Plasma and cerebral spinal fluid tranexamic acid quantitation in cardiopulmonary bypass patients.

A method for the determination of tranexamic acid (TXA) in human plasma and cerebral spinal fluid (CSF) was developed. Analyses were performed by ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS) using ɛ-aminocaproic acid (ACA) as an internal standard. TXA and ACA were extracted from a 50 µL sample of plasma or CSF using a methanol protein crash protocol, and chromatographic separation was performed on an ACQUITY™ TQD mass spectrometer using a UPLC C18 BEH 1.7 µm column with a water and methanol gradient containing 0.1% formic acid. The detection and quantitation was performed by positive ion electrospray ionization using the multiple reaction monitoring (MRM) mode. The method was linear over the concentration range of 0.1-10.0 µg/mL, with lower limit of quantitation of 0.1 µg/mL for TXA. The intra- and inter-assay precision was less than 12% and 13% respectively at the plasma and CSF TXA concentrations tested. The present method provides a relatively simple and sensitive assay with short turn-around-time. The method has been successfully applied to assess the plasma and CSF concentrations of tranexamic acid achieved with only one dosing regimen of tranexamic acid in patients undergoing cardiopulmonary bypass surgery (CPB).

Worst headache and subarachnoid hemorrhage: prospective, modern computed tomography and spinal fluid analysis.

STUDY OBJECTIVE: This study investigated the hypothesis that modern computed tomographic (CT) imaging is sufficient to exclude subarachnoid hemorrhage (SAH) in patients with severe headache. METHODS: All 38,730 adult patients who presented to Hermann Hospital in Houston, Texas, during a 16-month period were prospectively screened to detect those with "the worst headache of my life." Two neuroradiologists blinded to the study hypothesis interpreted the CT scans. Patients with negative scans underwent comprehensive cerebrospinal fluid (CSF) analysis including cell count in first and last tubes, visual and spectrophotometric detection of xanthochromia, and CSF D-dimer assay. RESULTS: A chief complaint of headache was elicited in 455 patients, and 107 of these had "worst headache" and were enrolled in the study. CT-confirmed SAH was found in 18 of the 107 (17%). Only 2 patients (2.5%, 95% confidence interval, .3% to 8.8%) had SAH detected by CSF analysis among those with negative CT imaging result. CSF spectrophotometric detection was the most sensitive test for blood. Three patients with less than 6 red blood cells in tube 1 had positive spectrophotometric results, but in all 3, tube 4 was negative on spectrophotometric analysis, suggesting a high false-positive rate. CONCLUSION: Modern CT imaging is sufficient to exclude 97.5% of SAH in patients presenting to the ED with "worst headache" symptoms.

[Antifibrinolytic therapy of subarachnoid hemorrhage. Permeation of oral paraaminomethylbenzoic acid in the cerebrospinal fluid]. / Beitrag zur antifibrinolytischen Therapie bei Subarachnoidealblutungen. Untersuchungen über die Permeation der oral applizierten para-Amino-methylbenzoesäure in den Liquor.

Studies of the permeation of PAMBA in the cerebrospinal fluid of patients with intact or disturbed BBB function after oral administration of 6 g and withdrawal of the spinal fluid after 120 minutes exclusively showed concentrations which were below the identification threshold of the method using 1 micron per millilitre. Patients suffering from subarachnoidal haemorrhages mainly showed a permeation of PAMBA in the cerebrospinal fluid which, however, only rarely reached the lower therapeutically necessary concentration.