An evidence-based oxytocin protocol for the third stage of labor to improve hemorrhage outcomes
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International Journal for Quality in Health Care, 2021, 00(00), 1–7
doi: 10.1093/intqhc/mzab005
Advance Access Publication Date: 7 January 2021
Original Research Article
Original Research Article
An evidence-based oxytocin protocol for the
third stage of labor to improve hemorrhage
outcomes
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SARA C. GONZALEZ1 , JEFFREY BUDGE2 , PATRICIA D. BUTLER3 ,
MAUREEN HIGGS4 , JUDD WHITING5 and MONICA A. LUTGENDORF6
1
Department of Anesthesiology, Naval Medical Center San Diego, San Diego, CA 92134, USA, 2 Department of Safety
and Quality, Naval Medical Center San Diego, San Diego, CA 92134, USA, 3 D.N.P Mother Infant Nursing Department,
Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA 92134, USA, 4 Department of Anesthesiology,
Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA 23708, USA, 5 Department of Anesthe-
siology, Naval Health Clinic Lemoore, 937 Franklin Ave, Lemoore, CA 93246, USA, and 6 Department of Obstetrics and
Gynecology, Naval Medical Center San Diego, San Diego, CA 92134, USA
Address reprint requests to: Monica A. Lutgendorf, Department of Obstetrics and Gynecology, Division of Maternal-Fetal
Medicine, Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA 92134, USA. Tel: +1-619-846-2188;
Fax: +1-619-523-5448; E-mail: Monica.a.lutgendorf.mil@mail.mil
Received 25 July 2020; Editorial Decision 3 January 2021; Revised 2 December 2020; Accepted 9 February 2021
Abstract
Objective: To assess the use of an evidence-based oxytocin protocol for management of the third
stage of labor to decrease non-beneficial clinical variation and improve clinical outcomes.
Design: This is a cohort study of pregnant patients delivering before implementation of an
evidence-based oxytocin protocol compared to patients delivering after implementation of an
evidence-based oxytocin protocol.
Setting: A level III maternal care referral hospital with an average delivery volume of approximately
3000 deliveries.
Participants: Pregnant patients delivering over a 60-month period from January 2013 to December
2017.
Intervention: An evidence-based oxytocin protocol: 3 units of oxytocin administered over 3 min-
utes, with a second 3-unit bolus if inadequate tone, then oxytocin infusion at 18 units/hour × 1 hour
and then 3.6 units/hour for 3 hours.
Main outcome measures: Postpartum hemorrhage (PPH) rate (EBL ≥500 ml for vaginal and
≥1000 ml for cesarean).
Results: Data from 14 603 deliveries were analyzed, 8408 pre-protocol and 6195 post-protocol. We
demonstrated a significant decrease in PPH from 5.2% to 2.9% (P < 0.001) and a small but non-
significant increase in the transfusion rate from 1.8% to 2.3% (P = 0.11).
Conclusion: A standardized oxytocin infusion protocol in the third stage of labor resulted in a
significant decrease in PPH for both vaginal and cesarean deliveries.
Key words: oxytocin infusion, postpartum hemorrhage, prevention, standardization, quality improvement
International Society for Quality in Health Care 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US. 12 Gonzalez et al.
Introduction evidence-based protocol. The working group consisted of representa-
tives from the departments of anesthesia, obstetrics and gynecology,
Worldwide postpartum hemorrhage (PPH) results in one maternal
maternal-fetal medicine and nursing.
