SEPSIS

1. SEPSIS

2. SEPSIS – A Spectrum – Definitions • Infection — Infection is the invasion of normally sterile tissue by organisms. • Bacteremia — Bacteremia is the presence of viable bacteria in the blood. Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 3/18/14

3. SEPSIS – A Spectrum – Definitions • Systemic inflammatory response syndrome — SIRS is the clinical syndrome that results from a dysregulated inflammatory response to a noninfectious insult. It requires that two or more of the following abnormalities be present: • Temperature >38.3ºC or <36ºC • Heart rate >90 beats/min • Respiratory rate >20 breaths/min or PaCO2 <32 mmHg • WBC >12,000 cells/mm3, <4000 cells/mm3, or >10 percent immature (band) forms Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 1/31/13 and 3/18/14

4. SEPSIS – A Spectrum – Definitions • Sepsis — Sepsis is the clinical syndrome that results from a dysregulated inflammatory response to an infection. Sepsis is defined as the presence (probable or documented) of infection together with systemic manifestations of infection. Diagnostic criteria for sepsis include infection (documented or suspected) and some of the following: Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 3/18/14

5. SEPSIS – A Spectrum – Definitions • General Variables T > 100.9 or < 96.8 HR > 90 bpm or > 2 std dev above ULN for age RR > 20 brpm Altered Mental Status Significant edema or positive fluid balance (>20 ml/kg over 24 hrs) Hyperglycemia >140 mg/dl in non-diabetic Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 3/18/14

6. SEPSIS – A Spectrum – Definitions • Inflammatory Variables Leukocytosis – WBC > 12,000 Leukopenia – WBC < 4,000 WBC WNL with > 10% bands Plasma ncCRP > 2 std dev above ULN Plasma procalcitonin > 2 std dev above ULN Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 3/18/14

7. SEPSIS – A Spectrum – Definitions • Hemodynamic Variables Arterial hypotension – SBP < 90, MAP < 70, or SBP decrease > 40 mmHg from baseline or SBP < 2 std dev below LLN Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 3/18/14

8. SEPSIS – A Spectrum – Definitions • Organ Dysfunction Variables Arterial hypoxemia – PaO2/FiO2 < 300 Acute oliguria – UO < 0.5 ml/kg/hr for 2 hrs Creatinine increase > 0.5 mg/dL Coagulopathy – INR > 1.5 or aPTT > 60 sec Absent bowel sounds Thrombocytopenia – plt < 100,000 Hyperbilirubinemia – bili > 4 mg/dL Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 3/18/14

9. SEPSIS – A Spectrum – Definitions • Tissue Perfusion Variables Hyperlactatemia – > 1 mmol/L Decreased capillary refill or skin mottling Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 3/18/14

10. SEPSIS – A Spectrum – Definitions • Severe sepsis — Severe sepsis refers to sepsis plus at least one of the following signs of hypoperfusion or organ dysfunction: • Hypotension – SBP < 90, MAP < 70, or SBP decrease > 40 mmHg from baseline or SBP < 2 std dev below LLN • Lactate above ULN • Urine output <0.5 mL/kg for at least two hours despite adequate fluid resuscitation • Acute lung injury with PaO2/FiO2 < 250 with no pneumonia • Acute lung injury with PaO2/FiO2 < 200 with pneumonia • Platelet count < 100,000 • Creatinine > 2 mg/dL • Bilirubin > 2 mg/dL • Coagulopathy with INR > 1.5 Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis www.uptodate.com, accessed 3/18/14

11. SEPSIS – A Spectrum – Definitions • Septic shock— Septic shock is distributive (vasodilatory) shock defined as sepsis induced hypotension persisting despite adequate fluid resuscitation = 30 ml/kg crystalloid Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis, www.uptodate.com, accessed 3/18/14

