WelcomeSuspecting and Treating Sepsis in

Maternal Medicine

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Stephen L. Davidow, MBA-HCM, APRManager, Quality Implementation ProgramsSociety of Critical Care MedicineMount Prospect, IL

Today’s webcast is funded by a generous grant from the Gordon and Betty Moore Foundation

Save the Date!

The Next Surviving Sepsis Campaign Webcast September 19, 2013

Topic: Pediatric Guidelines from the Surviving Sepsis Campaign: Considerations for CareFaculty: Margaret M. Parker, MD, FCCM

Professor of Pediatrics, Anesthesia, and Medicine, Stony Brook UniversityLearning objectives:• Apply the key recommendations of the Surviving Sepsis Campaign to the care of the pediatric sepsis patient • Describe the special considerations in the guidelines for care of pediatric sepsis patients and the differences

from adult patients

• Utilize data from central-line placement to benefit the patient’s care

Jeanne Sheffield, MD

Maternal Fetal MedicineUniversity of Texas Southwestern Medical SchoolDallas, TX

Brenda Downs, MSN, RN, ACNS-BC

Program Director, Clinical Performance ImprovementDignity HealthGilbert, AZ

Septic Shock in the Obstetric Patient

Jeanne S. Sheffield, M.D.Maternal Fetal Medicine

University of Texas Southwestern2013

I have no conflict of interest related to the content of this presentation.

The microorganisms that seem to have it in for us..turn out..to be rather more like bystanders..it is our response to their presence that makes the disease

Lewis Thomas NEJM 1972

Concept of Septic Shock in 2013

• Early in sepsis there is an increase in inflammatory mediators - then SHIFTS

• Mid- to late sepsis consistent with immunosuppression– loss of delayed hypersensitivity– inability to clear infection– predisposition to nosocomial infections

Why immune suppression which increases mortality?

• Shift to anti-inflammatory cytokines

? PathogenBacterial inoculum

Th1 cells Th2 cells

Inflammatory cytokinesTNF-IFN-IL-2

Anti-inflammatory cytokinesIL-4

IL-10

CD4 T cellsCD4 T cells

Why immune suppression which increases mortality?

• Anergy– Non-responsiveness to antigen– T cells fail to proliferate and secrete cytokines in

response to antigen

• Death of immune cells– Apoptosis (suicide or programmed cell death)– Decrease in B cells, CD4 T cells and follicular

dendritic cells

• The normal stress response is activation of anti-inflammatory mechanisms which predominate in sites outside of the affected systems– Not the previously believed uncontrolled

hyperinflammatory response

• Survival among patients correlates with recovery of inflammatory responses

Definitions• Shock: When the functional intravascular blood

volume is below that of the capacity of the body’s vascular bed– Hypovolemic

– Hemorrhagic

– Cardiogenic ( pump failure)

– Neurogenic ( loss of sympathetic control of resistance vessels)

Definitions• Systemic Inflammatory Response Syndrome (SIRS)

– Inflammatory process that can be generated by infection or by non-infectious causes (burns, trauma)

– Non-pregnant: 2 or more of the following• Temperature >38 C or <36 C

• HR > 90 beats/min

• RR >20 breaths/min or PaO2 <32 mmHg

• WBC > 12,000/mm3, < 4,000/mm3 or >10% bands

Definitions• Sepsis : the systemic inflammatory response

syndrome that occurs during infection (Society Critical Care Medicine 2001 consensus statement)

• Septic shock: vascular collapse secondary to an infectious process– Usually components of hypovolemic and cardiogenic

shock

National Guidelines for the Non-Pregnant Individual

• There are several “scoring systems” and national guidelines to help determine admission to the ICU, treatment regimens and predict morbidity and mortality.– Modified Early Warning System– SIRS Criteria– APACHE– Unfortunately not validated for the pregnant and non-

pregnant woman

Maternal Sepsis: Incidence• Septic shock: 0.002-0.01% of all deliveries• 0.3-0.6% of all septic patients are pregnant• Has increased over the last decade

– Older maternal age at delivery• Obesity, diabetes, CHTN, placental abruption and

placenta accreta• ART and multi-fetal gestation

– Obesity• HTN, DM, Cesarean, cardiopulmonary complications

Burton and Sibai 2012

Maternal Sepsis Mortality and Morbidity During Hospitalization for Delivery

• Bauer et al Anesth Analg 2013– Population based epidemiologic study in the United

