Maternal infection resulting in sepsis may cause up to 30% of the ICU admissions occurring in obstetric patients and contribute to 2%-3% of maternal mortality in developed nations.^1,2 Pregnancy renders women more susceptible to sepsis and to resulting severe complications. Also, microbiology of sepsis is distinct in pregnancy; endotoxin-producing Gram-negative rods such as E. coli are common etiologic agents, whereas Gram-positive bacteria are common culprits in nonpregnant patients with sepsis.³

Most of sepsis-related research and literature is centered on nonpregnant patients; management of severe infections in pregnancy requires integration of clinical skills associated with management of sepsis and the unique pathophysiology that can occur in pregnancy. These cases may be best managed by experienced teams of physicians (including MFM, anesthesia, infectious disease, and ICU physicians) with supporting nursing and ancillary ICU staff.^1,4,5,6

A list of infection sites and pathogens commonly seen in pregnancy is given in Table 1. Table 2 provides a clinical tool covering key principles.

Special Considerations in Pregnancy

Certain infections in pregnancy can be teratogenic to the fetus, particularly in the first trimester. These agents have been given the acronym of TORCH for toxoplasmosis, other (e.g., syphilis), rubella, cytomegalovirus, and herpesvirus. Although not teratogenic, HIV may be transmitted to the fetus and may be lethal in the child. Hence, the timely recognition and treatment of infections is important. Screening tests can be done by the admitting team.

Infection Sites

Infection in pregnancy is associated with increased frequency and severity in certain anatomic sites because of anatomic and physiologic changes associated with pregnancy, delivery, and especially with tissue injury and bacterial contamination associated with cesarean delivery.

Physiologic Changes of Pregnancy

Certain normal physiologic changes in pregnancy may cause delay in diagnosis of sepsis and/or promote difficulties or complications when treating sepsis in pregnancy. For example:

• Normal pregnancy may be associated with a heart rate >90 bpm and hyperventilation with PaCO2 <32 mm Hg, and normal labor is often associated with a WBC count >12,000 cells/mcL (all signs of systemic inflammatory response syndrome [SIRS] in the nonpregnant patient).
• Renal system smooth-muscle relaxation in pregnancy increases the rate and severity of urinary tract infections while delaying recognition of symptoms until pyelonephritis occurs.
• Decreased plasma colloid osmotic pressure and an increased tendency for capillary leakage in pregnancy may contribute to pulmonary edema or adult respiratory distress syndrome when IV fluid bolus treatment is needed in treating septic shock.
• Pregnancy increases concentrations of coagulation factors and the vulnerability to disseminated intravascular coagulation as a complication of severe sepsis.
• Compression of the inferior vena cava by the gravid uterus associated with the supine position of the patient may cause hypotension or contribute to cardiovascular collapse previously initiated by septic shock.
• The gravid uterus acts as a large arteriovenous shunt that cannot respond effectively to hypotension, leaving pregnant patients more vulnerable to shock.
• Markers of standard sepsis treatment are altered. Central venous pressure can be increased to 10 mm Hg in the third trimester, the mean arterial blood pressure is decreased, and the ScvO2 can be as high as 80%.

Fetal Considerations

The presence of the fetus may complicate the management of sepsis in pregnancy in several ways:

• The products of conception may be the source of infection (especially when rupture of membranes or chorioamnionitis is present), and the fetus may need to be delivered before maternal sepsis can be effectively treated. This may occur before or after potential fetal viability.
• The fetus is vulnerable to infection or the decreased perfusion of sepsis and may need to be delivered emergently to survive. Monitoring and intervening when needed for the sake of the fetus can complicate the management of sepsis in pregnancy significantly.
• Some of the physiologic changes of pregnancy that can promote maternal compromise associated with septic shock (such as inferior vena cava compression syndrome and the uterine A-V shunt effect) can be attenuated by delivery of the fetus.

Viral Infections

A number of viral infections commonly complicate pregnancy and in some cases can have profound effects on the fetus. Initial presentation may suggest bacterial sepsis. Unless a clear viral etiology is present without secondary bacterial infection, the EP will generally initiate empirical sepsis treatment. Studies have revealed that viral infection of the placenta can sensitize the pregnant mother to bacterial products and induce preterm labor, in addition to eliciting a fetal inflammatory response that can cause end-organ damage.^1,7

Testing will generally be initiated by the admitting team.

Diagnostic Studies

Several sepsis criteria (heart rate >90 bpm and WBC >12,000) can be seen in pregnancy in the absence of infection and sepsis. A good rule of thumb is to require a clinical diagnosis of primary infection (including site of infection, if possible) to diagnose sepsis. Most commonly, maternal infection is diagnosed by fever with additional systemic symptoms such as chills, sweats, syncope, nausea, dyspnea, or pain at the site of infection. Evaluation for site of infection commonly includes physical examination (general and obstetric) and testing for evidence of infection at appropriate sites (CBC, CMP, lactate, UA, urine culture, blood cultures, chest x-ray, and other tests as indicated).

Treatment

As with any serious prenatal event, initiate fetal monitoring ASAP for a viable fetus. If unable to provide L&D support, arrange for prompt transfer to a tertiary center.

Prevention of infection using appropriate hand washing and sterile technique may be the most effective method of decreasing sepsis in obstetrics.⁸ Infection prophylaxis for cesarean section using either cefazolin alone or an extended-spectrum regimen (including azithromycin) is recommended to reduce postoperative maternal infection.⁹ For uncomplicated infections in pregnancy, early therapy with appropriate antibiotics may prevent severe sepsis.

