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Maternal Sepsis

Dr. Anna G. Euser, MD, PhD Assistant Professor, Maternal-Fetal MedicineSeptember 6, 2019

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➧ I have no disclosures

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Why is this an important topic?➧ Sepsis is a significant cause of maternal morbidity and mortality (M&M)

§ Accounts for ~5% of maternal ICU admissions➧ Rate of sepsis appears to be increasing

§ Nationwide data suggests a 10% per year increase in maternal severe sepsis & sepsis-related death in the US

■ Recent US data report that maternal sepsis complicated 4-10 per 10,000 live births

➧ Recent UK data suggests that sepsis accounted for 25% of maternal deaths§ In 63% of cases independent reviewers identified substandard care,

usually a delay in recognition and management

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Sepsis

What is Sepsis?

➧ Sepsis is not a specific illness, but a syndrome

➧ Sepsis is generally understood as a “life-threatening organ dysfunction caused by a dysregulated host response to infection” (The Third International Consensus Definitions for Sepsis and Septic Shock, 2016)§ As part of this report, the terms SIRS

and severe sepsis were abandoned

What is the SOFA score?

What is Organ Dysfunction?

■ Acute increase of 2 or more points in the SOFA score

From SMFM Consult Series #47, 2019.

Sequential Organ Failure Assessment (SOFA) scoreOrgan System 0 1 2 3 4

Lungs – PaO2 (mmHg) ≥400 <400 <300 <200 <100

Coagulation – Plts ≥150k <150k <100k <50k <20kLiver – Bilirubin (mg/dL) <1.2 1.2-1.9 2.0-5.9 6.0-11.9 >12

Heart – MAP (mmHg) ≥70 <70 Increasing score with increasing requirements for pressors (gtt)

CNS – Glasgow Coma Scale Score 15 13-14 10-12 6-9 <6Kidneys – Cr (mg/dL) <1.2 1.2-1.9 2.0-3.4 3.5-4.9 >5.0

Adapted from Vincent et al. 1996. The SOFA score

Definition of sepsis in this way emphasizes organ dysfunction rather than signs of infection.

2+ points = Sepsis

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Quick SOFA (qSOFA)

➧ Rapid method for identifying patients at high risk of developing severe complications

➧ Positive score should prompt care team to evaluate for organ dysfunction, start or escalate treatments, increase acuity of monitoring, and consider transfer to ICU§ A proxy for organ dysfunction§ An early warning system, not diagnostic

qSOFA

SBP ≤ 100 mmHg

RR ≥ 22 bpm

Altered mental status

2+ criteria = Increased risk for poor-sepsis related outcomes

How does sepsis differ in pregnancy?➧ Current scoring systems were designed and validated in non-pregnant

populations and over-estimate M&M in the obstetric population➧ Scoring systems do not take pregnancy physiology into account

§ If 1992 sepsis criteria were applied, the sepsis cutoffs for RR, HR, pCO2

and WBC count all overlapped with normal pregnancy ranges§ Primary example is that it is not unusual in pregnancy to have a MAP

<70mmHg§ Creatinine criteria also not optimized for pregnancy

➧ Attempts to make pregnancy-specific scoring systems for sepsis§ SOS (Sepsis in Obstetrics Score)§ SOMANZ (Society of Obstetric Medicine Australia and New Zealand)

Guidelines, modified SOFA & qSOFA

Sepsis in Obstetrics Score (SOS)

➧ Used in ED, ability to predict ICU admission

➧ SOS score of ≥6§ PPV 15%§ NPV 98.6%§ 90% were given

antibiotics, but only 5% were within one hour

From Albright et al. 2017

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Obstetrically-modified SOFA score (omSOFA)

Organ System 0 1 2 3 4

Lungs – PaO2 (mmHg) ≥400 mmHg <400 mmHg <300 mmHg <200 mmHg <100 mmHgCoagulation – Plts ≥150k <150k <100k <50k <20kLiver – Bilirubin (mg/dL) <1.2 1.2-1.9 2.0-5.9 6.0-11.9 >12

Heart – MAP (mmHg) ≥70 <70 Vasopressors required

CNS – Glasgow Coma Scale Score 15 13-14 10-12 6-9 <6Kidneys – Cr (mg/dL) <1.2 1.2-1.9 2.0-3.4 3.5-4.9 >5.0

Adapted from SOMANZ

Scores of 3 or 4 removed for simplicity

2+ points = Sepsis

Alert Rouse to Voice Rouse to Pain

≤ 1.0 1.0-1.4 >1.4

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SOMANZ-modified qSOFA

qSOFA

■ SBP ≤ 100 mmHg■ RR ≥ 22 bpm■ Altered mental status

Suggested OB modifications

➧ SBP < 90 mmHg➧ RR >25 bpm➧ Altered mental status

What are the most common sources of sepsis in pregnancy?

