1. Dallas, TX November 2–4, 2012 Sepsis Recognition and Treatment of Severe Sepsis in the Pediatric and Adult Populations

2. Dallas, TX November 2–4, 2012 Can your staff recognize sepsis? Sepsis can be subtle until it is so obvious you can’t miss it

3. Dallas, TX November 2–4, 2012 62 year old admitted to hospital with hip infection On admission –T – 38.5 –RR – 24 –P – 104 –WBC – 19,000 Where should he be admitted?

4. Dallas, TX November 2–4, 2012 36 hours post admission Urine output drops – What should be done?

5. Dallas, TX November 2–4, 2012 48 hours post admission Pulse oximeter drops and becomes difficult to read – what should be done?

6. Dallas, TX November 2–4, 2012 Modified from criteria published in: Balk RA. Crit Care Clin. 2000;16:337-352. Kleinpell RM. Crit Care Nurs Clin N Am 2003;15:27-34. Cardiovascular Tachycardia Hypotension Altered CVP and PAOP Renal Oliguria Anuria  Creatinine Hematologic  platelets,  PT/INR/  aPTT  protein C  D-dimer Hepatic Jaundice  Liver enzymes  Albumin CNS Altered consciousness Confusion Metabolic Metabolic acidosis  Lactate level  Lactate clearance Respiratory Tachypnea  PaO 2  PaO 2 /FiO 2 ratio IDENTIFYING ACUTE ORGAN DYSFUNCTION AS A MARKER OF SEVERE SEPSIS

7. Dallas, TX November 2–4, 2012 Difference between Sepsis States Sepsis / ICD 995.91 Severe Sepsis/ ICD 995.92 Septic Shock/ ICD 785.52  Pulse ≥ than 90 beats per minute  Respiratory rate ≥ than 20 breaths per minute  Temperature > 38.0 o C or < 36.0 o C  WBC 12,000; or bands > 10%  Pulse ≥ than 90 beats per minute  Respiratory rate ≥ than 20 breaths per minute  Temperature > 38.0 o C or < 36.0 o C  WBC 12,000; or bands > 10%  Pulse ≥ than 90 beats per minute  Respiratory rate ≥ than 20 breaths per minute  Temperature > 38.0 o C or < 36.0 o C  WBC 12,000; or bands > 10%  Real or suspected infection:  Organ dysfunction: Organ Dysfunction  Hypotension  SIRS- Patient’s labs/vitals reflect any two of the following with an infectious or noninfectious etiology: Temp= 100.4RR= > 20/min or PaCO2 < 32 mmHG HR= > 90 bpmWBC= 12,000; or > 10% bands  Sepsis- Systemic Inflammatory Response Syndrome (SIRS) with an identified source or suspected source of infection.  Severe Sepsis- Sepsis associated with organ dysfunction, hypoperfusion or hypotension. Manifestations may include lactic acidosis, oliguria, and an acute alteration in mental status.  Septic Shock- Acute circulatory failure unexplained by other causes: SBP <90 or MAP < 60, Reduction in 40 mmHg from baseline despite adequate volume resuscitation or Patients who require inotropic or vasopressor support despite adequate fluid replacement. Definitions

8. Dallas, TX November 2–4, 2012 “Our arsenals for fighting off bacteria are so powerful, and involve so many different defense mechanisms, that we are more in danger from them than from the invaders. “We live in the midst of explosive devices; we are mined!” Lewis Thomas - 1972 Germs, New England Journal Of Medicine DR 32708 3000093662 1204.5 Copyright © 2004, Eli Lilly and Company. All rights reserved. Xigris is a registered trademark of Eli Lilly and Company.

9. Dallas, TX November 2–4, 2012 “Except on few occasions, the patient appears to die from the body's response to infection rather than from it.” Sir William Osler – 1904 The Evolution of Modern Medicine

10. Dallas, TX November 2–4, 2012 History of Treating Severe Sepsis Antibiotics, fluids, vasopressors - Have they been successful? Have we searched for better treatments?

11. Dallas, TX November 2–4, 2012 Key to Success Rapid Identification Nursing’s role in identifying and helping in the treatment of sepsis is more important than ever before Implementing protocols on the floor, ED and ICU Physician and coder’s working together to improve documentation

12. Dallas, TX November 2–4, 2012 12 Hemodynamics of Sepsis Concept of early resuscitation –Establishing urgency – use of Lactate –Normal 1-2 mmol –> 4 mmol with metabolic acidosis suggests tissue hypoxia Fluids with a goal –The role of mixed venous oxyhemoglobin (ScvO 2 )

13. Dallas, TX November 2–4, 2012 Early Sepsis Blood pressure88/52 mm Hg Pulse108 beats/min Stroke index14 Cardiac index1.6 Peak Velocity79 CVP5 mm Hg SvO 2 0.37

14. Dallas, TX November 2–4, 2012 Late Sepsis Blood pressure88/56 mm Hg Pulse104 beats/min Stroke index50 Cardiac index5.5 Peak velocity65 CVP7 mm Hg SvO 2 0.84

15. Dallas, TX November 2–4, 2012 Microvascular Blood Flow Is Impaired in Severe Sepsis: Role of Antithrombotics/Profibrinolytics Venous blood Arterial blood SO2 -.98 SO2 -.94 SO2 -.65 SO2 -.86 SO2 -.65 SO2 -.83 SO2 -.65

16. Dallas, TX November 2–4, 2012 Lactate Levels and SBP Lactate N= 529 < 2 (N=219)2-4 (N=177)> 4 (N = 104) SBP > 90158/219 (72%)116/177 (65%)64/104 (62%) SBP < 9061/219 (28%)61/177 (34%)40/104 (38%)

17. Dallas, TX November 2–4, 2012 Case Example – Is Action Needed? 29 year old male with history of Crohn’s disease is admitted from ED with perirectal abscess. Lactate 5.9 SI – 20 ml/m2 StO2 -.51 SpO2 -.94 BP – 92/50 HR – 81 RR – 20 T – 38.1 UO – 1 ml/kg/hr (55 ml/hr)

18. Dallas, TX November 2–4, 2012 Sepsis often progresses when the host cannot contain the primary infection a problem most often related to –characteristics of the microorganism, such as a high burden of infection the presence of superantigens and other virulence factors, resistance to opsonization and phagocytosis, antibiotic resistance.

