1. Welcome Suspecting and Treating Sepsis in Maternal Medicine

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4. 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

5. 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

6. Jeanne Sheffield, MD Maternal Fetal Medicine
University of Texas Southwestern Medical School
Dallas, TX

7. Brenda Downs, MSN, RN, ACNS-BC
Program Director, Clinical Performance Improvement
Dignity Health
Gilbert, AZ

8. Septic Shock in the Obstetric Patient
Jeanne S. Sheffield, M.D.
Maternal Fetal Medicine
University of Texas Southwestern
2013

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

10. The microorganisms that seem to have it in for us. turn out
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

11. 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

12. Why immune suppression which increases mortality?
Shift to anti-inflammatory cytokines
CD4 T cells
CD4 T cells ?
Pathogen
Bacterial inoculum
Th1 cells
Th2 cells
Inflammatory cytokines
TNF-a
IFN-g
IL-2
Anti-inflammatory cytokines
IL-4
IL-10

13. 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

14. 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

15. 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)

16. 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

17. 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

18. 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

19. Maternal Sepsis: Incidence
Septic shock: % of all deliveries
% 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

20. 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)
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

21. 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

22. 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 failure
AA Race HIV infection
Medicaid SLE
Retained POCs Multiple gestation
PROM Cerclage
CHF Chronic liver failure

23. Pathophysiology of Septic Shock
Decreased functional intravascular blood volume
Decreased BP and tissue perfusion
Cellular acidosis and hypoxia
End-organ tissue dysfunction and death

24. Bacterial Infections in Obstetrics
Postpartum endometritis
Cesarean delivery %
Vaginal delivery %
Lower tract UTI %
Septic abortion %
Pyelonephritis %
Chorioamnionitis %
Necrotizing fasciitis < 1 %
Toxic shock syndrome < 1
Creasy, Resnick and Iams 2010

25. 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.

26. 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 speticemia 4%
Pseudomonal septicemia 2.4%
Anaerobic septicemia 2%

27. 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%

28. 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

29. 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

30. 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

31. Courtesy of Dr. Robert S. Munford

32. 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

38. 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

39. 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

40. 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
???

44. 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

45. 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

46. Williams Obstetrics 2010

47. 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

49. Management of Septic Shock
Inotropic agents
Dopamine hydrochloride (a-adrenergic and b- adrenergic effects)
Dobutamine
Norepinephrine – now considered first line therapy
Increases mean arterial pressure
Can reduce uterine artery blood flow
Isoproterenol

50. 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

51. 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)

52. 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

53. 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

54. Prevention is Key Controlling chronic disease
Antimicrobial prophylaxis
Repeat if case > 4 hours
Increase dose in obese patients
Obesity epidemic ???
Appropriate vaccination

55. 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

56. Development of a Maternal Sepsis Screening Tool… from Scratch!
Brenda G. Downs RN, MSN, ACNS-BC
Program Director, Clinical Performance Improvement
Dignity Health

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

58. 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

59. 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

60. 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)

61. 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

62. Initial Maternal Screening Tool

63. Initial Maternal Screening Tool

64. Raw Results of Initial Audits
Known Sepsis/ Infection Group
Control Group
# Patients 35 25
Avg # 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%)
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* 15 91 1 2 4
We did retrospective chart audits to look at screening tool parameters.
We reviewed 25 random normal delivery charts – the control group- and 35 known infection cases. We asked that each patient be audited with the tool at the point of entry into the hospital, during labor, post partum and just prior to discharge. For the known sepsis/infectious patients there were 90 audits done amongst the 35 patients and 91 audits among the 25 control group patients.
*10 screenings with no RR taken

65. Changes (& Resources) Along the Way…
Barton & Sibai publication, Sept 2012, Severe sepsis and septic shock in pregnancy (Obstet Gynecol, 2012;120: )
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): )
Guidelines updated: added altered mental status; deleted chills/rigors; changed BG to 140

66. 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)
If you answer yes to both of these questions – we ask to notify physician and consider ordering a lactate and creatinine and also continue to the 3rd question to assess for acute organ dysfunction

67. 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)

68. 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

69. Challenges Along the Way…
Providers concerns about the process
Misconceptions on screening
Who will implement the bundles?

70. Questions?
Thank YOU!