Espresso: Zuranolone for Postpartum Depression

We’re back! While we’ll operate for a bit on a reduced schedule (new episodes every-other-week), we are so excited to get back to podcasting and covering the need-to-know in OB/GYN. Thanks for all the love and support over the last few months! <3 Nick & Fei

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Reading: Zuranolone for the Treatment of Postpartum Depression (ACOG Practice Advisory)

What is zuranolone and why is it important? 

• We know that postpartum/perinatal mental health conditions and some of the leading causes of preventable maternal mortality 

• PPD affects approximately 14% of women 

• Understanding/discussing/recommending medication and treatment can potentially decrease maternal morbidity and mortality 

• Medication type

• Neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator 

• Oral medication  

• Recent FDA approval for use in PPD 

Why is zuranolone recommended, and what else is out there? 

• Why is it recommended? 

• Two phase 3 randomized double-blind, placebo-controlled multicenter studies 

• Primary endpoint in both: change in depressive symptoms in the Hamilton depression rating scale (HAMD-17) 

• 17 point scale 

• Assesses somatic (physical ie. loss of appetite), affective (mood ie. sadness), cognitive (thinking, ie. difficulty concentrating), and behavioral (ie. social withdrawal) symptoms of depression 

• Reliable and valid method of assessing and measuring depression 

• In both studies, those on Zuranolone showed significantly more improvement in their symptoms compared those in placebo 

• Treatment effect maintained at day 42 (4 weeks after last dose of zuranolone) 

• Why the HAMD-17? 

• More used in research settings, but anticipated that other validated tools (like EPDS or PHQ9) will be used in clinical settings 

• What else is out there? 

• Brexanolone - first FDA approved medication specifically for postpartum depression

• However, unlike zuranolone which is oral, brexanolone consists of a 60 hour in-hospital IV infusion, which may not be readily accessible 

• May be difficult to arrange inpatient admission 

• May also be difficult for patients to leave their newborns for 60 hours to get infusion 

• SSRIs 

• Not specific for postpartum/perinatal depression 

• Can be effective, but also may be difficult to find the correct SSRI

• Many SSRIs also require uptitration of dosage 

• What to consider when prescribing zuranolone 

• Consideration of zuranolone in the postpartum period (within 12 months postpartum) for depression that has onset in the third trimester or within 4 weeks postpartum

• Benefits: 

• Significantly improved and rapid resolution of symptoms 

• Risks: 

• Potential suicidal thoughts or behavior 

• Sedation - can make it so you can’t drive 

• Lack of efficacy data beyond 42 days 

• How to prescribe and take zuranolone 

• Daily recommended dose is 50 mg 

• Take in evening with fatty meal (400-1000 calories, 25-50% fat) for 14 days 

• Can reduce dose to 40 mg if CNS depression effects occur 

• If hepatic or renal impairment, start dose at 30 mg 

• Can be used alone or as an adjunct to other oral antidepressant therapy like SSRIs 

• Recommendation is to have effective contraception during treatment and for 1 week after final dose. There is a registry if pregnancy occurs 

• Warn patients about adverse reactions 

• Impaired ability to drive 

• CNS depressant effects 

• Increased suicidal thoughts and behaviors 

• Zuranolone does pass into breastmilk, but relative infant dose is smaller than that of SSRIs 

Espresso: Cord Prolapse

What is cord prolapse? 

• Definition 

• When the cord moves out of the cervix in front of the fetal presenting part; can usually only happen when rupture of membranes has occurred 

• Otherwise, it is called funic presentation (cord presenting with intact membranes)

• Uncommon: 1.4-6.2/1000 

• Majority of them happen in singleton gestation, but there is an increased risk in twin pregnancies of the second twin 

• Risk Factors

• PPROM - especially if the fetus is not in the cephalic position 

• Multifetal gestation 

• Polyhydramnios 

• Fetal growth restriction 

• Preterm labor 

• AROM when fetal head is not well engaged 

• Nearly half of cases are attributed to iatrogenic causes 

• 57% occur within 5 minutes of membrane rupture, and 67% occur within 1 hour of rupture 

• Why do we care? 

