The Journal of ExtraCorporeal Technology Issue 55-4 | Page 45

N . Khurana et al .: J Extra Corpor Technol 2023 , 55 , 194 – 196 195

representing the “ patient ”. Circuits were primed with humanpacked red blood cells ( 330 mL ), fresh frozen plasma ( 150 mL ), plasmalyte ( 100 mL ), heparin ( 250 units ), sodium bicarbonate ( 3.5 mEq ), tromethamine ( 2 g ), calcium gluconate ( 325 mg ) and albumin ( 6.25 g ) and adjusted to maintain physiological conditions . The flow was set to 1 L / min to mimic flows for a 10 kg child . For the control , 30 mL of primed blood was drawn from the ECMO circuit and transferred to a tube , and maintained at 37 ° C in a water bath . Both the ECMO circuit and control were dosed with propofol at time 0 to achieve a target concentration of 50 lg / mL ( for clinical relevance ). Samples ( 1 mL ) were collected at different time points ( 1 , 5 , 15 , 30 , 60 , 120 , 180 , and 240 mins ). After the 240-minute sample , the ECMO circuit was dosed with a continuous infusion of 6 mg / h representing the low end of dosing for a 10 kg child . The infusion was discontinued after 2 hours . Samples were collected at the following time points : 15 , 30 , 60 , and 120 min after start of infusion and 1 , 5 , 15 , 30 , 60 , 120 , and 240 mins after discontinuing infusion . Collected blood samples were centrifuged immediately (@ 3000 rpm , 4 ° C ) and plasma samples were stored at �80 ° C until ready for further analysis . The samples were then analyzed for propofol concentration using HPLC , and then converted to propofol remaining ( propofol recovery ) using the following equation :

Recovery ð % Þ ¼ C t 100 ; ð1Þ

C i

where C t is the concentration at time t and C i is the concentration at time = 1 min for the bolus dose and C i is the concentration at time = 15 mins for the infusion dose .

Results

The percentage recovery of propofol was then plotted against time ( Figure 1 ). All circuits and controls were run in triplicate .

For the bolus dose , the control demonstrated a very high recovery of propofol ( above 80 % at all time points ) whereas in the ECMO circuit , a rapid decrease in propofol recovery was observed after the bolus dose , with a recovery of only 27 % at30mins ( Figure 1 and Table 1 ). However , when administered as a continuous infusion , propofol recovery was > 80 % during the infusion and that high level of recovery persisted even after the infusion was discontinued .

Discussion

Our results following a bolus dose of propofol are consistent with previous investigations on recovery of propofol [ 7 – 9 ]. As noted in those studies , approximately 70 % of propofol is adsorbed on the ECMO circuit components after 30 mins of a bolus dose . Our results were consistent with previous studies as we observed 72 % propofol to be absorbed on the ECMO circuit components after 30 mins of a bolus dose . Our results following a continuous infusion suggest that propofol adsorption is saturable when administered through the circuit . The saturation of the circuit can occur due to the hydrophobic interactions between the hydrophobic drug propofol and the

Figure 1 . Recovery of propofol at different time points . Bolus dose was given at t = 0 and infusion dose started at t = 4 h and stopped at t = 6 h with samples collected up to a total of 10 h . Propofol represents samples collected from the ECMO circuit and propofol control represents the samples collected from non-ECMO falcon tube controls . Data represent Mean ( n = 3 ) ± SD .

Table 1 . Recovery of propofol at different time points .

Time point

Recovery (%) ( Mean ± SD )

Control recovery (%) ( Mean ± SD )

P-value

hydrophobic material of the ECMO circuit components . The tubing of the ECMO circuit is made of poly ( vinyl chloride ) ( PVC ) and the oxygenators are made of poly ( methyl pentene ) ( PMP ), which are both hydrophobic . By saturating the circuit , propofol will then be available for its primary purpose : sedation of the patient . However , it is difficult to directly translate ex vivo results to a clinical setting because the experiments only quantify the drug-circuit interactions and it is unknown if propofol administered directly to the patient would achieve the same saturation . To address this , we have developed an approach that uses physiologically based pharmacokinetic modeling ( PBPK ) to translate ex vivo results into dosing recommendations . One limitation of this study is that we set up the circuit as we would for a pediatric patient and hence results may not translate directly to an adult circuit . However , although we used a pre-configured pediatric tubing set and set the flow rate to 1 L / min , our ex vivo