Objective: Percutaneous nephrolithotomy (PCNL) is most frequently performed procedure for renal stones 2 cm and larger. Perioperative hemorrhage being most common complication, warrants as important predicting factor of adverse outcomes. Prevention with inexpensive and safe drug like tranexamic acid (TA) would ultimately turn out to be cornerstone for establishing future guidelines. Aim of this study is to evaluate whether TA is efficacious in preventing blood loss during PCNL. Materials and Methods: Ethical review board approval taken. Sample size calculation yielded 240 patients, comprising 120 in each group. Group A receiving TA and group B receiving placebo. Age, gender, body mass index (BMI), stone size, volume and location, preoperative blood count, creatinine, urine analysis, coagulation profile and necessary radiological investigations done. Randomization through lottery method. Both patient and investigator were blinded. Hemoglobin (Hb) and hematocrit (Hct) levels done at 24 hours postoperatively and fall in values recorded. Results: Both groups were equal in characteristics like age, gender, BMI, stone size, volume and location (p>0.05). Operative variables like calyx punctured, position of puncture and operative time were also found to be similar in both groups. Median change in Hb in placebo group was 1.6 interquartile range (IQR) 4, while in TA group was 1.3 (IQR 7.8) (p=0.001). Similarly, median change in Hct level in placebo group was 3.6 (IQR 11.8) and in TA group was 2.4 (IQR 13) (p<0.001). Sixteen patients were transfused after surgery; 12 (75%) belonged to placebo group while 4 (25%) belonged to TA group (p=0.038). Hospital stay was not significantly different in both groups (p=0.177) with median of 4.0 and IQR of 0 in both groups. Conclusion: TA during PCNL reduces blood loss and minimizes blood transfusion rate
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