Abstract PR444: Propofol Esc Ec50 At Loss of Consciousness Differs Among Indians, Blacks, Chinese And Caucasians

Background & Objectives: Propofol is routinely used worldwide on patients of different races. During propofol sedation, inadvertent general anesthesia due to overdosing or patient sensitivity can be life-threatening if the airway cannot be rescued. Our aim is to reduce overdosing during sedation of patients from races sensitive to propofol. Materials & Methods: We compared in 4 races the median (EC50; Effective Concentration for 50% of a population) propofol concentration at the effect site compartment (ESC) at loss of consciousness (LOC), abbreviated as ESC EC50 @ LOC. A literature search yielded varied administration protocols and results in different formats and drug compartments. We used the Marsh Diprifusor model in Tivatrainer (v8, build 5), a commercial program, to re-run protocols, where needed, to obtain data in a standard format: ESC EC50 @ 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:Table.: Propofol ESC EC50 concentration @ LOC predicted by the Marsh model for 4 racesConclusion: 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. References: 1. Br J Anaesth 2003;90:127-31 2. Anesth Analg 2009;108:478–83 3. Anaesthesia 2011;66:15-9 4. J Clin Monit Comput 2011;25:309-14 Disclosure of Interest: None declared