Accepted Manuscript

Prevention and Management of Postpartum Hemorrhage: A Comparison of Four

National Guidelines

Joshua D. Dahlke, MD, Hector Mendez-Figueroa, MD, Lindsay Maggio, MD, Alisse K.
Hauspurg, MD, Jeffrey Sperling, MD, Suneet P. Chauhan, MD, Dwight J. Rouse, MD

PII: S0002-9378(15)00159-3
DOI: 10.1016/j.ajog.2015.02.023
Reference: YMOB 10282

To appear in: American Journal of Obstetrics and Gynecology

Received Date: 17 November 2014

Revised Date: 31 December 2014
Accepted Date: 19 February 2015

Please cite this article as: Dahlke JD, Mendez-Figueroa H, Maggio L, Hauspurg AK, Sperling J,
Chauhan SP, Rouse DJ, Prevention and Management of Postpartum Hemorrhage: A Comparison
of Four National Guidelines, American Journal of Obstetrics and Gynecology (2015), doi: 10.1016/
j.ajog.2015.02.023.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
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Dahlke et al 1

1 Prevention and Management of Postpartum Hemorrhage: A Comparison of Four

2
3 National Guidelines
4
5 Joshua D. DAHLKE MDa
6
Hector MENDEZ-FIGUEROA MDb

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7
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9 Lindsay MAGGIO MDc
10

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11 Alisse K. HAUSPURG MDc
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Jeffrey Sperling MDc

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13
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15 Suneet P. CHAUHAN MDb
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17 Dwight J. ROUSE MDc
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a
19 Nebraska Methodist Womens Hospital and Perinatal Center, Omaha, NE
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20 Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and
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21 Reproductive Sciences, UT Health- University of Texas Medical School at Houston, TX.

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22 Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, Warren
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23 Alpert Medical School of Brown University, Women & Infants Hospital, Providence, RI.

24
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25 The authors report no conflict of interest. Reprints will not be available.

26 Corresponding Author:
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27 Joshua D. Dahlke MD
28 Nebraska Methodist Perinatal Center
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29 717 N. 190th Plaza, Suite 2400

30 Omaha, Nebraska 68022
31 Telephone: 402-815-1970
32 Fax: 402-815-1595
33 Email: joshuadahlke@gmail.com or joshua.dahlke@nmhs.org
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35 Word Count: Abstract 249, Main Text 2,242
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36 CONDENSATION:

37 Substantial variation exists in four national guidelines on postpartum hemorrhage,

38 highlighting the need for synthesis of evidence regarding a leading cause of maternal

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39 mortality.

40

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41 SHORT TITLE: Postpartum Hemorrhage Guidelines

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42

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43 ABSTRACT

44 Objective: To compare four national guidelines for the prevention and management of

45 postpartum hemorrhage (PPH).

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46 Study Design: We performed a descriptive analysis of guidelines from the American

47 College of Obstetrician and Gynecologists (ACOG) practice bulletin, Royal Australian and

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48 New Zealand College of Obstetricians and Gynaecologists (RANZOG), Royal College of

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49 Obstetrician and Gynaecologists (RCOG), and Society of Obstetricians and

50 Gynaecologists of Canada (SOGC) on PPH to determine differences, if any, with regard to

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51 definitions, risk factors, prevention, treatment, and resuscitation.
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52 Results: PPH was defined differently in all four guidelines. Risk factors emphasized in the

53 guidelines which conferred a high risk of catastrophic bleeding (e.g. previous cesarean
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54 delivery and placenta previa). All organizations except ACOG recommended active
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55 management of the third stage of labor (AMTSL) for primary prevention of PPH in all
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56 vaginal deliveries. Oxytocin was universally recommended as the medication of choice

57 for PPH prevention in vaginal deliveries. RANZOG and RCOG recommended

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58 development of a massive transfusion protocol to manage PPH resuscitation.

59 Recommendations for non-surgical treatment strategies such as uterine packing, and

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60 balloon tamponade varied across all guidelines. All organizations recommended transfer
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61 to a tertiary care facility for suspicion of abnormal placentation. Specific indications for

62 hysterectomy were not available in any guideline, with RCOG recommending

63 hysterectomy sooner rather than later with the assistance of a second consultant.

64 Conclusion:
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65 Substantial variation exists in postpartum hemorrhage prevention and management

66 guidelines among four national organizations, highlighting the need for better evidence

67 and more consistent synthesis of the available evidence with regard to a leading cause

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68 of maternal mortality.

