Sepsis: Identification and Management in an Acute Care Setting Dr. Barbara M. Mills DNP Director Rapid Response Team/ Code Resuscitation Stony Brook University Medical Center SEPSIS LECTURE NPA 2018

oBJECTIVES To understand and be able to identify the differences between SIRS, Sepsis, Severe Sepsis, and Septic Shock. To understand the morbidity and mortality of Sepsis in relation to length of stay, current guidelines, cost to health care systems. To understand modalities of treatment which include management, such as fluid resuscitation and pharmacological interventions.

In-hospital death 8X higher compared to other diagnoses Data from the National hospital discharge survey, 2008. NCHS data brief June 2011. The number of sepsis cases more than doubled from 200-2008. In hospital deaths were more than 8x as likely among hospitalized for septicemia or sepsis (17%) compared with other diagnoses (2%). In addition, those hospialized for septicemia or sepsis were ½ as likely to be discharged home, twice as likely to be transferred to another short-term facility and 3x as likely to be discharged to a long-term care institutions, as those with other diagnoses. .http://www.cdc.gov/nchs/data/databriefs/db62.pdf accessed August 7, 2015

Sepsis Bundle Project (SEP) National Hospital Inpatient Quality Measures SEP-1 Early Management Bundle, Severe Sepsis/Septic Shock Discharges 10-01-2015 (4Q15) through 06-30-16 (2Q16)

Sepsis ECONOMICS Sepsis is a major and economically significant disease in the ICU, costing over $20 billion in the United States in 2011 (5.2% of all U.S. hospital costs) with costs growing to over $23 billion in 2013 (6.2% of all U.S. hospital costs)

Sepsis ECONOMICS Sepsis: major health problem with increasing prevalence, high costs, and poor outcomes.

Increased hospitalizations for more than 1 million people in 2008 Sepsis ECONOMICS Increased hospitalizations for more than 1 million people in 2008

Sepsis ECONOMICS Between 1999 and 2014: 2,470,666 deaths with sepsis on the death certificate with increase annual sepsis related deaths by 31%

Sepsis ECONOMICS Severe Sepsis and Septic Shock are subsets of sepsis conditions with at least one organ dysfunction, which accounts for 25-50% of in-hospital mortality…

…that can range with a 45%-65% mortality within 6 months of discharge. Sepsis ECONOMICS …that can range with a 45%-65% mortality within 6 months of discharge.

INFECTION INFECTION SEPSIS INFECTION SEVERE SEPSIS SEPSIS

Those who survive tend to have increasing complications, morbidity, high costs of care, and decreasing quality of life.

HISTORICAL PERSPECTIVE SIRS Criteria ( > 2) Temperature > 38 C < 36 C Heart rate > 90 bpm Respiratory rate > 20 /min or a PaCO2 < 32 mmHg White blood cell count > 12,000 / cu mm or < 4,000 / cu mm, or > 10 bands Source: CHEST 1992

NEW SEPSIS DEFINITION Guidelines were revised in 2008, 2012, and most recently updated in 2015. These guidelines have shaped how hospitals must identify and treat patients who are identified as having sepsis, severe sepsis, and septic shock.

NEW SEPSIS DEFINITION The Surviving Sepsis Campaign (SSC) international guidelines were developed for early detection and treatment of severe sepsis and septic shock

NEW SEPSIS DEFINITION “Sepsis is a life threatening organ dysfunction caused by a dysregulated host response to an infection.” The European Society of Intensive Care Medicine/Society of Critical Care Medicine Third International Consensus definitions for Sepsis and Septic Shock task force (the Sepsis-3 task force)

Serum lactate > 2 mmol/L New sepsis definition Persistent hypotension requiring vasopressors to keep MAP > 65 mmHg despite adequate fluid resuscitation Serum lactate > 2 mmol/L JAMA 2016

SEPSIS Scoring tool Quick SOFA / qSOFA SBP ≤100mmHg > 22/ min In patients with infection a qSOFA score > 2 is associated with higher mortality and prolonged ICU stay.

ProCESS ARISE Enrollment <2 hours from detection of shock Research trials ProCESS ARISE Enrollment <2 hours from detection of shock 2.8 hours (median) from presentation to ED Antibiotics 75% received prior to enrollment 70 minutes (median) from presentation to ED Fluids >2 liters prior ot enrollment 2515ml (mean) prior to enrollment Research trials in the emergency room.

SEP-1 Two Clocks 3 hour

SEP-1: EARLY MANAGEMENT BUNDLE SEP-1 Two Clocks SEP-1: EARLY MANAGEMENT BUNDLE Severe Sepsis Time Zero 3 hr. 6 hr. Interventions Required: Blood culture before antibiotics Antibiotics Lactate level Interventions Required: Lactate level repeated (If elevated) Set Measure ID # SEP-1-8; Early Management Bundle, Severe Sepsis/Septic Shock

TO BE COMPLETED WITHIN 3 HOURS OF TIME OF PRESENTATION: SEP-1 Two Clocks TO BE COMPLETED WITHIN 3 HOURS OF TIME OF PRESENTATION: Obtain blood cultures prior to administration of antibiotics. Measure lactate level. Administer broad spectrum antibiotics. Administer 30ml/kg crystalloid for hypotension, defined as a “mean arterial pressure” MAP<65 or lactate ≥4mmol/L. 2012 NQF: SEPSIS 0500

SEP-1 Two Clocks Focused Exam Importance of reassessment.

