What is the recommended regimen for a ketamine (ketamine hydrochloride) and propofol (propofol) mix for sedation?

Ketamine-Propofol Mix for Procedural Sedation

The combination of ketamine and propofol (often called "ketofol") is an effective alternative to propofol alone for procedural sedation, with evidence showing reduced respiratory depression and better hemodynamic stability, though the 2018 ASA guidelines note this combination produces deeper sedation with increased respiratory depression risk compared to propofol monotherapy. 1

Recommended Dosing Regimens

Two-Syringe Technique

• Administer ketamine 0.3-0.5 mg/kg IV bolus first, immediately followed by propofol 0.4-1 mg/kg IV bolus 2
• Maintain sedation with intermittent propofol boluses of 0.1-0.5 mg/kg as needed 2
• This approach allows independent titration of each agent 2

Single-Syringe Technique (1:1 Ratio)

• Combine equal volumes of ketamine 10 mg/mL and propofol 10 mg/mL in a single syringe 2
• This yields a final concentration of 5 mg/mL for each component 2
• Requires standardized protocols to minimize preparation errors 2

Alternative Dosing from Research

• Ketamine 0.5 mg/kg followed by propofol 1 mg/kg, with repeated propofol doses of 0.5 mg/kg as needed 3
• Target dose of 0.75 mg/kg for both ketamine and propofol has been studied 4

Efficacy and Safety Profile

Respiratory Effects

• Meta-analysis demonstrates ketamine-propofol reduces adverse respiratory events compared to propofol alone (29.0% vs 35.4%; RR 0.82) 5
• However, the 2018 ASA guidelines report that propofol combined with ketamine produces deeper sedation with more respiratory depression and greater frequency of hypoxemia compared to propofol alone 1
• This apparent contradiction reflects that while the combination may cause more respiratory events than propofol alone in some contexts, it still provides better hemodynamic stability 1, 5

Hemodynamic Advantages

• Ketamine-propofol results in significantly less hypotension than propofol alone (1.6% vs 12.5% decline in systolic blood pressure) 4
• The combination requires lower total propofol doses (92.5 mg vs 177.3 mg mean dose) 4
• Ketamine's sympathomimetic effects counterbalance propofol's cardiovascular depression 2

Provider and Patient Outcomes

• Greater provider satisfaction with ketamine-propofol compared to propofol alone 3
• Trend toward better sedation quality scores 3
• No significant difference in overall adverse event rates between groups 5

Critical Monitoring Requirements

Essential Monitoring

• Continuous pulse oximetry is mandatory, especially given the deeper sedation levels achieved 1, 6
• Consider capnometry for early identification of hypoventilation 6, 7
• Continuous heart rate and blood pressure monitoring 8
• Have airway management equipment immediately available 8

Titration Principles

• Administer medications in small, incremental doses or by slow infusion 6
• Allow sufficient time between doses to assess maximum effect before administering additional medication 6
• In high-risk patients (>60 years or significant comorbidities), reduce initial doses by 50% and titrate more slowly 6

Contraindications and Precautions

Avoid Ketamine Component in:

• Ischemic heart disease, cerebrovascular disease, or uncontrolled hypertension due to ketamine's dose-dependent increases in heart rate, blood pressure, and cardiac output 1, 7
• Patients with increased intracranial pressure 1
• Severe COPD or conditions where increased airway secretions would be problematic 7

Special Populations

• Emergence reactions occur in 10-30% of adults with ketamine, though combining with propofol appears to minimize this risk 1, 2
• In sepsis or critical illness, ketamine's hemodynamic response may be blunted or reversed 7

Clinical Context and Alternatives

When to Choose Ketamine-Propofol

• Patients at higher risk for respiratory depression or hypotension with propofol alone 2
• Procedures requiring both sedation and analgesia 2
• When hemodynamic stability is a priority 4

Comparison to Other Combinations

• Ketamine-midazolam showed superior efficacy to propofol-fentanyl in pediatric orthopedic sedation (OSBD-R scores 0.278 vs 0.084) 1
• Fentanyl-midazolam combinations carry Level B recommendation for increased respiratory depression risk, requiring particular monitoring vigilance 1

Implementation Considerations

Develop standardized institutional protocols for drug preparation and dosage to minimize medication errors 2. The combination requires appropriate training in airway management and rescue from deep sedation, as the ASA guidelines emphasize this combination produces deeper sedation levels than either agent alone 1.