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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.
References
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2. Baxter. Thiopental Sodium for injection prescribing information. Deerfield, IL; 1998 Sep.
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induction dose. Acta Anaesthesiol Scand. 1987; 31:30-2. [PubMed 3825473]
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79. (unused reference number)
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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]
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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]
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)
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108. Nguyen MT, Greenberg SB, Fitzhugh KR et al. Pediatric Imaging: Sedation with an injection formulation modifiedfor 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] [PubMed11437765]
111. Rantala H, Saukkonen AL, Remes M et al. Efficacy of five days’ barbiturate anesthesia in the treatment ofintractable 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 andGilman’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 prolongedhigh-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 ofoutcome. 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 ClinPharm. 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] [PubMed9105228]
120. Reviewers’ comments (personal observations).
121. Abbott Laboratories, Abbott Park, IL: Personal communication.
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