Sepsis and Septic Shock: An Update for the Primary Care Provider

1. Sepsis and Septic Shock: An Update for the Primary Care Provider National Association for Pediatric Nurse Practitioners Western NY branch, November 2016 Meeting Amanda B. Hassinger, MD, MS Director of Quality & Patient Safety Division of Pediatric Critical Care Women & Children’s Hospital of Buffalo Assistant Professor, Department of Pediatrics University at Buffalo Jacobs School of Medicine and Biomedical Sciences

2. Disclosure • No financial conflicts to report

3. Objectives • The evolution of the definition of sepsis • Recent epidemiology • Outpatient sepsis management • Progress on outcomes • CMS and NY State Mandates

4. The Evolution of “Sepsis” SEPSIS = life-threatening organ dysfunction* caused by a dysregulated host response to infection *even subtle amounts = 10% increase in mortality.

5. Previous Sepsis Paradigm SIRS = Systemic Inflammatory Response ↑↓WBC, ↑↓Temperature, ↑HR, ↑ RR

6. SIRSThe“Systemic Inflammatory Response Syndrome” • Sign of whole-body inflammation • At least 2 of 4 criteria:1,2 1. Core temperature: >38 or <36°C 2. White blood count: >12 or <4,000/mm3 OR > 10% immature neutrophils 3. Abnormal heart rate: >90bpm OR > 2 SD above normal for age, bradycardia in infants2 4. Abnormal respiratory rate: >20bpm OR> 2 SD normal for age *For children: One must be temperature or WBC2 • Bone et al. Chest. 1992; 101:1644. • Goldstein et al. PCCM. 2005;6:2.

7. SIRS: Lessons Learned • Do not necessarily indicate a “dysregulated, life-threatening response” • Occur in many normal physiologic conditions • 88% of ICU patients have SIRS on admission3 and 93% at some point during their stay4 • Approximately half of 270,000 adults on general floors meet SIRS criteria at some point5 • SIRS = APPROPRIATE host response • Dulhunty JM, et al. Intensive Care Med 2008;34:1654 • Sprung CL, et al. Intensive Care Med 2006;32:421 • Churpek MM, et al. Am J RespirCrit Care Med2015;192:958.

8. Is There a New SIRS? • SIRS was meant to be a screen for early signs of organ failure • Three common elements emerged as signs of organ failure: • Hypotension • Altered mental status • Tachypnea • qSOFA6 is a quick screen for these 3 elements 6. Singer, et al. JAMA. 2016;315:801.

9. 6. Singer, et al. JAMA. 2016;315:801.

10. 1992 Consensus Definition “SEPSIS” least sick stage of the continuum from SIRS to septic shock. • Bone et al. Chest. 1992; 101:1644.

11. 2016 SEPSIS-3 Paradigm Shift • Sepsis = Infection + ≥2 pt ↑SOFA score • Septic Shock = Sepsis + (vasopressor therapy needed to elevate MBP ≥65mm Hg + lactate >2mmol/L despite adequate fluid resuscitation) 6. Singer, et al. JAMA. 2016;315:801.

12. Pediatrics still using this one. 7. Vincent JL et al. Crit Care. 2016;20:210.

13. The Epidemiology of Sepsis • True incidence is unknown • Likely the leading cause of mortality and critical illness worldwide • “Septicemia” #9 on the CDC list of COD in 20008 • Annually, $20-25 billion of total US hospital costs (5.2% of all costs)8,9 • Increasing in incidence in all age-groups9 Vincent JL, et al. Lancet. 2013;381:774. Gaieski DF, et al. Crit Care Med. 2013;41:1167.

14. Severe Sepsis Estimates • Incidence* is rising by 13% per year • Highest increase in: • >85 year olds: 62.8118.3 cases per 1000 admits • Non-whites: 118.3203.6 cases per 1000 admits Vincent JL, et al. Lancet. 2013;381:774. Gaieski DF, et al. Crit Care Med. 2013;41:1167. Gohil SK et al. Clin Infect Dis. 2016;62(6):695 Cluzet VC et al. Clin Infect Dis. 2016;62:704.