death every 4 minutes [1]. PPH affects 4–6% of all deliveries and
The Plan-Do-Study-Act cycle for quality improvement was used
remains an important cause of morbidity and mortality in the USA
to complete the project. We identified our elevated PPH rate and the
[2, 3]. Active management of the third stage of labor decreases the
variation in oxytocin administration in the third stage of labor as
risk of hemorrhage following delivery and includes administration of
opportunities for quality improvement. Review of practices indicated
oxytocin, immediate cord clamping and cutting, controlled cord trac-
that postpartum oxytocin was administered in a non-standardized
tion and vigorous fundal massage. However, evidence-based analysis
fashion, at an unspecified and uncontrolled rate. Surveys of physician
of active management of the third stage of labor confirmed only oxy-
and nursing staff revealed that timing of postpartum oxytocin was
tocin administration as effective in decreasing PPH [4]. Though active
variable, with some initiating oxytocin with delivery of the anterior
management reduces the risk of bleeding after delivery, this reduc-
shoulder of the baby, while others initiated oxytocin with delivery
tion may be due to oxytocin alone, and prophylactic oxytocin is the
of the placenta. The amount and timing of oxytocin was also vari-
prevention strategy of choice in high-resource settings [5].
able, with the most common dose being 20 units oxytocin in 1 l of
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Though the literature supports the effectiveness of prophylactic
intravenous fluid. This was administered at a variable rate, with some
oxytocin at decreasing PPH and need for therapeutic uterotonics [6],
providers administering the oxytocin as a bolus, while others admin-
there are limited data regarding the most effective dose and timing
istering a bolus of oxytocin until adequate uterine tone was achieved,
after delivery [7]. Recent studies have shown that the dose of oxy-
and then the rate was slowed.
tocin needed to contract the uterus after cesarean delivery is lower
A rigorous review of the literature was conducted and five pub-
than previously used and there is a peak effect of bolus oxytocin [8].
lished articles were identified evaluating the use of oxytocin in the
Potential adverse effects have been associated with high-dose oxy-
third stage of labor after both cesarean and vaginal deliveries. Various
tocin, including significant cardiovascular side effects. There is also
oxytocin regimens were reported, as seen in Table 1. The published
limited information on ideal oxytocin dosing after vaginal deliveries
literature also supported a maximal effect of oxytocin following
[9, 10], and it is possible that higher doses of oxytocin are needed
cesarean delivery, and we determined that the standardized protocol
following labor due to saturation of oxytocin receptors.
should incorporate the studies demonstrating a minimum effective
We noted variable practices of oxytocin administration in the
dose of oxytocin [11]. Our goal was to develop an initial intravenous
third stage of labor at our institution, with oxytocin administered
infusion and a standard maintenance rate that could be applied to
at an unspecified and variable rate. Our goal was to develop an
both labored and unlabored cesarean deliveries and vaginal deliver-
evidence-based protocol for administration of postpartum oxytocin
ies. Using this evidence-based infusion protocol would also allow for
that would decrease non-beneficial clinical variation in oxytocin
rapid progression to other uterotonic medications and interventions
administration in the third stage of labor. Our objective was to
in the setting of PPH.
compare PPH rates in women who delivered before and after imple-
As our goal was to standardize the oxytocin infusion process for
mentation of the evidence-based PPH protocol.
both vaginal deliveries and cesarean deliveries, we developed a pro-
tocol that incorporated components of oxytocin infusions proven
Methods effective in both labored vaginal and cesarean delivery patients. The
This study was approved by the Institutional Review Board as a clin- standardized oxytocin concentration chosen for this protocol was
ical quality improvement project with a waiver of informed consent. 30 units of oxytocin in 500 mL of normal saline (the standard
The quality improvement project was conducted at Naval Medical oxytocin concentration also used for the induction and augmen-
Center San Diego, a large tertiary care academic medical center pro- tation of labor). The oxytocin infusion was administered on a
viding care to active duty personnel and eligible beneficiaries, with programmable intravenous pump with the infusion started with
∼3000 deliveries annually. We convened a multidisciplinary working delivery of the anterior shoulder of the baby (before delivery of
group to assess current practices related to administration of oxytocin the placenta). We chose an initial oxytocin bolus of 3-units over
in the third stage of labor, review the literature and develop an 3 minutes, which was the minimum effective dose of oxytocin to
Table 1 Comparison of published third stage of labor oxytocin regimens for the prevention of postpartum hemorrhage
Mode of delivery Start Bolus Infusion Postpartum infusion
Tita et al. (2012) [8] SVD After placenta – 10 units/500 ml × –
1 hour
Carvalho et al. (2004) [9] Unlabored CD With delivery 0.35 units 20 units/l @ 120 ml/hour –
in PACU
Munn et al. (2001) [10] Labored CD With cord clamp – 80 units/500 ml × 20 units/l at 125 ml/hour
30 minutes × 8 hours
Balki et al. (2006) [11] Labored CD With delivery 3 units + 0.5 units – 20 units/l at 120 ml/hour
× 8 hours
King et al. (2010) [15] CD with risk factors With cord clamp Five units 40 units/500 ml × 20 units/l at 125 ml/hour
30 minutes × 8 hours
DaGraca et al. (2013) [12] SVD and CD With delivery – 18 units/hour × 1 hour, 3.6 units/hour on L&D
double if atony
Abbreviations: SVD, Spontaneous vaginal delivery or vaginal delivery; CD, cesarean delivery; PACU, Post-Anesthesia Care Unit; (L&D), Labor and delivery.Postpartum oxytocin protocol • Original Research Article 3
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Figure 1 Evidence-based postpartum oxytocin protocol.
