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Selective spinal anesthesia for outpatient laparoscopy. IV: Population pharmacodynamic modelling

Himat Vaghadia, MB BS MHSC FCA FRCPC^*,, Linda Collins, MB BCH BAO FFARCSI^*, Huiying Sun, BSc and G.W.E. Mitchell, MB CHB MRCOG FRCS(Ed) FRCSC

^* From the Departments of Anesthesia,
Health Care and Epidemiology,
Gynecology and
Statistics, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

Address correspondence to: Dr. Himat Vaghadia, Department of Anesthesia (Room 3200), Vancouver General Hospital, 3rd Floor - 910 West 10th Ave, Vancouver, British Columbia, V5Z 4E3 Canada. Phone: 604-875-4304; Fax: 604-875-5209; E-mail: hvaghadi{at}vanhosp.bc.ca

Purpose: To apply a population pharmacodynamic model to small-dose hypobaric spinal anesthesia for outpatient laparoscopy.

Methods: The level of spinal analgesia after spinal blockade with small-dose (20–25 mg) hypobaric lidocaine was assessed by means of pinprick in patients undergoing outpatient laparoscopy. In 57 patients, 385 measurements were available for analysis. We first modelled the data for each patient with a mixed-effects model described by Schnider (Model 1). The population mean parameters, inter-individual variance, and residual variance were estimated. Clinically important endpoints (time to reach T₁₀ (onset), time to maximal level, duration and maximally attained level) of each patient were calculated based on the estimated time course of analgesia level for each patient. The model was used to predict the later data with respect to level of spinal analgesia of each patient from fits based on the observed data in the first 75 min.

Results: The mean ± SD onset time was 8.3 ± 1.9 min, time to maximal level was 20.8 ± 5.3 min, duration of effect was 37.9 ± 13.1 min, and mean maximal level was T₅. There was a good correlation (R²=0.90) between the observed levels of analgesia and those predicted from the model. Data from the first 75 min predicted the later observed data for each patient moderately well (R²=0.38).

Conclusion: A population pharmacodynamic model was applied to low-dose hypobaric lidocaine spinal anesthesia. Clinically important endpoints were determined and forecasting of later data with respect to level of spinal analgesia was attempted. Such an approach may be useful in the management of low-dose spinal anesthetic techniques in outpatients.

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