Course Authors

Martin J. Carey, M.D.

Dr. Carey reports no commercial conflict of interest.

Estimated course time: 1 hour(s).

Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 

Learning Objectives

Upon completion of this Cyberounds^®, you should be able to:

• List the common causes of abdominal pain in women of childbearing age

• Discuss the pitfalls in investigating abdominal pain in women of childbearing age

• Describe some complications associated with pregnancy.

 

Although many causes of abdominal pain are common to both sexes, there are a few additional diagnoses that must always be considered in women, especially those of childbearing age.

Case 1

A 23-year-old female presents to the emergency department at 03:30. She states that she awoke about an hour earlier to find the bed "full of blood." Since then she has experienced increasing abdominal cramps and the vaginal bleeding has continued. She states that she stopped taking the oral contraceptive about two months earlier and had a brief vaginal bleed of about 2 days within a couple of days of stopping. She has never been pregnant and has no other significant past medical history. She had been on oral contraceptives for some years. While on "the pill," her periods were generally "light," lasting only 3-4 days. Prior to using an oral contraceptive, her periods had always been regular, lasted 5-6 days and were "moderately heavy."

Examination revealed an African-American female of about 200 pounds, lying on the stretcher. She seemed in some discomfort. Abdominal examination demonstrated lower abdominal tenderness. Vaginal examination revealed tenderness over the uterus. There was active bleeding from the cervical os, which was closed.

Q. What is your differential diagnosis in this case?

A. The diagnoses to be considered include:

• Pelvic inflammatory disease
• Ovarian pathology
  • Ruptured corpus luteum cyst
  • Torsion
• Intra-abdominal pathology
  • Appendicitis
  • Endometriosis
• Pregnancy
  • Early intrauterine pregnancy
  • Threatened miscarriage
  • Inevitable miscarriage
  • Ectopic pregnancy

NOTE: Throughout this Cyberounds^®, I will use the term 'miscarriage' rather than 'abortion' as the latter can have negative connotations.

Q. What one test or investigation would help you most at this stage?

A. The first question that should be answered, after ensuring that the patient is hemodynamically stable, is "Is this patient pregnant?" The patient's pulse rate is 92 beats per minute, her blood pressure is 110/80, with a respiration rate of 20 and a temperature of 98.4°F. She is thus hemodynamically stable at this time. The easiest and quickest way to answer the pregnancy question in most ER departments is to do a urine pregnancy test. In this patient's case, the urine pregnancy test is positive.

Q. What is the difference between a 'threatened' and an 'inevitable' miscarriage?

A. A 'threatened' miscarriage is any amount of uterine bleeding in the first 20 weeks of pregnancy without passage of tissue or cervical dilatation. In contrast, an 'inevitable' miscarriage is a gestation of less than 20 weeks with bleeding and cervical dilatation but no passage of fetal tissue. If all fetal material is expressed, there is usually resolution of the abdominal pain and closure of the cervix. This is a complete miscarriage. Between the 6^th and 14^th weeks especially, an incomplete miscarriage may occur. In this case, some fetal products remain in the uterus. Surgical intervention is often required in these cases to remove all remaining tissue.

Q. What other investigations should be considered at this time and why?

A. At least two other investigations are required. First, consideration should be given to finding out this patient's blood type. In the United States, 15% of women are Rh-negative. Should the fetus be Rh-positive (something that we cannot know at this stage) the patient runs a high risk of becoming sensitized to Rh antigen. If they then have a subsequent pregnancy that is Rh-positive, Rh antibodies could cross the placenta and the fetus will suffer hemolysis, which can be fatal to the fetus.

