SMFM Guidance: Diagnosis and Management of Maternal Sepsis

SUMMARY: 

Sepsis accounts for about 14% of all pregnancy-related deaths despite occurring in only 4 per 10,000 live births, and the rate of maternal sepsis appears to be increasing. More than 50% of pregnant patients who die from sepsis have at least one chronic comorbidity, such as congestive heart failure or chronic renal disease. The diagnosis of sepsis in the early postpartum period can be difficult due to the rapid physiologic changes that occur postpartum, such as large fluid shifts, postpartum hemorrhage, and heart rate and blood pressure alterations. This consult series document refers to sepsis in individuals who are either pregnant or in the postpartum period. 

Sepsis Definition 

• Is not a defined illness, but a life-threatening organ disruption with a dysregulated host response to infection
• Septic Shock
  • Is a subset of sepsis in which persistent hypotension requiring the use of vasopressors despite adequate fluid resuscitation
• Fever is not necessary or sufficient to identify sepsis
• Consider the diagnosis if
  • Unexplained end organ damage if suspected infectious process
  • End organ damage in a previously healthy individual

Potential Sources of Infection

• Obstetric
  • Antepartum: Septic abortion | Chorioamnionitis
  • Postpartum: Endometritis | Wound infection
• Non-obstetric
  • Antepartum: UTI | Pneumonia | Appendicitis
  • Postpartum: UTI | Pneumonia | GI

Note: No source identified in 30% of cases  

Sepsis During Pregnancy

• Normal physiologic changes in pregnancy can delay the identification and diagnosis
  • Examples: Expanded blood volume | Increased cardiac output | Peripheral vasodilation
  • More complex immediately postpartum due to fluid shifts 
• Early recognition essential
• Associated with
  • Preterm birth
  • Prolonged recovery
  • Stillbirth
  • Maternal death

Tools for Recognizing Sepsis in Pregnancy

• No single, reliable screening test validated for pregnancy
• Quick Sequential Organ Failure Assessment (qSOFA) score
  • Bedside rapid assessment tool: 3 Clinical criteria
    • Systolic blood pressure ≤100 mmHg
    • Respiratory Rate ≥22
    • Altered mental status
  • If any two are present start therapy and consider ICU transfer

Note: Low sensitivity and has not been validated in pregnancy

Treatment

Initial Management: within the first hour of suspected diagnosis

• Perform cultures
• Send serum lactate
• Use broad spectrum antibiotics
  • Choice of antibiotics: Possible infection source | Likely microorganisms | Antibiotic resistance patterns
  • Cover anaerobic and aerobic Gram-positive and Gram-negative bacteria
• Fluids: 1 to 2 liters of crystalloid (or more as needed) in the first three hours

Proposed Antibiotic Coverage Based on Source

• Community-acquired pneumonia
  • Cefotaxime | Ceftriaxone | Ertapenem | Ampicillin plus azithromycin | Clarithromycin | Erythromycin
• Hospital-acquired pneumonia: Low risk
  • Ceftriaxone | Ampicillin-Sulbactam | Ertapenem | Meropenem | Imipenem | Cefepime
• Hospital-acquired pneumonia: High risk or mortality
  • Double coverage for Pseudomonas
    • Beta lactam plus an aminoglycoside or quinolone
    • MRSA coverage: Vancomycin or linezolid
  • Chorioamnionitis
    • Ampicillin plus gentamicin
    • Cesarean: Add clindamycin or metronidazole for anerobic coverage
  • Endomyometritis
    • Ampicillin, gentamicin, and metronidazole (or clindamycin) or
    • Cefotaxime or
    • Ceftriaxone plus metronidazole
  • UTI
    • Gentamicin plus ampicillin or
    • Carbapenem or
    • Piperacillin-tazobactam
  • Abdominal infections: Uncomplicated
    • Ceftriaxone | Cefotaxime | Ceftazidime | cefepime plus metronidazole
  • Abdominal infections: Complicated
    • Carbapenem | Piperacillin-tazobactam
  • Skin and soft tissues (necrotizing)
    • Vancomycin plus piperacillin-tazobactam
    • If Streptococcus Group A or Clostridium perfringens are present: Penicillin G plus clindamycin

