Propofol has both enhancing and suppressing effects on human platelet aggregation in vitro.

BACKGROUND: Volatile anesthetics are known to suppress platelet aggregation. In contrast, there is conflicting information regarding the effect of propofol on platelet function. The present study was designed to clarify the effects of propofol on platelet function and the mechanisms underlying these effects. METHODS: Propofol or an equivalent volume of 10% Intralipos (as a control) was added to test tubes 5 min before the induction of each reaction. Platelet aggregation induced by epinephrine, arachidonic acid (AA), prostaglandin G2 (PGG2), or STA2 (a thromboxane A2 [TXA2] analog) was measured using an eight-channel aggregometer. To determine type 1 cyclooxygenase activity, AA (0.5 mM) was added to an assay mixture containing type 1 cyclooxygenase, and the concentration of the final product, malonaldehyde, was measured by spectrophotometry. Epinephrine-, adenosine diphosphate-, AA-, and PGG2-induced TXA2 formation was measured using a commercially available radioimmunoassay kit. To estimate TXA2 receptor-binding affinity, 3H-S145, a specific TXA2 receptor antagonist, was added, and the radioactivity of receptor-bound 3H-S145 was determined using a liquid scintillation analyzer. Inositol 1,4,5-triphosphate formation was measured in STA2-stimulated platelets using a commercially available inositol 1,4,5-triphosphate assay kit. RESULTS: Propofol (40 microM) enhanced, whereas 100 microM suppressed, adenosine diphosphate- and epinephrine-induced secondary aggregation without affecting primary aggregation. Propofol (40 microM) also enhanced, but 100 microM suppressed, AA-induced aggregation. Propofol (100 microM) enhanced PGG2- and STA2-induced aggregation. Propofol (100 microM) suppressed AA-induced TXA2 formation but did not alter that induced by PGG2. Propofol (30-100 microM) suppressed AA-induced malonaldehyde formation, indicating inhibition of type 1 cyclooxygenase activity. Propofol did not alter TXA2 receptor-binding affinity. Propofol (30 and 100 microM) augmented inositol 1,4,5-triphosphate formation in STA2-stimulated platelets. CONCLUSIONS: The present findings clearly indicate that high concentrations of propofol suppress the activity of type 1 cyclooxygenase, the enzyme that converts AA to PGG2. Furthermore, propofol also enhanced STA2-induced inositol 1,4,5-triphosphate formation. These results may explain the inconsistent findings of previous investigators.

Anesthesia with sevoflurane, but not isoflurane, prolongs bleeding time in humans.

PURPOSE: Halothane has been shown to suppress platelet aggregation in vitro and ex vivo and to prolong bleeding time. In a previous in vitro study, we demonstrated that sevoflurane had a stronger suppressive effect on platelet aggregation than halothane. The present study investigated whether clinical use of sevoflurane affects bleeding time in vivo. METHODS: Thirty-four patients undergoing minor elective surgery were randomly assigned to sevoflurane or isoflurane. Anesthesia was induced with intravenous thiopental and maintained with sevoflurane or isoflurane with nitrous oxide. Bleeding time was measured by the Duke method. An initial (control) measurement was obtained in the operating room before the induction of anesthesia, and a second was obtained 5-10 min after endotracheal intubation but before starting the operation, when the end-expiratory concentration of sevoflurane or isoflurane had been stabilized at 1-1.5 times the minimum alveolar concentration (MAC), and the mean arterial pressures were between 80% and 120% of the preanesthetic values. RESULTS: Bleeding time was increased from the preanesthetic value of 2.07 +/- 0.82 min to 2.83 +/- 0.93 min (n = 15) in the sevoflurane group (P < 0.01) but was not significantly altered in the isoflurane group. CONCLUSION: Sevoflurane alters bleeding time in the clinical situation.

Suppression of cyclic guanosine monophosphate formation in rat cerebellar slices by propofol, ketamine and midazolam.

PURPOSE: The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system is involved in glutamatergic neurotransmission. The current study determined the effects of propofol, ketamine and midazolam on rat cerebellar cGMP formation, attempting to clarify whether the effect was due to suppression of NO-cGMP system or to direct interaction with glutamatergic receptors. METHODS: Cerebellar slices, obtained from six- to eight-day-old Wistar rats, were pretreated with propofol (10 microM-1 mM), ketamine (10-100 microM) or midazolam (1-100 microM) for 30 min. and then stimulated with L-glutamate (3 mM), N-methyl-D-aspartate (NMDA, 0.1 mM), kainate (0.1 mM) or sodium nitroprusside (SNP, 0.3 mM) (n = 5-11 for each group). The levels of cGMP were determined by radioimmunoassay. RESULTS: None of the anaesthetics studied altered cGMP levels when no stimulant was given. Propofol (10 microM-1 mM) suppressed L-glutamate-, NMDA-, kainate- and SNP stimulated cGMP formation in a concentration-dependent manner, the sensitivity to propofol was in the order of NMDA > kainate > L-glutamate. SNP. Ketamine (10-100 microM) suppressed L-glutamate- and NMDA-stimulated cGMP formation, but did not suppress kainate- or SNP-stimulated cGMP formation. Midazolam (10-100 microM) did not affect NMDA-, L-glutamate- or SNP-stimulated cGMP formation, but suppressed kainate-induced formation. CONCLUSION: The inhibitory effects of propofol, ketamine and midazolam on cGMP formation in rat cerebellar slices are due mainly to interaction with receptors for excitatory amines, and not due to the suppression of nitric oxide synthase or guanylate cyclase activities.

Does furosemide prevent hypertension during perioperative splenectomy in thalassemic children?

Hemodynamic changes of 50 thalassemic children who had splenectomy under general anesthesia were compared to 40 identical patients who, in addition, received intravenous furosemide 1 mg/kg immediate preoperation. During the anesthetic process, both groups showed a significant increase of heart rate, systolic and diastolic blood pressure more than the preanesthetic values. Hemodynamic variables in the furosemide group declined toward normal range on termination of anesthesia, whereas, the other group's variables were still significantly higher than their control. During the first 24 hours postoperatively, 20 per cent of the furosemide group had blood pressure rising higher than 130/90 mmHg, while 18 per cent was observed in the other group. Antihypertensive drugs were given to reduce the blood pressure in both groups. None of the patients in the furosemide group demonstrated any abnormal neurological symptoms, but 3 out of 50 patients in the other group developed convulsion. We, therefore, conclude that circulatory volume reduction with furosemide does not prevent hypertension during perioperative splenectomy in thalassemic children. However, it's role in prevention of neurological abnormalities needs to be further investigated.