All Rh-negative women with bleeding during the first or second trimester should have Rh immune globulin if unsensitized. Although a dose of 50 µg is sufficient if bleeding occurs in the first 12 weeks of pregnancy, 300 µg is required when the pregnancy is further advanced. Because questions about the exact gestational age are often difficult to answer accurately, most authorities recommend a dose of 300 µg for all unsensitized Rh-negative women with bleeding in the first two trimesters. Although, ideally, women should be given the immune globulin before leaving the emergency department, it is probably effective up to 72 hours after the vaginal bleed starts and there is some evidence it may be effective even 2-4 weeks later.

A quantitative b-hCG is useful in order to correlate findings from ultrasound with the expected findings for a given level of the hormone. Levels of b-hCG rise rapidly through the 10^th week of the pregnancy, then decline until the third trimester. During the third trimester, levels again rise but gradually. During the first 10 weeks of pregnancy, serial measurement of the b-hCG may be useful in cases of vaginal bleeding. On average, through the first 10 weeks, the level of the hormone should rise by about two-thirds every two days if the pregnancy is viable.

Ultrasound should also be considered. A good quality ultrasound will often allow a definitive diagnosis and guide therapy.

If the quantitative b-hCG is greater than 6000 mIU/mL, the gestational sac should be visible by abdominal ultrasonography. Trans-vaginal ultrasonography is even more sensitive, with a gestational sac visible if the serum b-hCG is greater than 1000 mIU/mL. This is equivalent to about 5-6 weeks after the last menstrual period. A fetal heartbeat should be visible by the end of the 6^th week or early in the 7^th week after the last period. By eight weeks, the gestational sac should be about 25 mm in diameter and there should be an embryo visible. If these findings are not appreciated on a good quality ultrasound, the pregnancy is abnormal and appropriate follow-up and review arrangements should be made for the patient. This may include a return visit to the emergency department for a repeat quantitative b-hCG, or ultrasound or follow up with an obstetrician within the next two or three days.

Other investigations that are recommended include a urinalysis and a complete blood count. The complete blood count may not accurately reflect acute blood loss but may act as a baseline value. A urinalysis is useful to exclude occult infection or other abnormalities.

Our patient proved to have a b-hCG value indicative of an 8-week pregnancy and the ultrasound confirmed an intrauterine pregnancy with an active heart rate. The bleeding settled and the pregnancy proceeded uneventfully. The diagnosis was, thus, a threatened miscarriage.

Let us review Case 1 described previously.

In this first case we came up with a differential diagnosis of miscarriage vs. normal period vs. ectopic pregnancy. The pregnancy test was found to be positive and we were able to make the diagnosis of threatened miscarriage.

Q. Now, let us assume that the urine pregnancy test is NEGATIVE. What is the differential diagnosis now?

A. The differential diagnosis is quite broad in the case of a woman of childbearing age,with lower abdominal pain and vaginal bleeding.

The diagnoses to be considered include:

• Pelvic inflammatory disease
• Ovarian pathology
  • Ruptured corpus luteum cyst
  • Torsion
• Intra-abdominal pathology
  • Appendicitis
  • Endometriosis
• Pregnancy
  • Early intrauterine pregnancy (± miscarriage)
  • Ectopic pregnancy

Q. Hey! Pregnancy is still in the differential. Doesn't a negative urine pregnancy test rule it out?

A. Of course this is a 'trick' question. However, the lesson is very important. The presence of a negative urine pregnancy test does not exclude the diagnosis of pregnancy, especially ectopic pregnancy. Ectopic pregnancy can be a difficult diagnosis to make. In fact, studies show that the diagnosis is missed about half the time on initial presentation at an office visit and about a third of the time on the first visit to an emergency department. The rate of increase in b-hCG is generally slower in cases of ectopic pregnancy than in normal pregnancies. This may lead to a negative urine pregnancy test. However, a serum pregnancy test will usually show an elevated level of b-hCG. The take-home message here is that if there is a suspicion of an ectopic pregnancy, consider doing a quantitative serum b-hCG.

