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

Abou‐Diwan, Charbel; Sniecinski, Roman M.; Szlam, Fania; Ritchie, James C.; Rhea, Jeanne M.; Tanaka, Kenichi A.; Molinaro, Ross J.

doi:10.1016/j.jchromb.2011.01.005

Cited by 32 publications

(32 citation statements)

References 17 publications

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“…In the earlier study, the TXA dose was significantly lower, and samples were taken at only two time points: 15 and 90 minutes after the start of TXA infusion (88). The discrepancy in results is probably related to two findings from the current study, specifically, that serum concentrations of TXA do not correlate well with CSF concentrations and that TXA concentrations peak in the CSF long after the start of drug infusion.…”

Section: Discussioncontrasting

confidence: 75%

“…TXA dosing was in accordance with recommended protocols (13), with a loading dose of 30 mg/kg plus additional 2 mg/kg added to the CPB prime followed by 16 mg/kg/h infusion until chest closure. TXA concentrations in serum and CSF were quantified using a modified liquid chromatography and a tandem mass spectrometry assay (88,107). At a functional coefficient of variance of 20%, the minimum detectable level of TXA is 0.05 μg/ml.…”

Section: Methodsmentioning

confidence: 99%

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Tranexamic acid concentrations associated with human seizures inhibit glycine receptors

Lecker¹,

Wang²,

Romaschin³

et al. 2012

J. Clin. Invest.

170

156

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Antifibrinolytic drugs are widely used to reduce blood loss during surgery. One serious adverse effect of these drugs is convulsive seizures; however, the mechanisms underlying such seizures remain poorly understood. The antifibrinolytic drugs tranexamic acid (TXA) and ε-aminocaproic acid (EACA) are structurally similar to the inhibitory neurotransmitter glycine. Since reduced function of glycine receptors causes seizures, we hypothesized that TXA and EACA inhibit the activity of glycine receptors. Here we demonstrate that TXA and EACA are competitive antagonists of glycine receptors in mice. We also showed that the general anesthetic isoflurane, and to a lesser extent propofol, reverses TXA inhibition of glycine receptor-mediated current, suggesting that these drugs could potentially be used to treat TXA-induced seizures. Finally, we measured the concentration of TXA in the cerebrospinal fluid (CSF) of patients undergoing major cardiovascular surgery. Surprisingly, peak TXA concentration in the CSF occurred after termination of drug infusion and in one patient coincided with the onset of seizures. Collectively, these results show that concentrations of TXA equivalent to those measured in the CSF of patients inhibited glycine receptors. Furthermore, isoflurane or propofol may prevent or reverse TXA-induced seizures.

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Section: Discussioncontrasting

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Tranexamic acid concentrations associated with human seizures inhibit glycine receptors

Lecker¹,

Wang²,

Romaschin³

et al. 2012

J. Clin. Invest.

170

156

View full text Add to dashboard Cite

show abstract

“…Furthermore, higher postoperative hemoglobin concentrations and decreased blood loss were observed in posterior lumbar surgery [25] and pediatric vertebral column resection procedures [26] when TXA were administrated. Although TXA has been widely applied in various surgical procedures, the techniques for assessing plasma and blood TXA levels have only been developed recently [27]. Further investigations on effects in different types of spinal surgery are required to achieve a better regimen with optimal dosage and administration timing.…”

Section: Discussionmentioning

confidence: 99%

Systematic Review and Meta-Analysis of Perioperative Intravenous Tranexamic Acid Use in Spinal Surgery

et al. 2013

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BackgroundTranexamic acid (TXA) is well-established as a versatile oral, intramuscular, and intravenous (IV) antifibrinolytic agent. However, the efficacy of IV TXA in reducing perioperative blood transfusion in spinal surgery is poorly documented.MethodologyWe conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-randomized (qi-RCTs) trials that included patients for various spinal surgeries, such as adolescent scoliosis surgery administered with perioperative IV TXA according to Cochrane Collaboration guidelines using electronic PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. Additional journal articles and conference proceedings were manually located by two independent researchers.ResultsTotally, nine studies were included, with a total sample size of 581 patients. Mean blood loss was decreased in patients treated with perioperative IV TXA by 128.28 ml intraoperatively (ranging from 33.84 to 222.73 ml), 98.49 ml postoperatively (ranging from 83.22 to 113.77 ml), and 389.21 ml combined (ranging from 177.83 to 600.60 ml). The mean volume of transfused packed cells were reduced by 134.55 ml (ranging 51.64 to 217.46) (95% CI; P = 0.0001). Overall, the number of patients treated with TXA who required blood transfusions was lower by 35% than that of patients treated with the comparator and who required blood transfusions (RR 0.65; 95% CI; 0.53 to 0.85; P<0.0001, I2 = 0%). A dose-independent beneficial effect of TXA was observed, and confirmed in subgroup and sensitivity analyses. A total of seven studies reported DVT data. The study containing only a single DVT case was not combined.ConclusionsThe blood loss was reduced in spinal surgery patients with perioperative IV TXA treatment. Also the percentage of spinal surgery patients who required blood transfusion was significantly decreased. Further evaluation is required to confirm our findings before TXA can be safely used in patients undergoing spine surgery.

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“…Both topical doses were shown to reduce postoperative bleeding by 20-25%, and 16-17% higher hemoglobin levels were maintained compared with the placebo. After topical application, mean plasma levels of tranexamic acid were 4.5 and 8.5 mg/ml (up to 120 mg/ml in cardiac surgery) [70,71] at which tranexamic acid is unlikely to exert systemic antifibrinolytic activity. This approach may be preferred in situations in which the wound is accessible, and any interference with venous thromboprophylaxis is undesirable.…”

Section: Recent Updates On Tranexamic Acidmentioning

confidence: 98%

Novel approaches in management of perioperative coagulopathy

Tanaka

Bader

Görlinger³

2014

Current Opinion in Anaesthesiology

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

Cited by 32 publications

References 17 publications

Tranexamic acid concentrations associated with human seizures inhibit glycine receptors

Tranexamic acid concentrations associated with human seizures inhibit glycine receptors

Systematic Review and Meta-Analysis of Perioperative Intravenous Tranexamic Acid Use in Spinal Surgery

Novel approaches in management of perioperative coagulopathy

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