It is important to identify exactly what postpartum haemorrhage (PPH) is and outline its prevalence within health care. Mousa and Alfirevic (2007) explain that the term PPH refers to blood loss greater than 500 mls following vaginal or Caesarean delivery. The RCOG (2009) further categorises PPH into minor (500–1000 mls); major (1000–2000 mls); and severe (>2000 mls) based on the volume of blood lost. They continue to explain that PPH, which occurs within 24 hours of delivery, is known as primary PPH—whereas blood loss that occurs more than 24 hours post delivery is known as secondary PPH. Aiken et al. (2011) detail that 95% of all secondary PPH occurs within the first month of delivery. This can be further subdivided into 19% within 7 days; 41% at 8–14 days; 23% at 15–21 days; and 12% at 22–28 days. In a cohort study based in the UK and comprised of 34 334 women, Fullerton et al. (2013) found that 10% of all women were diagnosed with PPH following their first birth.
Warren and Arulkumaran (2009) provide a list of causes of PPH (Table 1). Bick et al. (2009) explain that the risk for PPH is increased for those undergoing elective Caesarean sections; however, they suggest that the pathophysiology of the condition is the same whether delivery is vaginal or Caesarean.
| Cause of PPH (Primary or secondary) | Mechanism |
|---|---|
| Tone | Uterine atony |
| Tissue | Retained placenta or products of conception |
| Trauma | Genital tract injury including broad ligament haematoma |
| Thrombin/coagulation failure | Placental abruption |
Khan et al. (2006) explain that PPH is the dominant cause of deaths related to maternity. Through a systematic analysis of data from 115 countries, Say et al. (2014) found that maternal deaths of obstetric origin accounted for 73% of the participants included. The largest subgroup contributing to this was ‘deaths caused by haemorrhage’, accounting for 21.7% of all participants included. It is important to recognise that differences in health-care capabilities, protocols, cultures, and funding, as well as numerous other factors, all influence the health care provided to women suffering with PPH. Consequently, this statistic may not accurately reflect the prevalence of maternal morbidity caused by PPH in the UK.
According to Lewis (2004; 2007), an increase in maternal deaths caused by obstetric haemorrhage within the UK was observed during the years of 2000–2002, when 9 women died, and 2003–2005, when 14 women died. Paterson-Brown and Bamber (2014) later found, on behalf of MBBRACE, that between the years of 2009 and 2012, 17 women died as a result of obstetric haemorrhage; for 14 of these women, PPH was the causative factor. More recently, Knight et al. (2016) found on behalf of MBBRACE, that during 2012–2014, 13 maternal deaths were caused by obstetric haemorrhage. These incidences display an initial rise in the occurrence of maternal deaths caused by obstetric haemorrhage in the UK; however, more recently, a more static prevalence has been observed.
Out-of-hospital PPH management
The RCOG (2009) recognises that PPH is the leading cause of obstetric haemorrhage and suggested that the incidence of PPH is rising in the UK. Sentilhes et al. (2015a) outlines that PPH, of either severe or minor pathology, is diagnosed in 27% of births within developed countries such as the UK.
McCreesh (2012) argues that the presence of certain factors, coupled with the increasing rate of PPH incidence, is likely to result in a higher occurrence of paramedics managing out-of-hospital births where PPH develops. Rubenstein et al. (2014) explain that a ‘patient centred’ approach to care has been adopted by health-care services worldwide, in order to enable the service user to make decisions regarding their own health care, based upon their personal preferences. As a response to this, a list known as the ‘four choice guarantees’ was released by the Department of Health (DH) (2007) in order to provide mothers with the choice regarding where they would like to deliver. One of the available choices is to deliver at home supported by a midwife. Wilbur et al. (2015) suggest that this option should only be made available to those whose births are not expected to be complicated following relevant maternal assessments. However, Dudenhausen et al. (2012) suggest that PPH can occur as a result of circumstances that may not be discovered during maternal assessments. Consequently, these mothers may choose to deliver within their homes, only to then experience PPH. The option for women to deliver at home is likely to increase the UK paramedic out-of-hospital management of PPH. According to the Office for National Statistics (2014), home births accounted for 2.3% of all births in England and Wales during the years of 2012–2013, and equated to 15 552 births at home in 2013.
