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21/11/2012 Thiopental Sodium - Print Version 1/25 www.drugs.com/monograph/thiopental-sodium.html?printable=1 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: C 11 H 17 N 2 NaO 2 S 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 coma 3 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 26 85 88 105

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Thiopental Sodium

Class: BarbituratesVA Class: CN202Chemical Name: 5-Ethyl-dihydro-5-(1-methylbutyl)-2-thioxo-4,6(1H,5H)-pyrimidinedione monosodium saltMolecular Formula: C11H17N2NaO2S

CAS Number: 71-73-8Brands: 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 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

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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 (1–3 mL ofa 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 [torelieve 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

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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 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

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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 onresponses 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

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Increased Intracranial Pressure

Increased Intracranial Pressure Associated with Trauma†

IVChildren 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 onChild’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 adultsor 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

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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

IVInitial 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 10mg/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†

IVLow-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

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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 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, statusasthmaticus, 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

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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 ismore 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 andsecretions 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 roughlyfollows 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 hasnot 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 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 bedifferent 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 (SeePediatric 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 Dosageand 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 aminophyllineafter 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 inductionof anesthesia with thiopental reduced thiopental dosage

requirements by about 25 or 37%, respectively12 94

Some clinicians recommendreduction of thiopental dosage whenclonidine is administered as an

adjunct to anesthesia94

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 withother CNS depressants may potentiate hypnotic effect of

thiopental3 71

Adjustment of thiopental dosagemay be required with concomitant

use3 71

Chronic use of CNS depressants

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nitrous oxide,alcohol)

Possible reduction of antinociceptive effect of opiate

analgesics1 2 71(e.g., alcohol) may increasethiopental dosage required toachieve the desired anesthetic

effect3 75

Diazoxide

Hypotension reported during induction of anesthesia withthiopental in patients undergoing surgery for insulinomawho were receiving oral diazoxide (a highly protein-bound

drug) for several days prior to surgery1 2 84

KetamineAdditive anesthetic effects reported in 1 study;70 76 inanother study, increased thiopental doses required to

achieve unconsciousness70 76

Meprobamate

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

meprobamate3 7 67

Possible potentiation of hypnotic effects7

Metoclopramide

Administration of metoclopramide prior to induction ofanesthesia with thiopental can reduce thiopental dosage

requirements64

Midazolam Possible potentiation of hypnotic effect3 71

Reduce thiopental dosages forinduction of anesthesia by about15% in patients receiving

premedication with IM midazolam69

Phenothiazines(e.g.,chlorpromazine,promethazine)

Possible potentiation of hypnotic effects;68 concomitantuse of thiopental in patients receiving chlorpromazinereported 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 bindingsites by, or could displace from binding sites,

sulfisoxazole3 7 67

Potentiation of hypnotic effects reported7

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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 (2.5–5 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

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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 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

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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)

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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

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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 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

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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; consultspecific 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

RoutesDosageForms

Strengths Brand Names Manufacturer

ParenteralForinjection,for IV use

250 mgPentothal (C-III; with 10 mL sterile water for injection or sodiumchloride 0.9% injection; available with a disposable syringe andneedle)

Hospira

400 mgPentothal (C-III; with 20 mL sterile water for injection or sodiumchloride 0.9% injection; available with a disposable syringe andneedle)

Hospira

500 mg*Pentothal (C-III; with 20 mL sterile water for injection or sodiumchloride 0.9% injection; available with or without a disposablesyringe and needle)

Hospira

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

BaxterAnesthesia

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

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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

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 hereunderwas formulated with a reasonable standard of care, and in conformity with professional standards in the field. The AmericanSociety 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 suchinformation 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 theinformation is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thoroughunderstanding 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-SystemPharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

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79. (unused reference number)

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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.

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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]

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100. Chernin EL, Stewar JT, Smiler B. Stability of thiopental sodium and propofol in polypropylene syringes at 23 and4&#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 andthiopental. 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 JAnesthesiology. 1997; 24:251-3.

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

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

105. Stover JF, Pleines UE, Morganti-Kossmann MC et al. Thiopental attenuates energetic impairment but fails tonormalize cerebrospinal fluid glutamate in brain-injured patients. Crit Care Med. 1999; 27:1351-7. [IDIS 432495] [PubMed10446831]

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