K2i The ideal ICU sedative v Propofol

Physical

Ideal

Stable in H₂O

(pKa not at extremes)

Propofol

pKa 11

Insoluble in H₂O

Stable in solution & no preservatives/additives

Unstable (can precipitate) but has many additives to make it soluble → these have allergic potential

No reconstitution before use

None required, nicely drawn up to 10mg/mL

Also white and easily identifiable

Stable in air & light

No, promotes bacterial growth

Long shelf life

Yes, but in a glass ampoule → hazardous

Stored room temp

Yes, but not locked up & abuse potential

Compatible with other drugs + fluids in lines

No, incompatible with many drugs

No additives

Many additives & high E content ∴ caution with prolonged infusion & disorders of fat metabolism

Inexpensive

Expensive → cost per hr to maintain GA = desfluorane; complex mixture to prepare

PK

Onset

Rapid

Rapid, 1 arm-to-brain time ~15 secs

Distribution

Short effect

Site equilibration time (i.e. high lipid solubility to rapidly cross BBB)

Yes, LOC ~30 secs

Peak effect 2 mins

pKa 11 = 99% UNIONISED at pH 7.4

∴ highly lipophilic

No PPB

High PPB ∴affected by [plasma proteins] & drugs with high PPB

Small V_D

HUGE! 4L/kg after single bolus

Plasma levels rapidly ↓due to redistribution + elimination

CSHT

Short

Low CSHT < 40 mins with 8hr infusion

Rapid + predictable recovery

Yes, as above

Metabolism

Organ independent metabolism with no active/ toxic metabolites

Hepatic (CYP450) + extrahepatic metabolism

Inactive metabolites

Elimination

High clearance

Rapid offset

Clearance 30mL/kg/min

↓rate of elimination with renal disease