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Meta-Analysis
. 2014 Aug 15;2014(8):CD005355.
doi: 10.1002/14651858.CD005355.pub5.

Interventions to reduce haemorrhage during myomectomy for fibroids

Eugene J Kongnyuy  1 , Charles Shey Wiysonge
Affiliations
Meta-Analysis

Interventions to reduce haemorrhage during myomectomy for fibroids

Eugene J Kongnyuy et al. Cochrane Database Syst Rev. .

Abstract

Background: Benign smooth muscle tumours of the uterus, known as fibroids or myomas, are often symptomless. However, about one-third of women with fibroids will present with symptoms that are severe enough to warrant treatment. The standard treatment of symptomatic fibroids is hysterectomy (that is surgical removal of the uterus) for women who have completed childbearing, and myomectomy for women who desire future childbearing or simply want to preserve their uterus. Myomectomy, the surgical removal of myomas, can be associated with life-threatening bleeding. Excessive bleeding can necessitate emergency blood transfusion. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. This is an update of the review published in The Cochrane Library (2011, Issue 11).

Objectives: To assess the effectiveness, safety, tolerability and costs of interventions to reduce blood loss during myomectomy.

Search methods: In June 2014, we conducted electronic searches in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO, and trial registers for ongoing and registered trials.

Selection criteria: We selected randomised controlled trials (RCTs) that compared potential interventions to reduce blood loss during myomectomy to placebo or no treatment.

Data collection and analysis: The two authors independently selected RCTs for inclusion, assessed the risk of bias and extracted data from the included RCTs. The primary review outcomes were blood loss and need for blood transfusion. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). We assessed the quality of evidence using GRADE methods.

Main results: Eighteen RCTs with 1250 participants met our inclusion criteria. The studies were conducted in hospital settings in low, middle and high income countries.Blood lossWe found significant reductions in blood loss with the following interventions: vaginal misoprostol (2 RCTs, 89 women: MD -97.88 ml, 95% CI -125.52 to -70.24; I(2) = 43%; moderate-quality evidence); intramyometrial vasopressin (3 RCTs, 128 women: MD -245.87 ml, 95% CI -434.58 to -57.16; I(2) = 98%; moderate-quality evidence); intramyometrial bupivacaine plus epinephrine (1 RCT, 60 women: MD -68.60 ml, 95% CI -93.69 to -43.51; low-quality evidence); intravenous tranexamic acid (1 RCT, 100 women: MD -243 ml, 95% CI -460.02 to -25.98; low-quality evidence); gelatin-thrombin matrix (1 RCT, 50 women: MD -545.00 ml, 95% CI -593.26 to -496.74; low-quality evidence); intravenous ascorbic acid (1 RCT, 102 women: MD -411.46 ml, 95% CI -502.58 to -320.34; low-quality evidence); vaginal dinoprostone (1 RCT, 108 women: MD -131.60 ml, 95% CI -253.42 to -9.78; low-quality evidence); loop ligation of the myoma pseudocapsule (1 RCT, 70 women: MD -305.01 ml, 95% CI -354.83 to -255.19; low-quality evidence); and a fibrin sealant patch (1 RCT, 70 women: MD -26.50 ml, 95% CI -44.47 to -8.53; low-quality evidence). We found evidence of significant reductions in blood loss with a polyglactin suture (1 RCT, 28 women: MD -1870.0 ml, 95% CI -2547.16 to 1192.84) or a Foley catheter (1 RCT, 93 women: MD -240.70 ml, 95% CI -359.61 to -121.79) tied around the cervix. However, pooling data from these peri-cervical tourniquet RCTs revealed significant heterogeneity of the effects (2 RCTs, 121 women: MD (random) -1019.85 ml, 95% CI -2615.02 to 575.32; I(2) = 95%; low-quality evidence). There was no good evidence of an effect on blood loss with oxytocin, morcellation or clipping of the uterine artery.Need for blood transfusion We found significant reductions in the need for blood transfusion with vasopressin (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to 0.74; I(2) = 0%; moderate-quality evidence); peri-cervical tourniquet (2 RCTs, 121 women: OR 0.09, 95% CI 0.01 to 0.84; I(2) = 69%; low-quality evidence); gelatin-thrombin matrix (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low-quality evidence) and dinoprostone (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to 0.81; low-quality evidence), but no evidence of effect on the need for blood transfusion with misoprostol, oxytocin, tranexamic acid, ascorbic acid, loop ligation of the myoma pseudocapsule and a fibrin sealant patch.There were insufficient data on the adverse effects and costs of the different interventions.