15. 10. Gohil SK et al. Clin Infect Dis. 2016;62(6):695

16. 9. Gaieski et al. Crit Care Med 2013; 41:1167.

17. Adult Sepsis Epidemiology • Incidence has risen over the last 20 years • Due to aging population, more co-morbidities • Actual incidence rise is confirmed in data from the UK, Croatia, Australia, New Zealand11 • Likely slower than reported • Proven by stable US hospital admission rates • Overall mortality related to sepsis has been increasing while case-fatality is decreasing = “overuse” of the term in less sick patients 11. Cluzet VC et al. Clin Infect Dis. 2016;62:704.

18. Pediatric Sepsis Epidemiology…

19. Pediatric Sepsis Epidemiology • Estimated $4-5 Billion annually 12. Ruth A et al. PCCM. 2014;15:828. 13. Weiss SL et al. Am J RespirCrit Care Med. 2015;191:1147 14. Hartman ME, et al. PCCM. 2013;14:686.

20. PSS: Common Pattern? Pediatric Sepsis Definitions 12. Ruth A et al. PCCM. 2014;15:828.

21. 12. Ruth A et al, PCCM. 2014;15:828. 14. Hartman ME, et al. PCCM. 2013;14:686.

22. Pediatric Sepsis Epidemiology • Incidence has risen over the last 20 years • Very low birth weight infants, more comorbidities • Likely slower rise in incidence than reported • Overall mortality related to sepsis has been increasing while case-fatality is decreasing = “overuse” of the term in less sick patients

23. Outpatient Sepsis Management • Recognition • RECOGNITION • Early RECOGNITION!

24. What does “Sepsis” Look Like?

25. Presentation: Adult Sepsis qSOFA = RR> 22bpm, AMS, SBP<100mmHg

26. “Pediatric” SS ≠ “Small Adult” Sepsis • Children frequently get infections • “Normal” varies significantly by age • Children are poor historians • Early stages more subtle, pediatric cases recognized later • Hypotension is a verylate sign

27. Presentation: Pediatric SS

28. PSS ≠ Adult Sepsis qSOFA = AMS, RR> 22bpm, SBP<100mmHg • Signs of evolving organ dysfunction in children: • Change in mental status • Excessive tachycardia • Change in perfusion Where is BP!?! Hypotension is a late, late sign of decompensated shock in children = Slippery slope to irreversible shock and death You wait for hypotension, you’ve waited too long! qPOFA? = Excessive tachycardia, AMS, change in CR

29. “Excessive” Tachycardia • Data exist for the effects of fever* on HR *Measured as core temperature, can differ from axillary/oral temps by 1o • HR higher than expected = “excessive” • May be compensation for poor oxygen delivery, poor cardiac function or an underlying acidosis

30. Outpatient Sepsis Management • RECOGNITION • Source identification

31. Sepsis: Common Sources • ADULTS: • Resp • UTI • GI • PEDS: • Resp • Blood • GI Adults: 58% hospital-acquired Peds:43% hospital-acquired

32. PSS: Common Sources 1995 to 200514: Respiratory infections = 1/2 Primary bacteremia = 1/5 2004-2012 (PICU)12: Bacteremia = ~2/3 Respiratory = ~ 1/2 12. Ruth A et al. PCCM. 2014;15:828. 14. Hartman ME, et al. PCCM. 2013;14:686.

33. Outpatient Sepsis Management • RECOGNITION • Source identification • Empiric antibiotics

34. Cultures and Antibiotics • Surviving Sepsis Campaign recommends: • Blood cultures should be sent prior to antibiotic administration.* • Use of 1,3 beta-D-glucan assay, mannan and anti-mannan antibody assays • Empiric IV/IM antibiotics, as early as possible • Ideally < 1 hour after recognition15 ***Do not delay antibiotics if competing interests arise*** 15. Dellinger RP, et al. Crit Care Med. 2013;41:580.

