Care technologies to prevent and control hemorrhage in the third stage of labor: a systematic review

Objective to identify evidence concerning the contribution of health technologies used to prevent and control hemorrhaging in the third stage of labor. Method systematic review with database searches. First, two researchers independently selected the papers and, at a second point in time, held a reconciliation meeting. The Kappa coefficient was used to assess agreement, while the Grading of Recommendations, Assessment, Development and Evaluation was adopted to assess risk of bias and classify level of evidence. Results in this review, 42 papers were included, 34 of which addressed product technologies, most referred to pharmacological products, while two papers addressed the use of blood transparent plastic bags collector and the contribution of birth spacing and prenatal care. The eight papers addressing process technologies included the active management of the third stage of labor, controlled cord traction, uterine massage, and educational interventions. Conclusion product and process technologies presented high and moderate evidence confirmed in 61.90% of the papers. The levels of evidence confirm the contribution of technologies to prevent and control hemorrhaging. Clinical nurses should provide scientific-based care and develop protocols addressing nursing care actions.


Introduction
Postpartum hemorrhage (PPH) is one of the main causes of maternal morbidity and mortality worldwide (1)(2) . PPH is defined as blood loss above 500 ml, measured up to 24 hours postpartum, while this amount of blood loss after 24 hours is defined as secondary PPH (1,3) . Blood loss up to 500ml among healthy women does not lead to negative consequences; however, uncontrolled blood loss over 500ml can be fatal (1) . Primary PPH occurs in the first 24 hours after birth and is more likely to result in maternal morbidity and mortality, while secondary postpartum hemorrhage refers to bleeding that occurs from 24 hours up to six weeks after birth (1,3) .
In general, blood loss is diagnosed as PPH if one or more of the following occur: loss of uterine tone (atony); retention of placental tissue or blood clots; laceration of the genital tract; or coagulopathy (1,3) .
Procedures to prevent PPH are initiated by assessing a patient's risk profile and establishing how to respond to complications in order to prevent a small amount of bleeding from becoming a severe hemorrhage with the risk of death. PPH is one of the complications of the third stage of labor and this stage begins after the fetus is expelled; however, with the detaching of the placenta from the uterine wall and its expulsion through the birth canal, greater than expected bleeding may occur. Therefore, it is essential to know the physiology of childbirth and women's clinical conditions, as well as intercurrences that took place during the pregnancypuerperal period, which might contribute to the emergence of hemorrhaging (1,4) .
In order to prevent PPH, the staff needs to be prepared to use protocols with a multidisciplinary approach, which involves maintaining hemodynamic stability while, simultaneously, identifying and treating the cause of bleeding. A combination of prediction and prevention, early identification and rapid coordinated actions is essential to preventing PPH. Consequently, efficient communication among the members of the multidisciplinary obstetrical team is paramount (5) .
Prevention and control of PPH demand technologies that support labor and interventions in the event unwanted bleeding occurs. Therefore, health workers should be aware of and implement technologies supported by a higher level of evidence and with positive outcomes, which represent the least harm to women and babies.
Additionally, for safe and timely care to be provided, services need to have a well-established capacity to coordinate people, equipment and work processes.
Hence, having techniques and technologies as well as protocols does not ensure, by itself, the prevention and control of hemorrhaging; personnel of sufficient quality and number to meet demand is necessary.
Technologies, evidence-based practice, and interventions proposed by workers have grown exponentially in importance from the mid-twentieth century, so much so that providing quality services without such resources is inconceivable currently, with many of them being innovative in nature (6) . All these aspects a service is required to have are known as health technologies -a term that encompasses every intervention used to promote health. "In this sense, health technologies can be conceived as the practical application of knowledge, including machines, clinical and surgical procedures, medications, programs and systems intended to promote health care" (7) .
Similarly, the literature presents the elements that integrate health technologies, namely any and all methods/devices used to promote health, prevent death, and treat diseases and improve rehabilitation or the care of individuals or populations (8) . a scientific basis to strengthen healthcare delivery and produce evidence to innovate in regard to product and process technologies (9)(10) .
There are various systematic reviews addressing PPH showing it still accounts for high levels of morbidity and mortality, mainly in developing countries. For this reason, studies need to be conducted regularly, considering that all technologies should be revised and updated over time, especially when we consider the application of technologies in different contexts and populations (6)(7)(8)11) .
In order to overcome the causes of PPH and its determinants of a sociocultural, technical and technological nature in different geo-economic contexts, the results of systematic reviews should be disseminated among health services in order to contribute to the development of multidisciplinary protocols. In this context, nurses, especially those in the obstetrical field, can propose care processes, among others, such as those associated with patient safety, especially when applying pharmacological products 11) .
disproportion and placental abruption (1) , the need to prepare the staff to intervene appropriately, and lack of information regarding existing technologies in the field, the objective of this study was to identify evidence concerning the contribution of health technologies used to prevent and control hemorrhaging in the third stage of labor.