• Compression of the cord → vasoconstriction and → fetal hypoxia 

• Can lead to fetal death or brain damage if not rapidly diagnosed and managed 

How can I recognize cord prolapse? 

• Exam 

• Palpation of a pulsatile mass in the vaginal vault or at the cervix 

• No need for radiographic or laboratory confirmation 

• Fetal heart tracing 

• Usually can see recurrent variable decelerations or fetal bradycardia 

• Differential diagnosis 

• Another mass in the vagina could be fetal malpresentation 

• Other causes of fetal bradycardia/decelerations should also be considered 

How do I manage cord prolapse if it is found? 

• Reduction of the cord – if possible 

• This is usually not possible if there is large amount of cord in the vagina, and not recommended 

• However, if there is small amount of cord at the internal cervical os, at times, it is possible to reduce it back beyond the present part 

• However, if there is recurrent prolapse … 

• Expedient delivery

• Usually via cesarean delivery 

• Prior to getting to the operating room, the goal should be decompression of the umbilical cord 

• Elevate the fetal presenting part as interval to umbilical cord decompression can be associated with worse outcomes than interval to delivery 

• Decompression can be done manually: place finger or hand in the vagina and gently elevate the head or presenting part off of the umbilical cord 

• Do not put additional pressure on the cord → can lead to vasospasm 

• Another way of decompression 

• Place pregnant patient into steep Trendelenburg or knee-chest position 

• Usually if there is not a provider who is able to do manual decompression or if there is prolonged interval to delivery (ie. transfer to hospital) 

• If there is visible cord protruding from the introitus, try to place a warm, moist sponge or towel over the cord to prevent vasospasm

• Or can replace into vagina 

What are the outcomes, and how do I prevent prolapse? 

• Prognosis 

• Fetal mortality is <10% now that we are able to complete cesarean sections in a timely manner 

• In earlier studies, the range was 32-47% 

• Gestational age and location of prolapse (in or out of hospital) can significantly determine outcomes 

• Cord prolapse outside of hospital carries 18x increased risk of fetal mortality 

• Prevention 

• For patients who are at increased risk of cord prolapse (ie. PPROM, malpresentation), they should be encouraged to deliver at a hospital 

• Early recognition training by both patient and providers

• SIM! 

• ACOG recommend against routine amniotomy in normally progressing labor unless needed for fetal monitoring 

• AROM - if needed, make sure that there is engagement of the fetal head 

• If AROM is needed, but there is polyhydramnios or high fetal station, can use a fetal scalp electrode to rupture the amniotic sac to slowly release fluid 

Espresso: Uterine Rupture

What is uterine rupture? 

• Definition

• Spontaneous tearing of the uterine muscles which can lead to expulsion of the fetus into the peritoneal cavity

• In the literature, uterine rupture can also incorporate less catastrophic phenomena, like uterine window or asymptomatic scar dehiscence without expulsion of the fetus

• Focus today: intrapartum uterine rupture.

• The true incidence of uterine rupture across all populations in pregnancy is likely very low.

• With no history of surgery, the risk is 1/8000-17,000 deliveries 

• With one prior low transverse cesarean, the incidence has been reported to be between 0.2-1.5%, though usually quoted as <1% 

• With two prior low transverse cesareans, the incidence is reported to be between 0.8-3.9%, usually quoted as just over 1% 

• However, there are things that can modify this risk: 

• History of prior successful VBAC → reduce the risk of rupture from 1.1% to 0.2% 

• In other types of incisions such as T-incisions and classical incisions, the rate of rupture can be as high as 4-9%

• What are some other risk factors? 

• By far, the biggest one is previous uterine surgery,

• Other risk factors: 

• Uterine scar presence

• Uterine anomalies

• Prior invasive molar pregnancy

• History of placenta accreta spectrum

• Malpresentation

• Fetal anomaly

• Obstructed labor

• Induction of labor with use of prostaglandins

  • These other risk factors are much less significant than prior uterine surgery/presence of scar  

How do I recognize uterine rupture?

• Again — only be discussing uterine rupture in labor 

• There are a few studies looking at thinning of the myometrium on ultrasound, but this is controversial.