69

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70 KEY WORDS: guidelines, management, postpartum hemorrhage, prevention

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71 INTRODUCTION

72 Postpartum hemorrhage (PPH) is the most common cause of maternal mortality

73 and responsible for one quarter of maternal deaths globally, totaling approximately

140,000 deaths annually.1, 2 While PPH is common, with an incidence of 5 to 15% of

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74

75 births3, 4, life-threatening bleeding, defined by the Royal College of Obstetrician and

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76 Gynaecologists (RCOG) as an estimated blood loss greater than 2.5 liters or receipt of

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77 more than 5 units of blood products or treatment for coagulopathy is estimated to

78 occur in 3.7 per 1000 maternities.5

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79 An important component of patient safety and reducing adverse outcomes
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80 include developing unambiguous guidelines.6 Previous comparisons of national

81 guidelines on topics such as vaginal birth after cesarean7, intrapartum fetal

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82 surveillance8, fetal growth restriction9, and shoulder dystocia10 have highlighted

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83 differences in definitions, etiology, and recommendations. Because PPH is a leading

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84 cause of maternal morbidity and mortality, synthesis of national guidelines could inform

85 schema to optimize peripartum outcomes. The purpose of this descriptive review is to

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86 compare four national guidelines and recommendations for five aspects of PPH:

87 definition, risk factors, prevention, resuscitation, and treatment (non-surgical and

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88 surgical).
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89 MATERIAL AND METHODS

90 The American College of Obstetrician and Gynecologists (ACOG) practice bulletin

91 on postpartum hemorrhage, guidelines from the Royal Australian and New Zealand

92 College of Obstetricians and Gynaecologists (RANZOG), RCOG, and the Society of

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93 Obstetricians and Gynaecologists of Canada (SOGC) were accessed on July 1, 2014 and

94 compared. The following aspects of PPH were summarized: definition, risk factors,

95 prevention, resuscitation, and treatment (non-surgical and surgical). Recommendations

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96 and strength of evidence was reviewed based on each guidelines method of reporting.

97 Finally references were compared with regard to the total number of randomized

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98 control trials, Cochrane reviews, and systematic reviews/metaanalyses cited. IRB

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99 approval was exempted given the descriptive nature of our study and analysis.

100 RESULTS

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101 Definition
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102 All guidelines used different definitions of primary PPH. The ACOG practice

103 bulletin defines PPH as blood loss >500mL for vaginal deliveries and >1000mL for
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104 cesarean delivery. The RANZOG guideline states PPH can be defined as >500mL during
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105 puerperium and classifies severe PPH as blood loss >1000mL. The RCOG guideline
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106 divides PPH into three categories: minor (500mL to 1L), moderate major (>1L to 2L), or

107 severe major (>2L). Finally, the SOGC guideline is the only organization that defines PPH
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108 qualitatively: any amount of bleeding threatening hemodynamic stability. (Table 1)

109 Three guidelines (ACOG, RCOG, and SOGC) comment on the unreliability of
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110 estimated blood loss (EBL), such as using a visible estimate or through the use of blood
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111 collection drapes. None of the guidelines, however, recommended a preferred method

112 to estimate blood loss. Despite the noted unreliability, estimates of blood loss are

113 nonetheless used to initiate levels of treatment in RCOG guidelines. For example, minor

114 PPH (500mL to 1L) should prompt basic measures such as intravenous access, indwelling
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115 bladder catheterization, full blood count and type and screen, while major PPH (EBL >1L)

116 prompts a treatment protocol to achieve full resuscitation.

117 Risk Factors

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118 Risk factors described in the guidelines are summarized in Table 2. All guidelines

119 note that most women who experience PPH do not have any known risk factors, though

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120 none provide an estimate of what proportion of women with PPH are without risk

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121 factors. The RCOG guideline is the only one that provides approximate odds ratios (OR)

122 for various risk factors. Those identified as highest risk include women with suspected or

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123 proven placental abruption (OR 13; 99%CI, 7.6-12.9), known placenta previa (OR 12;
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124 99%CI, 7.2-23), multiple pregnancy (OR 5; 99%CI, 3.0-6.6), and pre-eclampsia/

125 gestational hypertension (OR 4; 99% CI, not specified), with delivery in a consultant-led
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126 maternity unit advised for women with these risk factors.
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127 Women at risk for abnormal placentation and subsequent hemorrhage such as
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128 those with a history of cesarean delivery and placenta previa are specifically discussed in

129 all four guidelines. RANZOG and SOGC guidelines recommend antenatal assessment of
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130 placentation and location in these high risk women in order to prompt transfer to a

131 tertiary care center or unit with rapid access to blood products or an intensive care unit.
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132 In addition, ACOG and RCOG guidelines recommend patient counselling about the
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133 likelihood of hysterectomy and blood transfusion, availability of blood products, cell

134 saver technology, and encourage planned delivery with preoperative anesthesia

135 assessment. None of the guidelines specify the preferred modality for evaluation of

136 abnormal placentation (e.g. ultrasound versus MRI).

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137 Prevention

138 There are no specific recommendations discussed in any of the guidelines with

139 regard to PPH prevention strategies prior to the onset of the third stage of labor. All

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140 guidelines, with the exception of ACOG, discuss active management of the third stage of

141 labor (AMTSL) with strong recommendations for its use in primary prevention of PPH.

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142 AMTSL traditionally involves three interventions designed to assist in placenta

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143 expulsion: uterotonics, immediate umbilical cord clamping, and controlled cord traction

144 (CCT). Despite strong recommendation of this practice, RCOG and SOGC guidelines

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145 separate and stratify these interventions, recommending delayed cord clamping for
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146 neonatal benefit when feasible.