Method
This Systematic Review adopted the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist (12) to present the results. The entire review process was guided by the question: What is the evidence available concerning the contributions of health technology used to prevent and control hemorrhaging in the third stage of labor?" The PIO (Patient, Intervention and Outcomes) support protocol (13) was used, in which P (population, participants) was After discussion, they decided to include four of these papers, with 42 papers being included in the final review. The Kappa coefficient (14)(15)(16)(17)(18) , with a confidence interval of 95%, was applied to assess inter-rater agreement. This coefficient has the following measure levels: less than zero, "insignificant"; between 0 and 0.2, "weak"; between 0.21 and 0.40, "reasonable"; between 0.41 and 0.60, "moderate"; between 0.61 and 0.80, "strong"; and between 0.81 and 1.0, "almost perfect".
The levels of evidence identified in the papers were classified according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) (19)(20) , a system sensitive to rating the quality of evidence.
In this system, quality of evidence is classified as: high, moderate, low, or very low ( Figure 1 In the third stage of the process, after reading the full texts and excluding those that failed to meet the inclusion criteria, according to two independent researchers, we proceeded to the systematization of studies.
In order to compile and synthetize the results of the different studies included in the review, we organized tables and grouped the technologies into two categories: product technologies and process technologies. Tables are presented in the results.

Results
After applying the search strategies, 6,999 papers were found. Of these, 6,726 were excluded due to the following: the titles and/or abstracts of 5,978 papers did not meet the inclusion criteria; 652 papers were published in more than one database; and 96 were not characterized as papers (e.g., theses, dissertations, integrative literature reviews, descriptive observational studies, papers other than scientific research, and qualitative studies) The full texts of 273 papers were read and 42 were included ( Figure 2). The Kappa coefficient (14)(15)(16)(17)(18) , which was equal to 0.86 in the first stage and equal to 1.00 in the second, revealed a high level of inter-rater agreement.   (33) Randomization was performed using a random number list.
Both drugs were encoded and packaged before recruiting.
Patients and physicians were blind 9.00% in the carbetocin and 7.00% follow-up loss in the syntometrine group
Drug packages were sealed and encoded using a computer-generated random number graph The head nurse not involved in the study opened the assigned package; the researcher was blind for the package's content There was none

--
Orji et al. (35) Randomly assigned to the oxytocin and ergometrine groups Sealed envelopes were used in the allocation

None
Uncertain/does not report

Uncertain
Uncertain/there was none Uncertain/does not report

--
Ugwu et al. (37) The method of blocked randomization was used and the participants were randomly assigned.
Opaque and sealed envelopes containing details of allocation were used Researchers and data analysts were blind in regard to assignment There was none

Small sample
Zachariah et al. (38) All women who experienced vaginal births were randomly assigned to one of the three groups using computer-generated random numbers.
Medication was given according to randomization

None
Uncertain/does not report Zuberi et al. (41) The sample was randomized into blocks of ten and stratified by site using a computer-generated random sequence.
Envelopes contained three misoprostol or placebo tablets All women, providers, and researchers were blind in regard to the treatment assignment Uncertain/does not report Small sample Patil (42) Each of the patients was assigned to one of the groups using the colored coin method (random sampling method)

Not reported
None Uncertain/does not report

--
Ononge et al. (43) Randomization was obtained using a computer-generated numeric The nursing staff was blind: the nature of the medications were not reported Uncertain/does not report

--
Widmer et al. (48) Randomization was computer generated and stratified by country To conceal the allocation, treatment boxes were sealed and numbered.
The workers and participants were blind in regard to the assignment of treatment There was none

--
Hofmeyr et al. (49) A sequence of random numbers generated by computer was used for random allocation and stratified by country Medications were placed in identical packages in terms of form, color, weight and feeling.

Reported as double blind
0.18% in the misoprostol group and 0.54% in the placebo group

--
Miller et al. (50) Computer-generated random list Packages tested in approved random sample Reported as double blind 0.84% misoprostol group and 0.61% in the ZB11 ¶ group --Su et al. (51) The randomization list with intervention mode allocation was sent to the Hospital Pharmacy Both medications were packaged and encoded.

