Induction with propofol via Infusion controlled target at Hospital in Brazil

Fernando Squeff Nora Brasil

Background: The development of a computerized pharmacokinetic model-driven infusion device was first described by Helmut Schwilden in 1981(4). He showed that it was possible to attain the desired plasma concentration of an intravenous anesthetic drug by using a computer-controlled pump programmed with the published pharmacokinetics of the drug. An effect compartment has been evaluated during the use of intravenous anaesthesia with TCI-Infusion controlled target. The plasma concentration of intravenous anesthetic drugs after a bolus peaks virtually instantaneously; however, the peak effect of the drug occurs later when the brain concentration equilibrates with the central compartment (plasma). This delay or hysteresis is because the site of action is at the biophase or where the drug acts (e.g. receptors), rather than at the plasma. The clinical effect has been quantified for several intravenous anesthetic drugs using electroencephalography (EEG) or spectral edge frequency(BIS). The authors evaluated that loss of responsiveness (LOR) was related to targeting an effect compartment concentration. We studied if its possible to have a linear relation between LOR and the value showed by pump infusion of effect compartment. We used clinical evaluations just such as LOR, because we don´t have BIS in many cities in Brazil. We would like to know how much effect concentrations the patients in a Hospital in Brazil must have to attain LOR and in how much time this happens. Methods: We studied 18 patients, scheduled to do general anesthesia with computer-controlled pump programmed with the pharmacokinetics of propofol by Marsh model. The concentration targeted for all subjects was 4mcg/ml, until LOR . All effect concentrations were recorded when occurred LOR. The evaluation of LOR was made with loss of verbal response. The time to LOR was assessed by investigator asking the patients in a loud voice to open their eyes and documenting the time that they failed to do so. The patients' ventilation was assisted. The study was terminated 10 min from the start of the infusion. The median time to LOR and the median effect concentration at this moment were calculated. No premedication was taken and no other drugs were taken until patients LOR. Results: The median weight was 60kg. The ASA were I or II, 14 female and 4 male with median of 35,1 years. The median time to effect concentration for LOR was 4,35min and at this time, the median effect concentration was 2,46ng/ml. The total dose at this moment was 1,95mg/kg. Discussion: In this population, we met that LOR occurred in median time of 4,32min. and the median effect concentration was 2,46mcg/ml. In Wakeling study the median effect compartment concentration for LOR in the effect compartment group was 4.7mcg/ml, thus validating the use of an effect compartment (4). The median time to LOR in the group targeted to a predicted effect compartment propofol concentration was 1.23 min when this concentration was 5.4mcg/ml and when the Keo was more fast. The time to achieve the Cp₅₀ of 4.5 mcg/ml increases from 1.3 min for a Keo of 0.63 min to 7.5 min for a Keo of 0.2 min..We sugest that Keo of Marsh´s model is between 0,63 and 0,2, but we don´t know exactly. The median total doses administered here were 1,95mg/kg and below of doses usually recommended for induction general anaesthesia, but exactly the same that Wakeling described(4). In a clinical investigation by Kazama et al the spectral edge frequency (BIS), was used as measures of propofol effect(1). The half-times for the plasma-effect-site equilibration for BIS were from 2.31 to 2.37 min. between 20 and 85 years old, respectively. Struys et al tested the comparing the performance of three control algorithms: plasma-control TCI and two algorithms for effect-site control TCI. One-hundred twenty women patients received propofol via TCI for 12-min at a target concentration of 5.4 µg/ml. They concluded that the effect compartment–controlled TCI can be safely applied in clinical practice(2). This approach was the same that we used here, but probably we met different results because the different Keo. In a Schnider et al research they studied the influence of age on the pharmacodynamics of propofol. The electroencephalogram (EEG) was used to measure drug effect. The predicted time to peak effect after bolus injection ranging was 1.7 min. The time to peak effect assessed visually was 1.6min (range, 1-2.4 min)(3). The steady state observations showed increasing sensitivity to propofol in elderly patients, with C₅₀ values for loss of consciousness around 2.35, 1.8, and 1.25 mcg/ml.Conclusions: We concluded that our patients are more stronger than in other countries or the pump infusion that we used had a different Keo from others, because our patients slept with higher effect concentrations and more lower than others too, instead of the same doses(mg/kg). This work isn’t finished, and we pretend to enlarge the study group and to do a division between gender end old.

Bibliography:

1.Kazama T, Ikeda K, Morita K. et al-Comparison of effect-site KeoS of propofol for blood pressure and EEG bispectral Index in Elderly and younger patients. Anesthesiology, 1999;90(6): 1517-1527

2.Struys M, De Smet T, Depoorter B et al- Comparison of plasma compartment versus two methods for effect compartment-controlled target-controlled infusion for propofol. Anesthesiology, 2000; 92(2):399

3.Schnider T, Minto CF, Shafer SL et al-The influence of age on propofol pharmacodynamics. Anesthesiology; 1999;90(6): 1502 – 1516

4.Wakeling HG, Zimmerman JB, Howell et al - Targeting Effect Compartment or Central Compartment Concentration of Propofol: What Predicts Loss of Consciousness? Anesthesiology,1999; 90(1):92-97