States• Nationwide Inpatient Sample (NIS) 1988-2008• Hospitalizations for delivery• American College of Chest Physician and Society of Critical care

medicine Definitions – Severe sepsis: sepsis with acute organ dysfunction, hypotension or

hypoperfusion

• Identified independent associations of severe sepsis

Maternal Sepsis Mortality and Morbidity During Hospitalization for Delivery

• Bauer et al Anesth Analg 2013– 44,999,260 hospitalizations for delivery

• Sepsis complicated 1:3333 deliveries• Severe sepsis 1:10,823 deliveries• Sepsis related death 1:105,384 deliveries

– Overall frequency of sepsis stayed the same during the study period

• Severe sepsis and death odds increased 10% per year

Maternal Sepsis Mortality and Morbidity During Hospitalization for Delivery

• Bauer et al Anesth Analg 2013– Independent risk factors for severe sepsis

Age >35 Chronic renal failureAA Race HIV infectionMedicaid SLERetained POCs Multiple gestationPROM CerclageCHF Chronic liver failure

Pathophysiology of Septic Shock

Decreased functional intravascular blood volume

Decreased BP and tissue perfusion

Cellular acidosis and hypoxia

End-organ tissue dysfunction and death

Creasy, Resnick and Iams 2010

Bacterial Infections in Obstetrics• Postpartum endometritis

– Cesarean delivery 15-87 %– Vaginal delivery 1-4 %

• Lower tract UTI 1-4 %• Septic abortion 1-2 %• Pyelonephritis 1-2 %• Chorioamnionitis 0.5 - 1 %• Necrotizing fasciitis < 1 %• Toxic shock syndrome < 1

Common Bacterial Isolates from OB Patients with Septic Shock

Escherichia coliGroup B streptococciBacteroides spp.PeptostreptococcusPeptococcus spp.Clostridium perfringensGroup A streptococci

Entercoccus spp.Staphylococcus aureusListeria monocytogenesKlebsiella pneumoniaePseudomonas aeruginosaEnterbacter spp.Proteus spp.

Maternal Sepsis Mortality and Morbidity During Hospitalization for Delivery

• Bauer et al Anesth Analg 2013– 1680 Women with severe sepsis had a ICD9 code for a known organism

• E. coli septicemia 27%• Staphylococcal septicemia 22%• Streptococcal septicemia 20%• Gram negative septicemia 19%• Pneumococcal speticemia4%• Pseudomonal septicemia 2.4%• Anaerobic septicemia 2%

Maternal Sepsis Mortality and Morbidity During Hospitalization for Delivery

• Bauer et al Anesth Analg 2013– Concurrent infections in women with severe sepsis

• Pneumonia 30%• GU infections 30%• Chorioamnionitis 18%• Endometritis 9%• Pyelonephritis 6%• Wound Infection 5%• Endocarditis 2 %• Meningitis 1%

Creasy, Resnick and Iams 2008

Lower Mortality in the Obstetric Patient

• 0-28 % versus 10-81% in the non-pregnant population

• Factors associated with the decreased mortality– Younger age– Types of organisms– Overall healthy population– Pelvis amenable to surgical and medical intervention– Transient bacteremia

Clinical Manifestations• Early stages

– RECOGNITION KEY TO SUCCESSFUL TREATMENT

– Shaking chills, fever (most common in pregnancy), tachycardia, flushing

– Warm extremities, nausea, vomiting, diarrhea

– Subtle changes in mental status

– May be difficult to diagnose early in pregnant women, particularly in labor

Clinical Manifestations• Laboratory findings

– mild leukopenia or leukocytosis, hyperglycemia

– early DIC : thrombocytopenia, decreased fibrinogen, increased PTT and PT

– transient respiratory alkalosis with increasing metabolic acidosis

• Increased serum lactate

• Low arterial pH

• Increased base deficit

Courtesy of Dr. Robert S. Munford

Clinical Manifestations• Later stages

– Generalized vasoconstriction - cold extremities– oliguria, peripheral cyanosis– tachycardia, severe hypotension– Depressed cardiac output, low SVR– Laboratory findings

