Breast reduction mammoplasty is a commonly performed procedure to reduce the physical and psychosocial symptoms in women experiencing macromastia. Breast reductions are considered relatively safe procedures that rarely require blood transfusion for significant blood loss. However, common complications include edema, ecchymosis, wound dehiscence, hematoma, seroma, asymmetry, nipple inversion, nipple loss, and cellulitis.1 Surgical techniques of minimizing blood loss and operative time have been shown to improve postoperative outcomes.2
At our institution, it is common practice in reduction mammoplasty to locally infiltrate the breasts with a tumescent solution containing a dilute amount of local anesthetic and epinephrine before surgical incision. This is due to the benefits of tumescent solution described in the literature, including reduced blood loss, operative time, and length of hospital stay.3 Its utility lies in its ability to minimize blood loss through epinephrine-induced vasoconstriction in addition to providing hydrostatic compression.4 Increasing evidence also supports the benefits of perioperative administration of tranexamic acid (TXA) in surgery.5
Tranexamic acid is a synthetic lysine analog that acts as an antifibrinolytic agent, preventing the breakdown of clots. Tranexamic acid adheres to the lysine binding sites on plasminogen, inhibiting its conversion to plasmin, the active form responsible for fibrin clot degradation. It is commonly used to reduce perioperative blood loss during surgical procedures.6,7 Furthermore, TXA has been found to reduce blood loss with little to no risk of thrombotic events and has anti-inflammatory properties that have been shown to decrease postoperative edema and ecchymosis, leading to improved recovery time.8 The use of TXA to minimize blood loss in surgical procedures has been increasingly described in orthopedic,9 trauma,10 cardiac,11 and obstetric12 procedures. However, the use of TXA is sparsely documented in plastic surgery and has not been well described in breast reduction surgery.
Wokes et al13 conducted an anonymous online survey to assess TXA use among current British Association of Aesthetic Plastic Surgeons members. Of the British Association of Aesthetic Plastic Surgeons members surveyed, 78% of respondents reported TXA use in their clinical practice, and of these respondents, 83% reported TXA use specifically in breast reduction procedures. The main benefits described were reduced intraoperative and postoperative bleeding and reduced ecchymosis.13 However, because of the nature of this survey study, the actual benefits of TXA use in breast reduction surgery remain unclear. As the use of TXA in plastic surgery continues to grow, it is important to elucidate its utility and we sought to determine what benefits, if any, TXA has in breast reduction surgery. The purpose of our study was to determine the impact of local TXA infiltration in addition to tumescent infiltration, as opposed to standard procedure with tumescent infiltration alone, on intraoperative blood loss and operative time in patients undergoing breast reduction surgery.
METHODS
After institutional review board (Pro00076583) approval was obtained for this study, a retrospective chart review was performed of all patients undergoing a bilateral reduction mammoplasty from a single surgeon between June 2020 and December 2021. Tumescent infiltration with TXA was used in all patients starting May 2021. All patients before this date received tumescent only infiltration. The patients were divided into 2 distinct cohorts: those who received local infiltration with TXA (TXA group) during surgery and those who received only tumescent solution (non-TXA control group). The standard tumescent solution was composed of 1 L of lactated Ringer's, 300 mg of lidocaine, and 1 mg of epinephrine. Each patient received approximately 200 to 300 mL of tumescent solution infiltrated into each breast with the exact volume based on estimated specimen resection weight, depicted in Figure 1. For patients included in the TXA group, 3 g of TXA were added to the tumescent bag, equivalent to a TXA concentration of 3 mg/mL. The TXA in addition to standard tumescent solution was then locally infiltrated into each breast accordingly. Patient data were accessed through the electronic medical record. Any patients receiving additional surgeries were excluded. The data collected included patient demographics (age and race), body mass index (BMI), comorbidities, smoking status, previous breast surgeries, and breast-related measurements such as sternal notch-to-nipple (SN-N) distance, resected breast specimen weight, pedicle technique, the number of days surgical drains remained in place, and postoperative complications. Postoperative complications were further subcategorized into T-junction dehiscence, large dehiscence (defined as a dehiscence equal to or greater than 3 cm), nipple-areolar complex (NAC) dehiscence, seroma, hematoma, cellulitis, abscess, suture granuloma, nipple inversion, fat necrosis, asymmetry, complete or partial NAC loss, and any emergency department (ED) visits or returns to the operating room (OR) within the 18 month study period. The postoperative outcomes recorded included operative time, measured from initial incision to close, and intraoperative blood loss, which was subjectively determined by the senior author at the time of surgery and then retrospectively obtained from the operative report.
