Postpartum Hemorrhage – Medications to Treat Uterine Atony
ACOG defines PPH as cumulative blood loss ≥ 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process (including intrapartum) regardless of route of delivery. Unfortunately, postpartum hemorrhage (PPH) is still a leading cause of maternal mortality worldwide. Following this summary, you can find excellent professional resources at the California Maternal Quality Care Collaborative (CMQCC) and ACOG Safe Motherhood Initiative sites.
CLINICAL ACTIONS:
In the setting of PPH, consider the 4 ‘T’s
Tone (atony)
Trauma (laceration)
Tissue (retained products)
Thrombin (coagulopathy)
Uterine atony is the single most common cause of PPH (70-80%)
250 micrograms IM (may repeat in q15 – 90 minutes, maximum 8 doses)
OR
Intramyometrial: 250 micrograms
Avoid: Asthma
Caution: Hypertension, Active Hepatic, Pulmonary, Cardiac Disease
Misoprostol (Cytotec)
600 – 1000 micrograms PR, PO or SL
Hypersensitivity to this medication
NOTE: Contraindications include hypersensitivity to the specific medication
More on Tranexamic Acid (TXA)
ACOG Update (2017)
In the WOMAN trial (see Related OBG Topics below) women with PPH received
1 g in 10 mL (100 mg/mL) of tranexamic acid intravenously at a rate of 1 mL per min (i.e., over 10 min)
If bleeding continued after 30 min or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid could be given
Tranexamic acid, administered within 3 hours of birth, has been shown to significantly reduce maternal death due to PPH by approximately 30%
Based on improved outcomes and lack of adverse events including thromboembolism, ACOG has updated the practice bulletin to include the following
Although the generalizability of the WOMAN trial and the degree of effect in the United States is uncertain, given the mortality reduction findings, tranexamic acid should be considered in the setting of obstetric hemorrhage when initial medical therapy fails. (Level B evidence)
World Health Organization Update (2017)
Based on evidence review, WHO also supports the use of tranexamic acid with postpartum hemorrhage
Early use of intravenous tranexamic acid (within 3 hours of birth) in addition to standard care is recommended for women with clinically diagnosed postpartum haemorrhage following vaginal birth or caesarean section (Strong recommendation, moderate quality of evidence)
Administration of TXA should be considered as part of the standard PPH treatment package and be administered as soon as possible after onset of bleeding and within 3 hours of birth
The reference point for the start of the 3-hour window for starting TXA administration is time of birth
If time of birth is unknown, the best estimate of time of birth should be used as the reference point
TXA should be used in all cases of PPH, regardless of whether the bleeding is due to genital tract trauma or other causes
CONSIDERATIONS IN COVID POSITIVE PATIENTS
Tranexamic Acid (TXA)
COVID-19 appears to be a hypercoagulable state
TXA can be considered for the treatment of PPH in keeping with guidance for non-COVID-19 patients
However, ACOG states
because of the possible additive effect of the increased risk of thrombosis from COVID-19 infection and the hypercoagulative state of pregnancy, it may be prudent to consider this increased likelihood of clotting before administering TXA for postpartum hemorrhage
Hemabate
While Hemabate is not used in asthma due to risk for bronchospasm, patients with COVID-19 have respiratory symptoms consistent with viral pneumonia
While there is no data specific to COVID-19 and this medication, “Hemabate is not generally withheld” in patients with viral pneumonia
SYNOPSIS:
The key to managing PPH is identifying the severity of the situation early and quantifying estimated blood loss (EBL). A second large bore (16 gauge or larger) should be placed and Ringers Lactate used to replace blood loss at 2:1 while, simultaneously as the team is notified, medications are administered to the patient and massive transfusion protocol is initiated. Initiate fundal massage and place a Foley catheter.
KEY POINTS:
ABCs
Airway: Assess and stabilize
Breathing: Supplemental oxygen, 5-7 L/min by tight face mask
Consider intrauterine balloon tamponade or compression sutures for refractory atony
Surgical Interventions may be a life-saving measure and should not be delayed while waiting to correct coagulopathy
Quantitative measurement of blood loss is more acurate than visual estimation (see ‘Learn More – Primary Sources’ below) and require 2 key elements
Direct measurement of blood loss
Protocols for collecting and reporting a cumulative record of blood loss following delivery
Note: The FDA, the World Health Organization, and other professional bodies have released an alert following drug-error deaths related to TXA | TXA use during cesarean delivery has been associated with fatal accidental intrathecal administration because the ampoules of local anesthetic and tranexamic acid are similar in appearance | TXA should not be stored on or near an anesthetic trolley
A New Intrauterine Device to Treat Postpartum Hemorrhage
BACKGROUND AND PURPOSE:
A new device has been developed that can apply low-level intrauterine vacuum (70–90 mm Hg) to facilitate uterine contractions and constrict blood vessels
D’Alton et al. (Obstetrics & Gynecology, 2020) evaluated the effectiveness and safety of this device to treat PPH
METHODS:
Multicenter, prospective, single-arm treatment study
Participants
Delivery ≥34 weeks
Normal uterine anatomy
Atony-related blood loss
Vaginal delivery: 500 to 1,500 mL
Cesarean: 1,000–1,500 mL
Unresponsive to uterotonics and uterine massage
Intervention
Intrauterine vacuum device
Primary effectiveness outcome
Proportion of participants treated with intrauterine vacuum device that did not require escalating interventions
Primary endpoints
Device-related adverse events
Incidence | Severity | Seriousness
Secondary endpoints
Time to bleeding control
Rate of transfusion
Device usability scored by each practitioner
RESULTS:
106 participants
Successful treatment: 94% (95% CI, 88 to 98%)
Median time to control: 3 minutes (IQR 2.0 to 5.0 min)
Adverse events related to the device
8 events
All were outlined as risks in the study
All were resolved without serious clinical sequelae
Postpartum Hemorrhage Prophylaxis: The World Health Organization Recommendations
SUMMARY:
Uterotonics for PPH prophylaxis are administered immediately prior to or after placental delivery. The World Health Organization (WHO), based on an extensive review, has provided guidance on the efficacy and safety of uterotonics for the prevention of PPH. In addition, the WHO recommendations provide evidence-based guidelines on the drugs of choice. These recommendations apply to both vaginal and cesarean delivery.
