Thiopental Maintenance Dosing for Anesthesia
Thiopental is not recommended for maintenance of general anesthesia in modern practice, as it has been largely replaced by propofol and volatile agents due to superior pharmacologic profiles and safety considerations. 1
Historical Context and Current Status
Thiopental's clinical role has fundamentally changed over the past two decades:
- Propofol has replaced thiopental for maintenance anesthesia due to better suppression of airway reflexes, fewer drug errors, greater clinician familiarity, and easier preparation 1
- Thiopental's mechanism of short-term action relies on rapid redistribution rather than metabolism, making it unsuitable for prolonged maintenance 2
- The liver is the sole organ responsible for thiopental elimination, with a relatively low hepatic extraction ratio of 0.29 and hepatic clearance of only 0.21 L/min 2
When Thiopental IS Used for Extended Periods
In the specific context of neurocritical care for cerebral protection (not routine anesthesia maintenance), the following applies:
Intermittent Bolus Regimen
- 250-500 mg IV boluses every 2 hours have been used for up to 7 days in neurosurgical patients 3
- Target steady-state trough concentrations: 4.8-30 mg/L (mean 16.0 mg/L) 3
- Peak concentrations typically range: 8.35-45 mg/L (mean 25.4 mg/L) 3
Continuous Infusion Alternative
- Continuous infusions have been administered for up to 9 days in neurosurgical patients 4
- Clearance varies dramatically between patients: 0.268-5.40 mL/min/kg 4
- Mean plasma clearance typically ranges 1-3 mL/min/kg for most patients 4
Critical Pharmacokinetic Considerations
After Single Bolus (Induction)
- Initial volume of distribution (V1): 0.481 L/kg 3
- Distribution half-life (t½α): 0.590 hours 3
- Elimination half-life (t½β): 5.89 hours 3
- Clearance: 5.41 mL/min/kg 3
After Multiple Doses (Prolonged Use)
- Clearance decreases by approximately 50% with repeated dosing (from 5.41 to 2.16 mL/min/kg) 3
- Elimination half-life increases to 16.3 hours with multiple doses 3
- Mean residence time extends to 21.9 hours 3
- Distribution half-life shortens to 0.122 hours 3
Major Safety Concerns
Unpredictable Clearance
- Interindividual variability increases progressively: from 37% on day 1 to 51% by day 7 4
- Some patients show clearance decreases >35% over 7 days 4
- Others demonstrate clearance increases >44% after 2 days 4
- Only 7 of 16 patients maintained stable clearance during treatment 4
Accumulation Risk
- Small amounts remain in body fat stores for 24-48 hours even after single doses 5
- With prolonged use, accumulation becomes clinically significant due to decreased clearance 3
Recommended Approach for Modern Practice
For routine anesthesia maintenance, use propofol (infusion at 5.4 mg/kg/h after 1-2 mg/kg bolus) instead of thiopental 5
Propofol Advantages Over Thiopental
- Recovery time: 19±7 minutes vs 35±20 minutes 5
- Time to discharge: 24±6 minutes vs 40±11 minutes 5
- Similar desaturation rates (4-5%) but faster resolution 5
- Comparable MRI/imaging quality scores 5
Special Population Considerations
Breastfeeding Women
- Amounts transferred to breast milk are very small 5
- No waiting period required before resuming breastfeeding 5
- Short half-life and poor bioavailability make it compatible with breastfeeding 5
Pediatric Patients
- In the limited context where thiopental is used (e.g., MRI sedation), initial bolus of 1-3 mg/kg followed by supplemental doses of 1-2 mg/kg have been described 5
- Propofol remains the preferred agent for pediatric procedural sedation 5
Common Pitfalls to Avoid
- Do not use thiopental for routine anesthesia maintenance when propofol or volatile agents are available 1
- Do not assume stable clearance during prolonged administration—therapeutic drug monitoring is essential 4
- Do not extrapolate single-dose pharmacokinetics to multiple-dose scenarios, as clearance decreases by 50% 3
- Avoid mixing with acidic drugs, as alkaline solutions will precipitate thiopental 1