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Suspecting and Treating Sepsis in
Maternal Medicine
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Stephen L. Davidow, MBA-HCM, APR
Manager, Quality Implementation Programs
Society of Critical Care Medicine
Mount 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 Care
Faculty: Margaret M. Parker, MD, FCCM
Professor of Pediatrics, Anesthesia, and Medicine, Stony Brook University
Learning 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 Medicine
University of Texas Southwestern Medical
School
Dallas, TX
Brenda Downs, MSN, RN, ACNS-BC
Program Director, Clinical Performance
Improvement
Dignity Health
Gilbert, AZ
Septic Shock in the
Obstetric Patient
Jeanne S. Sheffield, M.D.
Maternal Fetal Medicine
University of Texas Southwestern
2013
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
CD4
CD4TTcells
cells
?
Pathogen
Bacterial inoculum
Th1 cells
Th2 cells
Inflammatory cytokines
TNF-a
IFN-g
IL-2
Anti-inflammatory cytokines
IL-4
IL-10
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 NonPregnant 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
AA Race
Medicaid
Retained POCs
PROM
CHF
Chronic renal failure
HIV infection
SLE
Multiple gestation
Cerclage
Chronic liver failure
Pathophysiology of Septic Shock
Decreased functional intravascular blood volum
Decreased BP and tissue perfusion
Cellular acidosis and hypoxia
End-organ tissue dysfunction and death
Bacterial Infections in Obstetrics
• Postpartum endometritis
– Cesarean delivery
– Vaginal delivery
• Lower tract UTI
• Septic abortion
• Pyelonephritis
• Chorioamnionitis
• Necrotizing fasciitis
• Toxic shock syndrome
15-87 %
1-4 %
1-4 %
1-2 %
1-2 %
0.5 - 1 %
<1%
<1
Creasy, Resnick and Iams 2010
Common Bacterial Isolates from OB Patients
with Septic Shock
Escherichia coli
Group B streptococci
Bacteroides spp.
Peptostreptococcus
Peptococcus spp.
Clostridium perfringens
Group A streptococci
Entercoccus spp.
Staphylococcus aureus
Listeria monocytogenes
Klebsiella pneumoniae
Pseudomonas aeruginosa
Enterbacter 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
Staphylococcal septicemia
Streptococcal septicemia
Gram negative septicemia
Pneumococcal speticemia
Pseudomonal septicemia
Anaerobic septicemia
27%
22%
20%
19%
4%
2.4%
2%
Maternal Sepsis Mortality and Morbidity
During Hospitalization for Delivery
• Bauer et al Anesth Analg 2013
– Concurrent infections in women with severe sepsis
•
•
•
•
•
•
•
•
Pneumonia
GU infections
Chorioamnionitis
Endometritis
Pyelonephritis
Wound Infection
Endocarditis
Meningitis
30%
30%
18%
9%
6%
5%
2%
1%
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
Creasy, Resnick and Iams 2008
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
• ???
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
Creasy and Resnick 2008
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 (a-adrenergic and badrenergic 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-BC
Program Director, Clinical Performance Improvement
Dignity Health
[email protected]
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
Control Group
# Patients
Avg # times patients screened
• # Patients with suspected infection
 # of patients with 2 > general variables
 # of patients with severe sepsis
Known Sepsis/
Infection Group
35
2.6/pt
30 (86%)
17 (57%)
13 (43%)
Total # times patients screened
 Heart rate > 110
 Heart rate > 120
 Fetal heart rate > 160
 Respiratory rate > 20
 Altered temperature (> 38.3° or <36° C)
 WBC > 15K
90
16
11
9
5*
11
15
91
1
1
0
2
1
4
*10 screenings with no RR taken
25
3.6/pt
3 (12%)
0
0
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?
QUESTIONS?
THANK YOU!
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