CASE CONFERENCE pregnancy, infected

Infected Intrauterine Pregnancy Presenting As Septic Shock

[Lloyd T, Dougherty J, Karlen J: Infected intrauterine pregnancy presenting as septic shock. Ann Emerg Med 12:704-707, November 1983.]

INTRODUCTION James Dougherty,/KD: Today's case is that of a young woman who presented to the emergency department with lower abdominal pain associated with hypotension, fever, tachycardia, and tachypnea. The discussant will be John R Karlen, MD, Department of Obstetrics and Gynecology, Akron General Medical Center, Northeastern Ohio Universities College of Medicine. Thomas Lloyd, DO, chief resident in emergency medicine, will present the case.

CASE PRESENTATION Dr Lloyd: A 27-year-old, married woman presented with a chief complaint of lower abdominal pain associated with fever, chills, nausea, and vomiting. The symptoms had begun four days prior to admission, and consisted of a flu-like illness which gradually worsened.

Her last menstrual period was two weeks prior and was described as nor- mal. All prior periods had been regular, The patient denied any symptoms of pregnancy. Her husband had been using condoms for birth control, and she used tampons during menses. She had one previous pregnancy that was elec- tively terminated. Her only gynecologic complaint at the time of presenta- tion was that of a yellow-brown vaginal discharge.

The patient appeared "toxic." Blood pressure was 100/60 m m Hg; pulse, 150; respirations, 35; and temperature, 39.4 C orally. Principal physical find- ings were suprapubic tenderness and guarding, odiferous vaginal discharge and, on bimanual examination, a 16- to 18-week size uterus that was ex- quisitely tender.

There was no vaginal bleeding and no evidence of genital instrumentation or trauma. No fetal heart sounds were ultrasonographically detectable. Initial laboratory values included positive pregnancy test (Gravindex, Ortho Di- agnostic); white blood count, 8,600/cu m m with marked left shift; and platelets, 29,000. Arterial blood gas analysis on room air showed pH of 7.49; POz, 58 m m Hg; PCO2, 25 m m Hg; and HCO3, 18.5 mm/L.

The diagnosis of infected intrauterine pregnancy associated with severe sepsis and thrombocytopenia was made. The thrombocytopenia was prob- ably due to disseminated intravascular coagulation. The patient was given 40% oxygen by mask, intravenous fluids (lactated Ringer's), intravenous anti- biotics (clindamycin 300 mg and gentamicin 1 mg/kg), and steroids (methyl- prednisolone 30 mg/kg).

In spite of these measures, she deteriorated rapidly, requiring endotracheal intubation with ventilatory support, dopamine for blood pressure mainte- nance, platelet transfusions for multi-site bleeding and platelet count of 4,000, and Swan-Ganz catheterization. Even though the patient was severely compromised, it was deemed necessary to evacuate the uterus immediately. She was taken to the operating room where, under general anesthesia, dilata- tion and evacuation were carried out. The uterine contents were foul- smelling and consisted of two sets of fetal parts (twins) of at least 14 weeks gestational age. There was no excessive bleeding during the operation. E coli

Thomas Lloyd, DO James Dougherty, MD, FACEP John Karlen, MD, FACOG Akron, Ohio

From the Emergency Medicine Residency Program, Akron General Medical Center, Akron, Ohio.

Address for reprints: Thomas Lloyd, DO, Chief Resident, Department of Emergency Medicine, Akron GenerN Medical Center, 400 Wabash Avenue, Akron, Ohio 44307.

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INFECTED INTRAUTERINE PREGNANCY Emergency Medicine Residency Program-- Akron General Medical Center

was subsequently grown from the uterine contents as well as from previously obtained blood cultures.

The patient began to improve. Within an hour she be- came normotensive and afebrile, and platelet count re- turned to normal. She developed the classic syndrome of noncardiac pulmonary edema which necessitated four more days of ventilator assistance with positive end-expiratory pressure before she was able to breathe on her own. On the tenth post-operative day, the patient had improved suf- ficiently to be discharged home. At the time of follow up four weeks later, the pelvic examination was completely normal.

DISCUSSION Dr Karlen: This case represents an uncommon complica- tion of pregnancy, that of infection of the intrauterine con- tents in the absence of the usual history or symptoms and signs of spontaneous miscarriage, premature rupture of membranes, previous amniocentesis, or of internal genital instrumentation associated with induced abortion. It is also a classic example of how overwhelming an infection of the products of conception can be to the affected individual.