19. Dallas, TX November 2–4, 2012 Cell dysoxia Epithelial cells have diminished oxygen consumption – due to a depletion of nicotinamide adenine dinucleotide (NAD) Concept of cell stunning or hibernation

20. Dallas, TX November 2–4, 2012 Pathophysiology of Sepsis What do we need to know

21. Dallas, TX November 2–4, 2012

22. Immune Response

23. Dallas, TX November 2–4, 2012 Coagulation and Impaired Fibrinolysis In Severe Sepsis Reprinted with permission from the National Initiative in Sepsis Education (NISE). Endothelium Neutrophil Monocyte IL-6 IL-1 TNF-  IL-6 Inflammatory Response to Infection Thrombotic Response to Infection Fibrinolytic Response to Infection TAFI PAI-1 Suppressed fibrinolysis Factor VIIIa Tissue Factor COAGULATION CASCADE Factor Va THROMBIN Fibrin Fibrin clot Tissue Factor

24. Dallas, TX November 2–4, 2012 Hotchkiss, R. S. et al. N Engl J Med 2003;348:138-150 The Response to Pathogens, Involving "Cross-Talk" among Many Immune Cells, Including Macrophages, Dendritic Cells, and CD4 T Cells

25. Dallas, TX November 2–4, 2012 How do We Identify Sepsis Now? In absence of biomarkers, must rely on crude physical indicators

26. Dallas, TX November 2–4, 2012 SIRS AND SEPSIS Sepsis is defined as an infection plus  2 SIRS criteria Temperature >38°C or <36°C HR >90 beats/min Respirations >20/min WBC count >12,000/mm 3 or 10% immature neutrophils SIRS Severe sepsis MODS Septic shock SIRS Severe sepsis Sepsis Infection Other Pancreatitis Trauma Burns Sepsis Levy MM, et al. Crit Care Med. 2003;31:1250-1256.

27. Dallas, TX November 2–4, 2012 Case Study 1

28. Dallas, TX November 2–4, 2012 Case Study 1 63 year old male in MICU with CAP, pneumothorax Progressing well but on day 3 –Develops spontaneous pneumothorax –RLL infiltrate Temp increases to 39.1 –P – 122 –BP – 92/58 (following EGDT) WBC 16,500 Is SOB, requires intubation, 50% FIO2, AMV 12/14, Vt – 500 ccs, PEEP +10 Day 4 –SpO2 -.92, PaO2 64 (P/F ratio > 100), pH 7.28, PaCO2 32, HCO3 - 17 Sepsis is suspected with treatment rapidly started –Has received EGDT 4 L NS norepinephrine (Levophed) 30 mcg ScvO2 < 60 Is on hydrocortisone 50 mg Q 6 hrs Insulin to keep glucose < 150 Platelets – 110,000

29. Dallas, TX November 2–4, 2012

30. Day 5

31. Dallas, TX November 2–4, 2012 Case Study 2: Should Drotrecogin Alfa (Activated) Have Been Started? 62-year-old, 150 kg female with history of ovarian cancer –Undergoes debulking surgery for tumor –4 days post-op develops wound infection –Norepinephrine at 10 µg/min –PEEP 12 cm H 2 O, FiO 2 90% –Sedated (Ramsey – 6) Drotrecogin alfa (activated) (24 µg/kg/hr) started on day 5 –Day 6: norepinephrine off –Day 10: off ventilator Respiratory failure recurs on day 15 Dies on day 24

32. Dallas, TX November 2–4, 2012 ICU Admission Characteristics 40% are low risk Likely to recover without ICU admission 50% are mid risk Will benefit and usually recover due to ICU care 10% are high risk High mortality even with ICU care

33. Dallas, TX November 2–4, 2012 121,000 7,100 52,000 44,000 40,000 27,000 18,000 174,200 215,000 050,000100,000150,000200,000250,000 In-hospital CPR Mechanical ventilation in stroke rhEPO CABG Coronary angiography Lung transplantation Implantable defibrillators Coronary stent Drotrecogin alfa (activated) tPA Cost/QALY (dollars) Cost-Effectiveness of Various Interventions in Critically Ill Patients Angus DC, et al. Crit Care Med 2003;31:1-11.

34. Dallas, TX November 2–4, 2012 Erin K. Flatley/ Dr. Carl Flatley In 2002, sepsis claimed the life of Erin K. Flatley. Erin was a healthy, vibrant 23-year old graduate student in Florida. She went into the hospital for a "routine" surgery but a post-operative infection occurred and because of the lack of recognition and prompt treatment, it continued to advance. She died five days later. The killer was sepsis. Stop the dying www.remembererin.com

35. Dallas, TX November 2–4, 2012 Summary The bedside clinician, i.e. nurse or physician, is often the first to identify organ dysfunction as a marker of severe sepsis Treatments must be started rapidly to achieve benefit Cost issues are minimized by implementation of evidenced based practice