Just what is Methotrexate, anyway…?

22 yo female presents to the ER c/o 11 days of lower abdominal pain, crampy in nature, but unrelenting.  Pain is much worse when she moves, walks, bends over, or tries to walk up stairs.  Denies fever but has had occasional chills.  Able to keep down food, denies any dysuria.  She was seen in another ER 10 days ago and diagnosed with ectopic pregnancy and given methotrexate.  At day 2 post-administration of methotrexate, she was still having minimal abdominal pain with vaginal discharge so she returned to the original ER where she was given methotrexate for reevaluation.  At that time she was passing small clots, and a quantitative bHCG was somewhat reduced from her initial bHCG at diagnosis of ectopic pregnancy (3700 mIU to 3500 mIU). Since it was trending in “the right direction,” she was told she would feel better in a few days and that she could follow up with her PCP.  She can’t get in to she them, and she is at the point where she can barely walk without severe pain.  This was her first pregnancy and she has been sexually active since being given the methotrexate.  Other than still passing clots, denies other vaginal D/C.

PMH/PSH – bipolar D/O

Med: Lamictal

Allergies: None

She is a smoker and drinks occasionally – no illicit or recreational drug use.

BP 114/70
HR – 80
RR 16
O2Sat 98% RA
Pain 7/10 without movement, 10/10 with palpation or any movement involving belly

Physical Exam
AOx3, appears very uncomfortable, cannot find a comfortable position on the stretcher, cool to touch
Chest – RRR, no M/R/G
Abdomen – very TTP, (+ rebound tenderness in lower quadrants).  Does have good bowel sounds.  CVAT unremarkable.  10/10 pain elicited when palpating LLQ area
Vaginal – passing blood – speculum exam deferred until seen by OB
Skinis pale, cool and moist.
Rest of physical exam is non-contributory

Ok, a few things:

1)   What is the most likely diagnosis?
2)   What do you want to do to test for this?
3)   What is the definitive treatment?
4)   What argues against the most likely diagnosis?
5)   Can you postulate a theory that encompasses all of the facts as presented to provide a single, unifying diagnosis?

Feel free to ask about other labs, imaging, etc – but I want you to think through this first as to what’s going on before jumping into labs, etc.  This is one of those diagnoses that exam alone diagnoses.  You have everything you need.  I will post final picts as well, along with labs, once we get to that point.


Ectopic OR

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11 Comments on "Just what is Methotrexate, anyway…?"

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  1. MediMike says:

    1) What is the most likely diagnosis?

    Methotrexate is used to perform chemical abortions for ectopics…if I remember correctly. Also, if I can pull some more info from my already overworked brain, there is a definite number of cases where it doesn’t work. Ectopic pregnancy.

    2) What do you want to do to test for this?

    With a bHCG already obtained, and still high, although “trending down”, I believe an U/S would be appropriate in this situation.

    3) What is the definitive treatment?

    If I am correct in my assumption than a surgical approach is necessary at this time.

    4) What argues against the most likely diagnosis?

    The patient’s VS are all WNL, but her skin is throwing me off, actively compensating?

    5) Can you postulate a theory that encompasses all of the facts as presented to provide a single, unifying diagnosis?

    Methotrexate that was ineffective in aborting the ectopic, (also wasn’t followed up with misopstrol which I think is the proper procedure), with a still elevated bHCG and continued abdominal px I believe than an US would give us the answer we’re looking for…?

  2. EMEDPA says:

    I would also be concerned about the possibility of heterotopic pregnancy- that’s one IUP and 1 ectopic at the same time.
    her exam sounds like ruptured ectopic. given her rebound on exam/skin signs, etc.
    she needs repeat u/s(bedside best-don’t send potentially unstable pts to radiology), repeat hcg, type and cross, and stat ob eval for likely trip to o.r..
    if ob arrives before u/s they might just do bedside and go staright to o.r.
    I think she is in compensated shock and needs fluids now before her vs tank.