The Birthplace in England Collaborative Group (2011) carried out a study of 97% of home birth services provided by NHS trusts between 2008 and 2010. This study found that 45% of primiparous women at low risk of birth complications who had arranged to deliver within a non-obstetric unit, were then transferred to an obstetric unit during labour, or immediately after delivery because of birth complications. Ten per cent of multiparous women were transferred to obstetric units during labour. It is important to recognise that this statistic does not explicitly focus upon PPH during home delivery. However, it does emphasise the occurrence of obstetric complications such as PPH, following and during births that were considered to be of low risk. Numerous other complications such as concern for the health of the foetus and increased levels of pain, may have also contributed to the decision to transport the mother to an obstetric unit.
Furthermore, fertility rates within the UK have steadily risen from 2001 (Office for National Statistics 2014). Recently, the Office for National Statistics (2015) detailed that the total fertility rate of children per women is 1.83. An increased rate of fertility may result in a greater demand for paramedics to manage obstetric complications within the out-of-hospital setting.
Tranexamic acid
One increasingly recognised method of managing PPH involves the use of tranexamic acid (TXA). WHO (2012) recommends the use of TXA for PPH caused by mechanisms that fall into the trauma category of the ‘four T's’ (Table 1). Waller and Sampson (2014) explain that TXA, a drug that has been widely studied since the 1960s, is a fibrinolysis inhibitor that is routinely used to reduce bleeding during surgery. Furthermore, Roberts et al. (2013) found that TXA greatly reduced mortality caused by trauma-induced haemorrhage. Waller and Sampson (2014) explain that TXA inhibits fibrinolysis by binding to fibrin strands, resulting in a decreased level of plasminogen activation; this subsequently prevents the breakdown of clots at the site where vessel continuity is compromised.
Active management of the third stage of labour is routinely practised by midwives in order to prevent obstetric complications such as PPH (RCOG 2009). Schorn et al. (2015) explain that management of the third stage of labour refers to the process of using specialist interventions and methods, such as TXA, in order to haemodynamically support the mother once the baby has been delivered.
The methods routinely used by midwives during the active management of the third stage of labour are detailed within Table 2. It is important to recognise that midwives attending home births are not currently licensed to administer TXA; therefore, a further emphasis is placed upon paramedics to provide this intervention in response to PPH. WHO (2012) recommends that all women should undergo active management of the third stage of labour; however, Brown et al. (2016) outline that only physiological management of the third stage of labour is carried out by paramedics in the UK. In Brown et al. (2016), uterotonic drugs such as misoprostol and syntometrine are only indicated once methods such as fundal massage have been attempted to reduce PPH—whereas active management of the third stage of labour requires them to be prophylactically administered. No further guidance, other than the administration of intravenous fluids, is currently indicated by Brown et al. (2016) in order to manage PPH which is unresponsive to uterotonic drugs. WHO (2012) explains that the use of TXA is recommended when uterotonic drugs do not effectively manage PPH, and this intervention has been included within their treatment of PPH guidance. Previously, in Brown et al. (2016), TXA was only indicated for life-threatening internal/external haemorrhage caused by a trauma-related injury. RCOG (2009) classifies PPH caused by the separation of the placenta from the uterine wall as trauma. However, this particular method of trauma was not recognised within the Brown et al. (2016) TXA indications for administration. Following recent interest in the subject area and the publication of the WOMAN trial results, Brown et al. (2016) will soon be updating the indications for TXA to include PPH in order to reduce haemorrhage. Therefore, this systematic review seeks to answer the question: ‘Is TXA suitable for implementation within the UK paramedic management of out-of-hospital PPH?’. Prior to the development of this focused question, a scoping search was performed which found a gap in research on the UK paramedic use of TXA to manage out-of-hospital PPH.
