Techniques to reduce blood loss during abdominal or laparoscopic myomectomy

INTRODUCTION — Uterine leiomyomas (myomas or fibroids) are smooth muscle tumors and are the most common type of pelvic tumors in women. Myomectomy is removal of the myomas, while leaving the uterus in place.

Myomatous uteri have an increased number of arterioles and venules and myomectomy may involve significant blood loss [1]. However, studies show that the blood loss is no greater than for hysterectomy, when controlled for uterine size [2]. The average volume of blood loss during abdominal myomectomy (performed via laparotomy, also referred to as open myomectomy) is 200 to 800 mL [2-4] and for laparoscopic myomectomy is 80 to 250 mL [5,6]. Surgical hemorrhage may result in anemia, hypovolemia, and coagulation abnormalities.

Bleeding can be prevented or decreased with mechanical or pharmacologic methods. Allogeneic blood transfusion can be avoided by using methods of autologous blood transfusion (autologous blood donation, intraoperative and postoperative blood salvage, or acute normovolemic [isovolemic] hemodilution).

Techniques to reduce blood loss during abdominal or laparoscopic myomectomy are reviewed here. Preoperative and postoperative care and surgical technique for abdominal or laparoscopic myomectomy are discussed separately. (See "Uterine fibroids (leiomyomas): Open abdominal myomectomy procedure" and "Uterine fibroids (leiomyomas): Laparoscopic myomectomy and other laparoscopic treatments".)

VASCULAR ANATOMY OF THE UTERUS AND LEIOMYOMAS — The ascending blood supply of the uterus is from the uterine arteries, which pass through the cardinal ligament at level of the cervicouterine junction. The descending blood supply is from the ovarian arteries, which pass through the infundibulopelvic ligaments (suspensory ligaments of the ovary) and perfuse the ovaries, fallopian tubes, and uterine cornua (figure 1). The uterine and ovarian vessels anastomose to perfuse the uterus. Arcuate arteries run transversely within the uterine wall and radial arteries penetrate deeply into the myometrium [7].

The presence of leiomyomas in the uterus distorts normal vascular architecture [8]. Thus, the arcuate arteries may run in any axis, rather than transversely. Thus, either vertical or transverse incisions during myomectomy may transect these vessels. (See "Uterine fibroids (leiomyomas): Open abdominal myomectomy procedure", section on 'Uterine incision'.)

It has been the common teaching that there is a vascular pedicle at the base of each myoma and that ligation of this pedicle will achieve hemostasis during myomectomy. However, a study using vascular corrosion casting and electron microscopy revealed that myomas are surrounded completely by a dense, vascular layer supplying the myoma, which is separated from the myometrium by a narrow avascular cleft [9]. The key to reducing blood loss is to stay underneath this pseudocapsule when enucleating a fibroid.

PREOPERATIVE MEASURES — Several preoperative measures can be taken to reduce the likelihood of postoperative anemia.

Correction of anemia — Iron deficiency anemia associated with menorrhagia or dietary deficiency is the most common cause of anemia in the gynecologic patient population. In patients with abnormal uterine bleeding, a common symptom of uterine leiomyomas, laboratory testing for anemia should be part of the diagnostic evaluation. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management".)

Preoperative anemia increases likelihood of blood transfusion and also increases the risk of perioperative morbidity and mortality. A systematic review of 20 observational studies confirmed the association between preoperative anemia and blood transfusion [10]. No meta-analysis was performed to quantify the magnitude of this effect, but in one representative study of 212 patients who underwent colorectal surgery, the rate of transfusion was significantly higher in those with a hemoglobin ≤12.5 g/dL compared with >12 g/dL (49 versus 19 percent) [11]. The effect of preoperative anemia on perioperative morbidity was illustrated in a retrospective study of 1958 patients who underwent noncardiac surgery and declined blood transfusion for religious reasons [12]. A preoperative hemoglobin of ≤10 g/dL was associated with a threefold or higher increase in serious perioperative morbidity (cardiac events, respiratory failure, or serious bacterial infection) or mortality.

Preoperative anemia may be treated with iron supplementation. In surgical patients, intravenous iron alone increased hemoglobin levels by 1 to 2 g in as little as one week, and a review of 14 studies reported a clinically and statistically significant increase in hemoglobin in patients treated with intravenous iron alone [13,14]. Oral option is a good option in nonurgent cases. Strategies to correct anemia preoperatively are discussed in detail separately. (See "Management of hemorrhage in gynecologic surgery", section on 'Correction of anemia'.)

