Sepsis in Pregnancy: Contemporary Management in the Critical Care Setting

Dr Neeraj Manikath, Claude.ai

Abstract

Background: Sepsis remains a leading cause of maternal mortality worldwide, with pregnancy-related physiological changes creating unique diagnostic and therapeutic challenges. The intersection of sepsis pathophysiology with maternal-fetal physiology demands specialized critical care expertise.

Objective: To provide a comprehensive review of sepsis management in pregnant patients, highlighting evidence-based strategies, clinical pearls, and contemporary approaches for critical care practitioners.

Methods: Narrative review synthesizing current literature, international guidelines, and expert consensus on sepsis management in pregnancy.

Results: Pregnancy-specific modifications to sepsis recognition, resuscitation, and organ support are essential for optimal maternal-fetal outcomes. Early recognition, aggressive resuscitation, and multidisciplinary care significantly improve survival.

Conclusions: Successful management of sepsis in pregnancy requires understanding of pregnancy-specific pathophysiology, modified diagnostic criteria, and coordinated multidisciplinary care with obstetric and neonatal teams.

Keywords: sepsis, pregnancy, critical care, maternal mortality, resuscitation

Introduction

Sepsis complicates approximately 0.1-0.8% of pregnancies but accounts for 12.7% of pregnancy-related deaths globally. The physiological adaptations of pregnancy create a perfect storm of diagnostic challenges and therapeutic complexities that demand specialized critical care expertise. Unlike non-pregnant patients, management decisions must consider two patients simultaneously—mother and fetus—with interventions potentially having opposing effects on each.

The COVID-19 pandemic has further highlighted the vulnerability of pregnant patients to severe infections, with pregnancy being recognized as an independent risk factor for severe illness. This review synthesizes contemporary evidence and provides practical guidance for critical care management of sepsis in pregnancy.

Pathophysiology: The Pregnant Patient's Unique Vulnerability

Immunological Changes

Pregnancy induces a state of relative immunosuppression to prevent maternal rejection of the fetal allograft. Key changes include:

Cell-mediated immunity suppression: Decreased T-helper 1 (Th1) responses with shift toward Th2 dominance
Neutrophil dysfunction: Impaired chemotaxis and bacterial killing capacity
Complement system alterations: Reduced complement-mediated bacterial clearance
Cytokine dysregulation: Altered inflammatory response patterns

Cardiovascular Adaptations

Pregnancy-induced cardiovascular changes significantly impact sepsis presentation and management:

Increased plasma volume (30-50%): Masks early hypovolemia
Decreased systemic vascular resistance: Baseline hypotension obscures septic shock recognition
Increased cardiac output (30-50%): May maintain perfusion despite significant volume losses
Aortocaval compression: After 20 weeks, supine positioning reduces venous return by up to 25%

Respiratory System Changes

Functional residual capacity reduction (20%): Rapid desaturation during apnea
Increased oxygen consumption (20-30%): Accelerated development of hypoxemia
Compensated respiratory alkalosis: Baseline PCO₂ 28-32 mmHg complicates acid-base interpretation

Clinical Presentation and Diagnosis

🔍 Clinical Pearl: The "Rule of 30s"

In pregnancy, suspect sepsis when ANY of these occur:

Heart rate >120 bpm (not the traditional >90)
Respiratory rate >30 (accounting for pregnancy physiology)
Temperature >38.3°C or <35°C
Leukocytosis >30,000 (pregnancy baseline is 12,000-16,000)

Modified SOFA Scoring for Pregnancy

Traditional SOFA scores require pregnancy-specific modifications:

System	Non-pregnant SOFA	Pregnancy-Modified
Respiratory	PaO₂/FiO₂ <400	PaO₂/FiO₂ <350
Cardiovascular	MAP <70 mmHg	MAP <65 mmHg
Renal	Creatinine >1.2 mg/dL	Creatinine >0.9 mg/dL
Hepatic	Bilirubin >1.2 mg/dL	Bilirubin >1.0 mg/dL

⚠️ Red Flag Signs in Pregnant Sepsis

Fetal heart rate abnormalities: Often the earliest sign of maternal compromise
Decreased fetal movements: May precede maternal symptoms
Uterine tenderness with fever: Chorioamnionitis until proven otherwise
Persistent tachycardia >120 bpm: Cannot be attributed to pregnancy alone
Oliguria <0.5 mL/kg/hr: Significant given increased GFR in pregnancy

Source Identification and Microbiology

Common Pregnancy-Associated Infections

Obstetric Sources (60% of cases):

Chorioamnionitis (most common)
Endometritis
Septic abortion
Retained products of conception
Episiotomy/cesarean wound infections

Non-obstetric Sources (40% of cases):