• It is much more likely that you will encounter uterine rupture at time of labor and birth than during other times 

• Diagnosis

• High index of suspicion - know your patient’s risk factors and be on the lookout for uterine rupture given how catastrophic it can be for both maternal and fetal wellbeing 

• Some of the classical signs: 

• Sudden, tearing uterine pain

• Vaginal hemorrhage

• Cessation of contractions 

• Destationing of the fetal head 

• However, these classical signs are actually not necessarily reliable and not always present! 

• The most reliable presenting clinical symptom is actually fetal distress 

• One study of 99 patients with uterine rupture showed: 

• Only 13 patients reported pain and 11 had vaginal bleeding 

• However, bradycardia or signs of fetal distress (decelerations) were present in the majority.

• Ultrasound examination 

• Not necessarily reliable and if you are truly suspicious of uterine rupture, this should prompt immediate delivery 

• Why do we need to diagnose uterine rupture promptly? 

• Maternal complications

• Maternal circulatory system delivers 500 cc of blood to the uterus every minute 

• Uterine rupture increases the risk of hemorrhage, with studies showing that about 50% of cases result in EBL of 2000cc or greater 

• This can lead to need for blood transfusion, and in more dire circumstances, hysterectomy  

• Fetal complications 

• Depends on how quickly the neonate is delivered after recognition of uterine rupture 

• One study showed a neonatal mortality rate of 2.6%, and increases to 6% if uterine rupture occurs outside of the hospital

• Older literature report rates as high as 13%  

• Many neonates will require resuscitation and admission to the NICU 

Management

• The best form of management is prevention or setting expectations - ie. counseling 

• All patients who desires a trial of labor after cesarean section should be counseled about the risks and benefits of TOLAC 

• Patients should deliver at a location where labor and delivery staff, anesthesia staff, and neonatal staff are available 24 hours in order to facilitate prompt delivery if needed. 

• Patients who are at high risk of uterine rupture (ie. classical cesarean, T-incision, prior uterine rupture, >2 cesarean sections, history of prior fundal surgery) should be counseled against TOLAC 

• We did a whole episode on TOLAC counseling back in 2019, so check it out here: https://creogsovercoffee.com/notes/2019/9/22/trial-of-labor

• Note that the VBAC calculator we included in those notes is outdated! 

• There is a new VBAC calculator available that does not include race as a predictor: https://mfmunetwork.bsc.gwu.edu/web/mfmunetwork/vaginal-birth-after-cesarean-calculator

• What if it happens? The answer is prompt delivery via cesarean delivery 

• Urgent delivery - as quickly as possible, but within 30 minutes generally 

• Patient can be under general anesthesia or if they already have working regional anesthesia, this can also be used 

• Cesarean delivery should be performed, and if there is a uterine rupture, the neonate can often be delivered via the area of rupture without creating a new hysterotomy 

• However, if there is just a uterine window, a hysterotomy may be needed 

• Once the neonate is delivered, pediatrics should be there immediately to facilitate resuscitation 

• If uterine rupture is confirmed, a full exam of the uterus should be done to assess for other injury 

• Ie. bladder injury, broad ligament hematoma 

• If possible, the area of rupture should be repaired 

• However, if it is not possible to repair the rupture due to significant damage, patient is not stable, or significant hemorrhage, then the next step should be hysterectomy 

• Follow-up 

• Debriefing - this should occur with the team who was present for uterine rupture 

• But also, should discuss with your patient when they are at a place when they can discuss what happened 

• Counsel patient that if they desire future pregnancy, TOLAC should not be attempted due to increased risk of repeat rupture 

Espresso: Debriefing

What is a debrief?

• Conversation involving frontline workers taking part in a patient’s care that occurs shortly after the event takes place.

• Can be used for a number of purposes:

• Knowledge or skill attainment (individual learning)

• Describe threats to patient or worker safety, or threats to team dynamics (systems learning)

• Provide closure for individuals involved in a clinical situation (therapeutic)

• Debriefing is not the same as a true “root cause analysis” (RCA) but may be a first-step in performing RCA.

• Cornerstone of clinical and simulation-based education.

When should a debrief occur?