produce uterine tone in 90% of women who labored and then had During the Study phase, we analyzed the data using a before
a cesarean delivery [11]. At the end of this bolus (after 3 minutes), and after analyses of all charts coded with PPH. Data were col-
the nurse or anesthesiologist communicated with the delivering lected from the electronic medical record for deliveries in the pre-
provider to determine if uterine tone was adequate. If uterine implementation and post-implementation periods for a total of 60
tone was deemed inadequate or if the provider was concerned months, including the 34 months prior to implementation (January
about ongoing bleeding, a second 3-unit bolus was administered 2013 to September 2015) and the 26 months following implementa-
over 3 minutes. After one or two 3-unit boluses, the pump was tion of the oxytocin protocol (October 2015 to November 2017).
set at 18 units per hour for 1 hour, then 3.6 units for 3 hours The study period was selected to allow an adequate number of
to complete the 4 hour infusion protocol (Figure 1). This was based deliveries to monitor outcomes using control charts to monitor the
on DaGraca et al. [12] who studied a standardized third stage of labor process over time. For this study, with a pre-protocol hemorrhage
oxytocin protocol in women undergoing both vaginal and cesarean rate of 5.2% in 8408 subjects, and a post-protocol hemorrhage
deliveries. If there continued to be inadequate tone after the sec- rate of 2.9% in 6195 subjects, and an alpha of 0.05, the observed
ond 3-unit bolus, the oxytocin infusion was initiated at 18 units power is 99.8%. The electronic medical record was used to abstract
per hour and patients were treated for uterine atony using other charts for age, maternal weight, mode of delivery, birthweight, PPH
uterotonic medications and interventions such as uterine tampon- (defined as EBL ≥ 500 ml for vaginal delivery and EBL ≥ 1000 ml
ade balloon or other surgical interventions as needed. Data on PPH at delivery), transfusions and massive transfusions (≥4 units blood
(defined as estimated blood loss (EBL) ≥1000 ml), delayed PPH (PPH products).
after transfer from labor and delivery unit), transfusions and massive We compared the proportions of PPH, transfusions and massive
transfusions (≥4 unit blood products) were analyzed in the pre- and transfusions (4 or more units) using proportion charts (p-charts), to
post-implementation periods and interval analysis was planned. assess process changes and stability of data over time. Compliance
During the Do phase, we implemented the protocol on labor and with the new protocol was assessed with chart reviews. Categorical
delivery and the postpartum wards. This process involved planning, data were analyzed using Fisher’s exact test, and continuous data
training and education of anesthesia providers (anesthesiologists, were analyzed using the Mann–Whitney U test. Minitab 18 (State
residents, student nurse anesthetists and certified registered nurse College, PA) was used for statistical analysis.