Q. What may raise the suspicion for an ectopic pregnancy? In other words, what are the risk factors for an ectopic?

A. The risk factors for an ectopic pregnancy include:

• A history of pelvic inflammatory disease
• Tubal ligation surgery (or indeed any surgery previously to the Fallopian tubes)
• Previous ectopic pregnancy (8 times greater risk)
• Assisted reproduction techniques
  • In vitro fertilization
  • Ovarian stimulation therapy

The incidence of ectopic pregnancy has been steadily increasing over the years. It is now thought to occur in about 15 per 1000 pregnancies. Ectopic pregnancy is the second leading cause of maternal mortality overall and the commonest cause of maternal mortality among African-American women.

Q. Let's say our patient had a low-grade fever (100.4°F), wouldn't this eliminate the diagnosis of ectopic and make pelvic inflammatory disease much more likely?

A. This is an important point, too. Pelvic inflammatory disease (PID) is the diagnosis most often given in cases where a diagnosis of ectopic pregnancy has been missed. Ectopic pregnancy patients may have a low-grade fever up to about 100.4°F (38°C). Additionally, it should be noted that PID is rare in pregnancy. It is thought that the decidua and membranes protect against bacterial invasion by effectively sealing off the uterine cavity.

Q. Let's say an ultrasound demonstrates an intrauterine pregnancy, does this exclude an ectopic pregnancy?

A. No. This rare condition is called a heterotropic pregnancy (also called a combined gestation). The incidence of this condition is increasing.

Q. Although heterotropic pregnancy is still rare in the general population, where the incidence is estimated as about 1 in 6000 pregnancies, there is one group where this diagnosis needs to be carefully considered. Which group is this?

A. Patients who have undergone in vitro fertilization are at significantly increased risk. Estimates range from 1 to 8 per 100 patients in an in vitro fertilization program. The signs associated with a heterotropic pregnancy include abdominal pain, an enlarged uterus, together with an adnexal mass. Peritoneal irritation may be present.

The management of ectopic pregnancy involves considering and making the diagnosis. The patient should be stabilized if necessary and consultation with obstetric services sought. If the patient is thought to require an operation, laparoscopy will usually be the management of choice unless the patient is very unstable.

Increasingly, with early diagnosis of the condition, medical management is being employed. This involves the use of methotrexate. These patients must be carefully followed with serial quantitative b-hCGs and this is usually done under the care of the obstetrician. Occasionally, these patients may re-present to the emergency department after discharge with abdominal pain and vaginal bleeding. In these cases, vaginal examination should probably be deferred to the obstetrician, as there is a risk of rupturing the ectopic pregnancy if still present. The pain may be from tubal abortion but may also be caused by rupture of the ectopic. Differentiating between the two may be difficult and observation in hospital may be required for these patients.

Case 2

It is now some months later. You are called urgently to the car park outside the ER. A patient was in the process of being discharged from the obstetric unit. Sitting in a wheelchair, while her partner strapped their new baby in the car seat, the patient, a 24-year-old African-American female, had a well-described tonic-clonic seizure lasting about a minute or so. While she is placed on a stretcher and brought into the ER, you are able to talk with the nurse who accompanied the patient. She tells you that the patient delivered a healthy infant some 24 hours ago. The patient had complained of a headache earlier that morning but otherwise seemed well.

Q. What condition must you consider in your differential diagnosis?

A. This patient has a diagnosis of eclampsia until proven otherwise.

Q. But this patient has already delivered. Surely it's too late to have eclampsia now?

A. No. Eclamptic seizures may occur anywhere from the 20^th week of pregnancy through to at least 7 days post delivery. They have been described as occurring as late as 25 days after delivery.

Q. What symptoms and signs may be associated with the development of eclamptic seizures?

A. Generally, women who have eclamptic seizures will have a recognized case of pre-eclampsia. The diagnostic criteria for pre-eclampsia include:

• Hypertension
  • Systolic blood pressure above 139 mm Hg
  • Diastolic blood pressure above 89 mm Hg

(NOTE: that these readings should be on two separate occasions at least six hours apart)

• Proteinuria
  • More than 300 mg over 24 hours OR
  • More than 1 mg/ml on two occasions at least six hours apart
• Edema
  • Generalized edema OR
  • A weight gain of at least 5 pounds over one week.