• Defining set triggers in which debriefs should occur has been identified as best practice to:

• Set expectations amongst staff when they should occur, and how frequently

• Increase frequency of debriefs

• Promote system-wide goals

• In OB/GYN, there’s not a standard list of what should generate a debrief; but you might imagine there’s a few major events that we commonly think of as emergencies:

• Shoulder dystocia, or difficult extraction at cesarean

• Significant postpartum or surgical hemorrhage events

• Unexpected newborn complication

• Unexpected surgical complications or unexpected intraoperative findings

• Patient injury or serious complication, unanticipated ICU admission, or death

• Many of these events may be defined locally; and if you don’t have a list defined at your institution, it is worth asking about it and starting one!

• In general, it is good practice to also have a “staff member request” as a trigger for considering a debriefing to empower any person on the team to review events that may be unusual or uncomfortable.

• Best practice has identified that the “hot debrief” (i.e., shortly after the event) is helpful to staff immediately involved and provides opportunity to get a very clear clinical picture.

• “Cold debrief” (i.e., one done much later) will allow for more data to be collected, but worsens recall of participants and also removes some of the other advantages that a hot debrief may enable - i.e., finding time for staff to attend, identifying learning points immediately after event, etc.

• A cold debrief can certainly be performed later on - in some institutions, this is performed through the “M&M” process with which all residents are likely familiar!

How should a “hot debrief” be done?

• Three general stages of debriefing:

• Preparation

• Delivery

• Post-Debrief

• Preparation

• If a debrief is requested/triggered, all staff should be invited.

• A time and location should be identified, ideally soon after the event occurred.

• A facilitator should be named, and a second person can serve as a scribe for documentation (more on that later)

• Ideally, the facilitator should be a designated person who was not the team leader or heavily involved in the events. 

• At UW L&D, this is often our charge nurse or another senior nurse who serves to facilitate.

• This helps to eliminate any issues of hierarchy/power and encourages all voices to speak up.

• Any other concerns to allow for optimal debrief should be addressed - short time period for cross-coverage by other personnel, for instance. 

• Delivery

• Facilitator should set expectations at the start:

• Aim for brevity of debrief (5-10 minutes ideal)

• Establish psychological safety - not to blame or punish, but to review and characterize event.

• Invite the team leader to provide a summary of the case.

• The facilitator should encourage the team leader to provide an objective case overview at this point - the focus should be on the “actions” that occurred. 

• Provide reassurance that the next step of the debrief will be to focus on reflection and judgements.

• After the event summary, the Facilitator should then start conversation according to a specific structure to review the event:

• Many possible structures, but broadly fall into:

• Review things that went well.

• Review opportunities to improve.

• Identify points for action and “take home” learning points.

• Your institution likely has a “debrief form” that helps to guide these conversations. However, some of the more significant ones described include:

• TALK - Target, Analysis, Learning Points, Key Actions

• INFO - Immediate, not For personal assessment, Fast facilitated feedback, Opportunity to ask questions

• STOP5 - Summarize, Things that went well, Opportunities to improve, Points to action, Responsibilities

• Seven Step After Action Review - US Army tool which has been adapted to QI.

• And many more exist!

• Post-Debrief

• Facilitator and scribe can review that action points are recorded.

• If appropriate, can assign action items to specific individuals for follow up.

• Documentation should be completed at this time.

• Again, debrief forms are often present in hospitals for these purposes as part of QI review. Sometimes this may be incorporated into your patient safety reporting system.

• Medico-legally, debrief processes and forms are most frequently considered protected information through quality and safety structures. 

• Your legal department can help ensure all pieces are structured to meet this standard.

Additional Info: 

AHRQ https://psnet.ahrq.gov/primer/debriefing-clinical-learning 

Contemporary OB/GYN: https://www.contemporaryobgyn.net/view/debriefing-after-adverse-outcomes-opportunity-improve-quality-and-patient-safety  

Espresso: The Emergency Department Consult

Why do patients come to the ER with GYN complaints?

