Key Points
In hemodynamically stable patients, the history and physical are insufficiently accurate to either rule in
or rule out ectopic pregnancy. The threshold should be very low to enter a
patient with early pregnancy and symptoms or signs potentially referable to
ectopic pregnancy into a rule out ectopic process.
In contrast to what most of us were taught, the index beta HCG measurement
does not discriminate among ectopic pregnancy, failed/failing intrauterine
pregnancy, and early/healthy intrauterine pregnancy with sufficient accuracy to
guide decision-making. Put more simply, the beta does not help you. If
the ultrasound shows no IUP or ectopic, do not be reassured by a low beta and do
not be alarmed by a high beta. The patient may have a healthy IUP, she may have
a nonviable IUP that is miscarrying or will miscarry, or she may have an ectopic
pregnancy; the beta doesn’t make any of these three diagnoses more or less
likely enough to be a useful test to us, on the index visit. This is not
controversial, the evidence is plentiful [1, 2, 3, 4, 5, 6, 7], and ACEP’s recent clinical policy states at a Level B
recommendation, “Do not use the beta-hCG value to exclude the diagnosis of
ectopic pregnancy in patients who have an indeterminate ultrasound.” If the beta
is a million zillion, feel free to diagnose molar pregnancy.
If IUP is confirmed by ultrasound, measurement of quantitative beta is
unnecessary. If ultrasound shows no evidence of IUP or ectopic, a quantitative
HCG level should be sent but the result is not important for this visit–it is
useful in comparison to the beta drawn in followup. A low beta should never be
used as a reason to forgo pelvic ultrasound, and a high beta should never be
used as a reason to initiate treatment for ectopic pregnancy (in a stable
patient). The concept of the discriminatory zone is obsolete and has no
value to emergency clinicians [1, 2, 3].
There are a variety of abnormal early pregnancy conditions, and the
terminology is confusing. Threatened abortion refers to a patient with a
confirmed IUP who has bleeding or pain; these patients are not at risk for
ectopic pregnancy and threatened abortion should not be used as a diagnosis for
patients with pregnancy of undetermined location. Similarly, patients with
missed, inevitable, incomplete, and complete
abortion by definition to do not have ectopic pregnancy, and, like threatened
abortion, these conditions are generally not dangerous to mom. Often, these
diagnoses can only be made after repeat ultrasound and beta measurements. I
liken these diagnoses to migraine, tension, cluster, and other primary
headaches: the role of the emergency clinician is not to diagnose a benign
headache syndrome, it is to exclude dangerous causes of headaches. Confident as
you may be that your patient without a sonographic IUP is having some variant of
miscarriage and not an ectopic, to make that diagnosis prior to the beta falling
to zero (or the passing of what is unequivocally products of conception,
i.e. has a human form or characteristic features under a microscope) is unwise.
Septic abortion, while not an ectopic pregnancy, is dangerous, and
patients with early pregnancy and fever, unwell appearance, or significant
uterine tenderness should be managed with this condition–which generally
requires prompt surgical uterine evacuation in addition to parenteral
antibiotics–in mind.
Most patients who present to the ED with bleeding or pain in early pregnancy
are primarily concerned about the viability of their pregnancy, while the
emergency clinician’s priority is excluding the presence of a dangerous
condition–in this case, mainly ectopic pregnancy. It is important to recognize
and address this discordance. Attempting to determine if the pregnancy is
likely to succeed or fail on the index visit is imprudent in most cases, but not
acknowledging your patient’s concerns is equally imprudent.
“Using the ultrasound, I don’t see where your pregnancy is. Most likely, you
have either a normal pregnancy that I can’t see, or you’re having a miscarriage;
we can’t tell, and there’s nothing you or anyone can do to change your course
other than having a healthy lifestyle and taking care of yourself. But neither
of these situations is dangerous to you and our role in the emergency
department is to make sure that your symptoms aren’t caused by a problem that is
dangerous to you, most importantly, a pregnancy in the wrong location
such as the fallopian tubes. And since I don’t see where your pregnancy is
today, we need to repeat the ultrasound the day after tomorrow. If you have more
bleeding, or more pain, or feel faint or pass out, or develop a fever, come back
immediately, we’re here 24/7.”
Who does the ultrasound?