| Active management | Physiological management |
|---|---|
| Routine administration of uterotonic drugs such as oxytocin, syntometrine and misoprostol | No routine use of uterotonic drugs |
| The cord is clamped and cut between 1 and 5 minutes after birth | The cord is clamped and cut once it has stopped pulsating |
| Controlled cord traction is practised once the placenta has detached from the uterine wall of the uterus | Delivery of the placenta is made by maternal effort |
To date, a number of systematic reviews have been conducted worldwide with a focus on whether TXA is an effective intervention for the management of PPH. McClure et al. (2014) conducted a systematic review which focused on the relationship between the use of TXA in response PPH and its effects upon the rates of maternal mortality in sub-Saharan Africa. They found that maternal deaths could be reduced by 30%; accounting for 22 000 people, through the use of TXA. Additionally, Alam and Choi (2015) carried out a systematic review focused on the prophylactic use of TXA for postpartum bleeding, and found that TXA was associated with a decreased incidence of PPH following delivery. Sentilhes et al. (2015b) are currently conducting a double-blind RCT investigating whether TXA is effective for preventing PPH following vaginal delivery—otherwise known as the ‘TRAAP trial’.
More recently, the WOMAN Trial Collaborative (2017) conducted an international double-blind RCT involving over 20 000 women who experienced PPH during birth following either Caesarean or vaginal delivery. This trial is otherwise known as the ‘WOMAN trial’ and is focused on the use of TXA for the treatment of PPH. This trial found that death caused by PPH was significantly reduced in patients who received TXA (155 (1.5%) of 10 036) when compared with those who did not receive TXA intervention (191 (1.9%) of 9985).
Despite the growing interest in the relationship between TXA and its use for PPH, a systematic review solely based upon its suitability for use within the paramedic management of PPH had not been conducted. The current systematic review therefore addresses this gap in research by focusing upon blood-loss volumes, and provides further evidence in relation to TXA's use within the UK paramedic out-of-hospital management of PPH.
Objectives
This systematic review focuses on whether the use of TXA is suitable for the UK paramedic management of out-of-hospital PPH. In order to assess the suitability of this drug, the primary objective was to focus on whether TXA is effective at reducing blood loss following PPH. Research based on blood loss following PPH, with the intervention of TXA, was acquired in order to address the focused question. Discussion is included as to whether TXA could be implemented within the paramedic management of out-of-hospital PPH in the UK.
| Population | Intervention | Outcome |
|---|---|---|
| Recognition of PPH as blood loss greater than 500 mls | TXA | Focus upon the use of tranexamic acid as a means of managing PPH |
| vaginal or caesarean delivery | Randomised control trial | Blood loss measured objectively |
| Similar group characteristics | ||
| Women older than 18 years of age | ||
Methods
Methodology and review criteria
In order to address the focused research question outlined, a systematic review of evidence was performed. The criteria for inclusion consists of studies that:
Retrieved research was excluded if the publication was greater than 10 years old or the outcome measures did not focus upon the relationship between TXA and blood following PPH. Stevens (2013) clarifies that the use of the latest, most relevant evidence to support a systematic review ensures that its findings are evidence-based and, consequently, that it coincides with contemporary methods of practice and understanding.
Scoping search
As the scoping search identified a gap in research related to UK paramedic out-of-hospital use of TXA to manage PPH, the current study will attempt to generalise findings from studies conducted within hospital. As previously discussed, the incidence of PPH is not affected by the method of delivery. Therefore, the decision was made to use research focused on both vaginal and Caesarean delivery.
Search strategy
For this systematic review, the following online medical databases and libraries were searched electronically to locate research applicable to the focused question: CINAHL (1977–May 2016); EMBASE (1947–May 2016); MEDLINE (1946–May 2016); PubMed (1951–May 2016); and the Cochrane Central Register of Controlled trials library (2005–May 2016). Furthermore, a grey literature search was conducted using different search engines such as: the grey literature report; the system for information on grey literature in Europe; and Google Scholar. The references of all retrieved research were manually searched in order to locate additional research that was not initially found within the electronic search. Grey literature database searches were incorporated within the search strategy to counteract publication bias.
