9/9/15

1

Sepsis Update: Early identification and management

Blaizie Goveas, MS, APRN, AGACNP-

BC

2

•  Understanding what is sepsis and the severity of the disease process.

•  Epidemiology of sepsis •  Identifying high risk patient population •  Identifying early clinical signs and symptoms of sepsis •  Understanding sepsis pathophysiology •  Differentiating within the Sepsis continuum (SIRS, sepsis,

severe sepsis, and sepsis shock) •  Identifying the systemic clinical manifestation of sepsis •  Understanding new studies (ProCESS, ARISE, ProMISe) •  Importance of early recognition and intervention - SERRI

Objectives

3

•  Sepsis is the leading cause of death in non coronary ICUs11

•  In the United States, the incidence of severe sepsis is estimated to be 300 cases per 100,000 population1

•  Annual cost of hospital care for patients with septicemia is $14 billion in United States2

•  Septic shock is associated with the highest mortality, approaching 50%3

Incidence & Mortality

9/9/15

2

4

•  10th leading cause of death in the United States overall45

•  A fourth of patients who develop severe sepsis will die during their hospitalization3

Incidence

5

•  The number and rate per 10,000 population of hospitalizations for sepsis more than doubled from 2000 through 2008.

Incidence5

6

•  Patients > 65yrs old who were hospitalized for sepsis in 2008 were sicker and stayed longer than those hospitalized for other conditions.

Incidence5

9/9/15

3

7

Epidemiology3

•  People of older age, male gender, African American, and

preexisting chronic conditions are at highest risk to develop severe sepsis

•  Incidence is greatest during the winter

•  Respiratory source particularly pneumonia most common site and has the highest mortality rate

•  Urinary tract is the most common source of nosocomial infection

•  Gram-positive have increased over time and now are more common than gram-negative infections

•  Staphylococcus aureus is associated with the highest frequency in culture positive infected patients, followed by pseudomonas

8

Risk factors for Infection Central line/ Dialysis catheter Foley Catheter Drains Pressure ulcers/diabetic ulcers Prosthetic devices/ulcers Heart valve replacements Recent surgeries /procedures

Predisposing factors to develop infection

Age >65 yrs old Male African American Obesity COPD/Diabetes/Cancer Chronic renal/ liver disease Residence in long term facilities ICU stay Malnutrition Immunosuppression Transplant Immunosuppressive medications History of sepsis

Risk Factors3

9

Defined as “pathological process caused by invasion of normally sterile tissue or fluid or body cavity by pathogenic or potentially pathogenic micro-organisms” •  Documented or suspected •  Bacterial, viral, fungal, parasitic etc

Infection6

9/9/15

4

10

•  Circulating and fixed phagocytic cells are activated –  Generating proinflammatory (cyotokines) and

anti-inflammatory mediators •  Important mediators in fighting infection •  Regulates the immune response

•  Local response to control bacterial invasion, and

initiate the repair of injured tissue

Normal Response to Infection7

11

•  Profound intravascular inflammation process –  Releases cytokines, TNF, interleukins, and prostaglandins → Decreases fibrinolysis and increases coagulation

→ Causes microvascular thrombosis→ hypoperfusion to organs

•  Imbalance in proinflammatory and anti-inflammatory mediators –  Causes leaky capillaries leading to generalized vasodilation → Decreased cardiac output

→ Decreased vascular resistance → Hypoperfusion to organs

Sepsis pathophysiology7

12

Sepsis Continuum

9/9/15

5

13

SIRS

Systemic Inflammatory Response Syndrome

Temperature >100.9°F (38.3°C)

or <96.8°F (36°C)

Heart Rate > 90 bpm

Respiratory Rate > 20

WBC > 12,000 µ/L or < 4,000 µ/L

14

Sepsis

2 or more SIRS +

a suspected or confirmed source of infection

SEPSIS

15

Additional Signs of Sepsis8

•  Altered Mental Status •  Hyperglycemia >140 mg/dl in the absence of

diabetes •  Significant edema (>20 mL/kg over 24 hr) •  Normal WBC count with > 10% bands •  C Reactive Protein > 2 SD above normal •  Procalcitonin level > 2 SD above normal