Authors' conclusions: At present there is moderate-quality evidence that misoprostol may reduce bleeding during myomectomy, and low-quality evidence that bupivacaine plus epinephrine, tranexamic acid, gelatin-thrombin matrix, a peri-cervical tourniquet, ascorbic acid, dinoprostone, loop ligation and a fibrin sealant patch may reduce bleeding during myomectomy. There is no evidence that oxytocin, morcellation and temporary clipping of the uterine artery reduce blood loss. Further well designed studies are required to establish the effectiveness, safety and costs of different interventions for reducing blood loss during myomectomy.

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Conflict of interest statement

None known

Figures

1
1
Flow diagram showing screening of search outputs and study selection.
2
2
3
3
1.1
1.1. Analysis
Comparison 1 Misoprostol versus placebo, Outcome 1 Blood loss (ml).
1.2
1.2. Analysis
Comparison 1 Misoprostol versus placebo, Outcome 2 Need for blood transfusion.
1.3
1.3. Analysis
Comparison 1 Misoprostol versus placebo, Outcome 3 Duration of surgery (min).
1.4
1.4. Analysis
Comparison 1 Misoprostol versus placebo, Outcome 4 Postoperative haemoglobin (g/dl).
1.5
1.5. Analysis
Comparison 1 Misoprostol versus placebo, Outcome 5 Duration of hospital stay (days).
1.6
1.6. Analysis
Comparison 1 Misoprostol versus placebo, Outcome 6 Postoperative haemoglobin drop (g/dl).
1.7
1.7. Analysis
Comparison 1 Misoprostol versus placebo, Outcome 7 Postoperative complications.
2.1
2.1. Analysis
Comparison 2 Vasopressin versus placebo, Outcome 1 Blood loss (ml).
2.2
2.2. Analysis
Comparison 2 Vasopressin versus placebo, Outcome 2 Need for blood transfusion.
2.3
2.3. Analysis
Comparison 2 Vasopressin versus placebo, Outcome 3 Duration of surgery (min).
2.4
2.4. Analysis
Comparison 2 Vasopressin versus placebo, Outcome 4 Duration of hospital stay (days).
2.5
2.5. Analysis
Comparison 2 Vasopressin versus placebo, Outcome 5 Postoperative complications.
2.6
2.6. Analysis
Comparison 2 Vasopressin versus placebo, Outcome 6 Pregnancy after myomectomy.
2.7
2.7. Analysis
Comparison 2 Vasopressin versus placebo, Outcome 7 Conversion of laparoscopy to laparotomy.
3.1
3.1. Analysis
Comparison 3 Bupivicaine plus epinephrine versus placebo, Outcome 1 Blood loss (ml).
3.2
3.2. Analysis
Comparison 3 Bupivicaine plus epinephrine versus placebo, Outcome 2 Duration of surgery (min).
4.1
4.1. Analysis
Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 1 Blood loss (ml).
4.2
4.2. Analysis
Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 2 Need for blood transfusion.
4.3
4.3. Analysis
Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 3 Duration of surgery (min).
4.4
4.4. Analysis
Comparison 4 Peri‐cervical tourniquet versus no treatment, Outcome 4 Postoperative complications.
5.1
5.1. Analysis
Comparison 5 Oxytocin versus placebo, Outcome 1 Blood loss (ml).
5.2
5.2. Analysis
Comparison 5 Oxytocin versus placebo, Outcome 2 Need for blood transfusion.
5.3
5.3. Analysis
Comparison 5 Oxytocin versus placebo, Outcome 3 Duration of surgery (min).
5.4
5.4. Analysis
Comparison 5 Oxytocin versus placebo, Outcome 4 Postoperative complications.
5.5
5.5. Analysis
Comparison 5 Oxytocin versus placebo, Outcome 5 Duration of hospital stay (days).
6.1
6.1. Analysis
Comparison 6 Chemical dissection with mesna versus placebo, Outcome 1 Duration of surgery (min).
6.2
6.2. Analysis
Comparison 6 Chemical dissection with mesna versus placebo, Outcome 2 Duration of hospital stay (days).
6.3
6.3. Analysis
Comparison 6 Chemical dissection with mesna versus placebo, Outcome 3 Postoperative haemoglobin (g/dl).
6.4
6.4. Analysis
Comparison 6 Chemical dissection with mesna versus placebo, Outcome 4 Postoperative haematocrit.
6.5
6.5. Analysis
Comparison 6 Chemical dissection with mesna versus placebo, Outcome 5 Postoperative complications.
7.1
7.1. Analysis
Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 1 Blood loss (ml).
7.2
7.2. Analysis
Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 2 Duration of surgery (min).
7.3
7.3. Analysis
Comparison 7 Myoma morcellation versus standard technique of enucleation (no treatment), Outcome 3 Duration of hospital stay (days).
8.1
8.1. Analysis
Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 1 Blood loss (ml).