• profound metabolic acidosis• electrolyte imbalance• generalized DIC

– Multiple end-organ failure

Multiple Organ Effects with Sepsis and Shock

• CNS Effects : Confusion, coma,s omnolence, fever• Cardiovascular: Hypotension, increased CO,

myocardial depression tachyarrhythmia• Pulmonary: Hypoxemia, diffuse infiltrates• Renal: Hypoperfusion, acute tubular necrosis• Hematologic: Thrombocytopenia, leukocytosis,

consumptive coagulopathy

Laboratory Evaluation

• Complete blood count– differential and platelets

• Coagulation profile– PT,PTT,FSP,Fibrinogen

• Electrolytes, glucose• Creatinine and blood

urea nitrogen• Urinalysis and culture

• Blood culture and gram stain

• Cultures of infected sites

• Chest X-ray• CT, ultrasound, MRI to

localize infectious etiology

Why do women die from septic shock?

• Myocardial depression : Cardiac output usually maintained due to tachycardia and cardiac dilitation

• ARDS : death rare from hypoxemia or hypercarbia

• Renal failure : dialysis will prevent death• Liver dysfunction : hepatic encephalopathy rare• ???

Creasy and Resnick 2008

Management of Septic Shock• Overall goals

– Treat the mother! • Resuscitating the mother will resuscitate the fetus• Delivery attempts increase maternal and fetal

mortality assuming the source is not intrauterine

– Improve functional intravascular volume– Establish and maintain an adequate airway– Determine the septic foci– Empiric antibiotic therapy : know the most

common pathogens

Management of Septic Shock• Volume resuscitation

– Aggressive therapy will optimize afterload, preload and cardiac contractility

– Normalize mixed venous oxygen saturation, lactate concentrations, base deficit and pH

– Blood products, colloid, crystalloid– Central venous access recommended

• Pulmonary artery catheter may cause more harm

Williams Obstetrics 2010

Management of Septic Shock• Oxygenation/Ventilation

– Mechanical ventilation usually required– ARDS : hypoxemia, normal PCWP, diffuse infiltrates

and decreased pulmonary compliance• PEEP

– Keep at or above 96% if possible during pregnancy

– Blood transfusion can increase O2 content : keep Hgb ~ 10 g/dl

Management of Septic Shock

• Inotropic agents– Dopamine hydrochloride (-adrenergic and -

adrenergic effects)– Dobutamine– Norepinephrine – now considered first line therapy

• Increases mean arterial pressure• Can reduce uterine artery blood flow

– Isoproterenol

Management of Septic Shock• Empiric antibiotic therapy

– Find the underlying etiology of the sepsis– Start broad spectrum antibiotics immediately after

drawing cultures• Penicillin (if Staphylococcus aureus suspected, consider

Vancomycin) or derivative PLUS aminoglycoside PLUS Clindamycin

• Vancomycin and Piperacillin/Tazobactam

– Alter regimen as culture and sensitivity results available

Management of Septic Shock• Surgical drainage or removal of infected

tissues– uterine evacuation, hysterectomy, abscess

drainage, etc depending on the etiology

• Corticosteroids: high doses do not increase survival. Physiologic doses may be beneficial in extremely ill patients (relative adrenal insufficiency)

Management of Septic Shock• Activated Protein C

– First anti-inflammatory agent effective in the treatment of septic shock (NEJM 2001)

– Inactivates Factors Va and VIIIa, preventing thrombin generation

– 3.5% risk of serious hemorrhage– However, U.S. FDA, based on the PROWESS-SHOCK

clinical trial, issued a statement in 2011 that it should not be started in new patients with sepsis because it failed to show a survival benefit

Management of Septic Shock

• Insulin therapy with a goal of blood sugar <180 mg/dl– hyperglycemia impairs phagocytotic effects– More aggressive control increases risk of

hypoglycemia

• RBC transfusion: target a Hgb 7.0 g/dL or greater

• NUTRITION

Prevention is Key

• Controlling chronic disease• Antimicrobial prophylaxis

– Repeat if case > 4 hours– Increase dose in obese patients

• Obesity epidemic ???• Appropriate vaccination

Maternal Sepsis: Call to Action

• A standardized approach should be formulated for pregnant women with suspected sepsis– Admission disposition protocol e.g. ICU, labor and

delivery– Early diagnosis procedures– Management protocol to include both maternal and

fetal evaluation and treatment– Prevention strategies

Development of a Maternal Sepsis Screening Tool… from Scratch!