A search strategy was developed which involved the use of key search terms that were combined in order to retrieve results. This strategy was used within all of the mentioned databases where the medical subject headings (MeSH) were inputted and combined to retrieve relevant research. These keyword search terms were also used within the grey literature databases to promote the consistency of the search strategy.
Data extraction
The numerical data based upon the mean amount of blood loss in millilitres following PPH were extracted from studies that met the inclusion criteria. Data will be extracted by the author and a secondary independent reviewer. Interpretations of the data from the lead author who is the researcher, and the secondary reviewer, will be collated and cross-referenced to minimise error.
| Search identifier | Term |
|---|---|
| #1 | PPH |
| #2 | Postpartum Haemorrhage |
| #3 | Post-Partum Haemorrhage |
| #4 | Postpartum Bleeding |
| #5 | Obstetric Bleeding |
| #6 | Tranexamic Acid |
| #7 | TXA |
| #8 | (#1 OR #2 OR #3 OR #4 OR #5) AND (#6 OR #7) Limits: Humans, English language format, less than 10 years old |
Data analysis methods
Data such as the mean blood loss (mls) identified from each study were displayed using a table. In addition to this method of data analysis, a narrative synthesis was performed, whereby groups of studies with the same outcome measures were analysed. Boland et al. (2014) explain that narrative synthesis is a process of reporting data, in written form, that follows a particular theme or foundation.
Results
The searches performed using the AMED database did not return any results. Using the online medical databases, 744 articles were initially found (Embase, 565; CINAHL, 85; Medline, 85; and PubMed, 9). However, 395 articles were excluded after identifying duplicates. A further 386 articles were excluded after a title and abstract review. Nine full-text articles were then read and screened with the use of the inclusion/exclusion tool applied by both the researcher and the independent reviewer. Following this, three articles were excluded: two owing to their incomplete status; and one as a result of its low-quality study design in terms of its explicitly subjective measurement methods. A further two articles were identified by cross-referencing the included studies, and were added to the final collection of retrieved research. Eight studies were eligible for inclusion in this systematic review.
A total of 2167 participants were included from across five countries. Three studies, accounting for 718 participants, focused on PPH following vaginal delivery; four studies, accounting for 1449 participants, focused on PPH following delivery by Caesarean section. Each was able to meet their calculated power analysis for participant inclusion, promoting the generalisability of the studies. One study reported participants that were discontinued from participation. Participant characteristics across the studies were not significantly different and did not promote selection bias.
Each study involved the use of intravenous (IV) TXA: five studies administered 1 g of IV TXA; one study administered a 4 g loading dose of TXA; one study administered 10 g of TXA; and one study administered 10 mg/kg of TXA.
Blood loss was measured and reported in units of millilitres within all studies. The times of measurements of blood loss varied across the studies; however, all studies measured blood loss following the administration of TXA. Seven studies used objective methods of measurement to calculate total blood loss. One study used both a mixture of objective and subjective methods of measurement to estimate blood loss. Both arms of each individual study were subject to the same methods of measurement; therefore, a standardised method of measurement for all study groups was practised.
None of the studies were judged to have a low risk of bias according to all elements of the CASP (2017) quality assessment tool for RCTs. Four studies scored 10 out of a possible 11 when applied to the CASP quality assessment tool; four scored 9 out of a possible 11. The findings of all eight studies were calculated to have a p-value of <0.05% and are therefore statistically significant.