Urinary tract infections (ascending due to physiological changes)
Pneumonia (increased susceptibility)
Appendicitis (diagnostic challenge due to anatomical displacement)
Gallbladder disease
Central line infections

🧪 Diagnostic Hack: The "Golden Hour" Workup

Within 60 minutes of sepsis recognition:

Blood cultures × 2 sets (before antibiotics if possible)
Urinalysis and culture
Complete blood count with differential
Comprehensive metabolic panel
Arterial blood gas
Lactate level
Procalcitonin (remains elevated in pregnancy-related sepsis)
Obstetric ultrasound (assess fetal well-being and identify obstetric sources)

Resuscitation and Initial Management

The "SEPSIS-MOM" Protocol

S - Source control and cultures E - Early antibiotics (within 1 hour) P - Perfusion optimization (fluid resuscitation) S - Support failing organs I - Invasive monitoring considerations S - Steroid consideration in refractory shock

M - Maternal positioning (left lateral tilt) O - Obstetric consultation M - Monitor fetal status

Fluid Resuscitation

Initial Approach:

30 mL/kg crystalloid bolus within first 3 hours
Monitor closely: Pregnancy predisposes to pulmonary edema
Target MAP >65 mmHg (accounting for pregnancy baseline)
CVP target 8-12 mmHg (higher than non-pregnant due to increased blood volume)

⚡ Resuscitation Hack: Use point-of-care ultrasound to assess:

IVC collapsibility (>50% suggests volume responsiveness)
Lung sliding (early detection of pulmonary edema)
Cardiac function (assess for peripartum cardiomyopathy)

Vasopressor Selection

First-line: Norepinephrine

Preserves uterine blood flow better than dopamine
Avoid high-dose epinephrine (uterine vasoconstriction)

Second-line: Vasopressin

Safe in pregnancy
Particularly useful in catecholamine-resistant shock

Antibiotic Therapy

Empiric Regimens (Pregnancy Category B/C acceptable in severe sepsis):

Obstetric sepsis:

Ampicillin-sulbactam 3g q6h + Gentamicin 5-7 mg/kg q24h
Alternative: Cefoxitin 2g q6h + Doxycycline 100mg q12h (avoid in 1st trimester)

Non-obstetric sepsis:

Ceftriaxone 2g q24h + Azithromycin 500mg q24h (pneumonia)
Ceftriaxone 2g q24h (urinary source)
Add Metronidazole 500mg q8h for anaerobic coverage

🚨 Antibiotic Pearl: In chorioamnionitis, continue antibiotics for 48 hours post-delivery regardless of clinical improvement, as endometritis risk remains elevated.

Organ Support Strategies

Respiratory Support

Non-invasive Ventilation Considerations:

Pregnancy is NOT a contraindication to NIV
Higher PEEP requirements (8-10 cmH₂O) due to reduced FRC
Aspiration risk: Consider early intubation if altered mental status

Mechanical Ventilation Parameters:

Tidal volume: 6-8 mL/kg ideal body weight (pre-pregnancy weight)
PEEP: Start at 8-10 cmH₂O
FiO₂: Target SpO₂ >95% (higher than non-pregnant to ensure fetal oxygenation)
Plateau pressure: <30 cmH₂O
Permissive hypercapnia: Avoid PCO₂ <25 mmHg (compromises fetal oxygen delivery)

Renal Support

Indications for RRT in pregnant sepsis:

Severe acidemia (pH <7.1)
Hyperkalemia >6.5 mEq/L
Severe fluid overload with pulmonary edema
Uremia with altered mental status

RRT Considerations:

CRRT preferred over intermittent hemodialysis (hemodynamic stability)
Citrate anticoagulation safer than heparin
Monitor ionized calcium closely

💡 Hack for Fluid Balance:

Use daily weights + strict I/O rather than relying solely on CVP, as pregnancy-related volume changes make CVP interpretation challenging.

Fetal Considerations

Fetal Monitoring

Continuous fetal monitoring indicated when:

Gestational age ≥24 weeks
Viable fetus present
Maternal condition permits intervention

Concerning fetal patterns:

Persistent fetal tachycardia >160 bpm
Loss of variability
Late decelerations
Prolonged decelerations

Delivery Considerations

Indications for emergency delivery:

Severe maternal instability requiring interventions incompatible with pregnancy
Fetal compromise with viable gestational age (≥24 weeks)
Source control requiring delivery (chorioamnionitis, septic abortion)
Maternal cardiac arrest

🎯 Delivery Decision Algorithm:

<24 weeks: Focus on maternal resuscitation
24-32 weeks: Individualized decision with neonatology input
>32 weeks: Consider delivery if maternal condition deteriorating
>34 weeks: Delivery often beneficial for both mother and fetus

Special Scenarios

Postpartum Sepsis

Higher risk factors:

Cesarean delivery (5-fold increased risk)
Prolonged rupture of membranes
Chorioamnionitis during labor
Manual placenta removal
Operative vaginal delivery

🔍 Postpartum Pearl: New-onset fever >38.5°C within 48 hours postpartum should trigger immediate sepsis workup, as puerperal sepsis can progress rapidly.

