C18(15)

SEPSIS IN PREGNANCY

Incidence

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
mortalities in developed nations.1,2 Pregnancy renders women more susceptible
to sepsis and to resulting severe complications. 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
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.1,3,4,5

Sepsis is defined as a pathologic condition involving an infection and a resulting

systemic inflammatory response syndrome (SIRS).

SIRS is associated with any 2 or more of the following clinical findings: (1) body
temperature of >38 degrees C or < 36 degrees C; (2) heart rate > 90 per minute;
(3) hyperventilation [respiratory rate of > 20 per minute or Pa CO2 <32 mm/Hg];
and (4) white blood cell count of >12,000/microliter or <3,000/microliter.

Severe sepsis is defined by sepsis with organ dysfunction.

Septic shock is defined by acute circulatory failure in a septic patient who has
hypotension (MAP<60 mmHg or Systolic BP<90 mm Hg) unexplained by other
causes.6,7

Special Considerations in Pregnancy

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. A list of infection sites and
pathogens commonly seen in pregnancy is given in Table 1.

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 of >90 per minute,
hyperventilation with Pa CO2 <32 mm/Hg, and normal labor is often
associated with a WBC count of>12,000/microliter (all signs of 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 to
severe sepsis.
• Compression of the inferior vena cava by the pregnant uterus associated with
the supine position of the patient may cause hypotension or contribute to
cardiovascular collapse previously initiated by septic shock.
• The pregnant uterus acts as a large arteriovenous shunt that cannot respond
effectively to hypotension, leaving pregnant patients more vulnerable to
shock.
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.
TABLE 1. Clinical Maternal Infection
Common infections and pathogens leading to septic shock in pregnancy1
Infections that may lead to septic shock and Likely pathogens causing septic
usual organisms (in brackets) shock in pregnancy

Pyelonephritis (1, 4) 1 Escherichia coli

Perinephric abscess (1, 4) 2 Bacteroides

Pneumonia (6, 7) 3 Clostridium

Chorioamnionitis (1, 2, 8–12) 4 Klebsiella

Endomyometritis (primarily after caesarean 5 Pseudomonas aeruginosa

delivery) (1, 2, 5, 9, 12)

Septic abortion (1, 3) 6 Streptococcus species

Necrotizing fasciitis (2, 3, 6, 9) 7 Staphylococcus aureus

Caesarean wound infection (1, 2, 6, 7) 8 Group B streptococcus

Severe mastitis (7) 9 Peptostreptococcus

Malaria and other tropical infections 10 Enterococcus

11 Listeria monocytogenes

12 Enterobacter

Diagnostic Studies

A list of possible signs, symptoms, and laboratory findings associated with sepsis
in pregnancy is provided in Table 2. (LINK) Note that many of these items 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) before using the items below to diagnose sepsis.
Table 2. Diagnosis Criteria for Sepsis4

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 (Urinalysis, urine culture, blood cultures, chest x-ray, and other
tests as indicated).
Treatment

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 the first 6
hours of onset. Combinations of antibiotics given IV (such as ampicillin 2 gm, q 6
hrs; gentamicin 100 mg, q 8 hrs; and clindamycin 900 mg or metronidazole 500
mg q 8 hrs) should be started within one hour. Care may be best provided in the
ICU with 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 cardio respiratory 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 has been advocated to treat
the adult respiratory distress syndrome that often follows the successful fluid
resuscitation of this condition.10

In non-pregnant patients “Early goal-directed therapy” to maintain adequate CVP,

MAP, venous oxygen saturation, and urinary output was associated with
improved survival and decreased morbidity.11 This approach included
transfusion of packed red blood cells to achieve a hematocrit of at least 30 if
adequate CVP were not maintained by the 6-hour limit. 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.1 Recombinant
human activated protein C has recently been shown to increase survival in
nonpregnant patients with severe sepsis and has been used successfully in
treating pregnant patients (although it may increase bleeding risks).1,12,13

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 the 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).LINK
Upd V,5,10

References
1
Joseph J, et al: Sepsis in pregnancy and early goal-directed therapy. Obstet Med 2:93-99, 2009.

2
Ronsmans C, Graham WJ: Lancet maternal survival series steering group. Maternal mortality: who,
when, where, and why. Lancet 368:1189-1200, 2006.

3
Guinn DA, Abel DE, Tomlinson MW: Early goal directed therapy for sepsis during pregnancy. Obstet
Gynecol Clin North Am 34:459-479, 2007.

4
Fernandez-Perez ER, et al: Sepsis during pregnancy. Crit Care Med 33(10 Suppl): S286-293, 2005.

5
ACOG Practice Bulletin (Number 100): Critical Care in Pregnancy. Obstet Gynecol 113: 443-450,
2009.

6
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference:
Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit
Care Med, 20:864–74, 1992.

7
Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis
Definitions Conference. Crit Care Med, 31:1250–6, 2003.

8
Burke J: Infection Control – A Problem for Patient Safety. NEJM 348:651-656, 2003.

9
Tita ATN, et al: Emerging Concepts in Antibiotic Prophylaxis for Cesarean Delivery: A Systematic
Review. Obstet Gynecol 113:675-82, 2009.

10
Campbell LA, Klocke RA: Implications for the pregnant patient. Am J Respir Crit Med 163:1051-
1054, 2001.

11
Rivers E, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM
345:1368-77, 2001.

12
Medve L, Csitari IK, Nolnar Z, Laszio A: Recombinant human activated protein C treatment of septic
shock syndrome in a patient at 18th week of gestation: a case report. Am J Obstet Gynecol 193: 864-
5,2005.

13
Mikaszewska-Sokolwicze M, Mayzner-Zawadzka E: Use of recombinant human activated protein C in
treatment of severe sepsis in a pregnant woman with fully symptomatic ovarian hyperstimulation
syndrome. Med Sci Monit 11: CS27-32, 2005.