Three Compartment Model

Remifentanil vs. other opioids 100 10 Percent of peak plasma opioid concentration fentanyl 1 sufentanil alfentanil remifentanil 0.1 120 240 360 480 600 Minutes since bolus injection Minto et al, Anesthesiology, in press

Three Compartment Model plus an “Effect Site”

Remifentanil vs. other opioids 100 sufentanil 80 fentanyl 60 Percent of peak effect site opioid concentration 40 alfentanil 20 remifentanil 2 4 6 8 10 Minutes since bolus injection Minto et al, Anesthesiology, in press

50% effect site decrement curves

V1 and Clearance decrease with age V1 decreases about 20% from age 20 to 80 Common finding for anesthetic drugs Clearance decreases about 30% from age 20 to 80 Mechanism unknown

EC50 decreases with age EC50 is a measure of brain sensitivity Decreased EC50 means increased sensitivity Decreased EC50 with age also reported for: fentanyl alfentanil sufentanil

t 1/2 ke0 increases with age t 1/2 ke0 is the time required for the brain to equilibrate with the plasma an increase in t 1/2 ke0 would be expected to result in a slower onset of drug effect

Age delays onset but does not affect peak concentration

Bolus doses should be reduced by 50% in the elderly The reduction in bolus dose is because of the 50% increase in sensitivity in the elderly Adjusting the bolus for age is at least as important as adjusting it for body weight

Age effects on bolus dose Minto et al, Anesthesiology, in press

Infusion rates should be reduced by 2/3’s in the elderly The infusion rate is decreased because of increased sensitivity and decreased clearance Adjusting the infusion rate for age is more important than adjusting it for weight

Age effects on infusion rate Minto et al, Anesthesiology, in press

Age does not affect average time to emergence

Age affects variability in time to emergence Minto et al, Anesthesiology, in press

Hemodynamics in Elderly Blood pressure may decrease 10-40 percent in elderly (>70 yrs). Easily treated with ephedrine. May be associated with ST changes if patient has coronary artery disease.

Hemodynamics in Elderly Heart rate is usually stable but may increase abruptly on emergence. May be associated with ST changes if patient has coronary artery disease

Propofol/Alfentanil Interaction Adapted from Vuyk et al, Anesthesiology 83:8-22, 1995 Characterizes the concentrations for intubation maintenance on emergence Concentrations are 50% response level

Propofol/Opioid Technique

Propofol/Opioid Time to Awakening

Propofol/Opioid Infusion rates