The effect of propofol on the interaction of platelets with leukocytes and erythrocytes in surgical patients.
We tested the antiplatelet effect described for propofol in vitro in surgical patients. Platelet aggregation induced by adenosine diphosphate, collagen, and arachidonic acid was tested in samples of whole blood, platelet-rich plasma (PRP), PRP with red blood cells, and PRP with leukocytes. Also measured were platelet production of thromboxane (Tx)B(2) and leukocyte production of 6-keto-prostaglandin F(1 alpha) (a stable metabolite of prostacyclin) and plasma levels of nitrites + nitrates (indicator of nitric oxide production). Anesthesia was induced with a bolus IV injection of sodium thiopental 4 mg/kg (n = 10), with a bolus dose of 2.5 mg/kg of propofol (n = 20), or with propofol total IV anesthesia (n = 20). Sodium thiopental did not modify any of the analytical values. In patients who received a bolus injection of propofol, platelet aggregation was significantly reduced in whole blood and in PRP + leukocytes. Platelet production of TxB(2) was reduced by 35%; the inhibition of 6-keto-prostaglandin F(1 alpha) was not statistically significant. Plasma levels of nitrites + nitrates increased by 37%; this change correlated significantly with the decrease in systolic and diastolic blood pressure (both P < 0.05). Similar changes, albeit of larger magnitude, were seen in patients who were given total IV anesthesia with propofol. In conclusion, propofol inhibited platelet aggregation in surgical patients mainly as a result of the inhibition of Tx synthesis and the increase in nitric oxide production. These effects are thought to be related to the hypotensive effect of this anesthetic.


CONCLUSIONS
In vitro experiments have shown that propofol inhibits platelet aggregation and increases nitric oxide production. This study shows that doses habitually used to induce or maintain anesthesia also have these effects. These findings have potential applications for patients at increased risk for bleeding and may partly explain the hypotensive effect of propofol.
Mendez
D
D
*Anesthesiology and Resuscitation Unit, Carlos Haya University Hospital, Málaga; and †Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain.
De La Cruz
J P
JP
Arrebola
M M
MM
Guerrero
A
A
González-Correa
J A
JA
García-Temboury
E
E
Sánchez de la Cuesta
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D018686:Anesthetics, Intravenous; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D015742:Propofol; D013514:Surgical Procedures, Operative
D018686:Anesthetics, Intravenous; D009566:Nitrates; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D000244:Adenosine Diphosphate; D003094:Collagen; D015742:Propofol