FIGURE 1: Tumescent solution infiltration protocol for TXA versus non-TXA groups. Patients received local administration of tumescent solution into each breast with either 3 grams of TXA added to the tumescent solution (TXA group) or tumescent only (non-TXA control group). Once added to tumescent solution, TXA concentration was 3 mg/mL. The amount of tumescent solution infiltrated into each breast was determined by estimated breast resection weight. LR, lactated Ringer's.
Statistical analyses were completed using SPSS version 27 (IBM Corporation, Armonk, NY). To assess demographic information (eg, age, race, BMI, etc), patient comorbidities, and postoperative complication incidence rate, means and standard deviations were calculated for all continuous variables, and frequencies and percentages were calculated for all categorical variables. Variables with continuous outcomes differences were assessed using independent samples t tests with TXA (patients receiving tumescent and TXA) versus control (patients receiving only tumescent) serving as the independent groups. All continuous outcomes were examined using Levene test for equality of variances. If significant variance differences were found between groups, results were reported based on adjusted degrees of freedom using the Welch-Satterthwaite method. Categorical variables were assessed using χ2 analyses or Fisher exact tests as appropriate. Statistical significance was defined as a P value of less than 0.05.
RESULTS
There were 81 breast reduction patients identified, all of whom were female, for a total of 162 breasts. All patients included in this study underwent bilateral reduction mammoplasty with the inferior pedicle surgical technique. Data regarding patient demographics and breast-related measurements are presented in Table 1. The average patient age was 30 years (range, 16–68 years) and the average BMI was 31.57 kg/m2 (range, 21.6–40.8 kg/m2) for our study population. Of the 81 patients, there were 55 (67.9%) African American, 24 (29.63%) White, and 2 (2.47%) Hispanic patients. There were no statistically significant differences in patient demographics and BMI between the 2 cohorts. The average SN-N distance for all patients was 32.80 + 3.62 cm, and the average resected breast specimen weight was 903.21 + 336.50 g. No statistically significant differences in average SN-N distance and average resected specimen weight were found between the 2 cohorts.
TABLE 1 -
Patient Characteristics
Demographics |
Total (N = 81) |
TXA (n = 41) |
Non-TXA (n = 40) |
P
|
Age |
30.08 ± 13.44 (range, 16–68) |
31.39 ± 13.11 (range, 16–61) |
28.75 ± 13.97 (range, 16–68) |
0.383
|
Race, n |
White: 24 (29.63%) African American: 55 (67.90%) Hispanic: 2 (2.47%) |
White: 11 (26.83%) African American: 28 (68.29%) Hispanic: 2 (4.88%) |
White: 13 (32.5%) African American: 27 (67.5%) Hispanic: 0 (0%) |
0.337
|
BMI, kg/m2
|
31.57 ± 4.07 (range, 21.6–40.8) |
32.21 ± 3.94 (range, 23.4–40.8) |
30.92 ± 4.20 (range, 21.6–40) |
0.157
|
SN-N, cm |
32.80 ± 3.62 (range, 26.5–41) |
33.08 ± 3.29 (range, 26.5–41) |
32.51 ± 3.95 (range, 23–40.5) |
0.322
|
Specimen weight, g |
903.21 ± 336.50 (range, 304–1934) |
872.05 ± 292.45 (range, 374–1670) |
935.16 ± 377.44 (range, 304–1934) |
0.237
|
Pedicle technique, n |
Inferior: 81 |
Inferior: 41 |
Inferior: 40 |
N/A |
Drain duration, d |
7 ± 4.20 (range, 0–27) |
8 ± 4.48 (range, 4–27) |
6 ± 4.94 (range, 0–24) |
0.033*
|
Average patient demographics and breast-related measurements for the total study population, TXA group, and non-TXA group. Range and standard deviation were calculated. Race and pedicle technique are reported as number of patients. Two-tailed t test statistical analyses were performed to compare averages between the 2 cohorts.