12. SEPSIS – A Spectrum – Definitions • Multiple organ dysfunction syndrome — MODS refers to progressive organ dysfunction in an acutely ill patient, such that homeostasis cannot be maintained without intervention.It is at the severe end of the severity of illness spectrum of both SIRS and sepsis. MODS can be classified as primary or secondary: • Primary MODS is the result of a well-defined insult in which organ dysfunction occurs early and can be directly attributable to the insult itself (eg, renal failure due to rhabdomyolysis) • Secondary MODS is organ failure that is not in direct response to the insult itself, but is a consequence of the host’s response (eg, acute respiratory distress syndrome in patients with pancreatitis) There are no universally accepted criteria for individual organ dysfunction in MODS. However, progressive abnormalities of the following organ-specific parameters are commonly used as surrogate measures of organ function to diagnose MODS : • PO2/FiO2 ratio • Serum creatinine or urine output • Platelet count • Glasgow coma score • Serum bilirubin • Hypotension Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis www.uptodate.com, accessed 3/18/14

13. Case 1 • 75 Y.O.F. brought from N.H. with increased confusion, fever. In ED patient was lethargic, confused. Temp. 102.5 F, BP 60/35, P 120. WBC was 24,000 & U/A showed UTI What is your diagnosis? A. UTI B. Sepsis C. Severe Sepsis D. Septic Shock E. Who Cares

14. Case 1 • Above patient started on appropriate Abx as well as given Tylenol & 2 liter fluid bolus. 2 hours later pt. still lethargic, BP 70/40, P 110, temp. 99.4 F What is your diagnosis? A. Sepsis B. Severe Sepsis C. Septic Shock D. Refractory Septic Shock E. Who knows

15. Case 1 • Above patient admitted to ICU, continued on appropriate Abx, IVF and Levophed. Pt. still lethargic, BP 80/45, P 104, Temp 98.4 What is your diagnosis? A. Sepsis B. Severe Sepsis C. Septic Shock D. Refractory Septic Shock E. No idea

16. Case 2 • 72 Y.O.M. with history of Dementia had a fall at home. He has been having cough every time he eats and sometimes appeared to be choking with food. In ED temp. 101.5, BP 110/65( close to his baseline), P. 80. M.S. at baseline per family. CXR with RLL infiltrate What is your diagnosis? A. Pneumonia B. Aspiration Pneumonia C. Sepsis D. Septic Shock E. None of above

17. Case 2 • You admitted the patient the beginning of your shift and started appropriate Abx, IVF. Several hours later while doing your rounds you found pt. more confused. Temp. 102.2(despite Tylenol given), BP 108/62, P 110, R 24 What is your diagnosis? A. Pneumonia B. Aspiration Pneumonia C. Sepsis D. Septic Shock E. No idea

18. Case 3 • 75 Y.O.F. admitted for GI bleed. Foley catheter placed in ICU at time of admit. 4 days later pt. transferred to you with Foley in place. Several hours later you found patient confused, BP 120/70, P. 124, Temp 101.9 What is your diagnosis? A. Pneumonia B. UTI C. SIRS D. Sepsis E. GI bleed

19. Case 3 You call Dr. Alward regarding above pt. He ordered CXR, UA, CBC. CXR was negative, UA showed UTI, CBC pending. What is your diagnosis? A. Pneumonia B. UTI C. SIRS D. Sepsis E. All of above

20. SEPSIS Michael Williams DO, RPh Hospitalist Covenant HealthCare 2014

21. Objectives • Get to know more about sepsis • Get to know more about your patients • Get better at “seein’ it comin’ a mile away” • Get to know how you can start executing a series of interventions EARLY and just possibly save a patient’s life

22. SSC • Sepsis is a systemic, deleterious host response to infection leading to severe sepsis (acute organ dysfunction secondary to documented or suspected infection) and septic shock (severe sepsis plus hypotension not reversed with fluid resuscitation). Severe sepsis and septic shock are major healthcare problems, affecting millions of people around the world each year, killing 1 in 4 (and often more), and increasing in incidence. Similar to polytrauma, acute myocardial infarction, or stroke, the speed and appropriateness of therapy administered in the initial hours after sepsis develops are likely to affect the outcome.