Much practice variability exists around who performs the ultrasound–the
emergency clinician, obstetrician, or radiologist–in different rule out ectopic
scenarios. Emergency physician-performed ultrasound has been demonstrated to be
accurate in this context, and it is
reasonable and appropriate for emergency physician-performed ultrasound to be
used as the primary imaging modality in a rule out ectopic paradigm, especially
when the emergency physician has demonstrated proficiency in pelvic ultrasound
and the study is performed under a structured departmental ultrasound QA
process. But sometimes an ectopic pregnancy can look like an IUP, and calling what isn’t an
IUP an IUP is a very dangerous mistake (don’t neglect to evaluate the myometrial mantle all around what you think is an IUP). Also, we generally
rule out ectopic by ruling in IUP, and when an IUP is definitively identified in
a patient not at high risk for ectopic or heterotopic pregnancy, ectopic
pregnancy has been reasonably excluded. However, in a patient without
sonographic IUP, the second goal of imaging is to look for evidence of ectopic
pregnancy, and these findings, often in the adnexa, require more ultrasound
skill.
As usual, the most important strategy to manage physician risk is to decide
as a department and institution how these patients will be managed. Reasonable
approaches include, in order of decreasing emergency clinician risk (and
increasing patient inconvenience):
a. Discharge the patient after emergency physician-performed ultrasound
either with a diagnosis of intrauterine pregnancy and routine followup, or with
a diagnosis of pregnancy of undetermined location, strict ectopic precautions
and urgent followup, based on the results of the emergency physician-performed
ultrasound.
b. Discharge patients who do not have ectopic risk factors and have PUL after
emergency physician-performed ultrasound with ectopic precautions and urgent
followup; arrange immediate specialist-performed ultrasound for patients with
ectopic risk factors who do not have an IUP identified by the emergency
clinician. This is the strategy I use.
c. Arrange immediate specialist-performed ultrasound for all patients who do
not have IUP identified by the emergency clinician.
d. Arrange immediate specialist-performed ultrasound for all patients who
enter into the rule out ectopic flow.
There are other approaches and gradations within these approaches; for
example, if you usually discharge a rule out ectopic patient after your bedside
ultrasound but have a patient you are more concerned about than usual, but don’t
have access to specialist ultrasound or assessment, have the patient return for
repeat assessment not in 48 hours but in 24 or 12 hours.
Rhogam
The use of Anti-D rhesus prophylaxis in early pregnancy is controversial,
because “There are insufficient data available to evaluate the practice of
anti-D administration in an unsensitised Rh-negative mother after spontaneous
miscarriage. Thus, until high-quality evidence becomes available, the practice
of anti-D Immunoglobulin prophylaxis after spontaneous miscarriage for
preventing Rh alloimmunisation cannot be generalised and should be based on the
standard practice guidelines of each country.”
The use of Rhogam for threatened abortion or pregnancy of undetermined
location is even less likely to be beneficial than in cases of diagnosed
miscarriage, which was the subject of the quoted Cochrane review. ACOG recommends it “after a first-trimester
pregnancy loss” and suggests it “be considered” in cases of threatened abortion,
while British guidelines state, “Do
not offer anti-D rhesus prophylaxis to women who receive solely medical
management for an ectopic pregnancy or miscarriage, or have a threatened
miscarriage, or have a complete miscarriage, or have a pregnancy of unknown
location.” ACEP chimes in with their Level B
recommendation “Administer 50 μg of anti-D immunoglobulin to Rh-negative women
in all cases of documented first trimester loss of established pregnancy” and
Level C “Consider administration of anti-D immunoglobulin in cases of minor
trauma in Rh-negative patients.” See SMART-EM‘s treatment of the subject for
details. If you don’t use Rhogam routinely in threatened abortion, most of these
patients can return home to their loved ones immediately if IUP is identified,
without bloodwork, and even, some say, without a pelvic exam [1, 2].
Followup
Ideally all patients with pregnancy of undetermined location would be seen by
an obstetrician within 48 hours for repeat exam, ultrasound, and serum beta. If
the only option in your environment is for the patient to return to the ED, if
IUP is not identified on the repeat visit, have a low threshold to at least
discuss the case with an obstetrician. Interpreting beta trends and deciding on
therapies like methotrexate, or uterotonic agents, or dilation and curettage, is
ideally in the domain of obstetrics and not emergency medicine.
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