What are the elimination half-lives of Ketamine, Diazepam, Midazolam, and Propofol?

Elimination Half-Lives of Ketamine, Diazepam, Midazolam, and Propofol

The elimination half-lives are: Ketamine 2.5 hours, Diazepam 20-120 hours (with active metabolites extending effects significantly), Midazolam 2-3 hours, and Propofol 1-3 days (terminal phase). 1, 2

Detailed Pharmacokinetic Parameters

Ketamine

• Elimination half-life: 2.5 hours 1
• Highly lipid soluble with rapid onset of action (1 minute) and short duration of action (15-30 minutes) 1
• Possesses both analgesic and sedative properties, distinguishing it from other sedatives 1

Diazepam

• Elimination half-life: 20-120 hours (general adult range), with terminal elimination phase up to 48 hours 2
• Active metabolite desmethyldiazepam has a prolonged half-life up to 100 hours, significantly extending clinical effects 2
• Age-specific variations exist: children (3-8 years) have mean half-life of 18 hours, adolescents 18-20 hours, infants (1 month-2 years) 40-50 hours, and premature infants 54 hours (range 50-95 hours) 2
• Classified as a long-acting benzodiazepine with extensive accumulation during multiple dosing 3
• The prolonged half-life is due to saturation of peripheral tissues and accumulation of active metabolites, particularly in patients with renal insufficiency 4

Midazolam

• Elimination half-life: approximately 2-3 hours 1
• Water soluble benzodiazepine with rapid onset and brief duration of action in healthy individuals 1
• Less than 10% of the population exhibit prolonged effects due to impaired metabolism 1
• Classified as intermediate-acting with no active metabolites, making it safer in renal failure cases 4, 5
• Terminal half-life ranges from 200 minutes (range 300-700 minutes) in some references 4

Propofol

• Elimination half-life: 1-3 days (terminal phase) 1
• Rapid onset and short elimination half-life in the distribution phase, making it suitable for daily sedation interruption and neurological assessments 5
• Highly lipid soluble (99% plasma protein binding) 1
• Maintenance infusion dosing at 5-50 μg/kg/min in ICU settings 5

Critical Clinical Implications

Accumulation and Duration Considerations

• Diazepam's prolonged effects are especially pronounced in elderly patients, those with hepatic dysfunction, or renal insufficiency due to active metabolite accumulation 4, 2
• Benzodiazepine clearance decreases with age, making diazepam's prolonged effects even more significant in elderly populations 4
• The American Gastroenterological Association recommends reducing diazepam doses by 20% or more in patients over 60 years 4

Breastfeeding Considerations

• Desmethyldiazepam (diazepam's active metabolite) transfers into breast milk at significant levels; diazepam may be considered as a one-off dose before a procedure but is not preferred for routine use in breastfeeding women 2
• Midazolam has a milk:plasma ratio of 0.15 and relative infant dose of 0.63%, making it more favorable 1
• Propofol has a relative infant dose of 4.4% 1

ICU Sedation Context

• Propofol and dexmedetomidine are preferred first-line sedatives in ICU settings over benzodiazepines due to improved outcomes including shorter mechanical ventilation duration and reduced delirium 5
• Midazolam is considered second-line in ICU settings, associated with increased delirium risk and longer mechanical ventilation compared to propofol 5
• Benzodiazepine use is a strong independent risk factor for developing delirium in ICU patients 5