Antepartum PostpartumObstetric Septic Abortion Endometritis

Chorioamnionitis Wound InfectionNon-Obstetric Urinary Tract Infection Urinary Tract Infection

Pneumonia PneumoniaAppendicitis Gastrointestinal

Adapted from SMFM Consult #47

E. Coli

Streptococci, A & B Staphylococci

In 30% of cases, no source is identified.

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Risk factors

Demographic

➧ Nulliparity➧ Black Race➧ Public or no insurance

Obstetric

➧ Cesarean Delivery➧ Assisted reproductive technologies➧ Multiple gestation

More than 50% of women who die from sepsis have 1 or more chronic conditions, including chronic renal disease, chronic

liver disease & congestive heart failure.

Initial Treatment AlgorithmSepsis Suspected

Early source control

Imaging studies prn

Treat hypotension

If MAP <65 & evidence of

hypoperfusion; start norepinephrine

Start low dose steroid infusion if no response to

norepinephrine

Fetal (if >24w GA)

Consider continuous monitoring

Consider steroids for fetal lung maturity

Prophylaxis

DVT Prophylaxis

Early enteral feeding

Avoid hyperglycemia (>180)

Within 1 hour- Cultures & serum lactate

- Start broad antibiotics- Start fluid therapy

Adapted from SMFM Consult #47

Management within 1 hour

➧ Send cultures§ Blood, sputum, urine and others (wound, uterine, etc)

➧ Check serum lactate➧ Start broad-spectrum antibiotics

§ Initially should cover anaerobic and aerobic Gram-positive and Gram-negative bacteria➧ Local resistance patterns may also guide choices

§ Can be narrowed when and if culture results are available

SMFM Guideline #1Sepsis and septic shock should be considered medical emergencies and that treatment and

resuscitation begin immediately

SMFM Guideline #3Empiric broad-spectrum antibiotics be administered as soon as possible, ideally within 1 hour, in any pregnant woman in whom sepsis is suspected

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Antibiotic ChoicesPresumed Source Recommended AntibioticsPNA (community) Ceftriaxone, ertapenem, or ampicillin +

azithromycinPNA (hospital) Low risk: piperacillin-tazobactam, meropenum

High risk: cover for pseudomonas & MRSA alsoChorioamnionitis Ampicillin + gentamicin; add clindamycin or

metronidazole if CSEndomyometritis Ampicillin + gentamicin + clindamycin or

metronidazoleUTI Ampicillin + gentamicin, or ceftriaxone +

metronidazoleAbdominal Ceftriaxone, carbapenem, or piperacillin-

tazobactamSkin/Soft Tissue Vancomycin + piperacillin-tazobactam

Ceftriaxone

Amp + Gent + Clinda

Amp + Gent

Pip-Taz

Source Control

➧ Imaging is often required➧ If a specific focus is identified, appropriate steps should be taken for

control§ D&C for retained products§ I&D of abscess or wound infection

➧ Least invasive intervention should be used, i.e. percutaneous drainage§ The exception to this rule is necrotizing soft tissue infections, where

extensive debridement is required

SMFM Guideline #4Cultures (blood, urine, respiratory, etc) and serum lactate levels should be obtained if sepsis is suspected or identified and early source control should be completed as soon as possible

Treat Hypotension➧ Fluid resuscitation should occur early if hypotension or

hypoperfusion is present§ Fever, vasodilation, and capillary leak all contribute to limited

preload in the sepsis patient, i.e. hypoperfusion➧ Surviving Sepsis Campaign recommends an initial bolus of

30mL/kg of crystalloid, but this recommendation may be overly aggressive in pregnancy§ In pregnancy, remember that the colloid pressure is lower and

the risk of pulmonary edema is higher➧ In most pregnant women, initial administration of 1-2 L of crystalloid

is reasonable➧ If non-fluid responder, consider vasopressors

§ Current guidelines recommend norepinephrine as the first-line agent with a target MAP >65 mmHg

