Severe Sepsis A TIME CRITICAL Diagnosis Across the Spectrum of Care - PowerPoint PPT Presentation

Severe Sepsis A TIME CRITICAL Diagnosis Across the Spectrum of Care Steven Q Simpson, MD, FCCP, FACP Professor of Medicine Division of Pulmonary and Critical Care University of Kansas

21 st Century Sepsis Teaching? “as the physicians say it happens in hectic fever , that in the beginning of the malady it is easy to cure but difficult to detect, but in the course of time, not having been either detected or treated in the beginning, it becomes easy to detect but difficult to cure” Niccolò Machiavelli The Prince – 1513 or 1532

What is Sepsis? Life threatening organ dysfunction due to a dysregulated host response to infection

What is Sepsis? Life threatening organ dysfunction due to a dysregulated host response to infection

Interesting Case • 72 y.o. banker; flank pain and fever at nursing home • Recent admission to hospital for a stroke. • Aide notes mild confusion while getting him ready for breakfast • previous L. ureteral stent placement • Hx of CAD, HTN, Stroke with left leg weakness • Meds include terazosin, atorvastatin, metoprolol, aspirin • BP 105/43, P 117, R 22, T 39.1 o , SpO 2 87%

What should NH do now? A. 3 L bolus of LR B. Apply oxygen C. Point of care lactate level D. IV or PO levofloxacin, 2 L bolus of LR, transfer to hospital for ICU admission

What should NH do now? A. 3 L bolus of LR B. Apply oxygen C. Point of care lactate level D. IV or PO levofloxacin, 2 L bolus of LR, transfer to hospital for ICU admission In truth, none of these answers are wrong. But hospital transfer is key, based on the information we have.

What should EMS do when they arrive? A. Blood cultures B. Apply oxygen C. Point of care lactate level D. IV or PO levofloxacin, 2 L bolus of LR, transport to hospital for ICU admission

What should EMS do when they arrive? A. Blood cultures B. Apply oxygen C. Point of care lactate level D. IV or PO levofloxacin, 2 L bolus of LR, transport to hospital for ICU admission Again, any of these could be good. But transfer to the hospital is key.

What should happen on arrival to ER? A. Blood cultures B. Apply oxygen C. Point of care lactate level D. IV or PO levofloxacin, 2 L bolus of LR, ICU admission

What should happen on arrival to ER? A. Blood cultures B. Apply oxygen C. Point of care lactate level D. IV or PO levofloxacin, 2 L bolus of LR, ICU admission All of the above, actually.

At the hospital • Labs: WBC – 14.7, 33% bands • Plt – 96,000 • BUN – 47, Cr. – 3.2 • D-dimer – 4.7, fibrinogen – 72, PTT – 39 • Lactate – 2.6 • UA – not available

Severe Sepsis • THE major cause of morbidity and mortality worldwide – Leading cause of death in noncoronary ICU (US)* – 11th leading cause of death overall (US) † § • More than 750,000 cases of severe sepsis in US annually‡ • In the US, more than 500 patients die of severe sepsis daily‡ *Sands KE et al. JAMA. 1997;278:234-40; § Murphy SL. National Vital Statistics Reports. ‡Angus DC et al. Crit Care Med. 2001;29:S109.

Severe Sepsis How Common – How Deadly? Incidence of Severe Sepsis Mortality of Severe Sepsis 300 250,000 250 200,000 Cases/100,000 Deaths/Year 200 150,000 150 100,000 100 50,000 50 0 0 AMI † AIDS* Severe Cancer § CHF † Severe Breast AIDS* Colon Breast Sepsis ‡ Cancer § Sepsis ‡ †National Center for Health Statistics, 2001. § American Cancer Society, 2001. *American Heart Association. 2000. ‡Angus DC et al. Crit Care Med. 2001 (In Press).

Winters, et al. Crit Care Med 38:1276, 2010.

Iwashyna, et al. JAMA 304:1787, 2010.

Iwashyna, et al. JAMA 304:1787, 2010.

Age Related Incidence of Severe Sepsis Angus DC, et al. Crit Care Med . 2001.

Sepsis Incidence Compounding Growth Doubling time = 8.5 years Martin, G, et al. N Engl J Med 348:1546-54, 2003. Dombrovskiy V, et al. Critical Care Medicine 35:1244 – 1250, 2007.

Why is this is IMPORTANT? Because ALL previous epidemiological studies have been based on administrative or claims data.

Health Systems – HCA – VA – Univ of Pittsburgh – Cerner Health Facts – Institute for Health Metrics –Brigham and Women’s – Emory Healthcare

Study Hospitals vs. AHA 8.5% of hospitals; ~10% of US admissions

Clinical Criteria: Sepsis-3?

Patient Demographics

Patient Comorbidities

Patient Characteristics

Patient Outcomes Mortality: Hosp Acquired – 25.5%; POA – 13.4% Sepsis vs. Septic Shock - ??