When severe sepsis is present, early recognition and prompt treatment are critically important. Therapy includes fluid resuscitation, obtaining cultures (including blood cultures), and treatment with antibiotics, all within 6 hours of onset. Combinations of antibiotics IV (such as ampicillin 2 g, q 6 hrs; gentamicin 100 mg, q 8 hrs; and clindamycin 900 mg or metronidazole 500 mg q 8 hrs) should be started within 1 hour. Care may be best provided in the ICU with a Foley catheter, hourly intake and output, continuous cardiac and oxygen saturation monitoring, and frequent BP monitoring (using continuous arterial line measurements in septic shock cases). Oxygen supplementation is often required, and acetaminophen may be used to reduce excessive fever.

Fetal monitoring is appropriate when the possibility of fetal viability exists. Fetal tracings suggesting fetal hypoxia or acidosis may even be the first signs of impending maternal cardiorespiratory decompensation. Pulmonary capillary wedge pressure evaluations have been specifically suggested for monitoring appropriate fluid resuscitation in pregnancy complicated by septic shock, and early intubation with positive end-expiratory pressure and lower tidal volumes has been advocated to treat the adult respiratory distress syndrome that often follows the successful fluid resuscitation of this condition.^10,11 Steroids, though not contraindicated, are controversial. The largest randomized study showed no survival benefit in nonpregnant patients. Some authors recommend empiric therapy in pregnant patients.⁴

In nonpregnant patients, early goal-directed therapy to maintain adequate CVP, MAP, venous oxygen saturation, and urinary output was associated with improved survival and decreased morbidity.¹² This approach included transfusion of packed red blood cells to achieve a hematocrit of at least 30 if adequate CVP is not maintained by the 6-hour limit. Pressors (dobutamine, noradrenaline, dopamine, and/or vasopressin) have all been advocated for nonpregnant patients in septic shock unresponsive to fluid/antibiotic therapy alone. While studies reporting the use of these agents in pregnancy are not available, emergency situations may require their empiric use.

Risks to Fetus

Fetal compromise in utero may occur with septic shock due to hypoperfusion of the pregnancy. Maternal fever may increase the oxygen requirements of the fetus directly and by promoting fetal tachycardia that requires additional oxygen consumption. This combination of decreased oxygen supply and increased oxygen requirements may cause fetal hypoxia. If these components of maternal sepsis cannot be quickly improved, fetal death or emergency delivery may be the only options.

Premature birth can result not only from the emergency deliveries described above; preterm labor also often results from infections and sepsis. The fetus may also have risks of infection directly harming it in utero (such as with chorioamnionitis or transplacental infection) or of neonatal infections acquired at birth.

Risks to Mother

Sepsis may cause preterm labor and delivery. Associated fetal compromise may require emergency cesarean section that could be complicated by sepsis-induced maternal hypotension, pulmonary edema, or DIC. Long-term hospitalization, morbidity, and death can be seen as a result of maternal sepsis.

Risk Factors

Sepsis in pregnancy often results from urinary tract infections (especially chronic or recurrent infections), chorioamnionitis (especially with prolonged rupture of membranes), or from post–cesarean section infections. Any source of infection that could cause sepsis in the nonpregnant patient could cause it in pregnancy. (See Table 1.)

Special Population Consideration

HIV-positive pregnant patients represent high-risk pregnancy. Infections in these patients could be manifestations of either the usual bacterial or viral infections as detailed above, or could be presentations of opportunistic infections. All HIV-positive women should be on highly active antiretroviral therapy. If they are not, risk of infection is increased along with increased risk of transmission to the fetus.¹³

For management of sepsis in this subgroup of pregnant women, expert consultation should be sought.

References

1. Joseph J, et al. Sepsis in pregnancy and early goal-directed therapy. Obstet. Med. 2009;2:93-9.
2. Ronsmans C, Graham WJ. Lancet maternal survival series steering group. Maternal mortality: Who, when, where, and why. Lancet 2006;368:1189-1200.
3. Galvagno SM Jr, Camann W. Sepsis and acute renal failure in pregnancy. Anesth. Analg. 2009;108:572-5.
4. Guinn DA, Abel DE, Tomlinson MW. Early goal-directed therapy for sepsis during pregnancy. Obstet. Gynecol. Clin. North Am. 2007;34:459-79.
5. Fernandez-Perez ER, et al. Sepsis during pregnancy. Crit. Care Med. 2005;33(10 Suppl):S286-93.
6. ACOG Practice Bulletin (Number 100): Critical Care in Pregnancy. Obstet. Gynecol. 2009;113:443-50.
7. Cardenas et al. Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J. Immunol. 2010;185:1248-57.
8. Burke J. Infection Control – A Problem for Patient Safety. N. Engl. J. Med. 2003;348:651-6.
9. Tita ATN, et al. Emerging concepts in antibiotic prophylaxis for cesarean delivery: A systematic review. Obstet. Gynecol. 2009;113:675-82.
10. Sheffield JS. Sepsis and septic shock in pregnancy. Crit. Care Clin. 2004;20:651-60.
11. Campbell LA, Klocke RA. Implications for the pregnant patient. Am. J. Respir. Crit. Med. 2001;163:1051-4.
12. Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N. Engl. J. Med. 2001;345:1368-77.
13. Sperling RS, Shapiro DE, Coombs RW, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N. Engl. J. Med. 1996;335:1621-9.

Dr. Roemer is an Associate Professor in the Department of Emergency Medicine, University of Oklahoma (OU) School of Community Medicine, Tulsa.