Intervention to decrease severe postpartum haemorrhage
1
Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the 1
PITHAGORE6 cluster-randomised controlled trial 2
3
C Deneux-Tharaux
1
*, C Dupont
2
, C Colin
3
, M Rabilloud
4
, S Touzet
3
, J Lansac
5
, T Harvey
6
, V 4
Tessier
6
, C Chauleur
7
, G Pennehouat
8
,
X Morin
9
, MH Bouvier-Colle
1
, R Rudigoz
2
5
6
1
INSERM, UMR S953, UPMC, Epidemiological research unit on perinatal health and women’s and 7
children’s health, Paris, France 8
2
Aurore Perinatal network, Hospices civils de Lyon; EA 4129, Lyon 1 University, Lyon, France. 9
3
Department of medical information and health care evaluation, Hospices Civils de Lyon; EA4129, 10
Lyon 1 University, Lyon, France. 11
4
Hospices Civils de Lyon, Service de Biostatistique, Lyon, F-69003, France ; Université de Lyon, F-12
69000, Lyon ; CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe 13
Biostatistique Santé, Pierre-Bénite, F-69310, France. 14
5
PerinatCentre Perinatal network, Tours University Hospital, France 15
6
Port Royal St Vincent de Paul Perinatal network, Paris, France 16
7
Loire Nord Ardeche Perinatal network, Saint Etienne University Hospital, France 17
8
2 Savoie Perinatal network, Chambery Hospital, France 18
9
Alpes Isere Perinatal network, Grenoble University Hospital, France 19
20
* Corresponding author: INSERM U953, Batiment de recherche, Hopital Tenon, 4 rue de la Chine, 21
75020 Paris, France. Email: catherine.deneux-tharaux@inserm.fr; Tel: + 33 (0)1 56 01 83 67 22
23
Intervention to decrease severe postpartum haemorrhage
2
Abstract 24
Objective-Decreasing the prevalence of severe postpartum haemorrhages (PPH) is a major obstetrical 25
challenge. These are often considered to be associated with substandard initial care. Strategies to 26
increase the appropriateness of early management of PPH must be assessed. We tested the hypothesis 27
that a multifaceted intervention aimed at increasing the translation into practice of a protocol for early 28
management of PPH, would reduce the incidence of severe PPH. 29
Design- Cluster-randomised trial 30
Population- 106 maternity units in 6 French regions 31
Methods- Maternity units were randomly assigned to receive the intervention, or to have the protocol 32
passively disseminated. The intervention combined outreach visits to discuss the protocol in each local 33
context, reminders, and peer reviews of severe cases, and was implemented in each maternity hospital 34
by a team pairing an obstetrician and a midwife. 35
Main outcome measures- The primary outcome was the incidence of severe PPH, defined as a 36
composite of one or more of: transfusion, embolisation, surgical procedure, transfer to intensive care, 37
peripartum haemoglobin delta of 4 g/dl or more, death. The main secondary outcomes were PPH 38
management practices. 39
Results- The mean rate of severe PPH was 1.64% (SD0.80) in the intervention units and 1.65% 40
(SD0.96) in control units; difference not significant. Some elements of PPH management were applied 41
more frequently in intervention units –help from senior staff (p=0.005)-, or tended to – second line 42
pharmacological treatment (p=0.06), timely blood test (p=0.09). 43
Conclusion-This educational intervention did not affect the rate of severe PPH as compared to control 44
units, although it improved some practices. 45
Trial registration: ClinicalTrials.gov NCT 00344929 46
47
Keywords- Maternal health, postpartum haemorrhage, clinical practices, educational intervention, 48
cluster-randomised trial49
Intervention to decrease severe postpartum haemorrhage
3
Introduction 50
Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality(1, 2) and the main 51
component of severe maternal morbidity (3-5). Decreasing the prevalence of severe PPH is a major 52
obstetrical challenge, in both developed and developing countries. Because individual risk factors do 53
not predict PPH well(6, 7), interest has increasingly focused on factors related to the care provided, 54
which are potentially more amenable to change. 55
In the area of prevention of PPH, a high level of evidence supports the efficacy of the routine 56
administration of oxytocics during the third stage of labour (8) and the effective translation of these 57
results into clinical practice through behavioural interventions has been recently described (9, 10). 58
Conversely, improving obstetric care for the management of PPH remains difficult, although greatly 59
needed. Reports from confidential enquiries into maternal deaths show that most deaths due to PPH 60
involve delayed and substandard care in the diagnosis and management of haemorrhage (11-13). A 61
population-based study of severe non-lethal PPH reached a similar conclusion (14). A recent study 62
demonstrated a wide heterogeneity in maternity unit policies for the immediate management of PPH 63
within individual European countries as well as between them (15, 16). These findings suggest that 64
increasing the appropriateness of care should improve PPH-related health indicators. A number of 65
PPH-related clinical guidelines have therefore been developed, both nationally and internationally (17-66
21). 67
The harder job, however, is ensuring the actual translation of these guidelines into clinical practice. 68
Guidelines do not by themselves change professionals’ practices (22), and the effectiveness of active 69