*Bold values with an asterisk indicate statistical significance (P < 0.05).
N/A, not applicable.
The most commonly reported comorbidity in this patient population was obesity (52, 64.2%), followed by anxiety (15, 18.52%), asthma (14, 17.28%), hypertension (14, 17.28%), and depression (13, 16.05%). Of the 81 patients included in this study, 4 had previously undergone a breast surgery, such as lumpectomy. With regard to smoking status, there were 6 current smokers and 8 former smokers within our study population. Patient comorbidities are summarized in Table 2.
Comorbidity |
n (% of All Patients) |
Hypertension |
14 (17.28%) |
Diabetes |
2 (2.47%) |
Obesity |
52 (64.2%) |
Hypercholesterolemia |
7 (8.64%) |
Thyroid disease |
5 (6.17%) |
DVT/PE |
1 (1.23%) |
Anemia |
8 (9.87%) |
Cardiovascular disease |
0 (0%) |
Asthma |
14 (17.28%) |
Anxiety |
15 (18.52%) |
Autoimmune disease |
4 (4.94%) |
OSA |
2 (2.47%) |
Depression |
13 (16.05%) |
Current smoker |
6 (7.41%) |
Former smoker |
8 (9.88%) |
Prior breast surgery |
4 (4.94%) |
Incidence of patient comorbidities reported in the total patient population (N = 81). Smoking status and patients with a history of any previous breast surgery were recorded. Prior breast surgeries included lumpectomy, cyst excision, and biopsy.
DVT/PE, deep vein thrombosis/pulmonary embolism; OSA, obstructive sleep apnea.
Overall, there were a total of 32 postoperative complications during the time of the study (Table 3). There was no evidence of thromboembolic events in any of the patients. The overall complication rate for each cohort was 15 for the TXA group and 17 for the non-TXA group. Upon further analysis of postoperative complications, the incidence of T-junction dehiscence was found to be significantly lower in the TXA group (P = 0.016). In addition, there were no reports of suture granuloma within the TXA group as compared with 5 in the non-TXA group (P = 0.05). There were a total of 12 ED visits after surgery with relatively similar rates occurring in both cohorts (TXA, 6 patients; non-TXA, 6 patients; P = 0.963). There were 4 patients (TXA, 3 patients; non-TXA, 1 patient) who returned to the OR for management of surgical complications, including seroma and/or hematoma drainage, scar revision, and asymmetry correction (Table 4). There were no statistically significant differences in the number of postoperative ED visits, returns to OR, and overall complication incidence between the TXA and non-TXA groups (P = 0.963, P = 0.359, P = 0.94, respectively).
TABLE 3 -
Incidence of Postoperative Complications
Complication |
Total (N = 81) |
TXA (n = 41) |
Non-TXA (n = 40) |
P
|
T-junction dehiscence |
29 |
10 |
19 |
0.016*
|
Large dehiscence |
2 |
0 |
2 |
0.494
|
NAC dehiscence |
3 |
0 |
3 |
0.241
|
Seroma |
3 |
1 |
2 |
0.571
|
Hematoma |
5 |
2 |
3 |
0.665
|
Cellulitis |
1 |
1 |
0 |
0.494
|
Abscess |
2 |
0 |
2 |
0.494
|
Suture granuloma |
5 |
0 |
5 |
0.05†
|
Nipple inversion |
1 |
0 |
1 |
0.32
|
Fat necrosis |
6 |
2 |
4 |
0.548
|
Asymmetry |
8 |
4 |
4 |
0.971
|
NAC partial loss |
0 |
0 |
0 |
N/A |
ED visit |
12 |
6 |
6 |
0.963
|
Return to OR |
4 |
3 |
1 |
0.359
|
Any complication |
32 |
15 |
17 |
0.94
|
Complications within the 18-month study period after breast reduction surgery were recorded for the total study population. Individual complications are reported per breast(s) involved. Incidence of complications was compared between the TXA group and non-TXA group using χ2 analyses or Fisher exact tests as appropriate (ie, expected cell counts less than 5).