Midwives, obstetricians and participants were blind
There was none

--
Ducloy-Bouthors et al. (52) Computer-generated random sequence Uncertain Assessment of each endpoint was performed with researchers blind in regard to assignment of treatment 6.49% in the tranexamic and 2.70% in the placebo group

Small sample
Zhang et al. (53) The maternities were randomly assigned to groups using collector bags after vaginal delivery and not using collector bags

Reported as double blind
There was none --Jangsten et al. (54) Women were assigned to active or expectant management using computer-generated randomization          The papers were classified as product and process technologies (9) . Among the 34 papers classified as product technologies (Figure 4), most were represented by pharmacological products and only two papers refer to another type of product, that is, plastic collector bag and the contribution of birth spacing and prenatal care. with the exception of one study (32) .
In regard to blood loss, six studies (22,24,(32)(33)(34)(35) report that oxytocin presented a mean blood loss. Birth spacing influences this result; that is, greater blood loss in found among childbirths with intervals of less than two years (36) . Other studies (21,(25)(26)28,30) did not report significant differences in regard to this aspect. shorter than two years between births determined a greater occurrence of PPH (36) . Additionally, a drop in the concentration of hematocrit in the oxytocin group was significant in the postpartum (24,32) .
The administration of oxytocin, even by unskilled individuals, was efficacious to control PPH and also to decrease blood loss, as well as the need to refer patients to referral units (39) . One study (40) , however, reports greater amounts of blood loss in the oxytocin group.
The use of misoprostol was analyzed in studies with different compositions and administration routes to prevent PPH (21)(22)(23)(24)(25)(26)29,(31)(32)37,41) . These studies show that, regardless of the dosage of misoprostol, the duration of the third stage of the labor did not present significant differences, nor did the drop in the concentration of hematocrit/hemoglobin, except in those papers (24,32) that found a decrease in the concentration of these hematological components.
effective when used in the treatment of primary PPH caused by uterine atony (59) .
When considering the route of administration, sublingual misoprostol was more efficacious, decreasing the duration of the third stage of labor and mean blood loss in comparison to the rectal and oral routes.
Conversely, side effects like fever and tremors were more frequent when the sublingual route was used.
The group who received the medication through the oral route presented a greater need for additional uterotonics. In terms of acceptability, rectal misoprostol was better accepted by women and was the one with fewer side effects (46)(47) .
Side effects were common in all women who received misoprostol.
Seven studies (21,23,25,31,(43)(44)(45) recommend misoprostol be adopted in areas where routine uterotonics are not available, as it is the best option to prevent PPH, given its ease of application, stability at ambient temperature and low cost. This is a safe and efficacious alternative to be used by midwives and auxiliaries in home births.
Misoprostol is the most viable choice in communities (40) and is easy to store (42) . In areas where there are routine uterotonics available, however, the benefits of misoprostol might not outweigh the discomfort of side effects (49) .
In regard to the viability of using misoprostol in communities, a study that distributed it during prenatal care for women to self-administer it at home, no significant decrease of PPH was found. Nonetheless, the use of uterotonics increased as did the return visits of women to the health service. The self-administration of misoprostol with little monitoring and supervision was considered safe (43) , though women need to be better educated on when to use misoprostol in regard to placental deconditioning.
In regard to misoprostol, RCTs present a high level of evidence (21,24,31,34,40,44,50) recommending the use of this uterotonic via the oral, sublingual and rectal routes in different dosages, indicating it is efficacious, economically viable and easy to administer.
Therefore, the use of misoprostol in areas with few resources is a good alternative to oxytocin. Analysis of bias indicated there were no methodological limitations regarding the design or implementation of the individual papers presented. The RCTs (43,59) with moderate evidence indicate that oral misoprostol is the only pharmacological option available in areas with few resources to prevent postpartum hemorrhaging and bleeding. Other studies (25)(26)29,(41)(42)(43)46) addressed in this review and that address the use of misoprostol also make similar recommendations but, in accordance with GRADE ( Figure 3), present methodological limitations.
Further studies need to focus on the potential efficacy of misoprostol in areas where standard uterotonics are not available.
In regard to the use of oxytocin, RCTs with moderate level of evidence (35,39) recommend the prophylactic use of misoprostol to prevent PPH, while this is an essential intervention. Thus, oxytocin is the drug of choice whenever available and with a 10UI dosage; it is as efficacious as ergometrine in decreasing the incidence of PPH, though without the undesirable side effects associated with ergometrine. These studies present methodological limitations regarding the blinding of participants.
