Hypothesis / aims of study
Although vaginal surgery is not generally associated with a high risk of significant bleeding or transfusion, there are many benefits to minimization of more minor blood loss including: shorter operating time, potentially easier post-operative recovery, and improved ease of surgery. Minor bleeding complications are a common indication for reassessment in the emergency room or clinic in the early post-operative period and may be less often with excellent surgical hemostasis(1).
Hemostatic modalities in surgery are categorized as: caustic, physical, and pharmacologic. Limited data are available on the use of pharmacological agents such as thrombin and fibrin products in vaginal reconstructive surgeries and vaginal hysterectomy. Although tranexamic acid has been routinely used in elective gynecological surgeries in North America, its peri-operative use to decrease blood loss in pelvic reconstructive surgeries is not well established. Vasoconstrictive agents are commonly used for reduction of bleeding, hydro-dissection and decreased local anesthetic absorption at the time of vaginal surgery (2). Traditionally there have been hypotheses of impaired wound healing and increased risk of infection with use of vasoconstrictive agents but several studies have failed to demonstrate significant difference in complications.
The aim of this systematic review was to evaluate the effectiveness of pharmacologic agents in reduction of surgical blood loss in pelvic reconstructive surgeries. Our secondary aim was to summarize complications observed using these techniques of blood loss reducing agents.
Study design, materials and methods
A systematic review and metanalysis of randomized control trials (RCTs) was completed. We searched PubMed (1946-2022), Embase and CINAHL, using search terms related to vaginal hysterectomies and reconstructive surgeries combined with perioperative use of hemostatic agents. RCTs comparing hemostatic interventions to placebo or to standard care were analyzed with the primary outcome of estimated blood loss. Secondary outcomes included perioperative complications, length of stay, blood transfusion, and readmission.
A weighted random effects model was used to estimate the overall effect of the vasoconstrictive agents. Stata 15.1 (StataCorp, LLC, Texas, USA) was used for analysis. A funnel plot was used to evaluate potential publication bias. An influence analysis was conducted by removing each study sequentially and evaluating its impact on the stability and strength of the overall results. P < 0.05 was considered as being statistically significant.
Results
A total of 429 studies were screened and nine RCTs met inclusion criteria. All nine trials were considered to have an overall low risk of bias using the Risk of Bias 2 tool. One study assessed the use of tranexamic acid at start of elective abdominal, vaginal, and laparoscopic/robotic hysterectomy. Five studies involved use of peri-operative vasopressin in elective vaginal hysterectomies with/without concurrent anterior and posterior colporrhaphy, urethral suspension sling insertion, and salpingo-oophorectomy. Two studies included use of vasopressin analogues (ornipressin and terlipressin) in elective vaginal hysterectomies and laparoscopic assisted vaginal hysterectomies. One study assessed the use of local anesthetic bupivacaine in the context of elective vaginal hysterectomy or vaginal reconstructive surgeries.
Six studies comparing vasoconstrictive agents to normal saline were combined in a metanalysis using a weighted random effects model. Metanalysis favored use of vasopressin/ornipression over normal saline for reduction of blood loss. There was an estimated 70 mL with an overall 70 mL reduction in estimated blood loss for vasoconstrictive agent use. I2 was 92.4% and there was some heterogeneity noted in terms of surgery types included in addition to dosing of vasoconstrictive agent (Fig. 1). A funnel plot of the six studies showed no evidence of publication bias. Only one RCT evaluated tranexamic acid and found a benefit in prophylactic use of intravenous tranexamic acid preoperatively. Due to the heterogeneity of reported outcomes and interventions, no combined effect estimates were possible for the secondary study outcomes. A narrative summary of secondary outcomes was completed. Of note, five RCTs evaluated hemodynamic parameter changes after vasoconstrictive agent use and four of five noted transient changes.
Interpretation of results
When assessing the primary outcome of our study, meta-analyses showed 6 of 9 studies favoured the used of hemostatic/vasoconstrictive pharmacologic agents which significantly decreased estimated operative blood loss with no evidence of publication bias. There were no studies evaluating systemic vasodilator use or hemodilution at the time of vaginal surgery, although these techniques are described in elective surgeries at high risk for blood loss. Furthermore, there were no studies identified evaluating routine or prophylactic use of topical agents such as gelatin matrix, Oxidized regenerated cellulose, topical thrombin, fibrin sealants, topical tranexamic acid, or microfibrillar collagen.
Although 70 mL is a small volume, when considering the clinical relevance of vasoactive medications in vaginal surgeries, it is important to consider that a high proportion of patients present with preoperative anemia and as such, even small reductions in intraoperative blood loss may be beneficial in recovery. In addition to intraoperative blood loss, hemostatic agents may provide some benefit in terms of decreased hospital stay and operative time (3) but these outcomes were not evaluated in most studies. Additional research regarding these secondary outcomes may further justify vasoactive agent use at vaginal surgery. Both hospital length of stay and operative time are associated with additional complications such as thromboembolism, deconditioning, and increased need for physio/occupational therapy, especially in an elderly patient population. Notably, no trials evaluated surgeon satisfaction or patient satisfaction during the postoperative course with these agents.
The use of tranexamic acid in elective vaginal surgery was studied in only one RCT which found a benefit in decreased blood loss and decreased reoperation due to bleeding within 30 days. TXA has been proven to be an effective and safe hemostatic agent many other procedures, however its use in elective pelvic reconstructive surgeries is highly variable and centre specific. Further studies evaluating secondary outcome benefits could help to determine its use at vaginal surgery.