Full length article
Fluid resuscitation during persistent postpartum haemorrhage and maternal outcome: A nationwide cohort study

https://doi.org/10.1016/j.ejogrb.2019.01.027Get rights and content

Abstract

Objective

To determine the association between increasing volumes of crystalloids and colloids administered before transfusion of packed red blood cells in women with persistent postpartum haemorrhage and adverse maternal outcomes.

Study design

Retrospective cohort study in the Netherlands. Women with persistent postpartum haemorrhage and known clear fluids volume for resuscitation were included. Women who received ≤2 L of clear fluids were the reference group. We determined the effect of every additional litre of clear fluids on total blood loss, severe maternal morbidity and mortality. Results were adjusted for patient and bleeding characteristics.

Results

Of the 883 included women, 199 received ≤2 L of clear fluids. Median blood loss for the reference group was 2.9 L (interquartile range 2.2–3.4). Adjusted mean difference in blood loss compared with the reference group was 0.2 L (95% confidence interval −0.1 to 0.5) for women in the >2 to ≤3 L, 0.4 L (0.1–0.7) for the >3 to ≤4 L category, 0.6 L (0.5–0.7) for the >4 to ≤5 L category, and 1.9 L (1.5–2.3) for the >5 to ≤7 L category. Adjusted odds ratios for adverse maternal outcomes were 1.0 (0.7–1.6), 1.2 (0.8–1.9), 1.8 (1.1–3.1) and 4.4 (2.6–7.5) for women in the 2 to ≤3 L category, >3 to ≤4 L, >4 to ≤5 L, and >5 to ≤7 L volume categories respectively. Results were similar in strata of different severities of bleeding.

Conclusion

Clear fluids volume >4 L was independently associated with adverse maternal outcome in women with persistent postpartum haemorrhage.

Introduction

Almost 20% of maternal deaths worldwide are due to postpartum haemorrhage, the leading cause of maternal death and morbidity [1,2]. Following childbirth, women are at risk of postpartum haemorrhage, and when postpartum haemorrhage is refractory to first-line therapy, it may deteriorate to severe haemorrhage [3]. Management of postpartum haemorrhage consists of obstetric and haemostatic interventions to stop bleeding, and fluid resuscitation to prevent and treat haemorrhagic shock [3].

During fluid resuscitation, infusion of crystalloids and colloids precedes transfusion of red blood cells. Red-cell transfusion during ongoing haemorrhage not only maintains circulating blood volume and tissue oxygenation, but may also support haemostasis by improving coagulation [[4], [5], [6], [7], [8], [9], [10]]. Obviously, red-cell transfusions are also associated with adverse effects including transfusion reactions and transfusion-related acute lung injury [11,12]. And, fluid resuscitation with crystalloids and colloids may worsen maternal outcomes by causing dilution of clotting factors and platelets [[13], [14], [15]]. Moreover, colloid fluids have been associated with dysfunction of clotting factors [[16], [17], [18], [19], [20]]. The effects of fluid resuscitation on patient outcomes have been studied in patients with major trauma or surgery, but not in women with postpartum haemorrhage [18,[21], [22], [23], [24], [25]].

Because of the potential adverse effects of both red-cell transfusion and fluid resuscitation with crystalloids and colloids, timing of switch from fluid resuscitation to resuscitation with packed red blood cells in women with severe postpartum haemorrhage should be carefully balanced. Nonetheless, it is unknown which volumes of crystalloids and colloids potentially worsen maternal outcomes, and therefore, justify switching to red-cell transfusion.

We set out to describe the association between increasing volumes of clear fluids administered before transfusion of packed red blood cells in women with severe postpartum haemorrhage and adverse maternal outcomes.

Section snippets

Patients

We used the TeMpOH-1 (Transfusion strategies in women during Major Obstetric Haemorrhage) study, a nationwide, retrospective cohort study on transfusion strategies in women with major obstetric haemorrhage in the Netherlands. The cohort comprised consecutive women from 61 hospitals who, from 1 January 2011 to 1 January 2013, received either ≥4 units of red blood cells or a multicomponent blood transfusion within 24 h following birth because of postpartum haemorrhage (≥1000 mL blood loss). Women

Patients

We assessed 270,101 deliveries during the study period. A total of 1391 women (0.51%) received a transfusion of at least four units of packed red blood cells or a multicomponent blood transfusion, and 1260 (0.47%) women were classified as having persistent postpartum haemorrhage (Fig. 1). A total of 377 women were excluded due to incomplete data on volume of crystalloids and colloids (n = 340), start of administration of clear fluids after start of packed red blood cells transfusion (n = 10),

Principal findings

In this multicentre cohort study among 883 consecutive women with persistent postpartum haemorrhage, resuscitation with >4 L clear fluids was associated with subsequent bleeding and accompanying adverse maternal outcome. This association was observed within all strata of severity of bleeding.