Septic Shock in Pregnancy

Vasoplegia is common due to:

Progesterone-induced smooth muscle relaxation
Increased prostaglandin production
Relative vasopressin deficiency

Management modifications:

Earlier vasopressor initiation (after 20-30 mL/kg fluid)
Combination therapy often required
Stress-dose steroids (hydrocortisone 200-300 mg/day) for refractory shock

Multidisciplinary Care Coordination

Essential Team Members

Critical Care Physician: Primary management
Maternal-Fetal Medicine: High-risk obstetric expertise
Neonatologist: Fetal assessment and delivery planning
Anesthesiologist: Airway management and peripartum care
Infectious Disease: Antibiotic stewardship
Pharmacy: Pregnancy-safe medication dosing

🎯 Communication Hack:

Establish a "Code Sepsis OB" protocol with predetermined team activation criteria and response times to avoid delays in critical interventions.

Quality Improvement and Outcomes

Key Performance Indicators

Time to antibiotic administration: <1 hour from recognition
Time to source control: <6 hours when indicated
Fluid resuscitation completion: <3 hours
Maternal mortality: <2%
Perinatal mortality: <5% for viable gestations
ICU length of stay: Median 3-5 days

📊 Outcome Optimization Strategy:

Implement sepsis bundles modified for pregnancy with regular audit and feedback mechanisms to maintain compliance and improve outcomes.

Emerging Therapies and Future Directions

Novel Approaches Under Investigation

Immunomodulation:
- Selective cytokine inhibition
- Complement pathway modulation
- Mesenchymal stem cell therapy
Precision Medicine:
- Biomarker-guided antibiotic selection
- Genetic risk stratification
- Personalized resuscitation targets
Technology Integration:
- Continuous physiological monitoring
- Predictive analytics for early recognition
- Telemedicine for expert consultation

Clinical Pearls and Pitfalls

✨ Expert Pearls

The "Pregnancy Paradox": Normal pregnancy vital signs can mask early sepsis—maintain high index of suspicion
Fetal monitoring as a maternal monitor: Fetal heart rate changes often precede maternal vital sign deterioration
Left lateral positioning is crucial: Even during resuscitation, maintain 15-30° left lateral tilt to prevent aortocaval compression
Early delivery may be therapeutic: In severe sepsis >32 weeks, delivery often improves both maternal and fetal outcomes
Antibiotic dosing adjustments: Increased renal clearance and volume of distribution require higher doses of renally eliminated antibiotics

🚫 Common Pitfalls

Delaying antibiotics for cultures: In septic shock, never delay antibiotics >1 hour for culture collection
Under-resuscitation: Pregnancy physiology can mask hypovolemia—be aggressive with initial fluid resuscitation
Medication avoidance: Don't withhold life-saving medications due to pregnancy category concerns in severe sepsis
Inadequate monitoring: Standard monitoring may be insufficient—consider invasive monitoring early
Poor communication: Failure to involve obstetric team early leads to delayed source control and delivery decisions

Guidelines and Recommendations

Summary of Key Recommendations

Grade A Evidence:

Early antibiotic administration within 1 hour
Initial fluid resuscitation with 30 mL/kg crystalloids
Source control within 6 hours when feasible
Norepinephrine as first-line vasopressor

Grade B Evidence:

Modified SOFA scores for pregnancy
CRRT preferred over intermittent dialysis
Stress-dose steroids for refractory shock
Delivery considerations based on gestational age and maternal stability

Grade C Evidence (Expert Opinion):

Enhanced fetal monitoring in viable pregnancies
Multidisciplinary team approach
Modified resuscitation targets
Pregnancy-specific quality metrics

Conclusion

Sepsis in pregnancy represents one of the most challenging scenarios in critical care medicine, requiring expertise in both critical care and obstetric physiology. Success depends on early recognition using pregnancy-modified criteria, aggressive resuscitation with attention to unique physiological changes, appropriate antibiotic selection, and coordinated multidisciplinary care.

The key to optimal outcomes lies in understanding that pregnancy is not a contraindication to aggressive critical care interventions, but rather requires thoughtful modifications to standard approaches. Future research should focus on pregnancy-specific biomarkers, optimal resuscitation strategies, and the role of early delivery in improving maternal outcomes.

As critical care physicians, our goal is not just maternal survival, but optimal outcomes for both mother and child. This requires constant vigilance, rapid decision-making, and seamless coordination with our obstetric colleagues.

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Conflicts of interest: None to declare

Funding: None

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Sunday, September 7, 2025