available with transfer spikes) 2.5 g* Pentothal (C-III; with 100 or 150 mL sterile water for injection) Hospira

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Thiopental Sodium (C-III; with 100 mL sterile water for injection; available with transfer spikes) 5 g* Pentothal (C-III; with 200 or 250 mL sterile water for injection) Thiopental Sodium (C-III; with 200 mL sterile water for injection; available with transfer spikes)

Baxter

Hospira Baxter

Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use. The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care. AHFS Drug Information. Copyright, 1959-2012, Selected Revisions July 01, 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
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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 Gilmans 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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