GnRH agonists — Preoperative use of gonadotropin-releasing hormone (GnRH) agonists provides some short-term benefits for patients undergoing myomectomy regarding blood loss and uterine size but may increase the difficulty of surgery [15]. In the long-term, their use appears to increase the risk of persistent/recurrent myomas.

Preoperatively, GnRH agonists can help correct anemia by temporarily inducing amenorrhea [16,17]. However, the clinical impact of these agents is controversial. A meta-analysis of 11 randomized trials compared patients planning abdominal myomectomy who were treated with a GnRH agonist for three to four months with those receiving either placebo or no treatment [15]. Preoperative GnRH agonist therapy resulted in a small, but statistically significant, increase in preoperative hemoglobin (1.0 g/dL higher). A further benefit of treatment with these agents was a reduction in intraoperative blood loss (68 mL less). Ultimately, however, there was no significant decrease in the risk of blood transfusion in patients treated with GnRH (14 percent for both treatment groups, odds ratio [OR] 0.86, 95% CI 0.26-2.85). This analysis was limited by insufficient statistical power to detect this difference.

Another potential benefit of GnRH agonists is reduction in uterine size. This may permit the use of a transverse rather than vertical laparotomy incision or may make a laparoscopic approach possible. (See "Uterine fibroids (leiomyomas): Open abdominal myomectomy procedure", section on 'Role of GnRH agonists' and "Uterine fibroids (leiomyomas): Laparoscopic myomectomy and other laparoscopic treatments", section on 'Indication and alternatives'.)

There are several important disadvantages of preoperative use of GnRH agonists. These agents make enucleation of fibroids more difficult by obscuring the tissue plane between the myoma and the myometrium [18]. Operative difficulty associated with GnRH agonist pretreatment has been measured in only one randomized trial, which found no difference in difficulty between pretreatment with a triptorelin compared with immediate surgery [19]. In our experience, however, operative difficulty is noticeably increased after pretreatment with these medications.

There is concern that pretreatment with GnRH agonists may increase the risk of persistent myomas because small myomas would shrink in size and would not be palpable during myomectomy. The meta-analysis described above reported a higher rate of postmyomectomy myomas in patients treated with GnRH agonists (11 of 17 patients [65 percent]) compared with placebo or no treatment (7 of 25 patients [28 percent]; OR 4.0, 95% CI 1.1-14.7) [15]. The sample sizes and number of events in this analysis were small, and the follow-up period ranged widely from 6 to 38 months. A subsequent randomized trial (n = 108) that compared eight weeks of triptorelin therapy with no treatment had a similar finding (proportion of patients with myomas at six-month follow-up: 8 versus 2 percent) [19].

Most of the data regarding GnRH agonists and myomectomy are for open procedures. The only randomized trial to address this issue in patients undergoing laparoscopic myomectomy found that GnRH agonist treatment compared with no treatment resulted in a significant increase in operative duration (45 minutes longer) and no decrease in blood loss [20]. (See "Uterine fibroids (leiomyomas): Laparoscopic myomectomy and other laparoscopic treatments", section on 'Conversion to laparotomy'.)

GnRH antagonists are another type of agent that suppresses endogenous GnRH. Their effects are similar to those of GnRH agonists, with the exception that results would be seen sooner, since GnRH is immediately suppressed. However, these agents are not widely used for a preoperative indication, since they are more expensive than GnRH agonists and require a daily injection. There are no high-quality data regarding use of GnRH antagonists prior to myomectomy.

Treatment with either GnRH agonists or antagonists is accompanied by menopausal symptoms (eg, hot flashes, mood disturbance) that many patients find difficult to tolerate.

In summary, there is no evidence that use of GnRH agonists prior to myomectomy reduces the risk of blood transfusion and such use may increase operative difficulty and the risk of myoma persistence/recurrence. The primary advantage of use of these agents is the ability to use a more favorable laparotomy incision or, potentially, to use a laparoscopic approach. We suggest not using GnRH agonist pretreatment for patients undergoing open or laparoscopic myomectomy. Use of these agents is a reasonable option in patients for whom treatment would allow a transverse rather than a vertical incision or a laparoscopic rather than open myomectomy and who place a high priority on type of surgical incision and/or duration of recovery.