147 Oxytocin is universally recommended as the first line uterotonic of choice for
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148 prevention of uterine atony. ACOG and RANZOG guidelines do not specify dosing or
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149 route of administration. The RCOG guideline recommends 10U IM for uncomplicated
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150 vaginal deliveries and 5IU IV slow infusion after cesarean delivery. Finally, the SOGC

151 guideline recommends different uterotonic medications depending on the clinical

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152 scenario. For example, oxytocin 10U IM or 5 to 10U IV over 1-2 minutes is

153 recommended for low risk vaginal deliveries, while Carbetocin 100mcg IV over 1 minute
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154 is recommended for cesarean delivery or vaginal delivery in women with 1 risk factor for
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155 PPH. Carbetocin, a oxytocin analogue with a significantly longer half-life than

156 endogenous or synthetic oxytocin, is available in the United Kingdom, Ireland, Canada,

157 Australia and New Zealand, but not the United States.11 Misoprostol is recommended as

158 a second line preventive medication or when oxytocin is not available for PPH
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159 prevention by the RANZOG guideline, while SOGC guidelines recommends Ergonovine as

160 a second line agent or when oxytocin is not available. Syntometrine a fixed dose

161 combination of 5IU oxytocin and 0.5mg ergometrine is recommended by the RCOG

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162 guideline as second line prophylactic agents if available, emphasizing the higher side

163 effect profile of this medication.

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164 Resuscitation

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165 All four guidelines discuss resuscitative measures during PPH with emphasis on

166 fluid management and indications for blood products. A multidisciplinary approach with

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167 strong communication with anesthesia is strongly recommended. While the SOGC
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168 guideline suggests institutions develop and make available specific PPH trays, RANZOGs

169 advocates institutional development of a massive transfusion protocol (MTP) in cases of

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170 severe PPH and their guideline is the only one that provides a MTP algorithm template.
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171 Cell saver technology or autologous transfusion is briefly discussed in ACOG and RCOG
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172 guidelines to assist in resuscitative efforts.

173 Treatment
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174 Treatment modalities when PPH is identified can be categorized as non-surgical

175 or surgical. In general, there is large variation among guidelines with regard to PPH
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176 treatment. Notably, all guidelines except RANZOG recommend instituting a policy or
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177 establishing a protocol when postpartum hemorrhage is identified, yet the specifics to

178 the protocol vary or are not established. Regarding unique non-surgical management

179 options, the RCOG guideline discusses pneumatic anti-shock gear as a temporizing
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180 measure if available, though does not specify when in the management schema it

181 should be used.

182 Tranexamic acid, an antifibrinolytic amino acid derivative of lysine is discussed

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183 only in RCOG guidelines. While shown to significantly decrease bleeding in non-obstetric

184 procedures, particularly in trauma, RCOG recommends against its use. Similarly, another

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185 antifibrinolytic medication, recombinant factor VIIa, is mentioned in ACOG, RCOG, and

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186 SOGC guidelines. It is discussed extensively in the ACOG guideline, however indications

187 for its use are not specified. In contrast, recombinant factor VIIa is not recommended in

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188 SOGC and RCOG guidelines as a medical treatment option for PPH.
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189 All guidelines discuss eight surgical techniques: 1) uterine packing, 2) balloon

190 tamponade, 3) uterine curettage, 4) uterine artery ligation, 5) brace suture, 6)

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191 hypogastric artery ligation, 7) arterial embolization and 8) hysterectomy. In general, less
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192 invasive fertility sparing interventions are promoted. The SOGC guideline is the only one
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193 that provides figures of both B-Lynch and Cho compression suture techniques. The

194 ACOG guideline is the only guideline that discusses management of hemorrhage due to
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195 a ruptured uterus or inverted uterus. With regard to hysterectomy, the RCOG guideline

196 emphasizes early recourse to hysterectomy and not delaying this decision until the
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197 women is in extremis and further recommends subtotal hysterectomy unless trauma to
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198 the lower uterine segment or cervix is noted. Additionally, the SOGC guideline notes

199 that indications for hysterectomy include massive hemorrhage not responsive to

200 previous interventions and that the surgical intervention chosen should be familiar to

201 surgeons.
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202 Tables 3 and 4 summarize all recommendations by each respective national

203 guideline with regard to the classification or strength of evidence. Notably, none of the

204 recommendations with either strong or weak strength of evidence are endorsed by

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205 more than two of the national guidelines reviewed.

206 References

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207 The number of references cited in each guideline ranges from 12 (RANZOG) to

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208 110 (RCOG) with publication years between 1901 through 2010. Table 5 summarizes the

209 RCTs referenced with regard to PPH prevention or treatment in the setting of vaginal or

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210 cesarean delivery.12-23 Finally, Table 6 summarizes the number of randomized control
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211 trials (RCT), Cochrane reviews, and systematic reviews referenced in the guidelines.

212 Notably, the ACOG practice bulletin does not cite a single RCT or Cochrane review in its
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213 guideline.
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214 COMMENT
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215 Recent epidemiologic studies note that PPH particularly due to uterine atony, is

216 increasing in the US and abroad and it is the major cause of obstetric morbidity and
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217 mortality in the world.24-26 Recommendations in the four national guidelines reviewed

218 herein suggest significant differences in how this common complication is defined,
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219 anticipated, prevented and treated. Also notable is the types of studies used to make
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220 recommendations, suggesting variation in the methodology of the respective

221 organizations development of practice guidelines.