9/9/15

6

16

Severe Sepsis8

Sepsis

+ organ dysfunction, hypoperfusion,

& hypotension

Severe Sepsis

17

Severe Sepsis

18

Signs of Severe Sepsis6

Organ Dysfunction Variables

Arterial hypoxemia - Pa02/FiO2 <300

Acute oliguria- urine output <0.5 mL/kg/hr for at least 2 hours despite adequate fluid resuscitation

Creatinine - >0.5 mg/dL

Coagulation abnormalities- INR > 1.5 or a PTT > 60 secs

Ileus/absent bowel sounds Thrombocytopenia- Platelets < 100k µL

Hyperbilirubinemia- Total bilirubin > 4 mg/dL

9/9/15

7

19

Signs of Severe Sepsis6

Hemodynamic Variables

Sepsis-induced hypotension SBP < 90 mmHg; MAP < 70 mmHg; or SBP decrease > 40 mmHg from baseline

Mixed venous oxygen saturation > 70% Cardiac index < 3.5 L/min

Tissue Perfusion Variables Mottled skin or decreased capillary refill

Elevated lactate > 4 mmol/L

20

Severe Sepsis

Tachypnea •  Compensatory mechanism due to metabolic acidosis •  May be an early or first sign •  May be sign of impending respiratory failure

Tachycardia •  HR increases to maintain normal BP •  Suggests hemodynamic compromise •  Cardiac output (CO) = HR x SV

Altered Mental Status •  Decrease in level of consciousness, increase in

agitation, confusion, or psychosis •  Can be from infection, particularly if elderly •  May be caused by hypotension and hypoxia

21

Septic Shock6

Sepsis

+ Refractory hypotension

(despite adequate fluid resuscitation)

Septic Shock

9/9/15

8

Hemodynamic support8

Vasopressor therapy (to maintain MAP >65mmHg) •  Norepinephrine – 1st choice •  Epinephrine – added to maintain adequate MAP •  Vasopressin – added to MAP or NE dose •  Dopamine – alternate vasopressor to NE only in selected

pts (low risk tachyarrthmias or bradycardia) •  Phenylephrine – not recommended in septic shock

Inotrope •  Dobutamine – myocardial dysfunction with elevated

cardiac filling pressures and low cardiac output

Early goal directed therapy 9

Fluid resuscitation (to maintain MAP >65mmHg)

•  Crystalloids (NS or LR) •  30 ml/kg •  Hydroxyethyl starches not recommended •  Albumin –when patients require substantial amount of

crystalloids Blood products

•  Hgb < 7.0g/dL (target 7.0 – 9.0g/dL) Corticosteroids

•  Intravenous hydrocortisone only when fluid resuscitation and vasopressor therapy do not restore hemodynamic stability

Early goal directed therapy 9

Pan cultures - Blood cults x2, Urine, CXR, wound, sputum Broad spectrum antibiotics within ONE hour of recognition Source control - surgery, percutaneous drains, d/c lines/implants etc.

9/9/15

9

25

•  Central venous pressure 8-12 mmHg •  Mean arterial pressure > 65 mmHg •  Urine output > 0.5ml/hr/kg •  Mixed venous oxygen saturation >70%

or 65% •  Lactic acid < 1.5 mmol/L (normalized) •  Overall clinical improvement

Goals during the 1st 6 hours9

Lactic Acid

•  Product of anaerobic metabolism due to impaired tissue oxygenation

•  levels in severe sepsis/ septic shock •  Indicator of metabolic failure and tissue hypoperfusion •  Improves with fluid resuscitation •  Trend lactate levels when initially elevated (goal is 10%

clearance in 6 hours à end goal is normalized levels)