*Bold values with an asterisk indicate statistical significance (P < 0.05). A larger sample size and greater statistical power may reveal significance in suture granuloma incidence (†).
N/A, not applicable.
TABLE 4 -
Reasons for Postoperative Emergency Department Visits and Returns to the Operating Room
|
Reason for Encounter |
TXA group |
|
ED visits (n = 4) |
Leakage around drain site |
Fever and breast pain |
Headache |
Breast pain with outside hospital U/S revealing seroma |
Returns to OR (n = 3) |
Hematoma drainage |
Asymmetry revision |
Hematoma drainage |
Non-TXA group |
|
ED visits (n = 8) |
Postoperative N/V and drain questions |
Hematoma |
Wound dehiscence |
Dehydration and syncope |
Initial hematoma with subsequent wound dehiscence formation |
Fever |
Wound dehiscence after MVC |
Wound dehiscence |
Returns to OR (n = 1) |
Debridement and closure of chronic nonhealing wound/suture granuloma |
MVC, motor vehicle collision; N/V, nausea/vomiting; U/S, ultrasound.
The average drain duration was 8 days (range, 4–27 days) in the TXA group and 6 days (range, 0–24 days) in the non-TXA group, and we found drain duration to be statistically significantly higher in the TXA group (P = 0.033). The mean operative time was 162 minutes for patients in the TXA group and 157 minutes for patients in the non-TXA group. Comparison of intraoperative blood loss patterns between the 2 cohorts is shown in Table 5. There were no statistically significant differences in operative time or intraoperative blood loss between the 2 cohorts (P = 0.549 and P = 0.583, respectively). A Cohens d = 0.15 indicating a small effect size was calculated between the groups. Based on the parameters of our study, an effect size of 0.63 is needed to yield significant results based on 80% power.
TABLE 5 -
Outcome Measures
|
TXA |
Non-TXA |
P
|
Blood loss, n |
41 |
40 |
0.583
|
Operative time, min |
162 |
157 |
0.549
|
Drain duration, d |
8.35 |
6.03 |
0.033*
|
ED visit, n |
6 |
6 |
0.963
|
Return to OR, n |
3 |
1 |
0.359
|
Complications, n |
15 |
17 |
0.94
|
Perioperative outcomes were collected and compared between TXA (n = 41) and non-TXA (n = 40) cohorts. Intraoperative blood loss was recorded from the operative report performed by the senior author and operative time was measured from time of initial incision to close. Any ED visits, returns to OR, and complications occurring within the 18-month study period were recorded. Independent samples t tests were used to compare continuous variables between the TXA versus non-TXA group.
*Bold values with an asterisk indicate statistical significance (P < 0.05).
