Thiopental

 Thiopental (Thiopentone Sodium) 

Thiopental, also known as thiopentone sodium, is an ultra-short-acting barbiturate commonly used in anesthesia. It induces rapid unconsciousness by enhancing gamma-aminobutyric acid (GABA) neurotransmission. Due to its neuroprotective properties, it has applications in various neurological and anesthetic procedures.

Uses:

1. Induction of Anesthesia: Rapid onset makes it ideal for initiating general anesthesia.
2. Neurosurgical Procedures: Preferred due to its ability to decrease intracranial pressure (ICP) and cerebral metabolic rate.
3. Seizure Control: Effective in treating refractory status epilepticus.
4. Cerebral Protection: Provides neuroprotection during cerebral ischemia.

Dosage and Administration:

Adults:

• Induction of Anesthesia: 3-5 mg/kg IV bolus over 30 seconds.
• Seizure Control:
  • Initial Bolus: 3-5 mg/kg IV.
  • Continuous Infusion: 0.5-3 mg/kg/hr, titrated to seizure control and patient tolerance.

Pediatrics:

• Induction: 5-7 mg/kg IV bolus.
• Seizure Control:
  • Initial Bolus: 3-5 mg/kg IV.
  • Continuous Infusion: 1-5 mg/kg/hr for refractory status epilepticus.

Dose Adjustments in Special Conditions:

• Elderly Patients: Reduced doses required due to increased sensitivity to cardiovascular and respiratory depression.
• Renal Impairment: Dose adjustment recommended due to prolonged clearance.
• Hepatic Impairment: Use with caution as impaired metabolism may lead to prolonged sedation.

Presentation/Form:

• Powder for Injection: Available as a lyophilized powder, reconstituted with sterile water to create a 2.5% solution (25 mg/mL).

Pharmacokinetics:

• Onset: 10-30 seconds.
• Duration: 5-10 minutes after a single bolus dose due to rapid redistribution.
• Distribution: Rapid distribution into highly perfused tissues like the brain.
• Metabolism: Primarily metabolized in the liver.
• Excretion: Excreted through the kidneys.

Pharmacodynamics:

Thiopental enhances GABA-A receptor activity, increasing chloride influx and hyperpolarizing neurons. This results in profound central nervous system depression and induction of anesthesia.

Drug Interactions:

• CNS Depressants: Increased risk of profound sedation and respiratory depression when combined with opioids, benzodiazepines, or alcohol.
• Neuromuscular Blockers: Potentiation of non-depolarizing muscle relaxants like vecuronium.
• Antihypertensives: Increased risk of severe hypotension.
• MAO Inhibitors: Enhanced risk of central nervous system depression.
• Enzyme Induction: Can reduce the efficacy of drugs metabolized by the liver, such as warfarin and oral contraceptives.
• Anticoagulants: Accelerates the metabolism of anticoagulants like warfarin.

Comparison with Other Drugs in the Same Category:

• Thiopental vs. Propofol: Propofol has a faster recovery profile and is associated with less postoperative nausea.
• Thiopental vs. Etomidate: Etomidate is preferred in patients with hemodynamic instability due to its minimal cardiovascular effects.
• Thiopental vs. Midazolam: Midazolam has a slower onset but longer duration of sedation.

Precautions and Special Considerations:

• Extravasation Risk: Can cause severe tissue damage due to its alkaline pH, leading to necrosis.
• Allergic Reactions: Rare but may include anaphylaxis and rashes.
• Porphyria: Contraindicated in patients with acute intermittent porphyria.
• Cardiovascular Instability: Avoid in patients with significant hypotension or shock.
• Respiratory Depression: Use cautiously in patients with compromised respiratory function.
• Solution Stability: Use reconstituted solutions within 24 hours if refrigerated.

Side Effects:

• Common: Respiratory depression, hypotension, prolonged sedation, drowsiness, nausea.
• Serious: Apnea, myocardial depression, laryngospasm, severe hypotension.
• Extravasation Injuries: Local tissue necrosis.
• Allergic Reactions: Rare but may include anaphylaxis.

Recent Updates and Guidelines:

• Neuroprotection Updates: Recent studies highlight thiopental’s continued use in neurosurgical procedures due to its ability to lower ICP.
• Anesthesia Guidelines: Thiopental remains a recommended agent for induction in resource-limited settings and specific neurological conditions.
• Seizure Management: Updated guidelines emphasize thiopental as a third-line agent for refractory status epilepticus.

References:

1. Life in the Fast Lane (LITFL) - Thiopentone: https://litfl.com/thiopentone/
2. Thiopental in Neuroanesthesia - PubMed: https://pubmed.ncbi.nlm.nih.gov/22288930/
3. Thiopental Pharmacokinetics - NCBI: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999640/
4. Stoelting’s Pharmacology and Physiology in Anesthetic Practice, 5th Edition