The bigger picture

From  

9/9/15

10

28

ProCESS trial P •  Large RCT

•  1341 patients with septic shock –  2 SIRS +SBP <90 despite fluid challenge or lactate > 4mmol per liter

•  31 tertiary care ED’s in the US

29

•  Randomized to 1 of 3 protocols in the first 6 hours

1.  Protocol-based early goal directed therapy

(EGDT) -River’s protocol (ScV02, blood, dobutamine)

2.  Protocol-Based Standard therapy -CVC, inotropes, blood as needed, no ScV02 goal

3.  Usual care -What ERs in academic centers usually do

ProCESS trial10

The ProCESS investigators. (2014). A randomized trial of protocol-based care for early septic shock. New England Journal of Medicine, 370(18), 1683-1693.

30

ProCESS trial 10

The ProCESS investigators. (2014). A randomized trial of protocol-based care for early septic shock. New England Journal of Medicine, 370(18), 1683-1693.

9/9/15

11

31

Conclusion • “In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes”

• No difference in 60 day or 1 year cumulative mortality.

ProCESS trial10

The ProCESS investigators. (2014). A randomized trial of protocol-based care for early septic shock. New England Journal of Medicine, 370(18), 1683-1693.

32

ARISE trial 11 P

•  Large RCT with 1600 patients in septic shock –  2 SIRS, suspected infection, SBP <90 despite fluid challenge or lactate

>4

•  51 centers mostly in Australia/New Zealand •  Randomized to 2 protocols

–  EGDT vs. Usual care

33

ARISE trial11

The ARISE investigators and the ANZICS clinical trials group. (2014). Goal-directed resuscitation for patients with early septic shock. New England Journal of Medicine, 371(16), 1496-1506.

9/9/15

12

34

•  Primary end point all cause mortality at 90 days

ARISE trial11

The ARISE investigators and the ANZICS clinical trials group. (2014). Goal-directed resuscitation for patients with early septic shock. New England Journal of Medicine, 371(16), 1496-1506.

35

Conclusion – –  “In critically ill patients presenting to the emergency

department with early septic shock, EGDT did not reduce all-cause mortality at 90 days”

ARISE trials 11

The ARISE investigators and the ANZICS clinical trials group. (2014). Goal-directed resuscitation for patients with early septic shock. New England Journal of Medicine, 371(16), 1496-1506.

36

ProMISe trial12 P

•  April 2, 2015 •  Large RCT with 1260 patients •  56 hospitals in England •  Randomized to 2 protocols

–  EGDT vs. Usual care

9/9/15

13

37

•  Primary outcome all cause mortality at 90 days

ProMISe trial12

The ProMISe trial investigators. (2015). Trial of early, goal-directed resuscitation for septic shock. New England Journal of Medicine, 372, 1301-1311.

38

•  Also looked at cost effectiveness

ProMISe trial12

39

Conclusion – •  “In patients with septic shock who were identified

early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome”

ProMISe trial 12

The ProMISe trial investigators. (2015). Trial of early, goal-directed resuscitation for septic shock. New England Journal of Medicine, 372, 1301-1311.

9/9/15

14

40

•  No benefit to EGDT as defined by Rivers •  Usual care is ill defined •  CVC catheters are not essential •  CVC reserved for pressors, not monitoring •  EARLY RECOGNITON, EARLY ANTIBIOTICS,

EARLY SOURCE CONROL ARE ESSENTIAL!!!

What does this tell us…

41

Sepsis Early

Recognition and Response Initiative

SERRI

42

The projects described are supported by Funding Opportunity Numbers 1C1CMS3300975-01-00 and

1C1CMS331065 from Centers for Medicare and Medicaid Services, Center for Medicare and Medicaid Innovation. “Its contents are solely the responsibility of the authors and

do not necessarily represent the official views of HHS or any of its agencies.”

