Thiopentone (Thiopental) 

1. Pharmacology

Class

  • Barbiturate (thiobarbiturate)
  • Sulfur substitution → ↑ lipid solubility → rapid CNS entry

Mechanism of Action 

  • Enhances GABA-A receptor activity
    → ↑ duration of Cl⁻ channel opening
    → neuronal hyperpolarization
  • At high doses:
    • Direct GABA agonist effect
    • Inhibits glutamate (AMPA receptors)

Result:

  • Profound CNS depression
  • Decreased cerebral metabolic activity

 2. Pharmacokinetics

Parameter

Details

Onset

10–30 sec

Peak

1 min

Duration (single bolus)

5–10 min

Context-sensitive half-time

↑ markedly with infusion

Redistribution

  • Initial effect due to brain uptake
  • Rapid termination due to redistribution to muscle and fat

3. Effects on Organ Systems

 CNS Effects

Parameter

Effect

CMRO₂

↓↓↓ (up to 50%)

CBF

↓

ICP

↓↓↓

CPP

May ↓ if MAP falls

EEG

Burst suppression at high doses

Neuroprotective effect
→ Used in refractory intracranial hypertension

 Cardiovascular

  • ↓ MAP (dose-dependent)
  • ↓ SVR
  • Mild myocardial depression
  • Reflex tachycardia

 Mechanism:

  • Venodilation → ↓ preload
  • Direct cardiac suppression

 Respiratory

  • Dose-dependent respiratory depression
  • Apnea after bolus
  • ↓ ventilatory response to CO₂

 Others

  • No analgesia 
  • Decreases intraocular pressure
  • Decreases intrahepatic blood flow

4. Clinical Uses in Critical Care

 1. Induction of Anesthesia

  • Dose: 3–5 mg/kg IV bolus
  • Rapid sequence induction (older era; now replaced by Propofol and Etomidate)

 2. Refractory Intracranial Hypertension

  • Used as barbiturate coma therapy
  • Indicated when:
    • ICP refractory to:
      • Sedation
      • Osmotherapy
      • Ventilation

 Goal:

  • EEG burst suppression
  • ↓ CMRO₂ → ↓ ICP

 3. Refractory Status Epilepticus

  • Third-line after:
    • Benzodiazepines
    • Phenytoin / Levetiracetam
  • Continuous infusion:
    • Loading: 3–5 mg/kg
    • Maintenance: 1–5 mg/kg/hr

4. Neuroprotection (Historical / selective use)

  • Seen in:
    • TBI
    • Cardiac arrest (limited modern role)

5. Dosing in ICU

 Bolus

  • 3–5 mg/kg IV

 Infusion (Barbiturate coma)

  • Loading: 5–10 mg/kg
  • Maintenance:
    • 1–5 mg/kg/hr
    • Titrate to:
      • ICP < 20 mmHg
      • Burst suppression

 6. Adverse Effects

Cardiovascular Collapse

  • Severe hypotension
  • Shock (especially hypovolemia)

Respiratory

  • Apnea
  • Hypoventilation

CNS

  • Prolonged sedation (due to accumulation)

Others

  • Porphyria precipitation
  • Tissue necrosis if extravasation
  • Immunosuppression (long-term infusion)
  • Hypothermia

 7. Contraindications

  • Acute intermittent Porphyria
  • Severe hypovolemia
  • Shock states
  • Severe cardiac dysfunction