35. Microbiology of Sepsis • Staph • Strep • E. Coli #1

36. Microbiology of PSS • Staph • Strep • E. Coli #1 21% in 201313 13. Weiss et al, Am J RespirCrit Care Med. 2015;191:1147. 14. Hartman ME, et al. PCCM. 2013;14:686

37. Choice of Antibiotics • Broad spectrum • Gram +  Gram -  mixed infections • Depends on: • Local antibiograms • Suspected source • Patient circumstances

38. Abstracted from Kaleida Health WCHOB Pediatric Severe Sepsis Protocol

39. Outpatient Sepsis Management • Recognition • Source identification • Antibiotics • Prompt referral to a higher level of care if showing signs of organ failure Early recognition and treatment is life-saving!

40. Adult Severe Sepsis Outcomes • Total mortality ↑: 14.7-29.9% in 2009 • 229,044 deaths in 2009 (#3 COD) 9. Gaieski et al. Crit Care Med 2013; 41:1167.

41. Adult Severe Sepsis Outcomes • Case fatality ↓from 16-35% in 2004 to 12-25% in 2009 9. Gaieski et al. Crit Care Med 2013; 41:1167.

42. Pediatric SS Outcomes • Severe sepsis in U.S. PICUs, 2004-15: • Median of 17 hospital/7 ICU days and $77,000 • Mortality down-trending, but still >10% Overall case fatality rate dropped by 14% from 19952005 And by 37% from 2004-2012. 12. Ruth A et al. PCCM. 2014;15:828.

43. 14. Hartman ME, et al. PCCM. 2013;14:686.

44. Latest PSS: Outcomes • International point prevalence study: • Mortality rate 25% • Nearly 1 in 5 survivors with moderate/severe disability 13. Weiss et al, Am J RespirCrit Care Med. 2015;191:1147.

45. Early recognition 12. Ruth A et al. PCCM. 2014;15:828.

46. Has Care ReallyImproved? • Bundle use, EGDT, SS Campaign = ↓ mortality • Rely on RECOGNITION and IMPLEMENTATION • Recognition delays impact care and outcomes13 • 67% of severe sepsis patients have MODS at diagnosis • 1/3 go on to new/progressive organ dysfunction within week • Protocol implementation an issue • Example: Antibiotics after the “sick + sepsis” determination17 • Easy, right? • 60 minutes longer on wards than in ER • Delay = independently ⬆ mortality risk 13. Weiss SL et al, Am J RespirCrit Care Med. 2015;191:1147. 17. Weiss SL, et al. Crit Care Med 2014; 42:2409.

47. Where are the Roadblocks? • 1000 physicians from US, Europe interviewed18 • 90% agreed sepsis symptoms “easily misattributed” • < 25% of intensivists correctly defined “sepsis” • 9 in 10 agreed patients “often treated too late” • 250 nurses from 500-bed US children’s hospital19 • Knowledge of, attitudes towards SIRS and sepsis • Clinical scenarios testing: SIRS/Sepsis or not? • Average correct score of 61%, more difficulty with early stages • 20% “uncomfortable” recognizing SIRS • 10% “uncomfortable” recognizing septic shock 18. Poeze M et al. Crit Care. 2004;8:R409. 19. Jeffrey AD et al. Pediatric Nursing. 2014;40:271.

48. PRESS Study • 412 providers surveyed, 75% completion • Single-center free standing children’s hospital • MDs, RNs, RTs, mid-levels in the ED, PICU, General floors • Knowledge adequate • Average correct score for scenarios of 65% • Culture concerning • 11% ICU RNs uncomfortable telling others a patient has sepsis • 25% Peds MDs uncomfortable diagnosing shock if BP is normal • 42% ICU RNs, 75% Pediatric residents hesitate at least some of the timeto diagnose sepsis for fear of “making too big a deal” • Nearly 1/3 residents have been discouraged by a superior from using this diagnosis

49. To Make a Cultural Change… • Challenges to recognition and management everywhere • Inpatient & outpatient • Across disciplines, departments, provider roles WHERE DO WE GO FROM HERE?