8.2
8.2. Analysis
Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 2 Need for blood transfusion.
8.3
8.3. Analysis
Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 3 Duration of surgery (min).
8.4
8.4. Analysis
Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 4 Postoperative haemoglobin (g/dl).
8.5
8.5. Analysis
Comparison 8 Intravenous injection of tranexamic acid versus placebo, Outcome 5 Postoperative haematocrit.
9.1
9.1. Analysis
Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 1 Blood loss (ml).
9.2
9.2. Analysis
Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 2 Need for blood transfusion.
9.3
9.3. Analysis
Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 3 Postoperative vaginal blood loss (ml).
9.4
9.4. Analysis
Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 4 Duration of surgery (min).
9.5
9.5. Analysis
Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 5 Postoperative haemoglobin drop (g/dl).
9.6
9.6. Analysis
Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 6 Duration of hospital stay (days).
9.7
9.7. Analysis
Comparison 9 Gelatin‐thrombin matrix versus placebo or no treatment, Outcome 7 Postoperative fever.
10.1
10.1. Analysis
Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 1 Blood loss (ml).
10.2
10.2. Analysis
Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 2 Need for blood transfusion.
10.3
10.3. Analysis
Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 3 Duration of surgery (min).
10.4
10.4. Analysis
Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 4 Duration of hospital stay (days).
10.5
10.5. Analysis
Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 5 Posoperative haemoglobin drop (g/dl).
10.6
10.6. Analysis
Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 6 Pospoerative hematocrit drop (%).
10.7
10.7. Analysis
Comparison 10 Ascorbic acid versus placebo or no treatment, Outcome 7 Posoperative complications.
11.1
11.1. Analysis
Comparison 11 Dinoprostone versus placebo, Outcome 1 Blood loss (ml).
11.2
11.2. Analysis
Comparison 11 Dinoprostone versus placebo, Outcome 2 Need for blood transfusion.
11.3
11.3. Analysis
Comparison 11 Dinoprostone versus placebo, Outcome 3 Duration of surgery (min).
11.4
11.4. Analysis
Comparison 11 Dinoprostone versus placebo, Outcome 4 Duration of hospital stay (days).
11.5
11.5. Analysis
Comparison 11 Dinoprostone versus placebo, Outcome 5 Postoperative haemoglobin (g/dl).
11.6
11.6. Analysis
Comparison 11 Dinoprostone versus placebo, Outcome 6 Postoperative haemoglobin drop (g/dl).
11.7
11.7. Analysis
Comparison 11 Dinoprostone versus placebo, Outcome 7 Postoperative complications.
12.1
12.1. Analysis
Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 1 Blood loss (ml).
12.2
12.2. Analysis
Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 2 Need for blood transfusion.
12.3
12.3. Analysis
Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 3 Duration of surgery (min).
12.4
12.4. Analysis
Comparison 12 Loop ligation of myoma pseudocapsule plus vasopressin versus no treatment, Outcome 4 Duration of hospital stay (days).
13.1
13.1. Analysis
Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 1 Need for blood transfusion.
13.2
13.2. Analysis
Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 2 Duration of surgery (min).
13.3
13.3. Analysis
Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 3 Postoperative haemoglobin drop (g/dl).
13.4
13.4. Analysis
Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 4 Duration of hospital stay (days).
13.5
13.5. Analysis
Comparison 13 Temporary clipping of uterine artery versus no treatment, Outcome 5 Postoperative complications.
14.1
14.1. Analysis
Comparison 14 Fibrin sealant patch versus no treatment, Outcome 1 Blood loss (ml).
14.2
14.2. Analysis
Comparison 14 Fibrin sealant patch versus no treatment, Outcome 2 Postoperative blood loss in drainage bag.
14.3
14.3. Analysis
Comparison 14 Fibrin sealant patch versus no treatment, Outcome 3 Need for blood transfusion.
14.4
14.4. Analysis
Comparison 14 Fibrin sealant patch versus no treatment, Outcome 4 Duration of surgery (min).
14.5
14.5. Analysis
Comparison 14 Fibrin sealant patch versus no treatment, Outcome 5 Duration of hospital stay (days).
14.6
14.6. Analysis
