9/9/15. Sepsis Update: Early identification and management. Objectives. Incidence & Mortality. Blaizie Goveas, MS, APRN, AGACNP- BC

Transcription

1 Sepsis Update: Early identification and management Blaizie Goveas, MS, APRN, AGACNP- BC Objectives 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 2 Incidence & Mortality Sepsis is the leading cause of death in non coronary ICUs 11 In the United States, the incidence of severe sepsis is estimated to be 300 cases per 100,000 population 1 Annual cost of hospital care for patients with septicemia is $14 billion in United States 2 Septic shock is associated with the highest mortality, approaching 50% 3 3 1

2 Incidence 10 th leading cause of death in the United States overall 45 A fourth of patients who develop severe sepsis will die during their hospitalization 3 4 Incidence 5 The number and rate per 10,000 population of hospitalizations for sepsis more than doubled from 2000 through Incidence 5 Patients > 65yrs old who were hospitalized for sepsis in 2008 were sicker and stayed longer than those hospitalized for other conditions. 6 2

3 Epidemiology 3 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 7 Risk Factors 3 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 factors for Infection Central line/ Dialysis catheter Foley Catheter Drains Pressure ulcers/diabetic ulcers Prosthetic devices/ulcers Heart valve replacements Recent surgeries /procedures 8 Infection 6 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 9 3

4 Normal Response to Infection 7 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 10 Sepsis pathophysiology 7 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 11 Sepsis Continuum 12 4

5 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 13 Sepsis 2 or more SIRS + a suspected or confirmed source of infection SEPSIS 14 Additional Signs of Sepsis 8 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 15 5

6 Severe Sepsis 8 Sepsis + organ dysfunction, hypoperfusion, & hypotension Severe Sepsis 16 Severe Sepsis 17 Signs of Severe Sepsis 6 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 18 6

7 Signs of Severe Sepsis 6 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 19 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 20 Septic Shock 6 Sepsis + Refractory hypotension (despite adequate fluid resuscitation) Septic Shock 21 7

8 Hemodynamic support 8 Vasopressor therapy (to maintain MAP >65mmHg) Norepinephrine 1 st 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 g/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. 8

9 Goals during the 1 st 6 hours 9 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 25 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

10 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 28 ProCESS trial 10 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 The ProCESS investigators. (2014). A randomized trial of protocol-based care for early septic shock. New England Journal of Medicine, 370(18), 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),

11 ProCESS trial 10 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. The ProCESS investigators. (2014). A randomized trial of protocol-based care for early septic shock. New England Journal of Medicine, 370(18), ARISE trial 11 Large RCT with 1600 patients in septic shock 2 SIRS, suspected infection, SBP <90 despite fluid challenge or lactate P >4 51 centers mostly in Australia/New Zealand Randomized to 2 protocols EGDT vs. Usual care 32 ARISE trial 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),

12 ARISE trial 11 Primary end point all cause mortality at 90 days 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), ARISE trials 11 Conclusion In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days 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), ProMISe trial 12 P April 2, 2015 Large RCT with 1260 patients 56 hospitals in England Randomized to 2 protocols EGDT vs. Usual care 36 12

13 ProMISe trial 12 Primary outcome all cause mortality at 90 days The ProMISe trial investigators. (2015). Trial of early, goal-directed resuscitation for septic shock. New England Journal of Medicine, 372, 37 ProMISe trial 12 Also looked at cost effectiveness 38 ProMISe trial 12 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 The ProMISe trial investigators. (2015). Trial of early, goal-directed resuscitation for septic shock. New England Journal of Medicine, 372, 39 13

14 What does this tell us 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!!! 40 SERRI Sepsis Early Recognition and Response Initiative 41 Disclaimer The projects described are supported by Funding Opportunity Numbers 1C1CMS and 1C1CMS 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

15 What is SERRI? 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. 43 Screening tool 13 Validated screening tool for early identification of sepsis Decreased sepsis related mortality 44 SERRI 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

16 NP in action 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. 46 Summary Early identification à Early intervention à Prompt antibiotic administration à Source control à Aggressive management HELPS DECREASE MORTALITY!!! 47 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: ; Clemmer, T.P., Dellinger, R.P., Resar, R.K., Townsend, S. (2005). Implementing the surviving sepsis campaign. Retrieved from: %20Surviving%20Sepsis%20Campaign.pdf on November 29, HCUP Facts and Figures, 2006: Statistics on Hospital-Based Care in the United States. Rockville (MD)2008. Available at: gov/reports/factsandfigures/2008/toc_2008.jsp 3. Florian, M.B., Yende, S., Angus, D.C, (2014). Epidemiology of severe sepsis. Virulence 5:1, Xu JQ, Kochanek KD, Murphy SL, Tejada-Vera B. Deaths: Final data for National vital statistics reports; vol 58 no 19. Hyattsville, MD: National Center for Health Statistics Available from: 5. Hall M, Williams S, DeFrances C, Golosinsky A. Inpatient care for septicemia or sepsis: A challenge for patients and hospitals [Internet] Jun [cited 2011 Jun 30];Available from: 6. Levy MM, Fink MP, Marshall JC, et al: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. (2003). Intensive Care Medicine, 29: Jacobi J., Pathophysilogy of sepsis. Am J Health Syst Pharm. 2002, 59:S 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 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), Retrieved from on December 16, The ProCESS investigators. (2014). A randomized trial of protocol-based care for early septic shock. New England Journal of Medicine, 370(18), 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), The ProMISe trial investigators. (2015). Trial of early, goal-directed resuscitation for septic shock. New England Journal of Medicine, 372, 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: Acknowledgments: Stephen Jones, MD SERRI Program Director 16

17 17