KEY POINTS:
Efficacy and Safety
Only one of the following uterotonics should be used for PPH prophylaxis
Heat Stable Carbetocin: A Heat-Stable Alternative to Oxytocin?
BACKGROUND AND PURPOSE:
Oxytocin is the first line drug for prevention of PPH but due to the necessity for cold-storage, it is not always a viable option in many parts of the world
Heat-stable carbetocin is an oxytocin analogue
Maintains stability with ≥95% peptide purity over 36 months, even at 30°C and 75% relative humidity
6 months at 40°C
3 months at 50°C
Optimum pH 5.45 (5.25–5.65)
Not sensitive to freezing or light
Widmer et al. (NEJM 2018) compared the efficacy of heat-stable carbetocin to oxytocin for PPH prevention
Patients were randomized to the following study arms
Heat-stable carbetocin 100 µg IM
Oxytocin 10 IU IM
Postpartum blood loss calculated as follows
Blood collected in plastic drape
Blood collected for 1 hour or for 2 hours if bleeding continued
Drape (including the blood) was weighed (grams) converted to volume (mm) after weight of drape subtracted
Primary outcomes
Composite outcome of (1) proportion of women with blood loss of at least 500 ml; (2) Use of additional uterotonic agents at 1 hr and up to 2 hrs
Proportion of women with blood loss of at least 1000 ml
Secondary outcomes
Other measurements related to blood loss (e.g., additional medications/interventions)
Adverse effects
RESULTS:
29,645 women underwent randomization
Primary outcome #1: The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents
14.5% in the carbetocin group vs 14.4% in the oxytocin group
Consistent with non-inferiority of carbetocin
Primary outcome #2: The frequency of blood loss of at least 1000 ml
1.51% in the carbetocin group vs 1.45% in the oxytocin group
Close to showing non-inferiority of carbetocin but may have been underpowered (upper 95% confidence limit exceeded the noninferiority margin)
Researchers planned on 2% 1000 ml blood loss but in the study, 1000 ml blood loss was approximately 1.5%
The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between groups
CONCLUSION:
Heat-stable carbetocin performed similarly to oxytocin in preventing blood loss of at least 500 ml or use of other uterotonic agents
Noninferiority was not shown for the outcome of blood loss of at least 1000 ml (study was not sufficiently powered for this outcome)
The authors state “These data inform care of women in parts of the world where a lack of heat stability is a barrier to the effective prevention of postpartum hemorrhage.”
How Effective is Intrauterine Balloon Tamponade for Severe Postpartum Hemorrhage
BACKGROUND AND PURPOSE:
90% of maternal deaths from postpartum hemorrhage (PPH) are considered preventable
Recent publications report balloon tamponade success rates to be approximately 80%
Previous studies did not include control groups
Revert et al. (Obstetrics & Gynecology, 2017) compared the rates of invasive procedures for postpartum hemorrhage between a perinatal network that uses intrauterine balloon tamponade vs another that does not
METHODS:
Population-based retrospective cohort study (2011 – 2012)
Patients: All women who gave birth in two French perinatal networks
Both units used standardized French national PPH guidelines
Intervention cohort incorporated the use of intrauterine balloon tamponade for
PPH due to uterine atony unresponsive to prostaglandin E2 analog after vaginal delivery or
Delayed PPH after cesarean delivery
If PPH remained uncontrolled following noninvasive treatments, invasive procedures were initiated, including
Outcomes were quantified based on discharge data from the national French medical information system
General and obstetric characteristics were included in two separate models according to mode of delivery to estimate the independent association of the network with invasive procedures
RESULTS:
In the balloon tamponade cohort, there was
A significantly lower proportion of women undergoing at least one invasive procedure (3.0/1,000 vs 5.1/1,000; P<.01)
A significantly lower proportion of women undergoing arterial embolization (0.2/1,000 vs 3.7/1,000; P<.01)
After controlling for potential confounding factors
The risk of an invasive procedure among women who delivered vaginally remained significantly lower with the use of balloon tamponade for vaginal birth (adjusted odds ratio [OR] 0.14; 95% CI 0.08–0.27) but not cesarean (adjusted OR 1.19; 95% CI 0.87-1.61)
CONCLUSION:
The authors recognize study limitations including (1) the lack of coding for compression suture and (2) the two cohorts were not identical in application of anti-PPH invasive procedures
The results of this large population cohort study confirm previous literature
Intrauterine balloon tamponade for PPH following vaginal delivery is associated with lower use of invasive procedures
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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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