Methotrexate Failure in Non-Ruptured Ectopic Pregnancy – REBEL EM – Emergency Medicine Blog

by pregnancy journalist

Background: 1st trimester vaginal bleeding and abdominal pain is a common complaint seen in the ED.  As EM physicians it is important to make the diagnosis of ectopic pregnancy early in the clinical course as it can prevent rupture, difficulty with future fertility, and even death.  Typically, when non-ruptured, hemodynamically stable, ectopic pregnancy is diagnosed, our Ob/Gyn colleagues get consulted and the usual first-line treatment is methotrexate initiated in the ED with 24 – 72hours follow-up in an ideal world. Unfortunately, this does not always happen, and some patients will return to the ED for increased pain. It is important to be aware of methotrexate outcomes and have suspicion for failure of methotrexate in patients returning to the ED.

What They Did:








Author Conclusion:

“The proportion of patients failing methotrexate as first-line treatment was higher than previously reported.  Further investigation is needed to determine whether methotrexate failure was due to non-adherence to recommended guidelines.”

Clinical Take Home Point: Despite the authors quoting a 17.8% failure rate with medical management of non-ruptured, hemodynamically stable, ectopic pregnancy with methotrexate, a more appropriate statement would be that in patients who received methotrexate without relative contraindications (pre-treatment bHCG level >5000mIU/mL, presence of fetal cardiac activity ectopic pregnancy size >4cm), 12 (9.1%), had an ectopic rupture, which is a more accurate estimation.

Expert Peer Review

Jessica Pescatore, DO
Attending Obstetrician/Gynecologist
Jefferson OB/GYN Associates
Mullica Hill, NJ

First trimester bleeding occurs in approximately 20-40% of pregnancies, which may prompt patients to seek ER evaluation. Of these, most are secondary to threatened or spontaneous abortion.   However, the most worrisome cause of first trimester bleeding and one that must always be on a provider’s differential is that of ectopic or tubal pregnancies.  These only account for approximately 2% of all first trimester bleeding, but if misdiagnosed or mistreated, can have catastrophic outcomes.

Treatment of ectopic pregnancy can range from expectant management (rare but used on case-by-case basis), medical (methotrexate) and surgical (salpingostomy, salpingectomy).  The optimal treatment depends on a variety of factors, including patient reliability and compliance with laboratory testing and office visits, relative contraindications to medical therapies (HCG level, fetal cardiac activity, ectopic size), absolute contraindications (hypersensitivity to drug, renal or hepatic lab abnormalities), clinical exam findings and patient preference.

In this paper, the authors used a retrospective chart review to assess the outcomes of patients diagnosed and treated for an ectopic pregnancy using methotrexate.   Medical therapy with methotrexate has a success rate of approximately 90% in treating diagnosed tubal pregnancies with minimal side effects. These authors found that the failure rate of methotrexate was slightly higher in their patient population (17.8%), however this does not parse out patients who had one or more “relative” contraindications to this type of management.  In the patient population without any contraindications, failure rate of methotrexate was closer to the standard (9.1%).

I think it is important to reiterate that although a patient may have a relative contraindication to methotrexate; it does not preclude her from receiving this therapy.  Rather, it emphasizes the need for clinicians to have detailed discussions with their patients regarding worrisome signs and symptoms for which to return to the ER for evaluation.  In addition, patients should be counselled that while success rates can be as high as 90%, there is still a risk for tubal rupture, which would require emergent surgical intervention.


 Post Peer Reviewed By: Rick Pescatore, DO (Twitter: @Rick_Pescatore)

This content was originally published here.

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