222 The variation among the guidelines reviewed with regard to how PPH is defined

223 is worth highlighting. Part of this difficulty may be due to the difficulty and inaccuracies
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224 of estimating blood loss. Efforts such as the quantification of blood loss (QBL) proposed

225 by the Association of Womens Health, Obstetric and Neonatal Nurses (AWHONN) may

226 potentially improve the accuracy of blood loss estimation and subsequently improve the

definition of PPH.27 While our review compared four guidelines definition of PPH, it

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227

228 should also be noted that other definitions of PPH have been developed. For example,

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229 the ACOG reVITALize initiative has developed the following definition of early PPH in the

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230 United States: Cumulative blood loss of at least 1000ml or blood loss accompanied by

231 sign/symptoms of hypovolemia within 24 hours following the birth process (includes

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232 intrapartum loss).28 This contrasts with the World Health Organization definition of
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233 blood loss of 500ml or more within 24 hours after birth.2 Finally, a recent international

234 expert panel defined persistent (ongoing) PPH as active bleeding >1000mL within 24
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235 hours following birth that continues despite the use of initial measures including first-
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236 line uteronic agents and uterine massage, highlighting the clinical importance of
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237 identifying bleeding that continues despite preventative strategies.29

238 Women at high risk for abnormal placentation are understandably emphasized
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239 in all of the national guidelines. While most PPH cannot be predicted, this is one clinical

240 scenario in which, at least for some women, the risk is known and can be anticipated.
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241 Appropriate planning of delivery from timing to location, with transfer to a tertiary
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242 hospital as needed, is paramount. Notably, specific PPH prevention strategies are not

243 mentioned in the ACOG guideline despite significant emphasis in RANZOG, RCOG, and

244 SOGC guidelines. All of the guidelines, however, recommend institutional drills and/or

245 protocols to prepare for this inevitable event.

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246 Initiatives such as the National Partnership for Maternal Safety and the California

247 Maternal Quality Care Collaborative (CMQCC) have appropriately identified obstetric

248 hemorrhage as a key priority in improving maternal safety and provide

recommendations, resources and education to assist in this goal.30, 31 For example, the

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250 obstetric hemorrhage core bundle proposed by DAlton et al. recommends the following

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251 for all U.S. birthing facilities: 1) a standardized obstetric hemorrhage protocol and event

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252 checklist, 2) a hemorrhage kit or cart with appropriate medication and equipment, 3)

253 partnership with the local blood bank for rapid and sustained availability of blood

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254 products, and 4) universal use of AMTSL.30 Similarly, the CMQCC offers an obstetric
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255 hemorrhage toolkit consisting of: 1) a compendium of best practices, 2) care guidelines:

256 checklists, flowcharts, and table charts, 3) hospital level implementation guide, and 4)
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257 slide set for professional education.31 While it might seem self-evident that these
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258 initiatives will improve PPH outcomes, they nevertheless should be prospectively
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259 evaluated.

260 Despite the emphasis on patient safety and institutional quality improvement, a
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261 recent survey of academic US obstetric units demonstrated at least 20% did not have a

262 PPH protocol.32 Similarly, outcomes associated with implementation of massive

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263 transfusion protocols for severe postpartum hemorrhage have been shown to be
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264 favorable, yet such protocols are only explicitly recommended by RANZOG.33 Future

265 studies will undoubtedly shed light on optimal resuscitation and should be reflected in

266 updated national guidelines.

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267 AMTSL remains a recommended and highly studied preventive strategy for

268 PPH. Recent studies, however, suggest that the major driver of this preventive strategys

269 effectiveness is the administration of oxytocin. In a recent multicenter randomised

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270 controlled trial in five maternity units in France, Deneux-Tharaux et al. found that CCT

271 made minimal contribution to overall blood loss in high resource settings in those that

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272 received oxytocin.34 In addition, an increasingly large body of evidence suggests delayed

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273 cord clamping may have beneficial neonatal outcomes (improved long term iron stores

274 and hemoglobin concentration) without increasing the risk of maternal hemorrhage.35

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275 These data suggest that of the three interventions classically described in AMTSL
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276 (oxytocin, immediate cord clamping, controlled cord traction), oxytocin and oxytocin

277 alone remains most important intervention for the prevention of PPH.
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278 Research is ongoing to determine the optimal dose, route and timing of
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279 administration of oxytocin, but it remains the first line medication for PPH prevention.36
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280 Randomized trials of newer medications such as Carbetocin or Tranexamic Acid have

281 been conducted37, 38 but additional studies are necessary to determine what role, if any,
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282 these medications should play in PPH prevention or management.

283 As evidenced by the paucity of randomized controlled trials comparing different

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284 medical treatment strategies for PPH or optimal surgical interventions, the order for
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285 which these management options are to be employed remain vastly understudied.

