Thiopental Sodium

Usage

• Thiopental Sodium is an ultra-short-acting barbiturate primarily used for the induction of general anesthesia and for short surgical procedures lasting up to 15 minutes. It is also used as an adjunct to other anesthetic agents. Other uses include the control of convulsive states (e.g., status epilepticus), reduction of intracranial pressure in neurosurgical patients (with controlled ventilation), and rarely for narcoanalysis and narcosynthesis in psychiatric settings.
• Pharmacological Classification: Barbiturate, general anesthetic, anticonvulsant, hypnotic.
• Mechanism of Action: Thiopental enhances the inhibitory effects of gamma-aminobutyric acid (GABA) by binding to the GABA_A receptor complex. This binding increases the duration of chloride channel opening, leading to hyperpolarization of postsynaptic neurons and decreased neuronal excitability.

Alternate Names

• Thiopentone sodium
• Brand names: Pentothal (no longer available in the US)

How It Works

• Pharmacodynamics: Thiopental rapidly induces unconsciousness by depressing the central nervous system (CNS). It affects both the motor and sensory areas of the cerebral cortex. It causes dose-dependent respiratory and cardiovascular depression.

• Pharmacokinetics:

  • Absorption: Rapid absorption after intravenous administration. Rectal absorption is also possible but slower and less predictable.
  • Distribution: Rapidly distributes to highly perfused tissues, including the brain, followed by redistribution to muscle and fat.
  • Metabolism: Primarily metabolized by the liver via hepatic enzymes.
  • Elimination: Renal excretion of metabolites.

• Mode of Action: Thiopental binds to a specific site on the GABA_A receptor complex, distinct from the GABA binding site and the benzodiazepine binding site. This binding enhances GABA’s inhibitory effect by prolonging the opening of the chloride ion channel, increasing chloride influx into the neuron, hyperpolarizing the cell membrane, and decreasing neuronal excitability. This leads to reduced synaptic transmission and CNS depression.

• Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Thiopental binds to the GABA_A receptor, allosterically modulating it and enhancing the effect of GABA. It does not directly inhibit enzymes or affect neurotransmitter release.

• Elimination Pathways: Primarily hepatic metabolism followed by renal excretion of inactive metabolites.

Dosage

Standard Dosage

Adults:

• Induction of Anesthesia: 3-6 mg/kg intravenously titrated to effect. A test dose of 25-75 mg is recommended to assess sensitivity. Usual dose range is 210-280 mg for a 70 kg adult.

Children:

• 2-7 mg/kg intravenously titrated to effect. Maximum dose: 7 mg/kg.

Special Cases:

• Elderly Patients: Lower doses due to decreased metabolism and reduced clearance. Start with 2-2.5 mg/kg.
• Patients with Renal Impairment: Caution advised. Reduce dosage based on the degree of impairment.
• Patients with Hepatic Dysfunction: Lower doses are recommended due to reduced metabolism. Titrate carefully.
• Patients with Comorbid Conditions: Dosage adjustments might be necessary based on specific conditions.

Clinical Use Cases

• Intubation: Used for rapid sequence induction (RSI) at doses of 3-7 mg/kg.
• Surgical Procedures: For short procedures (up to 15 minutes), 3-6 mg/kg may be sufficient as a sole anesthetic agent.
• Mechanical Ventilation: Not typically used for maintenance of anesthesia during mechanical ventilation due to prolonged recovery after continuous infusion.
• Intensive Care Unit (ICU) Use: Thiopental coma may be used in some ICUs for refractory increased intracranial pressure (see dosage below)
• Emergency Situations: For status epilepticus: 75-125 mg intravenously initially, followed by additional doses as needed.

Dosage Adjustments

• Adjust doses based on patient response, age, weight, and comorbidities.
• Renal/hepatic impairment may necessitate dose reduction.

Side Effects

Common Side Effects

• Prolonged somnolence, delayed awakening
• Shivering, sneezing, coughing, hiccups
• Slowed breathing (respiratory depression)
• Slow heart rate (bradycardia)

Rare but Serious Side Effects

• Anaphylactic/anaphylactoid reactions (urticaria, bronchospasm, edema)
• Laryngospasm, bronchospasm
• Severe hypotension, myocardial depression, cardiac arrhythmias
• Apnea
• Immune hemolytic anemia with renal failure (rare)
• Radial nerve palsy (rare)

Long-Term Effects

• Potential for dependence with prolonged use.

Adverse Drug Reactions (ADR)

• Severe hypotension, anaphylaxis, laryngospasm, apnea.