US Sepsis Statistics - 2014 • 5.9% of hospitalizations involve sepsis • Hospital mortality 15.6% • 35% of hospital deaths • 1.7 million adult hospitalizations • 270,000 deaths • Remember – this is only adults

Sepsis Incidence: 2009 - 2014

Sepsis Mortality Rates: 2009 - 2014

• Important study using clinical findings • Would like an actual comparison of severe sepsis with Sepsis-3 • Did not use vital signs data • Would like to see septic shock mortality broken out

571,000 ED visits per year for severe sepsis

146 vs 111 minutes

Reduced by 29 minutes

Diagnosis Everything is vague to a degree you do not realize till you have tried to make it precise. Bertrand Russell (1872 – 1970)

Sepsis ≠ Hypotension

Sepsis ≠ Bacteremia

ACCP/SCCM Consensus Definitions • Infection • Sepsis - Inflammatory response to – Infection plus microorganisms, or ≧ 2 SIRS criteria - Invasion of normally sterile tissues • Severe Sepsis – Sepsis • Systemic Inflammatory – Organ dysfunction Response Syndrome (SIRS) • Septic shock - Systemic response to a variety of – Sepsis processes – Hypotension despite fluid - 2 SIRS criteria resuscitation Bone RC et al. Chest. 1992;101:1644-55.

SIRS: Systemic Inflammatory Response Syndrome • SIRS: nonspecific insult 2 of the following: SIRS – Temperature > 38 ° C or < 36 ° C – HR > 90 beats/min – Respirations > 20/min – WBC >12,000/µL or < 4,000/µL or > 10% bands or other Adapted from: Bone RC et al. Chest. 1992;101:1644-55. Opal SM et al. Crit Care Med. 2000;28:S81-2.

Acute Organ Dysfunction as the Hallmark of Severe Sepsis Altered Hypotension Consciousness SBP < 90 Confusion MAP < 70 Psychosis Tachypnea PaO2 <70 mm Hg SaO2 <90% PaO2/FiO2 < 300 T. Bilirubin  Platelets (< 100k) > 4 mg/dL INR>1.5, PTT>60 sec ↑ D -dimer Lactic acidosis

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Definition: Sepsis is life threatening organ dysfunction caused by a dysregulated host response to infection Drops the term “severe sepsis” Drops the use of SIRS and infection + SIRS

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Condition Sepsis-2 Sepsis-3 Sepsis Infection + SIRS Infection + ∆ SOFA ≥ 2 Severe Sepsis Infection + SIRS + NON-EXISTENT organ dysfunction Septic Shock Infection + Infection + Unresponsive Unresponsive Hypotension* Hypotension* + Serum Lactate > 2 mmol/L *Hypotension that does not respond to volume infusion and requires vasopressor administration

SOFA Score 1 2 3 4 Respiration < 200 < 100 PaO 2 /FiO 2 < 400 < 300 With respiratory with respiratory support support Cardiovascular Dopamine > 15 Dopamine > 5 or Hypotension Dopamine ≤ 5 or or epinephrine MAP < 70 mm epinephrine or dobutamine, any or Hg norepinephrine dose norepinephrine ≤ 0.1 > 0.1 Liver 1.2 – 1.9 2.0 – 5.9 6.0 – 11.9 > 12.0 Bilirubin (mg/dL) Renal 3.5 – 4.9 or ≥ 5.0 or Creatinine (mg/dL) 1.2 – 1.9 2.0 – 3.4 < 500 mL/24 hr < 200 mL/24 hr or urine output Coagulation < 150 < 100 < 50 < 25 Platelets x 10 3 /mm 3 CNS Glasgow Coma Scale 13 - 14 10 - 12 6 - 9 < 6

Quick SOFA • Also known as qSOFA • Any two of: - Glasgow Coma Scale < 15 - Respiratory rate ≥ 22/min - Systolic blood pressure ≤ 100 mm Hg

SIRS, qSOFA, Severe Sepsis Sensitivity and Specificity

Severe Sepsis: A Diagnostic Challenge • Timely and accurate diagnosis remains a challenge – 17% of physicians agreed on definition of sepsis, but 83% agreed the dx is often missed – Occurs throughout the institution – Clinical definition not applied at bedside – No single test or marker • Focus is on supporting underlying organ failure Poeze M, et al. Crit Care 2004, R409.

Diagnostic criteria for severe sepsis include: A. Positive blood cultures, hypotension B. Positive blood cultures, tissue hypoxia C. Positive blood cultures, SIRS, and lactic acidosis D. Suspected infection, SIRS, and organ dysfunction

Diagnostic criteria for severe sepsis include: A. Positive blood cultures, hypotension B. Positive blood cultures, tissue hypoxia C. Positive blood cultures, SIRS, and lactic acidosis D. Suspected infection, SIRS, and organ dysfunction

Sepsis: What Are We Talking About? • ICD- 9: “septicemia” • Positive blood cultures • Multiple positive blood cultures • Positive blood cultures + hypotension Roger C. Bone, MD • Syndrome: how shall we define it?