anesthetists), obstetrics providers (OB/GYN physicians, residents
and certified nurse midwives) and nurses on labor and delivery and
the postpartum wards on the new protocol. We provided the evidence
supporting the change, the rationale for the protocol, as well as insti-
Results
tutional baseline data to encourage individual buy-in and support. The evidence-based oxytocin protocol was implemented on
As oxytocin was to be administered on a programmable pump, addi- 1 October 2015. The 60-month study period encompassed 14 603
tional training was completed to ensure that all nurses and providers deliveries at our institution: 8408 deliveries pre-protocol and 6195
responsible for administering oxytocin were trained on the new pro- deliveries post-protocol. Patient characteristics before and after
tocol, and this required pump re-programming was coordinated to implementation of the evidence-based protocol are shown in Table 2,
ensure all pumps were programmed with the infusion rates prior to and patient characteristics for PPH cases before and after implemen-
implementation. tation of the evidence-based protocol are shown in Table 3. Over the4 Gonzalez et al.
Table 2 Characteristics of the 14 603 patients before and after implementation of the evidence-based pitocin protocol
Pre-protocol January 2013–September 2015 Post-protocol October 2015–December 2017 P value
(n = 8408) (n = 6195)
Age (y) mean ± SD 31.5 ± 5.4 (95% CI 31.4–31.6) 29.5 ± 5.4 (95% CI 29.4–29.6)Postpartum oxytocin protocol • Original Research Article 5
Table 4 Characteristics of PPH cases stratified by mode of delivery before and after implementation of the evidence-based pitocin protocol
Pre-protocol Post-protocol P value
January 2013–September 2015 October 2015–December 2017
Vaginal (n = 5722) Vaginal (n = 4543)
Cesarean (n = 1969) Cesarean (n = 1627)
Vaginal PPH (≥500 ml) 234 (4.1%) 88 (1.9%)6 Gonzalez et al.
variation exists between national guidelines on the prevention and impacted outcomes and, thus, might limit the internal validity of this
management of PPH [7]. The most specific guidelines are from the study. Additionally, the definition of PPH evolved over the course of
Association of Women’s Health, Obstetric and Neonatal Nurses, the study period, initially defined as ≥500 ml for vaginal deliveries
with the recommendation for an initial 10-unit bolus over 30 minutes and ≥1000 ml for cesarean deliveries. Thus, it is notable that this
followed by administration of an additional 10 units of oxytocin definition change likely affected PPH rates, since there was a slightly
for a total time of 4 hours [14]. Using the Association of Women’s higher PPH rate for vaginal deliveries with EBL ≥1000 ml following
Health, Obstetric and Neonatal Nurses (AWHONN) recommen- protocol implementation. It is also known that EBL can be subjec-
dations would administer oxytocin at a rate of 0.33 units/minute tive and new recommendations suggest that quantitative blood loss
for 30 minutes followed by 0.04 units/minute for 3.5 hours. We (QBL) may be a more accurate assessment of blood loss at delivery
administered a physiologically effective initial dose of 1 unit/minute and, however, may also be associated with increases in PPH rates,
for up to 2 doses, followed by 0.3 units/minute for 1 hour and then particularly with implementation [20].