286 While interventions such has balloon tamponade have made their way into

287 management protocols and guidelines, there has yet to be a randomized clinical trial

288 performed comparing it to any other treatment strategy.39

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289 The strengths of our analysis include synthesizing the major guidelines

290 recommendations on all aspects of PPH including definitions, risk factors, resuscitation,

291 medical and surgical management. In addition, we believe a critical evaluation of how

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292 the available evidence from randomized controlled trials, systematic reviews, and meta-

293 analyses is utilized to develop these guidelines may improve future guidelines and

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294 recommendations. We also recognize weaknesses in our descriptive analysis. First, we

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295 limited our review to four English language national guidelines despite other countries

296 and organizations such as the World Health Organization (WHO) producing similar

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297 guidelines for prevention and management of PPH.2 Our goal in doing this was to
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298 compare and contrast recommendations whose guidelines have been previously

299 compared7-10 but also are germane to similarly-resourced setting with similar intended
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300 audiences concerning this important topic. We also acknowledge that the authors or
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301 committees that developed the guidelines we reviewed may be subject to differing
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302 methodologies for establishing recommendations within each national organization.

303 In summary, PPH universally remains a major cause of maternal morbidity and
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304 mortality in both developed and developing countries. As the evidence-base for

305 postpartum hemorrhage and management improves, a convergence of national

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306 guidelines ought to occur to reflect best available practices.

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307 References:

308 1. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin:

309 Clinical Management Guidelines for Obstetrician-Gynecologists Number 76,
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313 2. WHO Recommendations for the Prevention and Treatment of Postpartum
314 Haemorrhage. Geneva: World Health Organization; 2012. WHO Guidelines
315 Approved by the Guidelines Review Committee.

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316 http://www.who.int/reproductivehealth/publications/maternal_perinatal_healt
317 h/9789241548502/en/. Accessed Nov 1, 2013

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319 3. Royal Australian and New Zealand College of Obstetricians and Gynaecologists.
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321 http://www.ranzcog.edu.au/college-statements-guidelines.html. Accessed Nov

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322 1, 2013
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324 4. Leduc D, Senikas V, Lalonde AB, Ballerman C, Biringer A, Delaney M, Duperron L,
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331 5. Royal College of Obstetrician and Gynaecologists. Postpartum Hemorrhage:
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332 Prevention and Management. April 2011. http://www.rcog.org.uk/womens-

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394 19. Dansereau J, Joshi AK, Helewa ME, Doran TA, Lange IR, Luther ER, Farine D,
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399 20. Chou MM, MacKenzie IZ. A prospective, double-blind, randomized comparison of
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404 21. Lokugamage AU, Paine M, Bassaw-Balroop K, Sullivan KR, Refaey HE, Rodeck CH.

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405 Active management of the third stage at caesarean section: a randomised
406 controlled trial of misoprostol versus syntocinon. Aust N Z J Obstet
407 Gynaecol.2001 Nov;41(4):411-4.
408

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409 22. Munn MB, Owen J, Vincent R, Wakefield M, Chestnut DH, Hauth JC. Comparison
410 of two oxytocin regimens to prevent uterine atony at cesarean delivery: a
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411 randomized controlled trial. Obstet Gynecol. 2001 Sep;98(3):386-90.
412
413 23. Blum J, Winikoff B, Raghavan S, Dabash R, Ramadan MC, Dilbaz B, Dao
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414 B,Durocher J, Yalvac S, Diop A, Dzuba IG, Ngoc NT. Treatment of post-partum
415 haemorrhage with sublingual misoprostol versus oxytocin in women receiving
416 prophylactic oxytocin: a double-blind, randomised, non-inferiority trial. Lancet.
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417 2010 Jan 16;375(9710):217-23.

418
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419 24. Kramer MS, Berg C, Abenhaim H, Dahhou M, Rouleau J, Mehrabadi A, Joseph KS.
420 Incidence, risk factors, and temporal trends in severe postpartum hemorrhage.
421 Am J Obstet Gynecol. 2013 Nov;209(5):449.e1-7.
422
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423 25. Mehrabadi A, Liu S, Bartholomew S, Hutcheon JA, Kramer MS, Liston RM, Joseph
424 KS; Maternal Health Study Group of the Canadian Perinatal Surveillance System
425 (Public Health Agency of Canada). Temporal trends in postpartum hemorrhage
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426 and severe postpartum hemorrhage in Canada from 2003 to 2010. J Obstet
427 Gynaecol Can. 2014 Jan;36(1):21-33.
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428
429 26. Lutomski JE, Byrne BM, Devane D, Greene RA. Increasing trends in atonic
430 postpartum haemorrhage in Ireland: an 11-year population-based cohort study.
431 BJOG. 2012 Feb;119(3):306-14.
432
433 27. Association of Womens Health, Obstetric and Neonatal Nurses (AWHONN)
434 Practice Brief Number 1: Quantification of Blood Loss.
435 http://www.pphproject.org/downloads/awhonn_qbl.pdf. Accessed December
436 27, 2014.
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437
438 28. American Congress of Obstetricians and Gynecologists. reVITALize Obstetric Data
439 Definitions. http://www.acog.org/-/media/Departments/Patient-Safety-and-
440 Quality-Improvement/2014reVITALizeObstetricDataDefinitionsV10.pdf. Accessed
441 December 27, 2014
442

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443 29. Abdul-Kadir R, McLintock C, Ducloy AS, El-Refaey H, England A, Federici AB,
444 Grotegut CA, Halimeh S, Herman JH, Hofer S, James AH, Kouides PA, Paidas MJ,
445 Peyvandi F, Winikoff R. Evaluation and management of postpartum hemorrhage:
446 consensus from an international expert panel. Transfusion. 2014 Jul;54(7):1756-

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447 68.
448

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449 30. DAlton ME, Main EK, Menard MK, Levy BS. The NaTonal Partnership for
450 Maternal Safety. Obstet Gynecol. 2014 May;123(5):973-7.
451
452 31. California Maternal Quality Care Collaborative. OB Hemorrhage Toolkit.