Fluid Management

• Maintain fluids to keep mean arterial pressure (MAP) >65 mmHg

Vasopressors and Inotropes

• Hypoperfusion: Start norepinephrine through central line
  • 0.25 mcg/kg/min
  • MAP of >65 mmHg target
• Cardiac dysfunction and hypoperfusion with adequate fluid resuscitation
  • Dobutatmine or epinephrine
  • If no response: Add vasopressin

Additional Management

• Hydrocortisone 50 mgs q6 hours IV infusion
  • Use if no response to norepiphrine
  • Betamethasone if fetal lung maturity indicated for management
• Electronic fetal monitoring if viable
• Imaging to identify source
• DVT prophylaxis
• Maintain glycemic control with insulin: Keep serum glucose <180
• Potential surgical debridement
• Comprehensive family support

When to Deliver

• Diagnosis of sepsis is not an indication for delivery
• If the uterus is the source
  • Delivery is indicated regardless of gestational age
• Delivery otherwise guided by obstetric indications

KEY POINTS:  

• Whether or not a fever is present, sepsis should be considered If unexplained end organ damage with a suspected or confirmed infection
• A serum lactate level should be sent if sepsis is suspected 
• Appropriate microbiologic cultures should be obtained as long as there are no delays in initiating antibiotics
  • If septic shock or a high suspicion of sepsis,   empiric broad spectrum antibiotics should be instituted 
• Within 1 to 3 hours, 1 to 2 liters of a balanced crystalloid solution should be given if hypoperfusion or hypotension is present
• Norepinephrine should be the first line vasopressor
  • If vasopressors are necessary, IV corticosteroids should be given 
• VTE prophylaxis should be instituted
• If glucose is ≥180, insulin should be initiated 
• If the uterus is the source of sepsis, prompt evacuation should occur regardless of gestational age
• Hospital systems should develop metrics and protocols for sepsis management 

Learn More – Primary Sources:  

Society for Maternal-Fetal Medicine Consult Series #67: Maternal Sepsis 

Alliance for Innovation on Maternal Health: Consensus Bundle

Does Intrapartum Fever Really Predict Neonatal Sepsis?

BACKGROUND AND PURPOSE:

• There is guidance from the CDC, ACOG and AAP that well-appearing newborns should undergo limited evaluation for possible sepsis if mothers have suspected chorioamnionitis
• In some hospitals, newborn sepsis work-up may require NICU admission
• Towers et al. (AJOG, 2017) sought to evaluate the rate of fever during labor and whether there is an association with early-onset neonatal sepsis

METHODS:

• Prospective cohort study (2011 – 2014)
• Patients with fever (≥38°C) at ≥36 weeks’ gestation were evaluated for
  • gestational age, parity, spontaneous or induced labor, group B streptococcus status, regional anesthesia, mode of delivery, treatment with intrapartum antibiotics, and whether a clinical diagnosis of chorioamnionitis was made by the managing physician
• Cases started labor afebrile but then developed fever prior to delivery with no other infectious cause identified
• Neonates were assessed for blood culture results, neonatal intensive care unit admission, length of stay, and any major newborn complications

RESULTS:

• 412 patients developed a fever in 6,057 deliveries (6.8%; 95% CI 6.2–7.5%)
• No cases of maternal sepsis
• There was no difference in rate of newborn sepsis in fever vs. control group (p=0.3)
  • Febrile group: 1 newborn out of 417 developed sepsis from Escherichia coli (0.24%; 95% CI 0.01–1.3%)
  • Non-febrile group: 4 cases of early-onset neonatal sepsis, 2 with GBS and 2 with Escherichia coli (0.07%; 95% CI 0.02–0.18%)

CONCLUSION:

• The incidence of intrapartum fever is common at 6.8% and consistent with retrospective studies, although is double the rate in the CDC guideline of 3.3%
• Neonatal sepsis incidence rate in the population of women with fever ≥36 weeks’ gestation is rare at 0.82/1000 live births
• Need to treat (NTT): 1/417 neonates
• Authors suggest that the practice of follow-up cultures and universal antibiotic treatment in well-appearing newborns in the setting of intrapartum fever may not be ‘clinically sound’

Learn More – Primary Sources:

Incidence of fever in labor and risk of neonatal sepsis