How long will a patient wake up after discontinuation of thiopental (barbiturate) IV infusion given for 28 hours?

Time to Awakening After 28-Hour Thiopental Infusion

After a 28-hour thiopental infusion, expect awakening to take 48-72 hours or longer, with potential delays extending several days due to the drug's extensive tissue accumulation and saturation kinetics during prolonged administration. 1, 2

Pharmacokinetic Basis for Prolonged Recovery

Thiopental exhibits nonlinear (Michaelis-Menten) kinetics during prolonged infusion, meaning elimination becomes saturated and progressively slower as tissue stores accumulate. 1

• After continuous infusion for 4-8 days at 3-4.5 mg/kg/h, the elimination half-life extends to 18-36 hours at the end of infusion, with predicted terminal half-lives of approximately 10 hours 1
• The volume of distribution at steady state is 4.35 ± 1.83 L/kg, indicating massive tissue accumulation 1
• Hepatic enzyme saturation reaches 35-85% during prolonged infusion, dramatically slowing clearance 1

Expected Timeline for 28-Hour Infusion

For a 28-hour infusion (shorter than the 4-8 day studies but still prolonged):

• Initial awakening: Expect 48-72 hours minimum based on clinical experience with shorter high-dose infusions 3
• Steady-state concentrations during infusion likely reached 30-50 mg/L depending on infusion rate 1
• Clearance during prolonged infusion decreases to approximately 2.16 mL/min/kg (50% lower than after single doses) 2

Factors Prolonging Recovery Time

The following factors will extend awakening time beyond standard predictions: 1, 2, 4

• Dose-dependent saturation: Higher infusion rates (>4 mg/kg/h) cause greater enzyme saturation and longer recovery 1
• Individual variability: Clearance varies dramatically between patients (0.268 to 5.40 mL/min/kg), with interpatient coefficient of variation reaching 51% by day 7 4
• Hepatic dysfunction: Any liver impairment further reduces already-saturated clearance 2
• Hypothermia: If used for cerebral protection with therapeutic hypothermia, metabolism is further slowed 5

Clinical Monitoring Recommendations

Monitor the following parameters during the awakening period: 1, 2

• Plasma thiopental concentrations: Levels >40 mg/L produce burst-suppression on EEG; awakening unlikely until levels drop below 20-30 mg/L 1
• Neurologic examination: Serial assessments every 12-24 hours, recognizing that sedative effects persist far longer than predicted by single-dose kinetics 2
• EEG monitoring: Burst-suppression patterns indicate continued excessive CNS depression 1

Critical Pitfall to Avoid

Do not assume awakening will follow standard single-dose half-life predictions (5-6 hours). 1, 2 The context-sensitive half-time after 28 hours of infusion is dramatically prolonged due to:

• Massive redistribution from fat stores (where thiopental accumulates extensively) 1
• Saturated hepatic metabolism requiring days to clear accumulated drug 1
• Nonlinear kinetics making standard half-life calculations invalid 1

Practical Timeframe

For clinical planning after a 28-hour thiopental infusion: 3, 1, 2

• Minimum expected: 48-72 hours to initial awakening
• More realistic: 3-5 days for meaningful neurologic recovery
• Worst case: Up to 7 days in patients with low clearance or high steady-state concentrations

This prolonged recovery is why thiopental has largely been replaced by shorter-acting agents like propofol for prolonged sedation, despite thiopental's superior efficacy for refractory status epilepticus (92% seizure control). 6