23. Definition 2 • Sepsis is a clinical syndrome that complicates severe infection and is characterized by systemic inflammation and widespread tissue injury…tissues remote from the original insult display the cardinal signs of inflammation…

24. Definition 3 • Sepsis is SIRS (Systemic Inflammatory Response Syndrome) due to either a culture proven infection or an infection identified by visual inspection

25. So What Is SIRS? • SIRS is characterized by the presence of two or more of the following: • Temp > 100.9°F or < 96.8°F • HR > 90 bpm • RR > 20 or PaCO2 < 32 mm Hg • WBC count > 12k or < 4k or > 10% bands

26. NOT SIRS

27. NOT Sepsis

28. Bedside Sepsis • Fever or Hypothermia • Hyperventilation or SOB or Dyspnea • Warm Skin or Cold and Clammy • Possible Rash or Eruption • Tachycardia • Weakness or Malaise • Chills and/or Rigors • Confusion and/or Delirium • Decreased Urine Output

29. So What Happens In Sepsis? • Simply this:

30. Let’s Break It Down • Sepsis results from the body’s natural inflammatory response directed against pathologic bacterial invasion, but the inflammation gets out of control and goes beyond the initial site of insult, affecting other distant organs and functions • Your septic patient is, therefore, just manifesting the signs and symptoms of this widespread inflammatory response

31. How Does This Get Started? • Remember, our environment (ie, the whole world) is populated with “critters” • Some good • Some bad

32. Good Critters • Beneficial organisms such as:

33. Bad Critters • Pathogenic bacteria, fungi, viruses such as:

34. Sepsis Is Extermination Gone Wild • Any critter can cause sepsis if in the wrong place at the wrong time

35. The Inner Terminator • Everyone with an intact immune system will launch an attack on foreign invaders; if not, we’d all be like the “bubble boy” “It says Moops!”

36. Hasta La Vista, Baby • The immune system releases powerful reactive species, cytokines and toxins to neutralize the threat

37. What Starts The Whole Mess? • Parts of the organism get recognized during the killing process and trigger an intense immune response in your patient

38. The Immune Response Intensifies • The normal process snowballs and a veritable feeding frenzy erupts

39. The Death Star Is Fully Functional • The cytotoxic efficacy of immunity is fine when targeted at the bad guys, but deadly when it overwhelms the patient’s body

45. On Your Mark, Get Set, Go! • Once you see the signs and symptoms of sepsis in your patient, the race is on to eliminate the infection before the body’s own extermination efforts spiral too far out of control • The body will try to kill the invader, but this can set off mechanisms that cause diffuse coagulation and resultant consumption coagulopathy, vascular leakage with tissue hemorrhage and edema, vascular dilatation and hypotension, etc, all leading to major organ dysfunction and failure

46. This Grim Story Is No Fairy Tale • Heart – decreased myocardial contractility aggravates systemic hypotension, decreasing blood flow to all of the body’s tissues, decreasing O2 delivery and removal of toxic waste products everywhere • Lung – vascular leakage allows fluid into the alveoli causing pulmonary edema – fluid filled alveoli have decreased O2 diffusion capacity, aggravating the decreased tissue oxygenation from circulatory collapse

47. Everything Means Everything • Liver – decreased blood flow and oxygenation lead to increased anaerobic metabolism (like everywhere else) and acidosis – shock liver, dysfunctional glucose control and decreased waste metabolism and elimination • Kidneys – hypotension and cytokine effects lead to decreased glomerular blood flow which decreases urine output leading to acute kidney injury which further decreases urine output – renal failure decreases systemic toxin removal

48. And I Mean Everything • Brain – decreased blood flow as well as glucose regulatory dysfunction and metabolic toxin build-up in the bloodstream leads to encephalopathy and altered mental status • Blood – nitric oxide, cytokines, acidosis and tissue factors released in the septic process cause vasodilatation and start the coagulation cascade – decreased effective circulating blood volume and thrombi blocking blood flow further, with, you guessed it, decreased O2 delivery, etc

49. The Bottom Line • As we can see, sepsis only affects organs which depend on adequate nutrient and O2 delivery and removal of waste products to maintain their normal function… • In essence the body’s immune response certainly seems like it can destroy the invader, but possibly only by destroying itself

50. So What Does All Of This Mean? • The signs and symptoms to recognize come from the underlying pathophysiology • Fever/Rigors – immune challenge • Tachypnea/Dyspnea – pulmonary edema and acidosis • Tachycardia – decreased cardiac output, hypotension and effective volume loss • Decreased UO – decreased renal blood flow and glomerular filtration cause kidney injury • Delirium – decreased cerebral blood flow, glucose problems and buildup of systemic toxins