SMFM Guideline #5Early administration of 1-2 L of crystalloid solutions in sepsis complicated by

hypotension or suspected organ hypoperfusion

SMFM Guideline #6Use of norepinephrine as the first-line vasopressor during pregnancy and

the postpartum period in sepsis with persistent hypotension and/or hypoperfusion despite fluid resuscitation

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Fetal Considerations

➧ The presence of sepsis alone is not an indication for delivery§ EXCEPT for chorioamnionitis§ No evidence that delivery improves maternal outcomes

➧ In most cases, improving maternal hemodynamics will improve uteroplacental perfusion and thereby should improve fetal condition

➧ Delivery should be reserved for the usual obstetric indications after maternal stabilization

➧ The decision to deliver should be individualized§ Depends on gestational age as well as maternal and fetal conditions§ Corticosteroids for fetal benefit are not contraindicated

SMFM Guideline #7Immediate delivery for the sole indication of sepsis is not recommended.

Delivery should be dictated by obstetric indications.

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Outcomes

Maternal

➧ Mortality rate difficult to quantify, reported rates vary from 1-4.6%§ Lower rates when H1N1 influenza

cases are excluded➧ Mortality rate associated with sepsis

in pregnancy seems to be lower than sepsis in the general population§ sepsis mortality varies with age§ Though difficult to have an age-

matched comparison

Fetal/Neonatal

➧ Preterm delivery is more common with maternal sepsis, even when the source is not uterine§ Not all iatrogenic

➧ Irish data: in women with bacteremia, preterm birth rate was 16.8% (3x control groups)

➧ French data: in women with bacteremia, preterm birth rate was 29%§ Overall fetal mortality rate of 10%

How can deaths from sepsis be prevented?

➧ Among women who died from sepsis, a majority had a delay in care and a delay in escalation of care.§ Most were afebrile, possibly delaying the recognition of the presence of

sepsis➧ Even after diagnosis 73% of women who were started on antibiotics that had

inadequate coverage

SMFM Guideline #2Providers should consider the diagnosis of sepsis in pregnant patient with otherwise unexplained end-organ damage in the presence of an infectious

process, regardless of the presence of fever

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Review SMFM Recommendations➧ 1) Sepsis and septic shock should be considered medical emergencies and

that treatment and resuscitation begin immediately➧ 2) Providers should consider the diagnosis of sepsis in pregnant patient with

otherwise unexplained end-organ damage in the presence of an infectious process, regardless of the presence of fever

➧ 3) Empiric broad-spectrum antibiotics be administered as soon as possible, ideally within 1 hour, in any pregnant woman in whom sepsis is suspected

➧ 4) Cultures (blood, urine, respiratory, etc) and serum lactate levels should be obtained if sepsis is suspected or identified and early source control should be completed as soon as possible

Review SMFM Recommendations➧ 5) Early administration of 1-2 L of crystalloid solutions in sepsis complicated

by hypotension or suspected organ hypoperfusion➧ 6) Use of norepinephrine as the first-line vasopressor during pregnancy and

the postpartum period in sepsis with persistent hypotension and/or hypoperfusion despite fluid resuscitation

➧ 7) Immediate delivery for the sole indication of sepsis is not recommended. Delivery should be dictated by obstetric indications.

Summary

➧ Sepsis and septic shock are medical emergencies➧ Fever is not necessary for diagnosis➧ Start broad with antibiotic coverage➧ Proper resuscitation of mom is the best treatment for baby

§ Delivery indicated in the setting of chorioamnionitis

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Questions?

Sources➧ Albright CM et al. Internal validation of the sepsis in obstetrics score to

Identify risk of morbidity from sepsis in pregnancy. Obstet Gynecol 2017; 130(4): 747-755.

➧ Critical Care in Pregnancy. ACOG Practice Bulletin No. 211. American College of Obstetricians and Gynecologists. Obstet Gynecol2019;133:e303-19.

➧ SMFM Consult Series #47: Sepsis during pregnancy and the puerperium. Am J Obstet Gynecol 2019;220(4):B2-B10.

➧ Bowyer L et al. 2017. SOMANZ Guidelines for the investigation and management of sepsis in pregnancy.

➧ Vincent et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22:707-10.