What is the expected time to wake up for a 65 kg patient with normal liver and renal function after 18 hours of thiopental (thiopental) sedation at 1-3 mg/kg Body Weight (BW)/hour, followed by propofol (propofol) at 1-2 mg/kg BW/hour?

Expected Wake-Up Time After Sequential Thiopental and Propofol Sedation

A 65 kg patient with normal hepatic and renal function who receives 18 hours of thiopental (1-3 mg/kg/hour) followed by propofol (1-2 mg/kg/hour) will likely require 1-3 days to fully awaken due to massive thiopental accumulation in peripheral tissues, despite propofol's short half-life.

Thiopental Accumulation: The Primary Determinant

The critical issue here is thiopental's pharmacokinetic profile after prolonged infusion:

• Thiopental is highly lipophilic and accumulates extensively in fat and muscle during prolonged administration 1
• After 18 hours of continuous infusion at 1-3 mg/kg/hour (65-195 mg/hour for this 65 kg patient), the total thiopental dose ranges from 1,170 mg to 3,510 mg 1
• This massive tissue saturation creates a reservoir that slowly redistributes back into plasma, dramatically prolonging emergence 1
• The context-sensitive half-time increases exponentially with infusion duration, making awakening unpredictable after such prolonged use 1

Propofol's Limited Impact on Recovery

While propofol is subsequently administered, its contribution to delayed awakening is minimal:

• Propofol has a terminal half-life of 1-3 days after a 10-day infusion, but rapid awakening within 10-15 minutes can occur even after long-term administration when appropriate doses are used 2
• The FDA label explicitly states that discontinuation after approximately 1 hour results in prompt decrease in blood propofol concentrations and rapid awakening 2
• However, longer infusions result in accumulation of significant tissue stores, slowing the reduction in circulating propofol and increasing time to awakening 2
• Propofol redistribution from fat and muscle to plasma can be significant and slow recovery if higher than necessary infusion levels have been maintained 2

Specific Timeline Estimation

Immediate Post-Discontinuation (0-2 hours):

• Patient will remain deeply sedated due to high plasma thiopental levels 1
• Propofol will clear relatively quickly (within 10-15 minutes if used at appropriate doses), but this is masked by persistent thiopental effect 2, 3

Early Phase (2-24 hours):

• Thiopental plasma levels begin declining through hepatic metabolism, but tissue stores continue redistributing 1
• Patient may show intermittent signs of lightening sedation but cannot maintain consistent wakefulness 1
• Delayed emergence from sedation with benzodiazepines and barbiturates results from prolonged administration due to saturation of peripheral tissues 1

Expected Awakening (24-72 hours):

• Most patients will achieve meaningful neurologic recovery within 1-3 days 2
• The FDA label confirms that the terminal half-life of propofol after a 10-day infusion is 1-3 days, and this patient's propofol exposure is much shorter 2
• Thiopental's redistribution from peripheral tissues is the rate-limiting step 1

Critical Clinical Considerations

Factors That May Prolong Recovery:

• Higher end of the thiopental dose range (3 mg/kg/hour) will substantially extend wake-up time 1
• Age-related decreases in volume of distribution and intercompartmental clearance prolong emergence in elderly patients 2
• Failure to reduce propofol infusion rate during extended periods results in excessively high blood concentrations 2

Monitoring Recommendations:

• Daily neurologic wake-up tests should be performed at least once per day to assess neurologic function 3
• Propofol is the preferred sedative for neurologic wake-up tests due to rapid onset and short duration 3
• Continuous monitoring of sedation depth is essential, as accumulation of sedatives during prolonged infusion results in delayed awakening 1

Safety Concerns:

• Both thiopental and propofol cause vasodilation, hypotension, and bradycardia through ablation of sympathetic tone 1
• Propofol causes dose-dependent decreases in cardiac output, systemic vascular resistance, and arterial pressure 4, 5
• Propofol Infusion Syndrome (PRIS) risk increases with doses >70 μg/kg/min for >48 hours, presenting with metabolic acidosis, rhabdomyolysis, and up to 33% mortality 1, 6

Practical Algorithm for Management

Hour 0 (Discontinuation):

• Stop both sedatives simultaneously 1
• Maintain hemodynamic support as needed 1
• Begin continuous neurologic monitoring 3

Hours 0-24:

• Expect deep sedation to persist 1
• Perform first neurologic wake-up test at 12-24 hours 3
• Monitor for PRIS signs (metabolic acidosis, hypertriglyceridemia, hypotension) 1

Hours 24-72:

• Anticipate gradual awakening during this period 2
• Perform daily neurologic assessments 3
• If patient remains deeply sedated beyond 72 hours, consider alternative causes (metabolic derangements, structural brain injury, seizures) 1

Beyond 72 Hours:

• Persistent deep sedation beyond 3 days is unusual with normal hepatic/renal function and suggests complications 2
• Reassess for propylene glycol toxicity (if lorazepam was used), PRIS, or other metabolic derangements 1

Common Pitfalls to Avoid

• Do not expect rapid awakening similar to short-term propofol use—the 18-hour thiopental infusion fundamentally changes the recovery profile 1
• Do not administer additional sedatives during the awakening period, as this will further delay recovery 1
• Do not assume neurologic injury if awakening is delayed up to 72 hours—this is expected with this sedation regimen 2
• Do not overlook the need for continued hemodynamic monitoring, as both agents cause prolonged cardiovascular depression 1, 4