Because these patients often present with nonlocalizing symptoms such as fever and malaise in the absence of pel- vic pain and vaginal bleeding, the diagnosis of infected preg- nancy can sometimes be difficult, even in the known gravid patient. When the pregnancy is not suspected because the bleeding of early pregnancy has mimicked normal men- strual periods, as was the case in our patient, this diagnosis is often the last to be considered. As the disease progresses, however, the source of the infection becomes evident in the form of uterine pain and tenderness associated with foul vaginal discharge and/or bleeding. 1

Once the diagnosis has been made, treatment should con- sist of stabilization of the patient, initiation of appropriate antibiotics, and early uterine evacuation. ~ In the absence of the latter procedure, the disease will progress to septic shock and its associated complications of disseminated in- travascular coagulation, renal failure, cardiac failure, and shock lung. ~

On the other hand, elimination of the infected products of conception usually results in dramatic improvement in the patient's condition. Occasionally, if such improvement does not occur with uterine evacuation, spread of the infec- tion to the deeper myometrium and/or adnexal structures is presumed, and hysterectomy and bilateral salpingo- oophorectomy may be necessary. 1

Question: What is the differential diagnosis in a patient who presents with an infected pregnancy?

Dr Karlen: As noted, the initial symptoms and signs of in- fected pregnancy may be nonspecific, and findings that localize the septic process to the uterus may be absent. Dur- ing this time, the picture may be that of a flu-like syndrome or of infection of unknown primary site. Subsequently, however, uterine pain and tenderness ensue, and may or may not be associated with foul vaginal discharge and/or bleeding.

Infection within the uterus can occur in any trimester of pregnancy and, once full-blown, the diagnosis is usually evi- dent. Few clinical conditions can imitate an intrauterine in- fection in the latter part of pregnancy, especially if there is a history of leakage of amnionic fluid from the vagina or of recent amniocentesis (a rare cause of chorioamnionitis). 3

Other septic processes can occur in the first trimester, however, which can confuse the diagnosis.

Even though spontaneous septic abortion may be consid- ered in the differential diagnosis, the infection in this case usually occurs in association with significant vaginal bleed- ing, severe cramps, and passage of tissue. 4 Toxic shock syn- drome in tampon users may have similar initial man- ifestations of malaise and fever, but symptoms and signs in this condition do not subsequently localize in the pelvis. In addition, toxic shock usually has its onset during menses and is accompanied by diarrhea and rash. 5

Acute salpingitis is a rare event in pregnancy due to the fact that the gestational sac effectively blocks ascension of microorganisms from the vagina to the upper genital tract. 3 However, it can occasionally occur, and could present with findings similar to infection within the amnionic fluid. 6 Also, a sequela of previous acute pelvic inflammatory dis- ease, tubo-ovarian abscess (ruptured or unruptured), should be included in the differential diagnosis.

Finally, infection of the intrauterine contents can occur as a result of an induced abortion that has not been appropri- ately completed. 4 Although such an event can usually be determined by history, self-attempted or criminal abortion must be considered and signs of lower genital tract trauma and/or chemical burns should be looked for, even in the face of patient denial.

Question: If membranes are intact and have not raptured o3 been violated by instrumentation, how does a pregnancy be- come infected, and what are the usual infecting organisms?

Dr Karlen: Unlike intrauterine infection which accompan- ies amniocentesis, abortion, or premature rapture of mem- branes, there is no obvious portal of entry for bacteria into the contents of the amnionic sac in an infection of an other- wise normal pregnancy. 3 Two mechanisms are postulated. First, it is possible that hematogenous spread of the organ- isms into the products of conception can occur, possibly from a distant site of maternal infection. 3 Second, minute, subclinical tearing of the membranes may occur allowing entry of bacteria into the amnionic fluid from the vagina. 3 In fact, the exact mechanism by which de n o v o infection of the pregnant uterus occurs is not known. However, when considering the possible mechanisms just mentioned, it may be significant that the infecting organisms are most commonly those found among the normal flora of the vagina. 7 These include the coliform bacteria, especially E coil, the anaerobic organisms and, occasionally, c]ostrid- iumo 8

Question: What are the fetal implications of intrauterine in- fection? Does the fetus ever survive?

Dr Karlen: Virtually the only time the fetus survives an epi- sode of intrauterine sepsis during pregnancy is if the preg- nancy is of sufficient duration to permit fetal viability out- side of the uterus, and then only if the fetus is delivered within a short time following the onset of infection.

