In Vitro Effect of Clinical Propofol Concentrations on Platelet Aggregation

Abstract

The inhibitory effect of propofol on platelet aggregation remains unclear, and studies on the subject disagree. Furthermore, although propofol infusions are widely used for general anesthesia and as sedatives for patients in intensive care units, little information is available on its concentration- and time-related effects on platelet aggregation. Here, the authors investigated the in vitro effect of propofol, at concentrations required for sedation and general anesthesia, on platelet aggregation after 1, 2, or 3 h. Blood from healthy volunteers (n = 9) was incubated at propofol plasma concentrations of 0, 2, 4, and 10 μg/mL in a water bath at 37°C. Platelet aggregation was measured using a platelet function analyzer (PFA-100) after 1, 2, or 3 h of incubation. Times to occlude collagen/epinephrine (CEPI) or collagen/adenosine 5'-diphosphate (CADP)-coated membranes (closure times, CTs) were measured. The CEPI and CADP CTs of non-incubated blood were 125.6 ± 19.5 s and 93.0 ± 12.2 s, respectively, and no significant difference in CEPI CTs was observed at propofol plasma concentrations of 0, 2, 4, and 10 μg/mL after incubation for 1, 2, or 3 h. CADP CTs were comparable at propofol concentrations of 0, 2, 4, and 10 μg/mL at each incubation time. These findings suggest that propofol at concentrations required for sedation and general anesthesia has no inhibitory effect on platelet aggregation after 3 h of incubation.

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“…The studies in animals [41] and humans [42] indicated that the measured/predicted brain concentration of propofol during maintenance of surgical anesthesia is above 4 µg/ml, and as high as 20 µg/ml [43,44]. Thus, in the in vitro experiments, the doses of propofol used that are within the range of concentrations found in the human brain during surgical anesthesia are referred to as anesthetic doses.…”

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“…23 The studies in animals 23 and humans 24, 25 indicated that the measured/predicted brain concentration of propofol during maintenance of surgical anesthesia is above 4 µg/ml, and as high as 20 µg/ml. 26, 27 Thus, in the in vitro experiments, the doses of propofol used that are within the range of concentrations found in the human brain during surgical anesthesia are referred to as anesthetic doses. The concentrations that are outside this range would be called either sub-anesthetic or supra-anesthetic concentrations.…”

Quinapril decreases antifibrinolytic and prooxidative potential of propofol in arterial thrombosis in hypertensive rats

“…On the other hand, Chung et al observed, that Pro in concentrations required for sedation and general anesthesia had no inhibitory effect on platelet aggregation after 3 h of incubation. 23 …”

“… 21 , 22 In vitro and ex vivo data suggest that Pro exerts antiplatelet and anti-inflammatory effects. 23 – 26 Moreover, Pro inhibits platelet thromboxane synthesis and NO production in leukocytes, stimulating the activity of guanyl cyclase in platelets. 27 In our preliminary study, we also observed NO release from endothelial cells, which indicates the significant involvement of endothelium in the effect of Pro on hemostasis.…”