Discussion
TXA effects upon blood loss following PPH
The aim of this systematic review was to explore whether TXA is suitable for implementation within the UK paramedic management of out-of-hospital PPH, by focusing on its effects on blood loss. All of the studies included within this review found a significant reduction in blood loss following the administration of IV TXA once PPH had been diagnosed. Clear evidence outlined within Table 5 supports this statement and clarifies the details of the findings of each individual study.
| Study | Result of the study in relation to blood loss following the administration of TXA |
|---|---|
| Mirghafourvand et al. (2015) | The mean calculated blood loss (mls) was lower in the study arm: 519 ± (320) in comparison to 659 ± (402) in the control group (p=0.036) |
| Ducloy-Bouthors et al. (2011) | The mean calculated blood loss (mls) between the time of inclusion and 6 hours following, was significantly lower within the intervention group of the study: 170 ± (323) and 221 ± (543) in the control group (p=0.041) |
| Asıcıoglu et al. (2013) | The mean calculated blood loss (mls) was significantly lower in the intervention group 261.5 ± [146.8] in comparison to 349.98 ± [188.85] in the control group (p=<0.001) |
| Movafegh et al. (2011) | The study found that the mean measurement of blood loss (mls) was significantly less within the intervention group 262.5 ± [39.5] in comparison to 404.7 ± [94.4] within the control group (p=< 0.001) |
| Xu et al. (2012) | Total mean blood loss (mls) measured from placental delivery until 2 hours later was significantly lower within the intervention group 379.2 ± [160.1] in comparison to the control group 441.7 ± [189.5] (p=< 0.02) |
| Abdel-Aleem et al. (2013) | Mean total blood loss (mls) was significantly lower within the intervention group 241.6 ± [6.77] in comparison to 510 ± [7.72] within the control group (p=0.0001) |
| Yehia et al. (2014) | Mean calculated total blood loss (mls) from placental delivery until the end of Caesarean surgery was significantly lower within the intervention group 369.5 ± [198.0] in comparison to 606.8 ± [193.0] (p=0.001) |
| Senturk et al. (2013) | Mean estimated blood loss (mls) was significantly lower within the intervention group 272.05 ± [143.23] in comparison to 346.87 ± [189.49] within the control group (p=0.001) |
Improving future studies
Research taking into account the further interactions of TXA when administered, may better the understanding of its applicability to the UK paramedic management of out-of-hospital PPH. Side-effects and interactions with comorbidities should be measured objectively in order to retrieve empirical results. Furthermore, research solely on women experiencing PPH in the out-of-hospital setting, would better represent the population this systematic review seeks to address.
Future studies may also obtain more reliable and valid data through the use of a recognised objective method of measurement that accurately measures the volume of blood lost during PPH. Additionally, the times at which these measurements are conducted should be standardised.
Overall conclusions
This systematic review was able to address the focused question: ‘Is TXA suitable for implementation within the UK paramedic management of out-of-hospital PPH?’ The current review found that TXA significantly reduces the volume of blood loss during PPH. This evidence seeks to support the decision made to include PPH within the indications for TXA within the Brown et al. (2016) guidelines. Furthermore, it supports the notion that the UK paramedic out-of-hospital intervention of TXA in response to PPH, could reduce the incidence of maternal mortality caused by PPH in the UK. Moreover, this could reduce the volume and severity of blood loss during PPH, resulting in better quality care that is more likely to effectively manage the patients' medical condition.
However, without further research solely based upon this topic area, it is difficult to explicitly recommend TXA for implementation within the UK paramedic out-of-hospital management of PPH. The need for further research in this area was highlighted, with suggestions of how future research may be improved upon in order to better address this focused question. The overall quality of the included studies was deemed to be good. However, certain aspects of these studies may have introduced bias, which consequently negatively influenced both internal and external validity—this resulted in a lower-confidence interpretation of their findings. Additionally, without the presence of studies solely focused upon the out-of-hospital UK paramedic management of PPH through the use of TXA, it is difficult to generalise the findings directly to the target population. This systematic review does however support and supplement the findings of past and current research based on the relationship between TXA and PPH. Further research into the UK paramedic administration of TXA in response to PPH in the out-of-hospital setting is clearly justified.