Tranexamic Acid in Wetting Solution for Liposuction: Serum Pharmacokinetic Profile

Goals/Purpose: The antifibrinolytic drug tranexamic acid (TXA) is routinely used for various surgeries in plastic surgery, cardiac surgery, orthopedic surgery, and trauma surgery with good effect in both IV and topical administration. Previous authors have reported their outcomes using topical and IV administration of TXA in various plastic surgery procedures. Only one previous study has reported on the pharmacokinetic profile of TXA after topical administration of TXA in abdominoplasty after massive weight loss. No studies have investigated the pharmacokinetic profile of TXA when used in wetting solution prior to liposuction. We do not have any knowledge of the systemic absorption profile of TXA when added to wetting solution prior to liposuction and if either this administration technique reaches therapeutic or potentially toxic levels. We believe that similar to lidocaine in wetting solution, systemic absorption of TXA is low, and can be administered in higher without causing adverse effects or reaching toxic levels.

Methods/Technique: The aim of this study is to evaluate the systemic absorption of tranexamic acid when administered subcutaneously within tumescent fluid. This is a prospective pilot study assessing serum TXA levels after administration of wetting solution containing 500 mg TXA, 12.5 cc lidocaine, and 1 mg epinephrine in 1 liter of normal saline in patients underlying going liposuction of the arms, thighs, abdomen, and/or flanks.

Methods: The authors investigated the systemic absorption of tranexamic acid in patients undergoing liposuction after infiltration of wetting solution in ten patients, which was administered until the tumescent stage was reached (waterfall effect). Blood samples were obtained before infiltration and after 30 minutes, 1 hour, 4 hours, 8 hours, and 12 hours. All blood samples were sent to the University of North Carolina Mass Spectrometry Core lab where they were prepared for evaluation. Blood samples (200 µL) were extracted with 1 mL of cold 80% methanol 20% water. Extracts were centrifuged for 10 minutes. The supernatant was transferred and dried down. Samples were reconstituted with 100 µL of 80:20 methanol to water and then diluted 20 fold into water for analysis.

Patients were monitored for any adverse effects in the first month which include:

• Nonfatal myocardial infarction
• Stroke
• Pulmonary embolism
• Renal failure
• Bowel infarction

Pharmacokinetic analysis:

Samples were analyzed with a Thermo TSQ Vantage (ThermoFisher, Bremen, Germany) mass spectrometer coupled to a Waters Acquity Ultra-Performance Liquid Chromatography (UPLC) system (Waters, Milford, Massachusetts). Samples were introduced via a heated electrospray ionization (HESI) source at a flow rate of 0.4 mL/min. HESI source conditions were set as: capillary temperature 300 deg C, sheath gas (nitrogen) 50 arb, auxillary gas (nitrogen) 15 arb, sweep gas (nitrogen) 0 arb, spray voltage 3000 V, and S-lens RF 78 V. Samples were analyzed in positive ionization mode using single reaction monitoring (SRM).

Methods/Technique

Results/Complications: After administration of 500 mg TXA mixed in 1 liter of normal saline, 12.5 cc 1% lidocaine and 1 mg epinephrine, the peak serum concentration was 227.7 nannograms after 240 minutes (4 hours). We did not observe any adverse effects in our study.

Conclusion: Administration of tranexamic acid in wetting solution undergoing liposuction results in low serum concentrations, which are highly unlikely to cause systemic effects. Previous studies have suggested therapeutic levels are approximately 10 ug/mL in adults to inhibit fibrinolysis. Transexamic acid has been reported to cross the blood brain barrier at approximately 10% of plasma concentration. There are studies to suggest a cerebrospinal fluid concentration of 14 micrograms/mL for CNS excitatory effect (seizures). Thus, our study suggests that low concentrations of tranexamic acid are absorbed systemically, and thus, can be administered in high doses safely without reaching toxic levels.