DISCUSSION
Broadly speaking, evidence supports the benefits of perioperative administration of TXA in reducing blood loss, operative time, and complications in surgery.6–8,14,15 Although previous studies have examined the utility of TXA in various surgical procedures, the impact of TXA administration in breast reductions remains unclear. In a systematic review of the current literature on TXA use in plastic surgery conducted by Scarafoni,8 the evidence primarily described TXA use in the setting of craniofacial procedures. While they found several studies noting reduced intraoperative blood loss as well as reduced edema and ecchymosis with the administration of TXA, there was little evidence regarding TXA use in breast reductions. Of the 4 studies identified regarding breast surgery, only one of the included studies, a randomized clinical trial conducted by Ausen et al16 reported on TXA use in breast reduction patients specifically. In this study, patients who received topical TXA were found to have significantly lower drain fluid production in the first 24 hours after surgery with no reported adverse effects (P = 0.038); however, they did not assess intraoperative blood loss.8
The results of our retrospective review of 81 patients who underwent bilateral reduction mammoplasty show that local administration of TXA has no significant effect on operative time and intraoperative blood loss. This could be explained by the relatively minimal blood loss associated with breast reduction surgery, when compared with more significant blood loss seen in other surgeries, such as trauma and obstetric procedures. For instance, previous studies had shown a reduction in blood loss when using TXA during major spine surgery. Therefore, Elmose et al17 conducted a double-blind randomized controlled trial to investigate the impact of TXA in minor lumbar spine surgery. They found no statistically significant impact on operative time, intraoperative blood loss, or complications much like our findings.17 In addition, our preexisting protocol of tumescent solution infiltration in breast reduction surgery may already achieve a significant level of reduction in blood loss and operative time, rendering the potential impact of TXA minimal at best. Although we did not assess the size of postoperative bruising, one prospective case control study looked at the impact of topical TXA in addition to tumescent solution as opposed to tumescent solution alone on patients undergoing flank liposuction and found a statistically significant smaller bruise area with TXA use.18
Interestingly, we found a significantly longer average drain duration of 8 days in patients who had received TXA, compared with 6 days seen in the non-TXA group (P = 0.033). Drain duration is often extended in the setting of larger, persistent drainage volumes. Our finding contradicts the findings of Ausen et al16 and Weissler et al,19 which report significantly decreased postoperative drain volumes in patients who received TXA. Of note, discrepancies between these studies and our findings could exist because differences in study design such as the amount of TXA used and the mode of TXA administration. Our study used local infiltration of TXA as opposed to the topical and intravenous methods described in Ausen et al16 and Weissler et al.19
Although we did not find any significant reduction in intraoperative bleeding or operative time in breast reduction patients receiving TXA, the utility of TXA may lie in its anti-inflammatory profile and potential to minimize complications. We found a lower incidence of T-junction dehiscence and suture granuloma in the group of patients who had received TXA (P = 0.016 and P = 0.05, respectively). This could be explained by TXA's ability to inhibit plasmin formation and subsequently reduce the activation of monocytes and neutrophils20 and inhibit complement activation,21,22 leading to an overall reduction in inflammation and edema. The resulting effect of this is decreased suture line tension, which decreases the risk of dehiscence. Furthermore, no patients developed suture granulomas in the TXA group in comparison to 5 patients in the non- TXA group. Again, this could be explained by TXA-mediated inhibition of the fibrinolytic cascade and its immunomodulatory effects, resulting in reduced infection rates as seen in the cardiac surgery literature.20,21,23,24 However, like a retrospective review of TXA use in breast reduction patients conducted by Weissler et al,19 we found no significant impact on seromas and hematomas with TXA use. In accordance with the literature, we found no significant increase in overall complications from TXA use.
It seems that very few, if any, studies investigating the impact of TXA use in breast reduction surgery have specifically evaluated intraoperative blood loss and operative time outcomes as we did. Rather, preexisting studies focus on complications or drainage production.13,16,19 Of note, there are limitations to our study. First, the study is retrospective and therefore inherently subject to selection bias as well as the potential for errors in data collection. It is also important to note that this study was performed at a single institution with a small sample size, and the patients included underwent breast reductions performed by a single plastic surgeon. Therefore, there is potential bias due to individual surgeon preferences and surgical technique. Further prospective studies using a larger, multicenter patient cohort should be conducted to better understand and generalize the impact of TXA use on intraoperative blood loss and operative time in breast reduction surgery. In addition, future studies may benefit from quantifying the optimal dose of TXA as well as administration method.
CONCLUSION
Overall, we found no significant decrease in intraoperative blood loss or operative time between patients who received local infiltration with TXA and those who did not during bilateral reduction mammoplasty. The application of TXA to these procedures may provide no significant added benefits in blood loss reduction; however, other benefits such as a reduction in inflammation, edema, wound dehiscence, and infection rate could be where the frank utility of TXA lies for this patient population. The rate of complications was not increased and the utility of TXA infiltration in breast reduction mammoplasty should be further explored.
REFERENCES
2. Simpson AM, Donato DP, Kwok AC, et al. Predictors of complications following breast reduction surgery: a National Surgical Quality Improvement Program study of 16,812 cases.
J Plast Reconstr Aesthet Surg. 2019;72:43–51.
