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Embracing diversity through precision, race-specific modeling of propofol-induced loss of consciousness
Upper Lobby
Embracing diversity through precision, race-specific modeling of propofol-induced loss of consciousness
University of Florida
Background & ObjectivesPropofol is routinely used worldwide and in the US on patients of different races. During propofol sedation, inadvertent general anesthesia due to overdosing or patient sensitivity... Read more

Description

Background & Objectives
Propofol is routinely used worldwide and in the US on patients of different races. During propofol sedation, inadvertent general anesthesia due to overdosing or patient sensitivity can be life-threatening if untrained personnel cannot rescue the airway and re-establish oxygenation. Our aim is to reduce overdosing and potential associated complications during sedation of patients from races sensitive to propofol.

Material & Methods
We compared in 4 races the EC05 (Effective Concentration for 5% of a population), EC50 (median) and EC95 propofol concentration at the effect site compartment (ESC) at loss of consciousness (LOC), abbreviated as ESC ECXX @ LOC. Below, we use EC50 as an example of how we obtained ESC ECXX values where they were missing.

A literature search yielded varied administration protocols and results in different formats and drug compartments. We used the Marsh Diprifusor TCI model in Tivatrainer© (v8, build 5), a commercial program, to re-run protocols, where needed, to obtain data in a standard format: ESC ECXX @ LOC.

Milne et al1 administered propofol to 40 (19M, 21F) ASA I, II Caucasians via Target Controlled Infusion (TCI; Diprifusor, sw v2) that predicted ESC propofol concentrations. The ESC EC50 @ LOC (95% C.I.) was 2.8 (2.7-2.9) μg/ml.

Xu et al2 administered propofol via TCI (Diprifusor, sw v2) to 405 (97M, 308F) ASA I, II Chinese. The ESC EC50 @ LOC (95% C.I.) was 2.2 (2.2-2.3) μg/ml.

Natarajan et al3 (2011) used a non-TCI pump to administer a constant propofol infusion of 40 mg/kg/hr. The mean (±sd) dose of propofol at loss of verbal response was lower (p < 0.001) in Blacks (n=50) at 1.17 (0.25) mg/kg compared to Caucasians (n=50) at 1.41 (0.4) mg/kg. When simulating Natarajan’s protocol on Tivatrainer, the mean ESC propofol concentrations for loss of verbal response in Blacks and Caucasians were 0.85 and 1.18 μg/ml respectively. To derive a median EC50 ESC @ LOC for Blacks, we used the ratio of Black to Caucasian mean ESC @ LOC from Natarajan to arrive at a scaling factor: 0.85/1.18 = 0.72. We then multiply the ESC EC50 @ LOC for Caucasians from Milne et al (2.8) by that scaling factor (0.72) to obtain a derived ESC EC50 @ LOC for Blacks of (0.72 * 2.8) = 2.02 μg/ml.

Puri et al4 used a TCI pump displaying only blood concentration with 18 ASA I/II Indians. Blood EC50 (95% C.I.) at LOC was 2.31 (2.16–2.45) μg/ml. Repeating Puri’s protocol with Tivatrainer, at a blood concentration of 2.31 μg/ml, ESC EC50 was 1.88 μg/ml.

Results
Figure. Propofol Effect Site Compartment EC05, EC50 and EC95 concentrations @ LOC predicted by the Marsh model for 4 races

Conclusions
Our data suggest reduced initial doses for Indians, Blacks and Chinese during propofol sedation, if using dosing guidelines or PK models based on Caucasian populations.

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