Serum Concentration of Tranexamic Acid After Topical Administration in Massive Weight Loss Skin Reducing Surgery

Serum Concentration of Tranexamic Acid After Topical Administration in Massive Weight Loss Skin Reducing Surgery

Serum Concentration of Tranexamic Acid After Topical Administration in Massive Weight Loss Skin Reducing Surgery

Tranexamic acid is a drug that prevents clotted blood from dissolving and hence reduces bleeding. It is routinely given intravenously in many surgical situations where there is a risk of major bleeding. Concerns regarding possible adverse effects from intravenous use prevents a more widespread use, even in smaller surgeries. Topical application - using the drug directly on the wound surface- may give a higher concentration at the site of bleeding but a lower concentration in the rest of the body, and hence a lower risk of adverse effects. Here it will be investigated to what extent a defined dose of the drug is absorbed systemically - into the blood stream - when it is applied topically. This will then be compared to the concentration in the blood stream when administered intravenously. Blood samples will be obtained at defined time intervals after administration from patients receiving topical and patients receiving intravenous administration of the same single dose of tranexamic acid. Will less of the drug enter the blood stream if it is applied directly to the wound?

Hemostasis, Surgical, Tranexamic Acid, Antifibrinolytic Agents, Administration, Cutaneous, Administration, Intravenous, Administration, Topical

12 participants will be included in each of 3 groups: wound moistening group (skin reduction surgery), wound bolus group (after skin reduction surgery), and (for comparison) a group getting usual intravenous tranexamic acid before orthopedic surgery. It is not possible to conduct a formal power calculation, as it is completely unknown which concentrations could be expected after topical use; however, these concentrations are expected to be considerably lower than after intravenous use. Consequently, it is expected that the AUC values in all subjects in the topical (skin reducing surgery) group are far lower than in all subjects in the intravenous (orthopaedic surgery) group. 12 subjects is therefor considered an appropriate number.

Wound surface moistened with 20 ml of tranexamic acid 25 mg/ml (total dose 500 mg) prior to wound closure

200 ml of tranexamic acid 5 mg/ml (total dose 1 g) as a bolus instilled into the wound cavity after wound closure, which will remain in the cavity until the activation of drains one hour later

1 g of tranexamic acid administered intravenously in accordance with prevailing routines directly prior to planned surgical procedure.

as described by the Area Under the (time-concentration) Curve (AUC) from 0 to infinity, alternatively from 0 to 240 minutes if drug levels after 24 hours do not allow for such extrapolation

Possible adverse reactions or other complaints observed or reported by the patient - telephone interview

Possible adverse reactions or complaints observed or reported on the first postoperative day - clinical observation

Inclusion Criteria: planned for major skin reduction surgery (abdominoplasty/panniculectomy) after massive weight loss, or planned for orthopaedic hip replacement surgery Exclusion Criteria: pregnancy breastfeeding known allergy to tranexamic acid/Cyklokapron® ongoing or former thromboembolic event known kidney failure, as defined by estimated glomerular filtration rate (eGFR)<60 ml/min

Ausen K, Pleym H, Liu J, Hegstad S, Nordgard HB, Pavlovic I, Spigset O. Serum Concentrations and Pharmacokinetics of Tranexamic Acid after Two Means of Topical Administration in Massive Weight Loss Skin-Reducing Surgery. Plast Reconstr Surg. 2019 Jun;143(6):1169e-1178e. doi: 10.1097/PRS.0000000000005620.