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453 https://cmqcc.org/ob_hemorrhage. Accessed December 27, 2014
454
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455 32. Kacmar RM, Mhyre JM, Scavone BM, Fuller AJ, Toledo P. The use of postpartum
456 hemorrhage protocols in United States academic obstetric anesthesia units.
457 Anesthn Analg. 2014 Oct;119(4):906-10
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458
459 33. Gutierrez MC, Goodnough LT, Druzin M, Butwick AJ. Postpartum hemorrhage
460 treated with a massive transfusion protocol at a tertiary obstetric center: a
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461 retrospective study. Int J Obstet Anesth. 2012 Jul;21(3):230-5

462
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463 34. Deneux-Tharaux C, Sentilhes L, Maillard F, Closset E, Vardon D, Lepercq J,

464 Goffinet F. Effect of routine controlled cord traction as part of the active
465 management of the third stage of labour on postpartum haemorrhage:
466 multicentre randomised controlled trial (TRACOR). BMJ. 2013 Mar 28;346:f1541.
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467
468 35. McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical
469 cord clamping of term infants on maternal and neonatal outcomes. Cochrane
C

470 Database Syst Rev. 2013 Jul 11;7:CD004074

471
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472 36. Westhoff G, Cotter AM, Tolosa JE. Prophylactic oxytocin for the third stage of
473 labour to prevent postpartum haemorrhage. Cochrane Database Syst Rev. 2013
474 Oct30;10:CD001808
475
476 37. Su LL, Chong YS, Samuel M. Carbetocin for preventing postpartum haemorrhage.
477 Cochrane Database Syst Rev. 2012 Apr 18;4:CD005457
478
479 38. Novikova N, Hofmeyr GJ. Tranexamic acid for preventing postpartum
480 haemorrhage. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007872
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481
482 39. Wright CE, Chauhan SP, Abuhamad AZ. Bakri balloon in the management of
483 postpartum hemorrhage: a review. Am J Perinatol. 2014 Nov;31(11):957-64
484

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ACOG RANZOG RCOG SOGC

(reaffirmed 2013) (reviewed 2014) (2011) (2009)

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Definition >500mL (vaginal) >500mL during puerperium Minor (500mL-1L) Any amount threatening

>1000mL (cesarean) Severe postpartum Moderate Major (1-2L) hemo-dynamic stability

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hemorrhage >1000mL Severe Major (>2L)

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Incidence 4-6% of pregnancies 5-15% in Australia 3.7/1000 (>5U pRBC) 5% of all deliveries

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Prevention Not discussed AMTSL AMTSL AMTSL

AN
Determine placental Determine placental location Carbetocin 100mcg over 1

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location Oxytocin, 5IU IV (CD) minute IV (cesarean or

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Oxytocin, dose not specified Ergometrine 0.5mg/ Oxytocin vaginal + 1 risk factor)

TE 5IU IM 2nd line

EP
Resuscitation Ample IV access Massive hemorrhage IV access x 2 IV access x 2

Crystalloid, Blood as protocol activation Crystalloid, rapid and warmed Crystalloid solution
C
AC

needed VTE prophylaxis Postpartum hemorrhage

Blood bank notification tray

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Medical Management

Oxytocin- 10-40U IV or 10U IM Dose not specified, IV/IM 5U IV, may repeat or 40U IV 10U IM/ 5U IV or 20-40U

PT
Syntocinon in 500mL at 125mL/hr IV at 500 to 1000mL/hr

Carbetocin 100mcg IV over 1 minute

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Ergots Methyl-ergonovine Ergometrine, dose not Ergometrine 0.5mg IV or IM Ergonovine 0.25mg IM or

SC
0.2mg IM q 2-4hr specified IV q 2 hr

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PGF2a- 0.25mg IM q 15-90 500mcg IM incrementally 0.25mg IM q 15, 8 dose max 0.25mg IM q 15, 8 dose

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Carboprost minutes, 8 dose up to 3mg or 0.5mg intramyometrial maximum

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maximum

D
PGE2- 20mg PV or PR q 2hr

Dinoprostone
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EP
PGE1- 800-1000mcg rectal 1000mcg rectal 1000mcg rectal 400 -1000mcg oral or
C

Misoprostol rectal
AC

Factor VIIa 50-100 mcg/kg q 2hr Base on coagulation results Not recommended

Tranexamic Not recommended Not recommended

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Acid

Surgical Management

PT
Uterine 4 inch gauze, 5000U

Packing thrombin in 5mL saline

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Balloon Foley: 60-80mL saline Type or Technique not 1st line surgical intervention Ensure entire balloon is