3. Uslu AB. Effect of tumescent lidocaine and epinephrine
infiltration on blood loss in inferior pedicle wise-pattern breast reduction: a prospective randomized study.
Aesthetic Plast Surg. 2021;45:442–450.
4. Conroy PH, O'Rourke J. Tumescent anaesthesia.
Surgeon. 2013;11:210–221.
5. Wong J, George RB, Hanley CM, et al. Tranexamic acid: current use in obstetrics, major orthopedic, and trauma surgery.
Can J Anaesth. 2021;68:894–917.
6. Reed M, Woolley T. Uses of tranexamic acid.
Contin Educ Anaesth Crit Care Pain. 2015;15:32–37.
7. Heyns M, Knight P, Steve AK, et al. A single preoperative dose of tranexamic acid reduces perioperative blood loss: a meta-analysis.
Ann Surg. 2021;273:75–81.
8. Scarafoni EE. A systematic review of tranexamic acid in plastic surgery: what's new?
Plast Reconstr Surg Glob Open. 2021;9:e3172.
9. Goldstein M, Feldmann C, Wulf H, et al. Tranexamic acid prophylaxis in hip and knee joint replacement.
Dtsch Arztebl Int. 2017;114:824–830.
10. Shakur H, Roberts I, Bautista R, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo-controlled trial.
Lancet. 2010;376:23–32.
11. Habbab LM, Semelhago L, Lamy A. Topical use of tranexamic acid in cardiac surgery: a meta-analysis.
Thorac Cardiovasc Surg. 2020;68:212–218.
12. Shakur H, Elbourne D, Gülmezoglu M, et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial.
Trials. 2010;11:40.
13. Wokes JET, Erdmann MWH, McLean NR. The role of tranexamic acid in aesthetic plastic surgery: a survey of the British Association of Aesthetic Plastic Surgeons.
Aesthet Surg J. 2021;41:244–249.
14. Hui S, Xu D, Ren Z, et al. Can tranexamic acid conserve blood and save operative time in spinal surgeries? A meta-analysis.
Spine J. 2018;18:1325–1337.
15. Larson E, Evans T, Long J, et al. Does prophylactic administration of TXA reduce mean operative time and postoperative blood loss in posterior approach lumbar spinal fusion surgery performed for degenerative spinal disease?
Clin Spine Surg. 2019;32:E353–E358.
16. Ausen K, Fossmark R, Spigset O, et al. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty.
Br J Surg. 2015;102:1348–1353.
17. Elmose S, Andersen MØ, Andresen EB, et al. Double-blind, randomized controlled trial of tranexamic acid in minor lumbar spine surgery: no effect on operative time, intraoperative blood loss, or complications.
J Neurosurg Spine. 2019;12:1–7.
18. Fayman M, Beeton A, Potgieter E, et al. Efficacy of topical tranexamic acid (Cyclokapron) in “wet” field
infiltration with dilute local anaesthetic solutions in plastic surgery.
Aesthetic Plast Surg. 2021;45:332–339.
19. Weissler JM, Kuruoglu D, Antezana L, et al. Efficacy of tranexamic acid in reducing seroma and hematoma formation following reduction Mammaplasty.
Aesthet Surg J. 2022;42:616–625.
20. Zec T, Di Napoli R, Fievez L, et al. Efficacy and safety of tranexamic acid in cancer surgery. An update of clinical findings and ongoing research.
J Multidiscip Healthc. 2022;15:1427–1444.
21. Barrett CD, Vigneshwar N, Moore HB, et al. Tranexamic acid is associated with reduced complement activation in trauma patients with hemorrhagic shock and hyperfibrinolysis on thromboelastography.
Blood Coagul Fibrinolysis. 2020;31:578–582.
22. Draxler DF, Hanafi G, Zahra S, et al. Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery.
Thromb J. 2022;20:17.
23. Draxler DF, Yep K, Hanafi G, et al. Tranexamic acid modulates the immune response and reduces postsurgical infection rates.
Blood Adv. 2019;3:1598–1609.
24. Myles PS, Smith JA, Forbes A, et al. Tranexamic acid in patients undergoing coronary-artery surgery.
N Engl J Med. 2017;376:136–148.