Current knowledge

The Royal College of Obstetricians and Gynaecologists recommends crystalloids and colloids up to 3.5 L before start of blood transfusion [30]. Thus far, this recommendation was based on expert opinion and

Authors’ contributions

DH, KB, JZ, JR, JJZ and JvdB were responsible for study concept and design. DH monitored data collection for the whole trial, wrote the statistical analysis plan, cleaned and analysed the data. RM collected data and helped development of the data collection tool. DH and JvdB drafted and revised the paper. KB, JZ, JR and JJZ critically reviewed the manuscript and approved the final version. All authors had full access to the data and take responsibility for the integrity of the data and the

Data statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Role of the funding source

None.

Acknowledgements

We would like to thank all 61 participating hospitals and the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology - NVOG Consortium 2.0, medical students R.M. Loeff, R.J. van Goeverden, B. Eijlers, A. Hillebrand, S.E. Spelmink, T.J. Beunder, V. Harskamp, M. Wind, M.D. Koning, R.A. Cramer, A. Veenstra, S.M. Smith and E.E. Ensing, datamanagers C.J. van Brussel-de Groot and O. Zouitni, research nurses C. Kolster-Bijdevaate, M.S. Bourgonje-Verhart, C.E.

References (32)

  • R. Abdul-Kadir et al.

    Evaluation and management of postpartum haemorrhage: consensus from an international expert panel

    Transfusion

    (2014)
  • P.A. Aarts et al.

    Blood platelets are concentrated near the wall and red blood cells, in the center in flowing blood

    Arteriosclerosis (Dallas, Tex)

    (1988)
  • R.I. Litvinov et al.

    Role of red blood cells in haemostasis and thrombosis

    ISBT Sci Ser

    (2017)
  • V. Peyrou et al.

    Contribution of erythrocytes to thrombin generation in whole blood

    Thromb Haemost

    (1999)
  • M.T. Santos et al.

    Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. A new approach to platelet activation and recruitment

    J Clin Invest

    (1991)
  • V.T. Turitto et al.

    Red blood cells: their dual role in thrombus formation

    Science (New York, NY)

    (1980)
  • Cited by (18)

    • Directive clinique n<sup>o</sup> 431: Hémorragie post-partum et choc hémorragique

      2022, Journal of Obstetrics and Gynaecology Canada
      Citation Excerpt :

      L’utilisation d’un volume unique de perte sanguine pour lancer un PHM peut faire en sorte que des patientes sont transfusées trop tôt ou trop tard. En cas d’hémorragie active, lorsque la perte approche de la PSMT, il faut envisager la transfusion de culots globulaires en premier lieu94,96,97,105,106. Les recommandations canadiennes en matière de normes de soins indiquent qu’il faut pouvoir mobiliser l’équipe au lancement du PHM et obtenir les produits dans un délai de 10 minutes109.

    • Guideline No. 431: Postpartum Hemorrhage and Hemorrhagic Shock

      2022, Journal of Obstetrics and Gynaecology Canada
      Citation Excerpt :

      Testing for fibrinogen levels when blood loss is <1500 mL is not predictive of severe PPH, and routine administration of fibrinogen in the absence of hypofibrinogenemia does not improve outcomes. Levels will drop more rapidly in the setting of abruption and amniotic fluid embolism than in the setting of atony.94,96,97 Each unit of cryoprecipitate contains 150–350 mg of fibrinogen and a typical dose is 8–10 U. Thawing is required prior to use, and multiple donors are required for sufficient amounts, which increases the risk of transfusion reactions.102,103

    • Management of patients with suspected placenta accreta spectrum

      2022, BJA Education
      Citation Excerpt :

      For ongoing obstetric bleeding, more concentrated fibrinogen sources should also be considered, including fibrinogen concentrate or cryoprecipitate, along with surveillance for coagulopathy (discussed next). The use of greater than 4 L of crystalloid or colloid is independently associated with adverse maternal outcomes, even when stratified for severity of bleeding, and should be avoided when possible.25 If blood loss exceeds 1,500 ml, prophylactic antibiotics should be redosed.3

    • Assessing and managing hypovolemic shock in puerperal women

      2019, Best Practice and Research: Clinical Obstetrics and Gynaecology
      Citation Excerpt :

      Again, considering the physiological response of the cardiovascular system in the puerperal women, they may behave similar to adult trauma patients. In women with severe PPH, fluid resuscitation with high volumes of crystalloids may induce dilution of clotting factors and platelets and cause dilutional coagulopathy [72,73]. A large volume of crystalloids is associated with more severe deterioration of coagulation parameters corresponding to dilution severe PPH [74].

    View all citing articles on Scopus
    1

    The Center for Clinical Transfusion Research, Sanquin Research is the scientific collaboration between the Department of Clinical Transfusion Research Sanquin Research, and the Department of Transfusion Medicine, Sanquin Blood Bank.

    2

    Present address: Department of Obstetrics, Birth Center Wilhelmina’s Children Hospital, Division Woman and Baby, University Medical Center Utrecht, Utrecht, the Netherlands.

    3

    The TeMpOH-1 study group is listed in the Acknowledgements.

    View full text