SEP-1 Two Clocks “Delays in administering all four guidelines recommendations, even when they did not exceed 3 hours, were associated with a significant increase in in-hospital mortality.” Studies done and published in the SCCM journal April 2018. Volume 46. Number 4 have made some conclusions: SCCM journal April 2018. Volume 46. Number 4

SEPTIC SHOCK ONLY Severe Sepsis Time Zero 3 hr. 6 hr. Interventions Required: Persistent Hypotension Within 1 hour of fluid add VASOPRESSOR OR Lactate > 4 Shock Assessment (1 of 2) Interventions Required: ALL of Severe Sepsis + Fluid 30 ml/kg (NO exclusionary criteria) Physical Exam (ALL) Vital Signs (T, HR, RR, BP) Cardiopulmonary exam Capillary refill evaluation Peripheral Pulse evaluation Skin evaluation Hemodynamics (2 of 4) CVP SVO2 Bedside cardiovascular ultrasound Passive leg raise / fluid challenge Shock Assessment

SEP-1 Two Clocks TO BE COMPLETED WITHIN 6 HOURS OF TIME OF PRESENTATION: Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure (MAP) ≥65mmHg) 2012 NQF: SEPSIS 0500

Mean arterial pressure 65 mm Hg 75 mm Hg 85 mm Hg F/LT Urinary output (mL) 49 +18 56 + 21 43 +13 .60/.71 Capillary blood flow (mL/min/100 g) 6.0 + 1.6 5.8 + 11 5.3 + 0.9 .59/.55 Red Cell Velocity (au) 0.42 + 0.06 0.44 +016 0.42 + 0.06 .74/.97 Pico2 (mm Hg) 41 + 2 47 + 2 46 + 2 .11/.12 Pa-Pico2 (mm Hg) 13 + 3 17 + 3 16 + 3 .27/.40 Adapted from Table 4, page 2731, from LeDoux, Astiz ME, Carpati CM, Rackow ED. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 2000; 28:2729-2732

TO BE COMPLETED WITHIN 6 HOURS OF TIME OF PRESENTATION: SEP-1 Two Clocks TO BE COMPLETED WITHIN 6 HOURS OF TIME OF PRESENTATION: In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥4 mmol/L (36mg/dl): Measure central venous pressure (CVP) Measure central venous oxygen saturation (ScvO2) Remeasure lactate if elevated 2012 NQF: SEPSIS 0500

FLUID RESUSCITATION

RESEARCH SUPPORTING FLUID RESUSCITATION BUNDLE

Choice of Fluids Crystalloids Colloids Ringers Lactate Normal Saline Gelatins Hetastarch Albumin

IV FLUID COMPOSITIONS

FLUID REPLACEMENT CHALLENGES End Stage Renal Disease on Dialysis Compensated Congestive Heart Failure

HEMODYNAMIC CHANGES IN SEPTIC SHOCK Interstitial Edema in Septic Shock Lungs Brain Kidney

Dellinger RP. Cardiovascular management of septic shock Dellinger RP. Cardiovascular management of septic shock. Crit Care Med 2003;31:946-955.

During Septic Shock End Diastole Systole 10 Days Post Shock This slide demonstrates radionuclide angiography in a patient during septic shock and following recovery. The top left panel shows end-diastole and demonstrates increased diastolic size of the ventricles (increased compliance), which is thought to be an adaptive mechanism. The top right image shows end-systole in this patient demonstrating a very low ejection fraction (little change in chamber size compared to end-diastole). The bottom two frames following recovery demonstrate a decrease in end-diastole volume, smaller ventricle at end systole and therefore significant improvement in ejection fraction. Courtesy of Joe Parrillo Hackensack NJ

RESEARCH RECOMMENDATION SCCM recommends that, in the resuscitation of sepsis-induced hypoperfusion, at least 30 ml/kg of IV crystalloid fluid be given within the first 3 hours (strong recommendation, low quality of evidence).

Started within 3 hrs after severe sepsis presentation ANTIBIOTIC THERAPY Started within 3 hrs after severe sepsis presentation Monotherapy vs. Combination Therapy

Choose Aminoglycosides or Aztreonam or Ciprofloxacin COMBINATION THERAPY Choose Aminoglycosides or Aztreonam or Ciprofloxacin Cephalosporins, (1st and 2nd Generation) - or – Clindamycin - or - Daptomycin - or - Glycopeptides - or - Linezolid - or - Macrolides - or - Penicillins

Choice of vASOPRESSERS Norepinephrine First Line Low Dose Vasopressin (.01-.03 units/min) Epinephrine Second Line Dopamine (sinus bradycardia) Niche Drugs Phenylephrine (high cardiac output or serious tachyarrhythmias and salvage)

Surviving sepsis campaign 2016 We suggest against using IV hydrocortisone to treat septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. If this is not achievable, we suggest IV hydrocortisone at a dose of 200 mg per day

Surviving sepsis campaign 2016 No ACTH stimulation tests or serum cortisol testing No additional mineralocorticoid 7 days Taper

Tapering of steroids is recommended. WHAT DO WE KNOW? Hydrocortisone provides adequate glucocorticoid and mineralocorticoid effects so fludrocortisone is not needed. Tapering of steroids is recommended. Although the current hypothesis for the use of steroids in septic shock is to treat relative adrenal insufficiency, current evidence suggests no value in measuring this with a corticotropin response test.

Low dose steroid therapy reduces time to reversal of septic shock WHAT DO WE KNOW? Steroids are of no benefit in the treatment of severe sepsis in the absence of shock. Low dose steroid therapy reduces time to reversal of septic shock Still controversial as to whether or not there is a meaningful reduction in mortality. The more severely ill and hemodynamically unstable the patient is the more likely to benefit from stress-dose steroids.

To Save Lives..... Early identification Early antibiotics Insert vent, kumar article EGDT article sedation vacation bundles scattered Early fluid resuscitation

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