• A whole host of reasons! But some of the most common:

  • Bleeding irregularities – heavy bleeds, mistimed bleeds, unusual bleeding

  • Pain – PID, ovarian cysts, ectopic pregnancy, ovarian torsion, endo, non GYN pain issues

  • Infections – Bartholin’s and other cysts, UTIs, PID

  • Urinary complaints – most often retention or incomplete voiding

  • OB - patients who haven’t established prenatal care, or otherwise sick OB patients (trauma, medical issues) may be first evaluated in the ED

  • Sexual assault and injuries, such as lacerations

Before the Consult: What the EM Clinician Should Do

• Normal EM things – obtaining your acute history and HPI, vital signs, physical exam, and getting the “sick vs not sick” intuition.

  • Consider pregnancy test and pelvic exam as part of your basics.

    • Pregnancy tests should mostly be protocolized for appropriate patients in EDs, but also frequently missed in the evaluation of reproductive-aged patients.

      • If positive – be sure that your labs include a type-and-screen for Rh status, and likely plan on an ultrasound (especially if the diagnosis of pregnancy is new).

    • Pelvic exams are controversial, and we see the argument:

      • OBs are specialized in performing the exam, and we’re likely to repeat it.

      • However, particularly with bleeding – having a sense of whether the bleeding is light, moderate, or heavy/rapid helps us triage the consult urgency and a differential! 

        • Contraindications to digital pelvic exam –

          • Suspected rupture of membranes at 34 weeks or less (unless laboring);

          • Bleeding in pregnancy without confirmation of placental location.

        • OB residents – this is a long-standing controversial issue and training / advice will differ based on region and one’s own biases.

          • If it hasn’t been done and you can’t go to evaluate immediately, ask kindly for it to be performed and for a call back if the bleeding is concerning. 

      • EMs, consider bouncing back with your OB/GYN colleagues when they do a pelvic exam!

        • Getting to do these exams and then comparing your findings will help you to gain comfort with making calls when you’re in the community on your own!

What constitutes an emergency consult?

• Sometimes, things can’t wait!

  • If you have clinical suspicion of ovarian torsion or ruptured ectopic pregnancy, those are surgical emergencies and so merit a rapid response from your GYN colleagues.

  • Heavy vaginal bleeding (>1 maxipad per hour) and/or hemodynamically unstable patient – can range from ectopic pregnancies to gynecologic cancers - need an expert in exam present to help triage.

  • Major OB traumas – ideally, this should prompt OB to be present at the time of patient arrival or rapidly.

  • The “sick” OB patient – this should also prompt OB to be present rapidly, especially if the patient is “viable” or the uterus is at/above umbilicus. Considerations for delivery might need to be made.

    • Common reasons for this could be DKA in pregnancy, sepsis in pregnancy or septic abortion, or other decompensated illness.

Framing the ED Consult

• For our EM colleagues, we love the mnemonic BLUF: bottom line, up front.

  • “This is a consult for possible ectopic and hemodynamic instability” immediately grabs our attention.

  • Follow with that history though so we can help:

    • Gs and Ps – even we mess these up, so just sharing some important pregnancy history can be more helpful (i.e., G3P0020 is less helpful than “two prior ectopics.”)

    • Nature of presenting complaint: as you normally would

    • Vitals / hemodynamic status

    • Laboratory and imaging evaluation done or ongoing

  • In the less-emergent patient, lead off with your BLUF by starting with the specific question or ask:

    • I.e., “This is a consult for a pregnancy of unknown location, and we need your assistance in confirming the findings and coordinating follow up.”

• For our OB colleagues, help facilitate this conversation:

  • Ask for the BLUF – “before we get to her history, can you tell me what your primary clinical concern or question is? That just helps me to triage more appropriately.” 

  • Recognize you’re not going to always get a history or question on a silver platter.

  • Formulate your differential even if it seems like a slam dunk – and make sure you’re asking the right questions to get there

    • For instance, common misses include pregnancy tests, Rh status.

  • When in doubt, go see the patient faster! You’re the expert here and your expertise is being requested. 

  • Follow up with colleagues after you see the patient, or even better as you are getting ready to see them – particularly at training facilities, your EM resident colleagues may want to go see the patient again with you to get confirmatory findings, pearls of wisdom for their independent practice, and help with counseling.