SC
Tamponade (1 or more) specified if due to atony: 4-6 hours, positioned past the

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Sengstaken-Blakemore ideally remove during cervical canal, consider

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tube: Technique not daytime, deflate but leave antibiotic prophylaxis, 8

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specified in place to 48 hours

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Bakri: 300-500mL saline

Brace suture B-Lynch, Square B-Lynch

TE B-Lynch, Square B-Lynch, Square
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Vessel Uterine artery, Internal Uterine artery, Internal Uterine artery, Internal Uterine artery, Internal
C

Ligation Iliac artery Iliac artery Iliac artery Iliac artery

AC

Hysterectomy Indication not specified Indication not specified Sooner rather than later Indication not specified

2nd consultant recommended

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Embolization If bleeding stable, Yes, doesnt preclude Yes, consider Yes, if stable, ongoing & no

persistent, non- surgical management surgical options

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excessive

Table 1: Summary of Definitions, Risk Factors, Prevention and Resuscitation recommendations among four national guidelines.

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Risk Factor National Guideline

Pre-existing factors

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History of Postpartum hemorrhage ACOG, SOGC, RCOG

Preeclampsia ACOG, SOGC, RCOG

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Overdistended uterus (macrosomia, twins, hydramnios) ACOG, SOGC, RCOG

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Obesity RCOG

Anemia RCOG

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Asian or Hispanic ethnicity ACOG, RCOG
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Uterine anomalies (fibroids) or previous uterine surgery SOGC

Hereditary coagulopathies SOGC

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High Parity SOGC

D

Fetal demise SOGC

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Placental factors

Placental Abruption RCOG

EP

Placenta previa SOGC, RCOG

Fundal placenta SOGC

C

Retained placenta RCOG

AC

Abnormal Placentation SOGC, RCOG, RANZOG

Intrapartum factors

Prolonged Labor ACOG, SOGC, RCOG

Augmented Labor ACOG, SOGC

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Rapid Labor ACOG, SOGC

Episiotomy ACOG, RCOG

Operative delivery ACOG, SOGC, RCOG

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Infection (chorioamnionitis, pyrexia) ACOG, SOGC, RCOG

Prolonged rupture of membranes SOGC

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Anesthetics, Nitroglycerin SOGC

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Malposition SOGC

Deep engagement SOGC

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Excessive cord traction SOGC
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Amniotic fluid embolism SOGC

Induction of labor (oxytocin use) RCOG, SOGC

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Cesarean Delivery RCOG

D

Table 2 Risk factors associated with postpartum hemorrhage in four national

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guidelines. ACOG: American College of Obstetrician and Gynecologists RANZOG: Royal

Australian and New Zealand College of Obstetricians and Gynaecologists, RCOG: Royal
EP

College of Obstetrician and Gynaecologists, SOGC: Society of Obstetricians and

Gynaecologists of Canada
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Classification or Strength of Recommendation (A or B, or Strong)

Definition Clinical markers preferred over EBL quantification measures (SOGC-B)

Risk Factors None

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Prevention

AMTSL Recommended to all women (SOGC-A and RCOG-A)

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Oxytocin 5-10 IU IM for management of 3rd stage labor without risk factors (RCOG-A,

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SOGC-A)

20-40 IU in 1L, 150mL/hr acceptable alternative to AMTSL (SOGC-B)

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Other 10U IV over 1-2 minutes for VD (SOGC-B)
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Misoprostol, if oxytocin not available (RCOG-A, SOGC-B)

Ergonovine 0.2mg IM second line, more maternal side effects (SOGC-A)

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Carbetocin 100mcg IV over 1 minute for CD (SOGC-B)

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Carbetocin 100mcg IM decreases need for uterine massage in VD (SOGC-B)

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Treatment Internal iliac artery ligation, compression sutures, hysterectomy for intractable

PPH unresponsive to medical therapy (SOGC-B)

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Resuscitation All obstetric units should have emergency PPH equipment tray (SOGC-B)

Other Prophylactic pelvic artery occlusion for accreta is equivocal (RCOG-B)

C

Table 3: Summary of recommendations with Level A or B classification or Strong

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strength of evidence in four national guidelines. ACOG: American College of

Obstetrician and Gynecologists, RANZOG: Royal Australian and New Zealand College of

Obstetricians and Gynaecologists, RCOG: Royal College of Obstetrician and

Gynaecologists, SOGC: Society of Obstetricians and Gynaecologists of Canada, EBL:

 ACCEPTED MANUSCRIPT

estimated blood loss, AMTSL: active management of third stage labor, VD: vaginal

delivery, CD: cesarean delivery, PPH: postpartum hemorrhage

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Classification or Strength of Recommendation (C, L, or weak)

Diagnosis None

Risk Factors High clinical suspicion for conditions associated with placenta accreta (ACOG, C)

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All women with previous CD must rule out placenta accreta/ increta (RCOG, C)

Deliver accreta/increta in facility with ICU, blood, consultants (RCOG, C)

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Accelerating placenta delivery before 30-45 minutes wont reduce PPH (SOGC, C)