Comparison 14 Fibrin sealant patch versus no treatment, Outcome 6 Conception after surgery.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Agostini 2005 {published data only}
    1. Agostini A, Ronda I, Franchi F, Bretelle F, Roger V, Cravello L, et al. Oxytocin during myomectomy: a randomized study. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2005;118:235‐8. - PubMed
Assaf 1999 {published data only}
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Benassi 2000 {published data only}
    1. Benassi L, Lopopolo G, Pazzoni F, Ricci L, Kaihura C, Piazza F, et al. Chemically assisted dissection of tissues: an interesting support in abdominal myomectomy. Journal of the American College of Surgeons 2000;191:65‐9. - PubMed
Caglar 2008 {published data only}
    1. Caglar GS, Tasci Y, Kayikcioglu F, Haberal A. Intravenous tranexamic acid use in myomectomy: a prospective randomized double‐blind placebo controlled study. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2008;137(2):227‐31. - PubMed
Celik 2003 {published data only}
    1. Celik H, Sapmaz E. Use of a single preoperative dose of misoprostol is efficacious for patients who undergo abdominal myomectomy. Fertility and Sterility 2003;79:1207‐10. - PubMed
Frederick 1994 {published data only}
    1. Frederick J, Fletcher H, Simeon D, Mullings A, Hardie M. Intramyometrial vasopressin as a haemostatic agent during myomectomy. British Journal of Obstetrics and Gynaecology 1994;101:435‐7. - PubMed
Ikechebelu 2010 {published data only}
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Kalogiannidis 2011 {published data only}
    1. Kalogiannidis I, Xiromeritis P, Prapas N, Prapas Y. Intravaginal misoprostol reduces intraoperative blood loss in minimally invasive myomectomy: a randomized clinical trial. Clinical and Experimental Obstetrics and Gynecology 2011;38(1):46‐9. - PubMed
Leone Maggiore 2011 {published data only}
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Pourmatroud 2012 {published data only}
    1. Pourmatroud E, Hormozi L, Masoud H, Golshahi R. Intravenous ascobi acid (vitamin C) administration in myomectomy: a prospective, randomized, clinical trial. Archives of Gynecology and Obstetrics 2012;285:111‐5. - PubMed
Raga 2009 {published data only}
    1. Raga F, Sanz‐Cortes M, Bonilla F, Casan EM, Bonilla‐Musoles F. Reducing blood loss at myomectomy with use of a gelatin‐thrombin matrix hemostatic sealant. Fertility and Sterility 2009;92(1):356‐60. - PubMed
Shokeir 2013 {published data only}
    1. Shokeir T, Shalaby H, Nabil H, Barakat R. Reducing blood loss at abdominal myomectomy with preoperative use of dinoprostone intravaginal suppository: a randomized placebo‐controlled pilot study. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2013;166:61‐4. - PubMed
Sinha 2005 {published data only}
    1. Sinha R, Hedge A, Warty N, Mahajan C. Laparoscopic myomectomy: Enucleation of the myoma by morcellation while attached to the uterus. Journal of Minimally Invasive Gynecology 2005;12:284‐9. - PubMed
Taylor 2005 {published data only}
    1. Taylor A, Sharma M, Tsirkas P, Spiezio Sardo A, Setchell M, Magos A. Reducing blood loss at open myomectomy using triple tourniquets: a randomized controlled trial. International Journal of Obstetrics and Gynecology 2005;112:340‐5. - PubMed
Vercellino 2012 {published data only}
    1. Vercellino G, Erdemoglu E, Joe A, Hopfenmueller W, Holthaus B, Kohler C, Schneider A, Hasenbein K, Chiantera V. Laparoscopic temporary clipping of uterine artery during laparoscopic myomectomy. Arch Gynecol Obstet 2012;286(5):1181‐1186. - PubMed
Wang 2007 {published data only}
    1. Wang CJ, Lee CL, Yuen LT, Kay N, Han CM, Soong YK. Oxytocin infusion in laparoscopic myomectomy may decrease operative blood loss. Journal of Minimally Invasive Gynecology 2007;14(2):184‐8. - PubMed
Zhao 2011 {published data only}
    1. Zhao F, Jiao Y, Guo Z, Hou R, Wang M. Evaluation of loop ligation of larger myoma pseudocapsule combined with vasopressin on laparoscopic myomectomy. Fertility and Sterility 2011;95(2):762‐6. - PubMed
Zullo 2004 {published data only}
    1. Zullo F, Palomba S, Corea D, Pellicano M, Russo T, Falbo A, et al. Bupivacaine plus epinephrine for laparoscopic myomectomy: a randomized placebo‐controlled trial. Obstetrics and Gynecology 2004;104:243‐9. - PubMed