Contraindications

• Hypersensitivity to barbiturates
• Porphyria
• Status asthmaticus
• Severe respiratory obstruction or compromise
• Severe shock
• Dystrophia myotonica
• Constrictive pericarditis

Drug Interactions

• CNS depressants: Synergistic effect with other CNS depressants (e.g., opioids, benzodiazepines, alcohol), potentially requiring dose reduction of thiopental.
• Enzyme Inducers/Inhibitors: Thiopental induces hepatic enzymes, decreasing levels of some drugs metabolized by these enzymes (e.g. antiepileptics). Concomitant use of enzyme inhibitors may prolong thiopental’s effects.
• Other: Metoclopramide and droperidol reduce the dose of thiopental required for anesthesia. Sulfonamides enhance thiopental’s effects. Interactions with medications affecting blood pressure (e.g., antihypertensives, diuretics) can enhance hypotension.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C. Thiopental crosses the placental barrier and can potentially cause fetal respiratory depression. Use only if clearly needed, and consider the potential risks and benefits.
• Breastfeeding: Thiopental is excreted in breast milk in small amounts. Breastfeeding should be temporarily suspended for at least 12 hours after thiopental administration.

Drug Profile Summary

• Mechanism of Action: Enhances GABAergic inhibition.
• Side Effects: Respiratory depression, hypotension, laryngospasm, shivering, prolonged somnolence.
• Contraindications: Hypersensitivity to barbiturates, porphyria, status asthmaticus, severe respiratory compromise.
• Drug Interactions: CNS depressants, enzyme inducers/inhibitors, sulfonamides.
• Pregnancy & Breastfeeding: Category C; excreted in breast milk.
• Dosage: Induction: 3-6 mg/kg IV (adults); 2-7 mg/kg IV (children).
• Monitoring Parameters: Respiratory rate, heart rate, blood pressure, oxygen saturation.

Popular Combinations

• Often used with opioids (e.g., fentanyl) for analgesia and muscle relaxants (e.g., atracurium, cisatracurium) during surgery.
• Premedication with atropine or scopolamine to reduce secretions.

Precautions

• General Precautions: Administer in a setting equipped for airway management and cardiovascular support. Pre-screening for contraindications and potential drug interactions is essential.
• Specific Populations: Use with caution in pregnant women, breastfeeding mothers, children, and the elderly.
• Lifestyle Considerations: Patients should avoid driving or operating machinery for at least 24 hours after thiopental administration.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Thiopental Sodium?

A: For adults, the induction dose is 3-6 mg/kg IV, with a test dose of 25-75 mg recommended. Children’s dosage is 2-7 mg/kg IV (maximum 7mg/kg). Elderly patients and those with hepatic dysfunction generally require lower doses.

Q2: How is Thiopental Sodium administered?

A: Intravenous administration is the standard route for thiopental.

Q3: What are the common side effects of Thiopental Sodium?

A: Common side effects include respiratory depression, hypotension, slowed heart rate, shivering, prolonged drowsiness, and laryngospasm.

Q4: What are the contraindications for using Thiopental Sodium?

A: Thiopental is contraindicated in patients with hypersensitivity to barbiturates, porphyria, status asthmaticus, severe respiratory compromise, severe shock, and dystrophia myotonica.

Q5: How does Thiopental Sodium interact with other medications?

A: It interacts with other CNS depressants, enzyme inducers/inhibitors, and drugs affecting blood pressure. Consult a comprehensive drug interaction database for a complete list.

Q6: Can Thiopental Sodium be used during pregnancy?

A: It’s a pregnancy category C drug and should only be used if the benefits clearly outweigh the potential risks to the fetus.

Q7: Is it safe to breastfeed while using Thiopental Sodium?

A: Breastfeeding should be temporarily suspended for at least 12 hours after thiopental administration.

Q8: What precautions should be taken when administering Thiopental Sodium?

A: Administer in a setting equipped for airway management and cardiovascular support. Closely monitor vital signs. Pre-screening for contraindications is essential.

Q9: What is the mechanism of action of Thiopental Sodium?

A: Thiopental enhances the inhibitory effect of GABA by binding to the GABA_A receptor complex, leading to increased chloride influx, neuronal hyperpolarization, and decreased CNS excitability.

Q10: How long does the effect of Thiopental Sodium last?

A: The duration of effect is short, typically 5-15 minutes after a single dose, but can be prolonged with repeated doses or continuous infusion due to redistribution from fat tissues.