0.06 units/minute for 3 hours. Ultimately, prior studies have not The strengths of our project include the fact that this was a robust
determined the optimal dose, route and timing for the administra- process improvement project monitored over a 4-year period that
tion of oxytocin in the third stage of labor for the prevention of PPH. included 14603 deliveries, with a decrease in PPH rates and transfu-
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Our protocol implements current evidence supporting a maximum sions related to PPH at our institution. As we continue to monitor our
effective dose of oxytocin at the time of cesarean delivery [11]. data, we can further refine and improve the project. The standardiza-
The evidence regarding the relative benefit of bolus adminis- tion of our postpartum oxytocin administration process regardless of
tration versus infusion of oxytocin is mixed, with some studies mode of delivery are potential factors contributing to the protocol’s
supporting a benefit of bolus administration [9, 11, 15] and others success. Another strength of this protocol is the increased commu-
finding no benefit [12]. In this case, we chose to incorporate both a nication between delivering providers and anesthesia providers and
bolus and an infusion of oxytocin based on the available literature nurses, including the ability to efficiently move on to other uterotonic
and published guidelines [16]. We specifically chose to incorporate medications and interventions after the initial 2 boluses of oxytocin
an initial oxytocin bolus of 3 units over 3 minutes, which was the (6 minutes). This allows providers to quickly administer an effective
minimum effective dose of oxytocin to produce uterine tone in 90% dose of oxytocin and then move on to other agents without wast-
of women who had a cesarean delivery after labor [11]. With the rela- ing time administering additional oxytocin, when other uterotonics
tive lack of studies on the optimum dosing of postpartum oxytocin in are more likely to be effective. It is also notable that women deliver-
women who delivered vaginally, it is important to emphasize that our ing after exposure to oxytocin in labor may require higher oxytocin
improvements in PPH were seen in both vaginal and cesarean deliv- infusion rates [21]. Another benefit we noted with the standardized
eries. The fact that our protocol is standardized after delivery for all oxytocin protocol was the decrease in total intravenous fluids admin-
women is a benefit, and the robust use of standardized checklists and istered in the third stage of labor, by ∼40–50%, from 1 to 2 l to
protocols has been shown to improve outcomes and is recommended 530 to 580 ml (depending on whether patients received 1 or 2 initial
by the American College of Obstetricians and Gynecologists [16]. oxytocin boluses).
Our project has several strengths and weaknesses. The limitations
of our project include the wide variation of the studies on which
this protocol is based. The lack of clear evidence to base decisions Conclusions
is challenging; however, in the interest of process improvement, a
Our protocol has now been adopted across Navy Medicine facili-
process or protocol does not need to be superior to produce a ben-
ties, allowing consistency across facilities at which Navy physicians
efit. If a protocol has demonstrated equivalence, a benefit will be
and nurses may practice during their career. With this data, we
realized when applied in a standardized fashion across a population
propose that similar benefits and improvements may be realized in
[17]. Another limitation of our project is the fact that this evidence-
decreasing PPH on a large scale with the application of similar stan-
based protocol was implemented in the setting of increased attention
dardized evidence-based dosing of oxytocin in the third stage of
and focused on PPH with a comprehensive PPH bundle [18]. The
labor. Such improvements are important to improve outcomes and
bundle included adoption of a standardized definition of PPH (blood
decrease hemorrhage-related morbidity and mortality.
loss of ≥1000 ml at delivery), introduction of standardized PPH
carts, emergency checklists including hemorrhage management and
massive transfusion, massive transfusion protocol, ongoing regular
simulation and training, and systems reporting with real-time track- Funding
ing of PPH and transfusions. Such bundles and comprehensive safety None declared.
programs have been shown to produce improvements in outcomes
[13, 19], and we are unable to specifically prove that other factors
did not also contribute at least in part to the improved outcomes we Data availability statement
note after initiating this protocol. We note that the PPH bundle was
Due to its proprietary nature and ethical concerns, supporting data
adopted over 12 months prior to our oxytocin protocol; however,
cannot be made openly available.
ongoing improvements related to adoption of the oxytocin protocol
are possible.
We also noted differences in the baseline demographics of the
pre-protocol and post-protocol groups, with statistically significant Disclaimer
decreases in patient age, increases in patient weight, decreases in The views expressed in this article are those of the author(s) and do
birthweight and decreases in vaginal delivery rates. Despite the fact not necessarily reflect the official policy or position of the Depart-
that the absolute differences are small and likely to be of minimal ment of the Navy, Department of Defense, or the United States
clinical significance, it is possible that these differences could have Government.Postpartum oxytocin protocol • Original Research Article 7
Several of the authors are military service members. This work 10. Munn MB, Owen J, Vincent R et al. Comparison of two oxytocin regimens
was prepared as part of their official duties. Title 17 U.S.C. 105 to prevent uterine atony at cesarean delivery: a randomized controlled trial.
provides that ‘Copyright protection under this title is not available Obstet Gynecol 2001;98:386–90.
for any work of the United States Government.’ Title 17 U.S.C. 11. Balki M, Ronayne M, Davies S et al. Minimum oxytocin dose requirement
after cesarean delivery for labor arrest. Obstet Gynecol 2006;107:45–50.