INTRAOPERATIVE MEASURES — Bleeding can be prevented or decreased with mechanical or pharmacologic methods. Unfortunately, none of these interventions has been proven to reduce the rate of blood transfusion. Allogeneic blood transfusion can be avoided by using methods of autologous blood transfusion.

Pharmacologic interventions — Several pharmacologic agents reduce blood loss during myomectomy, although none has been proven to reduce the risk of blood transfusion. No studies have compared directly between these medications. Surgeons should use the agent with which they are most experienced, barring any individual patient contraindications. The most commonly used agent is vasopressin.

Vasopressin and other vasoconstrictors — Intramyometrial vasopressin injected into the planned uterine incision site for each fibroid reduces blood loss. Vasopressin acts by constricting the smooth muscle in the walls of capillaries, small arterioles, and venules. Randomized trial data show that blood loss during myomectomy with vasopressin is significantly less than with placebo (299 mL less [21]) and less than or comparable to use of a uterine artery tourniquet [22-24].

●Safe use of vasopressin – Vasopressin use during myomectomy has been associated with rare cases of bradycardia, cardiovascular collapse, and death [24-28]. Vasopressin use may be contraindicated in patients with medical comorbidities (eg, cardiovascular, vascular, or renal disease). The use of vasopressin to decrease blood loss during myomectomy has not been approved by the US Food and Drug Administration.

Safe use of vasopressin depends upon the surgeon's knowledge of its pharmacodynamics and use of safe practices. Care should be taken to avoid intravascular injection; before injecting, the surgeon should pull back on the plunger of the syringe to check for blood. However, complications may result even if intravascular injection does not occur. The maximal safe dose of vasopressin is not well established. Cardiovascular complications following intramyometrial injection have been reported in isolated cases with total vasopressin doses ranging from 5 to 11 units [25-27,29,30]. A classic prospective cohort study found no cardiovascular complication in 13 patients undergoing myomectomy who received a maximum of 4 units of intramyometrial vasopressin [31]. An upper limit of a cumulative total vasopressin dose per procedure of 4 to 6 units has been proposed [32]. Use of a dilute solution helps to limit the total dose. In our practice, we dilute 20 units of vasopressin in 100 mL of saline; 4 to 6 units of vasopressin equals 20 to 30 mL of this solution. The half-life of intramuscular vasopressin is 10 to 20 minutes and the duration of action is two to eight hours.

Epinephrine is another vasoconstrictor that is effective in reducing blood loss during myomectomy. One randomized trial found that intramyometrial injection of bupivacaine with epinephrine (50 mL bupivacaine hydrochloride 0.25 percent and 0.5 mL of 1 mg/mL epinephrine) reduced blood loss compared with saline (69 mL less) [29]. There were no differences in blood pressure or heart rate between groups. Intravascular injection of epinephrine may cause acute cardiovascular adverse events, similar to vasopressin. A disadvantage of epinephrine is that clinical experience during myomectomy is limited, since most gynecologic surgeons use vasopressin in this setting.

Uterotonics — Uterotonics have been used during myomectomy. One small randomized trial (n = 25) found that use of vaginal misoprostol (400 mcg, one hour before surgery) compared with placebo significantly reduced blood loss (149 mL less) [33]; further study of use of this agent during myomectomy is needed.

Data from a meta-analysis of two randomized trials including 77 patients showed that intravenous oxytocin does not reduce blood loss compared with physiologic serum (mean difference in blood loss -69 mL, 95% -297 to 157) [21].

Tranexamic acid — In our practice, we administer tranexamic acid (10 mg/kg intravenously [IV] infused over 10 minutes) 20 minutes prior to surgical incision; larger doses have been described [34]. Tranexamic acid is contraindicated in patients with a history of thrombotic events [35].

However, randomized trials evaluating the efficacy of tranexamic acid on blood loss at time of myomectomy have yielded mixed results:

●In a randomized trial including 100 patients undergoing open abdominal myomectomy, patients receiving tranexamic acid (10 mg/kg IV administered 15 minutes prior to incision) compared with placebo had a lower total blood loss (1047 [mean] versus 804 mL), but need for transfusion and postoperative hemoglobin were similar between groups [36]. Neither tourniquets nor other vasoconstrictive agents were used in either group.

●In a randomized trial including 60 patients undergoing myomectomy (93 percent laparoscopic or robotic) for symptomatic fibroids and preoperative imaging demonstrating at least 1 fibroid ≥10 cm, any intramural or broad ligament fibroid ≥6 cm, and/or ≥5 total fibroids, those pretreated with tranexamic acid (15 mg/kg IV administered 20 minutes prior to incision) compared with placebo had similar total blood loss [34]. However, other methods to reduce blood loss during myomectomy (eg, tourniquets, vasoconstrictive agents) were used at the surgeon's discretion, and may have influenced results.