  3. MediMike, E,

    Recheck on the quant bHCG at this visit was 515, very reassuring that the methotrexate itself worked. Knowing this, would it alter how to approach this patient?

    Of note, a transvag bedside U/S was indeed done, and there were findings consistent with clotted blood vs. free fluid in the cul-de-sac. Does knowing this change your thoughts on any of it?


  4. emedpa says:

    given the belly findings I am still thinking ruptured ectopic although certainly other stuff could be responsible for the peritoneal signs at the same time. there is no law that says you can’t have a ruptured appy for example and an ectopic at the same time, etc.
    I had a great case a few years ago of a pt with acute cholecystitis and R sided pyelo at the same time.
    what is the white count and h+h?
    in “the old days” might even do a DPL on this pt.
    did the u/s look at stuff other than gyn pathology or was a ltd study done? would consider a stat noncontrast ct at this point unless an obvious dx is found with full abd u/s.

  5. E,

    That is a very important point. Just because one pathology has occurred doesn’t mean another one cannot as well. Sounds like we have had similar cases… pathology begets pathology.

    Hct was 32.1
    WBC 18.5
    rest was unremarkable except the bHCG at 515.

    So far, working diagnosis of ruptured ectopic after methotrexate treatment. Any other takers?

    I’ll put up the picts from the OR in a few days. She did go to the OR…


    • PM2PA says:

      Every time I see LLQ pain, I think of diverticulosis. Perhaps this one ruptured? Skin signs sounds like she’s going into shock, but surprised she’s not tachy yet.

      • Agreed – diverticular disease is high on the list when I think of LLQ pain. But in this instance, sexually active young female with known ectopic pregnancy, and peritoneal signs, tic disease was low on the differential. However, I gave a lot of thought to PID, ruptured ectopic, ovarian torsion, colitis, or even a ruptured appy.

        Do you think she is in a stage of shock? If so, which stage? What supports that assumption? What does pain itself do to you? And what does peritonitis do to you? She does have peritoneal signs… does that suggest anything in terms of systemic pathology?


        • PM2PA says:

          If anything she is most likely in the very early stages of compensated hypovolemic shock due to cold and clammy skin, but tachycardia is the first classic sign. She is also still normotemsive (no narrowed pulse pressure) and not tachypnic.

          I can’t say for sure what peritoneal signs are for certain right now, but I’d guess her inability to walk without severe pain and rebound tenderness are two of them. She also cannot find a comfortable position on the stretcher so there might be widespread peritonitis from the ectopic/whatever she has secondary to it.

          • MediMike says:

            Okay good point about the px leading to an adrenergic response hence the skin signs, the v/s are still throwing me off a little bit though, anecdotally I rarely seem patient’s in such px without some elevation of either BP or HR. Since the peritoneal signs (rebound tenderness) were localized to the LLQ quadrant on exam the seems to rule out an infectious peritonitis and lean more towards a localized acute pathology. Ovarian torsion slipped my mind! It is easy to get tunnel vision in situations like these while sitting at a computer!

  6. I have posted the picts from the OR above.

    So what happened? It appears she actually did rupture, but it was a small rupture at best. You can see the blood-soaked and clotted off Fallopian tube that contained the ectopic pregnancy. She had 400-500cc of clotted blood in her lower pelvis, and she ended up having her L Fallopian tube and ovary removed. Her appendix looked fine and everything else was unremarkable. She was an ectopic pregnancy that the methotrexate did indeed terminate, but not until after she ruptured. She clotted off and because she was no longer actively dividing cells while growing (fetus), she was able to sustain the tamponade and not get pushed over the edge. She likely developed peritoneal signs due to the blood in her belly, but she was aggressively washed out.

    Methotrexate works – but we always have to remember that medicine is very much time dependent, and pathology evolves. This is a great case showing it.


  7. emedpa says:

    great case Greg, thanks!

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