Q. The nurse described our patient as having 'mild' pre-eclampsia with a blood pressure of 135/90 and 'slight' edema. Do these findings make eclamptic seizures much less likely?

A. Unfortunately not. Up to 30% of patients who have eclamptic seizures will not have hypertension, edema or proteinuria of major degree, or will have only minor signs of pre-eclampsia. In essence, the presence of seizures does not correlate with the severity of other signs.

Q. How should the patient be managed in the ER?

A. The patient should be moved expeditiously to a resuscitation room. She should be administered high flow oxygen and intravenous access assured. If adequate ventilation cannot be provided via a bag valve mask, then intubation may be required. Traditionally, seizures in patients with eclampsia have been managed with magnesium sulfate (MgSO₄). There are a number of regimens described. A typical example is that espoused by Sibai -- the use of 6 g of MgSO₄ over 15 minutes intravenously followed by an infusion of 2g/hr.(3)

Q. What are the signs of magnesium toxicity?

A. The signs of magnesium toxicity include:

• Hypotension
• Cardiac and respiratory depression
• Slurring of speech
• Muscle weakness and areflexia.

During infusion, patients should be closely monitored clinically, as serum magnesium levels are often not available rapidly. With knowledge of the side effects of the therapy, it is possible to identify critical areas for observation. These include the blood pressure for signs of hypotension, the respiratory rate for signs of hypoventilation, and the deep tendon reflexes for evidence of muscle weakness and the onset of areflexia.

Q. Should the patient become toxic, how may this be managed?

A. Stop the infusion. In addition, if symptoms are severe, then 10 ml of calcium gluconate may be administered intravenously over about 5 minutes.

For the seizures, some authorities have suggested using other agents such as lorazepam and phenytoin. In our case, these agents would certainly be reasonable. However, in cases occurring before delivery, lorazepam may result in neonatal respiratory depression, a problem if the patient requires urgent delivery. In a number of studies, magnesium has been found to be effective first line therapy. Note that should the patient have concomitant hypertension, as a part of the eclamptic picture, this must also be managed aggressively.

Q. How should hypertension associated with eclampsia be managed?

A. Treatment for hypertension in eclampsia is not much different from that of hypertension from other causes with which the emergency physician may be more familiar. The agents commonly used include:

• Labetalol
  • 20 mg IV, followed by an infusion of 1-2 mg/min titrated against effect. Further bolus doses of 40-80 mg may be given every 10-15 minutes, up to a total of 300 mg, if required.
• Nitroglycerin
  • An intravenous infusion is used, starting at 5 µg/min [NB: This is MICROGRAMS/min], increasing as needed every 5 minutes until an adequate reduction is achieved.
• Sodium Nitroprusside
  • An intravenous infusion is used, starting at 0.25 µg/kg body weight per minute. [NB: This is MICROGRAMS again] This rate is increased every 5 minutes until adequate effect.
• Hydralazine
  • An initial bolus dose of 2.5 mg intravenously. This is followed, if needed, by further bolus doses of 5-10 mg every 10 minutes, until effect, or until a total of 40 mg has been given.

Side effects of these medications include significant hypotension. Therefore, particularly with the use of nitroglycerin infusions and sodium nitroprusside, many would advocate the use of intra-arterial blood pressure monitoring. In addition, nitroglycerin is associated with the production of methemoglobinemia and sodium nitroprusside is associated with the development of cyanide toxicity.

Our patient was admitted to the hospital for observation. She had no further seizures and suffered no significant complications. She was discharged home two days later.

In our next Cyberounds^®, we will discuss the management of trauma in pregnancy.