●In a randomized trial including 80 patients undergoing open abdominal myomectomy, patients treated with tranexamic acid (10 mg/kg IV administered 10 to 15 minutes prior to incision) compared with placebo had similar intraoperative blood loss and rates of transfusion [37]; all patients also received an intraoperative tourniquet. However, when the estimated blood loss per 100 grams of fibroid removed was adjusted according to logarithm, patients receiving tranexamic acid compared with placebo had lower blood loss (104 versus 140 mL).

Use of tranexamic acid prior to gynecologic surgery for benign indications is discussed in more detail elsewhere. (See "Management of hemorrhage in gynecologic surgery", section on 'Prophylactic tranexamic acid'.)

Other agents — Sodium-2-mercaptoethanesulphonate (mesna; used for chemical dissection) has been investigated but has not been found to be successful [38].

Tourniquets — Use of tourniquets to occlude the uterine blood supply reduces blood loss during myomectomy. (See 'Vascular anatomy of the uterus and leiomyomas' above.)

The use of a tourniquet depends on the preoperative hemoglobin and the expected blood loss, usually related to the number of fibroids more than the size. A higher number of fibroids leads to more uterine incisions and more blood loss. There are no absolute criteria, but in our practice, we almost always use tourniquets to avoid as much blood loss as possible.

The benefit of use of a uterine artery tourniquet was illustrated in a randomized trial of 28 patients [39]. Use of a uterine artery tourniquet compared with no tourniquet resulted in a decrease in blood loss (an average of 1870 mL less).

Data conflict regarding whether tourniquet use is as effective as use of vasopressin. Blood loss with use of a uterine artery tourniquet compared with intramyometrial vasopressin was lower in one randomized trial (an average of 225 mL less) [23] but was comparable in another trial [22]. There are no data regarding whether the combined use of a vasoconstrictor and tourniquets decreases blood loss more effectively than either measure alone. In our practice, we use vasopressin in addition to a tourniquet.

Procedures to apply a tourniquet vary. One technique is to place a catheter (eg, Robinson catheter, Penrose drain) around the lower uterine segment below the ovaries and fallopian tubes (figure 2); a latex-free tourniquet should be used in latex-allergic patients. Another method is to create bilateral small (ie, 1 cm) incisions in the broad ligament, just about the level of the internal os; the tourniquet is then passed through these incisions with the ends protruding anteriorly. Vascular clamps to the ovarian vessels may also be used (figure 3).

With either technique, care must be taken to avoid lacerating the ovarian vessels, compressing the ureter, and avoid injury to the distal portion of the fallopian tubes. The tourniquet is tightened and secured (with a Kelley clamp or tied) anteriorly. If lower segment fibroids are removed, the tourniquet may loosen and should be tightened again.

Use of number one suture as a uterine artery tourniquet during laparoscopic myomectomy has been reported [39]. In general, however, it is difficult to secure a tourniquet using laparoscopic instruments.

There are no high-quality data regarding the safe duration of tourniquet use to prevent uterine tissue damage. Some studies refer to releasing the tourniquet every 20 minutes, but outcomes for this practice have not been evaluated [23,39]. In addition, although the tourniquet may incorporate the ovarian vessels, studies evaluating anti-müllerian hormone levels before and after tourniquet placement suggest that the ovaries are resistant to hypoxia [40,41].

Autologous blood transfusion — Autologous blood transfusion methods include autologous blood donation (rare), intraoperative or postoperative blood salvage, and acute normovolemic (isovolemic) hemodilution.

While there is no consensus regarding which method is most cost effective or acceptable to patients, perioperative autologous blood donation is rarely used. (See "Surgical blood conservation: Preoperative autologous blood donation", section on 'Reasons for declining use'.)

Intraoperative blood salvage — In our practice, in procedures in which significant blood loss (≥300 mL) is anticipated, we have intraoperative blood salvage available. In a study of 91 patients who underwent open myomectomy for uterine size greater than 16 weeks, the operative blood loss ranged from 50 to 3000 mL [3]. The Cell Saver blood salvage was used for the 70 patients with a blood loss ≥300 mL; 7 patients received a homologous (non-autologous) blood transfusion in addition to blood salvage. The cost of using a cell-saver compared with donation of autologous blood has not been studied for abdominal myomectomy. Tourniquets were not used during this study, and since we implemented the routine use of tourniquets, we have rarely needed to use the cell-saver in our practice.