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Prevention

Oxytocin 5U IV for CD (RCOG, C)

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Other PPH of 5001000 ml should prompt basic resuscitation (RCOG, C)
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PPH of >1000 ml should prompt full resuscitation protocol (RCOG, C)

Syntometrine (Alliance) may be used in the absence of hypertension (RCOG, C)

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Intraumbilical misoprostol (800 g) or oxytocin (10 to 30 IU) for manual placenta

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removal (SOGC,C)
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Treatment Uterotonic agents should be first-line treatment for PPH due to atony (ACOG, C)

Exploratory laparotomy is next step if uterotonics fail (ACOG, C)

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Mild or Severe PPH protocols should be initiated when identified (RCOG, C)

Four components of PPH management: communication, resuscitation,

C

monitoring, investigation (RCOG, C)

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Recombinant activated factor VII cannot be recommended (SOGC, L)

Balloon tamponade controls PPH from uterine atony not responsive to

medication (SOGC, L)
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Resuscitation None

Other PPH management requires a multidisciplinary approach (ACOG, C and SOGC, C)

Table 4: Summary of recommendations with Level C or L classification or Weak strength of

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evidence in four national guidelines. ACOG: American College of Obstetrician and

Gynecologists, RANZOG: Royal Australian and New Zealand College of Obstetricians and

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Gynaecologists, RCOG: Royal College of Obstetrician and Gynaecologists, SOGC: Society of

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Obstetricians and Gynaecologists of Canada, EBL: estimated blood loss, AMTSL- active

management of third stage labor, VD: vaginal delivery, CD: cesarean delivery

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N Intervention Results

PPH Prevention

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Boucher et al12 160 100mcg Carbetocin IM vs 10U No difference in need PPH indicators, Oxytocin group

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(Canada, 2004) oxytocin infusion required additional uterine massage (P<.02)

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RCOG, SOGC

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Glmezoglu et al13 18,459 600mcg Oral misoprostol vs 10U Oxytocin group lower incidence of EBL >1000mL, need for

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(Switzerland, 2001) oxytocin IV or IM additional oxytocics. Misoprostol with higher shivering

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SOGC and raised body temperature

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Jackson et al14 1486 20U oxytocin IV bolus before or after No difference in need for additional oxytocics, PPH

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(USA, 2001) placenta delivery incidence, 3rd stage duration, incidence of retained
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SOGC placenta

Leung et al15 329 100mcg Carbetocin IM vs 1mL No difference in Hb concentration, need for additional
C
AC

(Hong Kong, 2006) Syntometrine (5U oxytocin + 0.5mg oxytocics, PPH or retained placenta. Carbetocin had lower

RCOG, SOGC ergometrine) nausea, vomiting, hypertension but higher maternal

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tachycardia

Nordstrm et al16 1000 IV oxytocin vs. Saline Oxytocin reduced mean total blood loss, PPH frequency,

PT
(Sweden, 1997) need for additional oxytocics and postpartutum Hb

RI
SOGC <10g/dL

SC
Parsons et al17 450 800mcg Rectal misoprostol vs 10U No difference in Hb, shivering more common in

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(Netherlands, 2007) oxytocin IM misoprostol group

AN
SOGC

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Boucher et al18 114 100mcg Carbetocin vs Oxytocin Carbetocin mean blood loss 41mL less, increased uterine

D
(Canada, 1998) infusion involution, decreased need for additional oxytocics

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RCOG

Dansereau et al19
EP
694 100mcg Carbetocin vs Oxytocin Carbetocin reduced need for additional oxytocic

(Canada, 1999) infusion intervention

C
AC

RCOG, SOGC

Chou et al20 60 0.125mg PG F2 alpha vs. Oxytocin No difference in estimated blood loss, Hb, side effects
 ACCEPTED MANUSCRIPT

(Taiwan, 1994) 20U IV

RCOG

PT
Lokugamage et al21 40 500mcg Oral misoprostol vs 10U No difference in estimated blood loss, need for additional

RI
(UK, 2001) oxytocin oxytocics, need for transfusion, degree of shivering

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RCOG

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Munn et al22 321 10U/500 mL vs 80U/500 mL oxytocin Additional uterotonics required in low dose group, similar

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(USA, 2001) IV infusion over 30 minutes rate of hypotension

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RCOG

D
PPH Treatment

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Blum et al23 809 800mcg misoprostol vs 40U IV No difference in bleeding parameters, shivering and fever
EP
(Multiple, 2010) oxytocin more common in misoprostol arm

RANZOG
C
AC

Table 5: Summary of randomized controlled trials for prevention and management of postpartum hemorrhage (PPH) cited in four

national guidelines
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ACOG RANZOG RCOG SOGC

(2011) (2014) (2011) (2009)

Total number of 40 12 110 55

References

PT
Years published 1901-2006 2000-2010 1986-2009 1969-2009

Randomized Trials cited 0 1 8 7

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Cochrane Reviews cited 0 3 8 10

SC
Systematic Reviews or 1 2 3 3

Meta-analysis cited

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Table 6: Summary of References for prevention and management of postpartum hemorrhage
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by number, year and citation type in four national guidelines.
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