intervention strategies must be assessed. Results from educational interventions strictly focused on 70
PPH prevention cannot be generalized to PPH management, because of the differential nature of care 71
involved – routine versus emergency care. A few previous reports have described the effectiveness of 72
local strategies in individual institutions aimed at improving the management of PPH (23, 24). The 73
relevance of their results in other and more diverse settings is however questionable. 74
We present the results of a cluster-randomised controlled trial to test the hypothesis that a multifaceted 75
educational intervention, aimed at improving practices for early PPH management, would reduce the 76
rate of severe PPH in diverse obstetric care settings. 77
Intervention to decrease severe postpartum haemorrhage
4
78
Methods 79
Design 80
The study was a cluster-randomised controlled trial, with the maternity unit as the randomisation unit. 81
One group of maternity units was assigned to receive a multifaceted intervention to implement 82
guidelines for PPH management. The control group of maternity units received no intervention. 83
Setting 84
The trial was conducted in six perinatal networks in France. A 1998 French statute aimed at 85
optimising the organisation of obstetric care made it mandatory for all maternity units to belong to a 86
perinatal network (25), organised around one or more level 3 units (reference centres with an onsite 87
neonatal intensive care unit) and including units rated as level 1 (no facilities for non-routine neonatal 88
care) and 2 (with a neonatal care unit), both public and private. The six perinatal networks were the 89
Perinat Centre network around Tours (23 units), the Port-Royal St Vincent de Paul network in Paris 90
(25 units), and the 4 networks of the Rhône-Alpes region: the Aurore network around Lyon (33 units), 91
the Savoie network around Chambery (14 units), the Grenoble network (5 units), and the St-Etienne 92
network (9 units). 93
Participants 94
Maternity units were eligible if they belong to one of the six networks. No other eligibility criterion 95
was applied, in accord with our population-based approach. Two units were excluded because they 96
were involved in a concomitant clinical study not compatible with our trial. One unit decided not to 97
participate. Our sample therefore included 106 maternity units of the 109 in the six regional networks 98
(listed in the Appendix). They accounted for about 17% of all French maternity units, and 20% of 99
deliveries nationwide. 100
The trial took place between September 2004 and November 2005 in the Aurore network, and between 101
September 2005 and November 2006 in the other five. 102
Randomisation 103
The random allocation was produced centrally by the Biostatistics department of the Hospices Civils 104
de Lyon, France. A design stratified according to perinatal network and size was used to ensure that 105
Intervention to decrease severe postpartum haemorrhage
5
the two arms of the trial were as similar as possible at baseline. Perinatal network was divided into 106
five classes, with the Grenoble and St-Etienne networks regrouped in one class because of their 107
geographic proximity and small number of units. Size was classified in two categories: an annual 108
number of deliveries equal to or greater than the 50
th
percentile for the network, or less than the 50
th
109
percentile. In each stratum, a balanced number of maternity units was assigned at random to one of the 110
two arms (intervention or control). For each stratum, a random allocation was made using a random 111
number generator available in SAS software, with a different seed value for each stratum. 112
113
Intervention 114
Protocol for early management of PPH 115
The protocol for stepwise management of PPH was consistent with the national clinical 116
guidelines.(26) Overall, the main recommended steps were the following: examination of the uterine 117
cavity and/or manual removal of placenta within 15 minutes of PPH diagnosis; call for additional staff 118
obstetrician or anaesthetist within 15 minutes of PPH diagnosis; instrumental examination of the 119
vagina and cervix; immediate intravenous administration of therapeutic oxytocin; and if PPH 120
persisted, intravenous administration of sulprostone (second line oxytocic) within 30 minutes of the 121
initial diagnosis, and a blood test within 60 minutes of it. 122
Intervention group 123
The multifaceted intervention consisted of a combination of three components an outreach visit 124
with academic detailing, reminders, and peer review of deliveries with severe PPH- to facilitate the 125
translation into practice of the protocol for the early management of PPH. 126
For each network, an obstetrician and a midwife identified as opinion leaders in their professional 127
community were teamed to implement the intervention’s components in each maternity unit. The 128
demonstrated role of opinion leaders in facilitating the adoption of guidelines derives from their 129
influence and power, as people of social importance.(27) These six teams met together during two 130
one-day meetings for training in the different facets of the intervention. 131
The components of the intervention were implemented in two phases. The first phase lasted three 132
months and consisted of outreach visits to each maternity unit (two visits per unit). During these visits, 133