References to studies excluded from this review

Alborzi 2009 {published data only (unpublished sought but not used)}
    1. Alborzi S, Ghannadan E, Alborzi S, Alborzi M. A comparison of combined laparoscopic uterine artery ligation and myomectomy versus laparoscopic myomectomy in treatment of symptomatic myoma. Fertility and Sterility 2009;92(2):742‐7. - PubMed
Alessandri 2006 {published data only}
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Alessandri 2010 {published data only}
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Al‐Shabibi 2010 {published data only}
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Chang 2009 {published data only}
    1. Chang WC, Huang SC, Sheu BC, Shih JC, Hsu WC, Chen SY, Chang DY. Changes in uterine blood flow following laparoscopic myomectomy with or without uterine artery ligation on two‐ and three‐dimensional power Doppler ultrasound. Ultrasound in Obstetrics and Gynaecology 2009;33(2):221‐7. - PubMed
Chang 2011 {published data only}
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Chang 2012 {published data only}
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Fletcher 1996 {published data only}
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Frederick 2013 {published data only}
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Ginsburg 1993 {published data only}
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Kathiresan 2011 {published data only}
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Kimura 2002 {published data only}
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Lee 2009 {published data only}
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Lin 2008 {published data only}
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Liu 2004 {published data only}
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Morita 2004 {published data only}
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Mousa 2012 {published data only}
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Narin 2007 {published data only}
    1. Narin MA, Caliskan E, Kayikcioglu F, Haberal A, Meydanli MM. Blood loss and power Doppler ultrasound characteristics of uterine artery blood flow after 2 levels of bilateral internal iliac artery ligation before extensive myomectomies. The Journal of Reproductive Medicine 2007;52(8):696‐702. - PubMed
Ngeh 2004 {published data only}
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Rossetti 1999 {published data only}
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Sapmaz 2003B {published data only}
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Sapmaz 2003C {published data only}
    1. Sapmaz E, Celik H. Comparison of the effects of the ligation of ascending branches of bilateral arteria uteria with tourniquet method on the intra‐operative and post‐operative hemorrhage in abdominal myomectomy cases. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2003;111:74‐7. - PubMed
Wang 2011 {published data only}
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References to ongoing studies

Atashkhoei 2012 {unpublished data only}
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Behdad 2013 {unpublished data only}
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