Except for those pregnancies beyond 28 to 30 weeks gestation, then, fetal outcome is not a factor to be consid- ered in the management of infected pregnancy. Indeed, it is irrelevant when one considers that the probable effect of allowing the infected uterine contents to remain in utero is maternal death.

Question: If infected pregnancy is suspected following ini-

78/705 Annals of Emergency Medicine 12:11 November 1983

tial history and physical examination, how does one pro- ceed with further diagnostic work up?

Dr Karlen: The evaluation of this clinical condition will be, to some extent, dictated by the patient's overall condition. As in most septic conditions that present to the emergency department, complete blood count including platelets, uri- nalysis, and appropriate cultures are indicated. If the patient is severely ill, as ours was, serum chemistry screen, chest film, electrocardiogram, arterial blood gas analysis, and im- mediate blood typing and crossmatching should" be per- formed. If time permits, other studies intended to localize and define the infection are also in order. In the case of in- fected pregnancy, these would include ultrasound of the pel- vis, flat plate x-ray film of the pelvis (KUB), and amniocen- tesis wi th Gram stain and culture of the withdrawn fluid. (Remember, because of the intact membranes surrounding the pregnancy, cervical and vaginal sampling for Gram stain and culture may not be helpful in determining the infecting organism.)

Ultrasonography can help to determine the presence of pr%~lancy and can give information about fetal age and viability. Also, it is used to help guide the tip of the amniocentesis needle to a pocket of amnionic fluid to be withdrawn for Gram stain and culture. A KUB film is per- formed specifically to identify gas in the uterus or adnexal structures. Such a finding indicates the presence of gas- forming organisms such as clostridium, which is potentially the most virulent and lethal of all the infecting pathogens.

Question: Because the infecting organism and its drug sensitivities are often not known until the culture results are available, what is the initial antibiotic of choice?

Dr Karlen: As noted, intrauterine infections during pregnan- cy often are caused by opportunist ic bacteria normally found in the vagina. These include most of the Gram- negative bacteria, the anaerobes and, less frequently, clos- tridium, s For coverage of these organisms, I prefer to initiate therapy wi th a combina t ion of c l indamycin, effective against anaerobes and most Gram-positive bacteria, and an aminoglycoside antibiotic such as gentamicin, which is highly effective against the coliform bacteria. Other drug combinations with similar, broad-spectrum coverage may also be used. 4

Question: In addition to administration of antibiotics, what other major therapeutic principles are involved in the initial management of the pregnant patient with an intrauterine infection?

Dr Karlen: Therapy will, of course, be determined by the condition of the patient. Assuming severe sepsis (which is most often the case, for most women do not come to the emergency depar tmen t unti l the infect ion is well es- tablished and highly symptomatic) initial measures should be directed toward stabilizing the patient. 9 Such measures include intravenous fluid replacement, oxygen, and blood transfusions, if necessary. Careful monitoring of vital signs and urine output is essential. Almost all these patients should have insertion of a central venous pressure line and, if initial fluid replacement fails to stabilize blood pressure and pulse, a Swan-Ganz catheter should be inserted for measurement of left ventricular function and as a guide to further fluid replacement. 9

High-dose, intravenous steroid administration (methyl-

prednisolone 30 mg/kg) may be helpful for those patients in impending or overt septic shock and, if hypotension is pro- found and refractory, a vasoactive drug such as dopamine may be necessary. 2

Liberal use of aggressive ventilatory support for patients in shock has become routine at our institution and, if the patient is unable to maintain an arterial POz of 50 m m Hg with an FiO2 of 0.5, endotracheal intubation is carried out and ventilator assistance is initiated. Even though the pre- ceding measures will serve to stabilize the patient, the clini- cal course of the disease will be progressively downhill until the infecting source is eliminated. 1 In this regard, a septic pregnancy behaves much like an abscess in that it is refrac- tory to antibiotics. Therefore, the ultimate goal of the man- agement of intrauterine infection during pregnancy is rapid emptying of the uterine contents.

In pregnancies beyond 28 weeks gestation where fetal sal- vage is desirable, induction of labor with oxytocin should be attempted, but if such labor is not immediately forthcom- ing and rapidly progressive, cesarean section should be per- formed. 1

In earlier stages of pregnancy where fetal survival is not an issue~ steps should be taken to empty the uterus as soon as the diagnosis of infected pregnancy is made. Initially this will consist of administration of an intravenous oxytoxic solution. The solution can be given concurrently with other measures being undertaken to stabilize the patient.