As noted in the previous paragraph, in addition to misoprostol and oxytocin, the efficacy of ergometrine, syntometrine and PGF2α in preventing PPH was also compared. Studies addressing ergometrine (33)(34)(35)38) report no significant differences in regard to the remaining uterotonics assessed in terms of blood loss, drop in hematocrit, duration of the third stage of labor, or the additional need of other drugs. The risk of side effects (nausea, high blood pressure, headaches and vomiting), however, was greater in the group receiving ergometrine.
For this reason, the recommendation to use ergometrine depends on the relevance of risks (35) .
In regard to syntometrine, the studies intending to determine the severity and incidence of this drug's side effects report no significant differences in terms of the duration of the third stage of labor, amount of blood loss, and use of additional uterotonics (33,46) . Significant differences, however, were reported by another study (51) , in regard to nausea, tremors, vomiting, uterine pain, and sweating.
In the comparison performed between syntometrine and carbetocin in the prevention of PPH (33,51) , carbetocin was more efficacious than syntometrine, though one of the studies (51) does not report relevant differences between the efficacies of both. The study with carbetocin identified fewer side effects and, even though an analysis of cost/efficacy was not performed, the author reports that the cost of carbetocin is ten times greater than the cost of syntometrine, while emphasizing that carbetocin was associated with fewer side effects, so that its use can contribute to reduced costs and time required for professionals.
PGF2α in one RCT (42) was more efficacious than misoprostol in decreasing mean blood loss and the duration of the third stage of labor and the drop in hemoglobin levels. The associated gastrointestinal side effects, however, were significantly greater and included nausea, vomiting, diarrhea and abdominal cramps.
One RCT (50) conducted in China addressed the ZB11 uterotonic, used in Tibetan traditional medicine to prevent PPH. The results show higher rates of PPH in the ZB11 group in comparison to the misoprostol group. No significant differences were found in terms of blood loss.
Side effects such as diarrhea, tremors, and fever were less recurrent. The authors (50) suggest that other studies be undertaken in that geographic area because home births performed by the pregnant women themselves, or without the assistance of qualified workers, is not uncommon. Thus, research addressing efficacious uterotonics with accessible prices is especially relevant in areas with these characteristics and can contribute to women's easier access to safe technologies (50) . This specific RCT was assessed using the GRADE system and was considered to have a high level of evidence, presenting no methodological limitations.
Another drug that was addressed in order to verify its efficacy and safety in preventing and treating PPH was tranexamic acid (TA) (52) .  (53) .
In regard to process technologies, we initially verified that some authors conducted RCTs (54,60) and an observational study (61) to verify changes in hematological parameters caused by blood loss among women who Decreased blood loss has a greater impact on the health of women in low-income countries (54,60) ; however, if active management is the preferred option for AMTSL among low-risk women in high-level hospitals in developed countries, the only benefit will be to decrease drops in hemoglobin caused by childbirth (54) .
Another technology used to prevent PPH is the controlled cord traction (CCT) adopted in vaginal Still in regard to the prevention of PPH, the efficacy of skin-to-skin contact and breastfeeding after birth in decreasing PPH rates were also investigated. Risk for PPH decreased by almost four times among women practicing these. The highest effect in this study was among women at a lower risk of PPH. Both practices, when implemented immediately after birth, might be efficacious in decreasing PPH rates, regardless of the already existing risk factors for PPH (62) .
According to the authors, these practices promote the release of endogenous oxytocin, and they emphasize that pregnant women should be educated and supported in the implementation of these practices during the third and fourth stage of labor (62) . Note, however, these that the application of such practices should include a rigorous assessment of the clinical conditions of the women, because such a resource is not viable for those with at-risk pregnancies.
In regard to technology intended to prevent and control severe PPH and maternal morbidity and mortality, one paper addressed here focuses on sustained transabdominal uterine massage. The multicenter RCT (57) verified whether this technology can decrease blood loss receiving the massage and asked for it to be stopped (57) .
Routine uterine massage is not a technology indicated for the prevention of PPH after vaginal childbirth. It is a time-consuming and painful procedure and eliminating this practice from AMTSL benefits the obstetrical team because, in addition to saving effort, the time used in its application can be directed to other tasks (57) .
Another technology addressed is an educational intervention. Whether the implementation of a protocol of early PPH prevention decreased the incidence of severe PPH was assessed. The pregnant women involved were randomly assigned to the educational intervention (where sensitization meetings were held and the protocol was discussed) or only received the protocol without interventions. The results show that the mean rate of severe PPH did not differ in the units that received the educational intervention. Some elements of the PPH prevention protocol, however, were more frequently used in the units that received the intervention, such as asking for the help of specialized personnel and asking for specialized service within 15 minutes of PPH being diagnosed (58) . The authors emphasize that educational