Investigation of effective anesthesia induction doses using a wide range of infusion rates with undiluted and diluted propofol.
BACKGROUND
The influence of infusion rate on the induction dose-response relation has not been investigated over a wide range of infusion rates. In this study, the authors defined the effect of different propofol infusion rates on the times and doses necessary to reach clinical induction of anesthesia.


METHODS
The subjects of the study were 250 patients classified as American Society of Anesthesiologists physical status I or II aged 25-55 yr. For induction with undiluted propofol, 180 patients were allocated randomly to one of two groups of 90 patients each (A and B). Each group was further divided into nine subgroups (10 patients each) that were administered propofol infusion at rates of 10, 15, 20, 30, 40, 60, 100, 200, and 300 mg/kg-1/h-1. The remaining 70 patients (group C) were allocated randomly into seven subgroups (10 patients each), and these groups were induced with diluted propofol (0.5 mg/ ml) at the rates of 10, 15, 30, 60, 100, 200, and 300 mg/kg-1/ h-1. Group B was given crystalloid at the same infusion rates as group C via a catheter in the opposite arm. Induction time, induction dose, plasma arterial propofol concentration at loss of consciousness, and percentage decrease of systolic blood pressure were measured. A previously reported three-compartment model with an effect-site rate constant for propofol of 0.456/min was used to predict the induction time and dose at each infusion rate.


RESULTS
The differences between predicted induction time and dose and the observed time and dose could be explained by factoring in the lag time from infusion site to central compartment (lag time circulation) and the amount of propofol in transit during this time (residual dose circulation). Residual dose circulation and lag time circulation correlated with infusion time from 20 to 60 s for undiluted and from 0 to 40 s for diluted propofol. At the infusion rates greater than 80 mg/kg-1/h-1, rapid circulation because of incomplete mixing in the central compartment decreased the excess induction time and dose. The use of diluted propofol significantly attenuated the decrease in systolic blood pressure provoked by the residual dose circulation.


CONCLUSIONS
Induction dose and time are dependent on infusion rate in a complex manner, and residual dose circulation was a factor in overdose and hemodynamic depression. Hypotension during induction was attenuated by diluted propofol.
Kazama
T
T
Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Japan.
Ikeda
K
K
Morita
K
K
Kikura
M
M
Ikeda
T
T
Kurita
T
T
Sato
S
S
D000328:Adult; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001835:Body Weight / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019999:Pharmaceutical Solutions; D015742:Propofol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D018686:Anesthetics, Intravenous; D019999:Pharmaceutical Solutions; D015742:Propofol