Mechanical evacuation will invariably be necessary to completely eliminate the infected tissue within the uterus, and this should be performed as soon as the patient's condi- tion permits. In fact, it may be necessary to salvage a rapid- ly deteriorating situation even in the presence of refractory shock, as was the case in our patient.

In the first 16 weeks of pregnancy, suction evacuation of the uterus followed by sharp curettage is the method of choice. In more advanced pregnancies, because of fetal bone development, maceration and withdrawal of the fetus with special instruments will be necessary. Occasionally, in well- advanced pregnancies, laparotomy and hysterotomy may be required.

Obviously, anesthesia should be minimized, but in most cases some general anesthesia will be necessary.

Question: When, if ever, is hysterectomy indicated?

Dr Karlen: Hysterectomy should be reserved for those pa- tients who fail to respond to uterine evacuation. In this event, it is presumed that the infection has spread to the myometr ium and/or adnexal structures and is therefore not amenable to curettage. Because by this time the infection is frequently life-threatening, its elimination takes precedence over preservation of childbearing potential. The entire uter- us should be removed and, if the adnexal structures are obviously involved, bilateral salpingo-oophorectomy should be performed. Preservation of an infected ovary runs the risk of persistent or recurrent infection and the subsequent requirement for re-operation.

The predominance of clostridia on Gram stain and/or the associated finding of gas in the uterus or parametrium on x-ray examination lends special urgency to removal of the internal genitalia. 3 IP_ such cases, extirpative surgery is often the only way to save the patient's life.

The authors thank Ms Dolores Watson of the AGMG Department of Emergency Medicine for her help in the preparation of this case.

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REFERENCES 1. Cavanagh D: Septic shock in a pregnant or recently pregnant woman. J Postgrad Med 62(4):62-68, 1977. 2. Kuhn M: Volume resuscitation, in Shine KI {moderator): Aspects of the management of shock. Ann Intern Med 93:723-734, 1980.

3. Schwarz RH, Fruiterman JP: Life-threatening infections in preg- nancy. Clin Obstet Gynecol 19:561-575, 1976.

4. Schwarz RH: Septic abortion revisited. Contemp Ob/Gyn 19:135- 156, 1982. 5. Richmond J: Advisory on toxic-shock syndrome. FDA Drug Bull

10(2), July 1980. 6. Acosta AA, Mabray RC, Kaufman RH: Intrauterine pregnancy and coexistent pelvic inflammatory disease. Obstet Gynecol 37:282-285, 1971.

7. Pritchard JA, MacDonald PC {eds): Williams Obstetrics, ed 16. New York, Appleton-Century-Crofts, 1980, p 57Z 8. Bartlett JG, Onderdonk AB, Drude E, et al: Quantitative bacteriology of the vaginal flora. ] Infect Dis 136:271-277, 1977. 9. Cavanagh D, Knuppel RA: Treatment Priorities for the Ob pa- tient in shock. Contemp Ob/Gyn 18:87-98, 1981.

UAEM Call for Abstracts

The Hyatt Regency Hotel in Louisville, Kentucky, will be the site of the 14th UAEM Annua ! Meeting May 23-26, 1984.

Program Chairman Judith E. Tintinalli, MD, ha s announced that she will accept abstracts for the scientific papers to be presented at the Annual Meeting. Members and others in the field are urged to submit original contributions relating to emergency medicine.

Abstracts m u s t b e limited to one 81/2 ', x 11" sheet typed double spaced. Do not include the names of the authors or sponsoring insti tutions in the abstract. A cover sheet mus t be attached to the abstract, and must include the full names, titles, and mailing addresses of all authors as well as their institutions. Indicate which author will be presenting the paper at the Annual Meeting.

Deadline for submission is February 15, 1984. Mail five copies of the abstract to UAEM, 900 West Ottawa, Lansing, Michigan 48915.

Presentations at the Annual Meeting will be limited to 10 minutes followed by a five-minute discussion period. A completed manuscript mus t be submitted no later than the day of the presentation at the meeting. Annals of Emergency Medicine, the official journal of the American College of Emergency Physicians and the University Association for Emergency Medicine, reserves the right of first refusal on all scientific papers presented at the UAEM Annual Meeting. If Annals does not notify authors, in writing, of its intent to publish by September 3, 1984, authors reserve the right to submit papers to other publications.

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