Normovolemic (isovolemic) hemodilution — There is only one report of normovolemic (isovolemic) hemodilution during myomectomy [42], but we have not used this approach in our practice.

Methods of autologous transfusion and their use in gynecologic surgery are discussed separately. (See "Surgical blood conservation: Preoperative autologous blood donation" and "Surgical blood conservation: Intraoperative blood salvage" and "Surgical blood conservation: Acute normovolemic hemodilution" and "Management of hemorrhage in gynecologic surgery", section on 'Autologous transfusion methods'.)

Other measures — Uterine artery ligation or embolization or internal iliac artery ligation may also be used to avoid hysterectomy when heavy bleeding is anticipated or occurs during myomectomy [43,44]. The uterine vessels will recannulate, so future fertility should theoretically be preserved. However, the impact on fertility and obstetric outcomes following uterine artery embolization as a primary procedure is not well established. For this reason, we reserve these techniques for situations in which other measures have failed and additional hemostasis is needed to avoid hysterectomy. (See "Management of hemorrhage in gynecologic surgery", section on 'Internal iliac artery ligation' and "Uterine fibroids (leiomyomas): Treatment with uterine artery embolization".)

CLINICAL APPROACH — There is no consensus about the optimal combination of preoperative or intraoperative measures to decrease blood loss or prepare for autologous blood transfusion. Few studies have compared among interventions. Also, most interventions have not been proven to reduce the risk of blood transfusion and/or avoid hysterectomy, the most important outcomes to patients.

Our approach is to employ basic methods for all procedures, and then use additional measures when significant blood loss (≥300 mL) is anticipated or occurs. Blood loss during myomectomy is correlated with the size and number of myomas, and also with operative duration, (which depends in large part upon the first two factors) [22]. During the preoperative evaluation of each patient, we assess the characteristics of the myomas and make our best clinical estimate of the risk of excessive blood loss.

In our practice, for all patients undergoing myomectomy, we do the following:

●Correct preoperative anemia.

●Inject vasopressin before each uterine incision.

●Many surgeons apply a uterine artery tourniquet (for open myomectomy only) in all patients. In our practice, we reserve the use of tourniquets for patients with large fibroids.

For patients in whom we anticipate significant blood loss (≥300 mL), we additionally do the following:

●Prepare for the use of blood salvage.

Preoperative banking of autologous blood is also an option, but should be limited to patients in whom this will not result in anemia at the time of surgery.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gynecologic surgery".)

SUMMARY AND RECOMMENDATIONS

●Patients with leiomyomatous uteri have an increased number of uterine arterioles and venules and myomectomy may involve significant blood loss. The average volume of blood loss during abdominal myomectomy is 200 to 800 mL and for laparoscopic myomectomy is 80 to 250 mL. (See 'Introduction' above.)

●We suggest not using a gonadotropin-releasing hormone (GnRH) agonist pretreatment for patients undergoing abdominal or laparoscopic myomectomy (Grade 2B). Use of these agents is a reasonable option in patients for whom treatment would allow a transverse rather than a vertical laparotomy or a laparoscopic rather than abdominal myomectomy and who place a high priority on type of surgical incision and/or duration of recovery. (See 'GnRH agonists' above.)

●To reduce intraoperative blood loss for patients undergoing laparoscopic or abdominal myomectomy:

•We recommend intramyometrial injection of vasopressin before each uterine incision (Grade 1B). (See 'Vasopressin and other vasoconstrictors' above.)

•We suggest placement of a tourniquet to occlude the uterine blood supply (Grade 2B). (See 'Tourniquets' above.)

•In our practice, we use tranexamic acid 20 minutes prior to surgical incision. (See 'Tranexamic acid' above.)

The above measures may be used in combination, although it is uncertain whether combined use further decreases blood loss.

•Other agents that appear to reduce blood loss include epinephrine and misoprostol, but further study of these agents is needed. We recommend not using oxytocin for the purpose of reducing blood loss during myomectomy (Grade 1B). (See 'Pharmacologic interventions' above.)

●In our practice, in procedures in which significant blood loss (≥300 mL) occurs, we use intraoperative blood salvage. (See 'Autologous blood transfusion' above.)