101 defines a United States Government work as a work prepared
12. DaGraca J, Malladi V, Nunes K et al. Outcomes after institution of a new
by a military service member or employee of the United States
oxytocin infusion protocol during the third stage of labor and immediate
Government as part of that person’s official duties.
postpartum period. Int J Obstet Anesth 2013;22:194–9.
13. Shields LE, Wiesner S, Fulton J et al. Comprehensive maternal hemorrhage
protocols reduce the use of blood products and improve patient safety. Am
References J Obstet Gynecol 2015;368:272–80.
1. AbouZahr C. Global burden of maternal death and disability. Br Med Bull 14. Association of Women’s Health, Obstetric and Neonatal Nurses. Guide-
2003;67:1–11. lines for oxytocin administration after birth: AWHONN practice brief
2. Mhyre JM, D’Oria R, Hameed AB et al. The maternal early warning number 2. JOGNN 2014;44:161–3.
criteria. Obstet Gynecol 2014;124:782–6. 15. King KJ, Douglas MJ, Unger W, Wong A, King AR. Five unit bolus oxytocin
Downloaded from https://academic.oup.com/intqhc/article/33/1/mzab005/6067347 by guest on 09 April 2021
3. Main EK. Pregnancy related mortality in California. Obstet Gynecol at cesarean delivery in women at risk of atony: a randomized, double-blind,
2015;125:938–47. controlled trial. Anesthes Analg 2010;111:1460–6.
4. McDonald SJ, Middleton P, Dowswell T et al. Effect of timing of umbil- 16. American College of Obstetricians and Gynecologists. Clinical guidelines
ical cord clamping of term infants on maternal and neonatal outcomes. and standardization of practice to improve outcomes. ACOG Committee
Cochrane Database Syst Rev 2013;7:CD004074. Opinion No. 629. Obstet Gynecol 2015;125:1027–9.
5. Begley CM, Gyte GM, Devane D et al. Active versus expectant manage- 17. Clark SL, Belfort MA, Byrum SL et al. Improved outcomes, fewer cesarean
ment for women in the third stage of labour. Cochrane Database Syst Rev deliveries, and reduced litigation: results of a new paradigm in patient
2019;2:CD007412. safety. Am J Obstet Gynecol 2008;199:105e.1–7.
6. Salati JA, Leathersich SJ, Williams MJ et al. Prophylactic oxytocin for 18. Main EK, Goffman D, Scavone BM et al. National partnership for mater-
the third stage of labour to prevent postpartum hemorrhage. Cochrane nal safety consensus bundle on obstetric hemorrhage. Obstet Gynecol
Database Syst Rev 2019;4:CD001808. 2015;126:155–62.
7. Dahlke JD, Mendez-Figueroa H, Maggio L et al. Prevention and manage- 19. Einerson BD, Miller ES, Grobman WA. Does a postpartum hemorrhage
ment of postpartum hemorrhage: a comparison of 4 national guidelines. patient safety program result in sustained changes in management and
Am J Obstet Gynecol 2015;213:76.e1–10. outcomes?. Am J Obstet Gynecol 2015;212:140–4.
8. Tita AT, Szychowski JM, Rouse DJ et al. Higher-dose oxytocin 20. American College of Obstetricians and Gynecologists. Quantitative blood
and hemorrhage after vaginal delivery. Obstet Gynecol 2012;119: loss in obstetric hemorrhage. ACOG Committee Opinion No. 794. Obstet
293–300. Gynecol 2019;134:e150–6.
9. Carvalho JC, Balki M, Kingdom J et al. Oxytocin requirements at 21. Foley A, Gunter A, Nunes KJ et al. Patients undergoing cesarean delivery
elective cesarean delivery: a dose-finding study. Obstet Gynecol 2004; after exposure to oxytocin during labor require higher postpartum doses.
104:1005–10. Anesth Analg 2018;126:920–4.You can also read