Brenda G. Downs RN, MSN, ACNS-BCProgram Director, Clinical Performance Improvement

Dignity HealthBrenda.Downs@DignityHealth.org

I have no conflict of interest related to the content of this presentation.

Background and Significance

• We experienced a significant increase in maternal sepsis cases over the year prior to the start of this project, with 4 cases progressing to septic shock in the 4 months prior to the project start date

• All 4 cases experienced adverse outcomes, including 2 with mortalities

• In all 4 cases, SIRS/general variables and organ dysfunction were missed

What is (or is Not) in the Literature?• Large body of research in the adult population…

However, very limited studies in the maternal patient population

• To date, publications have been either case studies or retrospective, small sample size studies

• Identified gap: These studies did not identify or discuss a screening tool with maternal specific parameters

Steps to Developing a Tool• Formed a Multidisciplinary Team (July 2012)• Consulted experts in “both worlds” – OB and Sepsis • Defined populations – gestational age >20 weeks• Completed a comprehensive literature review and

developed a pilot maternal sepsis screening tool (August 2012)

• Developed a maternal sepsis abstraction tool for collecting data to help determine parameters – HR, RR (August 2012)

Tool Development• Built on a foundation of literature reviews, expert

review, and current resources• Retrospective chart audits:

– 15 random, uncomplicated deliveries– 15 high risk diagnosis – (infections)– Any patients diagnosed with severe sepsis or

septic shock diagnosed over last 2 years• Time Points: triage, ante, intra, post partum and

within 2 hours of discharge

Initial Maternal Screening Tool

Initial Maternal Screening Tool

Raw Results of Initial Audits Known Sepsis/

Infection GroupControl Group

# Patients 35 25Avg # times patients screened 2.6/pt 3.6/pt• # Patients with suspected infection # of patients with 2 > general variables # of patients with severe sepsis

30 (86%)17 (57%)13 (43%)

3 (12%)00

Total # times patients screenedHeart rate > 110Heart rate > 120Fetal heart rate > 160Respiratory rate > 20Altered temperature (> 38.3° or <36° C)WBC > 15K

9016119

5*1115

91110214

*10 screenings with no RR taken

Changes (& Resources) Along the Way…

• Barton & Sibai publication, Sept 2012, Severe sepsis and septic shock in pregnancy (Obstet Gynecol, 2012;120:689-706)

– Validated our screening parameter selections– Guided our HR parameter decision

• Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012, 3rd Ed publication (CCM, 2013; 41(2):580-637)

– Guidelines updated: added altered mental status; deleted chills/rigors; changed BG to 140

Final Screening Tool• Is there a suspected or confirmed

infection?• Are there 2 or more altered general

variables?– Temp > 38 C or < 36 C– FHR > 160 bpm (gestational age >20wks)– Maternal HR >110 bpm– RR > 24 bpm– WBC >15,000 or <4000 or >10% bands

with normal WBC– AMS– BG > 140 (in absence of DM)

Final Screening Tool • Is at least one of the following acute

organ dysfunctions present?– Decreased Cap refill/mottling skin– Lactic acid above normal values– Bilirubin >2mg/dL– Urine output < 0.5ml/kg/hr x2 hrs– Serum creatinine > 1.5 mg/dL or increase

>0.5mg/dL from baseline– INR >1.5 or PTT >60 w/o meds– SBP decrease >40mmHg from baseline– MAP <65 mmHg– Acute lung injury with PaO2/FiO2 ratio <250

(RT can calculate with ABG)

Final Screening Tool

• Last Section has recommendations for Bundle Elements and to call RRT– LA within 3 hrs– BC drawn prior to Abx– Abx within 1 hour for inpt and

3 hours from triage– Crystalloids 30ml/kg for

hypotension or LA >4

Challenges Along the Way…

• Providers concerns about the process• Misconceptions on screening• Who will implement the bundles?

THANK YOU!

QUESTIONS?