Disclaimer

9/9/15

15

43

SERRI is a bedside nurse driven sepsis screening protocol that focuses on:

▪  vital signs ▪  white blood cell count ▪  mental status changes

The values of these parameters are entered into a rigorously validated algorithm that derives a score of the likelihood that a patient has sepsis.

What is SERRI ?

44

•  Validated screening tool for early identification of sepsis

•  Decreased sepsis related mortality

Screening tool 13

45

Mission Save lives and reduce costs in patients with sepsis through

▪  Leadership ▪  Communication ▪  Education ▪  Implementation of SERRI

Vision Our vision is a health care system where patients no longer suffer the extreme morbidity and mortality that sepsis brings when it is not caught and treated early in its course.

SERRI

9/9/15

16

46

•  If the score is high enough, it triggers an evaluation by second level responders - Dedicated NPs that respond, assess the patient and initiate early treatment when appropriate.

NP in action…

47

Early identification

à Early intervention àPrompt antibiotic administration àSource control àAggressive management

HELPS DECREASE MORTALITY!!!

Summary

References

1.  Angus D.C., Linde-Zwirble W.T., Lidicker J., Clermont G., Carcillo J., Pinsky M.R., Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29:1303-10; Clemmer, T.P., Dellinger, R.P., Resar, R.K., Townsend, S. (2005). Implementing the surviving sepsis campaign. Retrieved from: http://ssc.sccm.org/files/Implementing%20the%20Surviving%20Sepsis%20Campaign.pdf on November 29, 2008.

2.  HCUP Facts and Figures, 2006: Statistics on Hospital-Based Care in the United States. Rockville (MD)2008. Available at: http://www.hcup-us.ahrq. gov/reports/factsandfigures/2008/TOC_2008.jsp

3.  Florian, M.B., Yende, S., Angus, D.C, (2014). Epidemiology of severe sepsis. Virulence 5:1, 4-11 4.  Xu JQ, Kochanek KD, Murphy SL, Tejada-Vera B. Deaths: Final data for 2007. National vital statistics reports; vol 58 no 19. Hyattsville,

MD: National Center for Health Statistics. 2010. Available from: http://www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_19.pdf 5.  Hall M, Williams S, DeFrances C, Golosinsky A. Inpatient care for septicemia or sepsis: A challenge for patients and hospitals [Internet].

2011 Jun [cited 2011 Jun 30];Available from: http://www.cdc.gov/nchs/data/databriefs/db62.pdf 6.  Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. (2003). Intensive

Care Medicine, 29:530-538. 7.  Jacobi J., Pathophysilogy of sepsis. Am J Health Syst Pharm. 2002, 59:S3-8 8.  Dellinger RP, et. al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004 Vol.

32, No. 3, pgs. 858-873 9.  Rivers, E., Nguyen, B., Havstad, S., Reesler, J., Muzzin, A., Knoblich, B., Peterson, E., Tomlanovich, M. for the Early Goal-Directed

Therapy Collaborative Group. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19), 1368-1377. Retrieved from www.nejm.org on December 16, 2008

10.  The ProCESS investigators. (2014). A randomized trial of protocol-based care for early septic shock. New England Journal of Medicine, 370(18), 1683-1693.

11.  The ARISE investigators and the ANZICS clinical trials group. (2014). Goal-directed resuscitation for patients with early septic shock. New England Journal of Medicine, 371(16), 1496-1506.

12.  The ProMISe trial investigators. (2015). Trial of early, goal-directed resuscitation for septic shock. New England Journal of Medicine, 372, 1301-1311.

13.  Moore, L.J, Jones, S.L., Kreiner, L.A., McKinley, B., Sucher, J.F., Todd, S.R., Turner, K.L., Valdivia, A., Moore, F.A. . (2009). Validation of a screening tool for the early identification of sepsis. J Trauma. 66: 1539-1547.

Acknowledgments: Stephen Jones, MD SERRI Program Director

9/9/15

17