In 1968, Kruger-Theimer illustrated how pharmacokinetic models can be used to design efficient dose regimens. This Bolus, Elimination, Transfer (BET) regimen consists of:
a bolus dose calculated to fill the central (blood) compartment,
a constant-rate infusion equal to the elimination rate,
an infusion that compensates for transfer to the peripheral tissues: [exponentially decreasing rate]
Traditional practice involved calculating the infusion regimen for propofol by the Roberts method. A 1.5 mg/kg loading dose is followed by an infusion of 10 mg/kg/hour that is reduced to rates of 8 and 6 mg/kg/hr at ten minute intervals.
Effect site targeting
The principal effects of anaesthetic intravenous agents are the sedative and hypnotic effects and the site at which the drug exerts these effects, termed the effect site is the brain. Unfortunately it is not feasible in clinical practice to measure brain concentration [effect site]. Even if we could measure direct brain concentration, it would be necessary to know the exact regional concentrations or even receptor concentrations where the drug exerts its effect.
Achieving a constant propofol concentration
The diagram below illustrates the infusion rate required at an exponentially decreasing rate after a bolus dose in order to maintain a steady state blood concentration of propofol. It also shows the lag between the blood and effect site concentration.
Post time: Nov-05-2024