Antiaggregatory effect of midazolam on human platelets during monitored anesthesia care for trans-vaginal oocyte retrieval

Abstract

BackgroundMidazolam plays a major role in sedation and large doses might be used under certain circumstances. Trans-vaginal oocyte retrieval is one of the most painful procedures in which monitored anesthesia care (MAC) is needed. The mechanism by which midazolam exerts anti-aggregation of human platelets is still unclear.This work aimed to investigate the in vivo suppressing effect of midazolam on human platelet aggregation.MethodsSixty adult females ASA I–II, scheduled for trans-vaginal ultrasound oocyte retrieval by combined intravenous midazolam sedation with paracervical local nerve block were included. At the end of the procedure, it was found that the range of total midazolam consumption was 4.9–9 mg. Thereby, patients were divided into three groups according to the total consumption of midazolam: Group I (4.9–6.2 mg), Group II (6.3–7.6 mg), Group III (7.7–9 mg). Patients who needed other drugs for sedation were excluded. Pre- and post-operative Bleeding Time (BT) were recorded. Two blood samples were collected from each patient to test the inhibitory effect of midazolam on platelet aggregation. Platelet aggregation was tested using platelet-aggregometer. ELISA was used to measure thromboxane B2 formation. Flowcytometry was used to evaluate whether glycoprotein IIb–IIIa complex is the receptor site for the antiplatelet action of midazolam.ResultsOnly 51 patients completed the study: Group I (n = 16), Group II (n = 24), and Group III (n = 11). Bleeding Time (BT) showed significant prolongation in group III compared to basal levels. Midazolam suppressed platelet aggregation in a dose-dependent manner as detected by aggregometer. Glycoprotein IIb–IIIa complex is not its site of action as shown by flowcytometric analysis. Lastly, thromboxane B2 was significantly inhibited by midazolam.ConclusionThis study revealed that midazolam dose-dependently inhibits platelet aggregation by a mechanism not involving the binding of glycoprotein IIb–IIIa complex (fibrinogen receptor). It was also found that midazolam inhibits thromboxane A2 formation.