Scope of the Problem. $20 billion of total 2011 US hospital costs

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Sepsis Kirth W Steele, DO, FCCP St. Luke s University Health Network Pulmonary & Critical Care Associates Diplomate, American Board of Internal Medicine Diplomate, European Society of Intensive Care Medicine

Objectives Define sepsis and septic shock Understand the pathophysiology of sepsis Recognize the features of early diagnosis and treatment Understand the Surviving Sepsis Campaign recommendations

Scope of the Problem $20 billion of total 2011 US hospital costs Reported incidence increasing Aging populations with more comorbidities Greater recognition Reimbursement-favorable coding

The Scope of the Problem A condition which is difficult to recognize High mortality rate Variable clinical presentations Few unifying pathophysiological features No gold standard test exists

Sepsis history 700 BCE Greeks decomposition and rot Life threatening condition associated with infection and a high risk of death

Sepsis history Bone, et al. Crit Care Med. 1992;20(6):864-874. Systemic inflammatory response syndrome (SIRS) Temperature > 38 C or < 36 C Heart rate >90/min Respiratory rate >20/min or Paco2 <32mm Hg White blood cell count >12,000 or <4,000 or >10% immature forms

Severe sepsis Organ dysfunction Hypoperfusion Hypotension Hypoperfusion includes but not limited to: lactic acidosis, oliguria, mental status change, etc.

Septic shock Ongoing hypotension despite adequate fluid resuscitation Includes hypoperfusion abnormalities Patients receiving vasopressors or inotropic agents may not be hypotensive at the time perfusion abnormalities are measured

Sepsis history For more than two decades little has changed regarding the consensus definitions as laid out by Bone et al. However, despite the efforts of the Surviving Sepsis campaigns, many clinicians still do not recognize nor treat appropriately

Rivers et al Early Goal Directed Therapy In addition to usual vital signs and urine output: CVP, central venous oxygen saturation, lactate Demonstrated significant survivability if predetermined goals were met within a six hour window.

Recent controversies ARISE EGDT did not reduce all-cause mortality at 90 days (Oct 2014 NEJM) ProCESS protocol based resuscitation of patients with septic shock did not improve outcomes May 2014/NEJM ProMISe a strict EGDT protocol did not lead to an improvement in outcome March 2015/NEJM

Sepsis 2016 Where are we now? New Sepsis 3 definitions Surviving Sepsis Campaign response What the heck is a clinician in a community hospital to do??? What to do till the intensivist arrives??

Sepsis - 3 SCCM/ESICM convened panel 19 experts in critical care, infectious disease, surgery, pulmonary Reexamination of current definitions based upon most recent literature and understanding of the pathophysiology of sepsis Task force recommendations were circulated to major international societies for peer review and endorsement 31 endorsing societies

Sepsis - 3 SIRS has been abandoned SIRS felt to be nearly ubiquitous in hospitalized patients and occurs in many benign conditions, some not related to sepsis SIRS not adequately specific for sepsis diagnosis New concepts: Sequential Organ Failure Assessment (SOFA) and qsofa (quick SOFA)

qsofa Respiratory rate >/= 22/min Altered mentation Glasgow Coma score of 13 or less Systolic blood pressure </= 100 mmhg

Key sepsis concepts The primary cause of death from infection especially if not recognized and treated promptly A syndrome shaped by pathogen factors and host factors Evolves over time Different from uncomplicated infection by dysregulated host response and the presence of organ dysfunction Organ dysfunction may be occult. Consider it in any patient presenting with infection New onset organ dysfunction may signal unrecognized infection Dysregulated host response may be absent but local organ dysfunction may be present

New Terms and Definitions Sepsis is a life threatening organ dysfunction caused by a dysregulated host response to infection Organ dysfunction identified as an acute change in total SOFA score >/= 2 points consequent to the infection SOFA >/=2 reflects overall mortality risk of 10% in general hospital population qsofa can promptly identify, at the bedside, patients with suspected infection who are likely to have a prolonged ICU stay or die in hospital

New Terms and Definitions Septic shock sepsis with persisting hypotension requiring vasopressors to maintain MAP >/=65 mmhg and lactate >2 mmol/l despite adequate volume resuscitation Septic shock is a sepsis subset in which the underlying circulatory and cellular/metabolic derangements substantially increase mortality Hospital mortality is in excess of 40% JAMA. 2016;315(8):801-810

New Terms and Definitions Although endorsed by 31 societies, these new definitions have not changed the way CMS is grading participating institutions regarding meeting certain sepsis recognition and treatment parameters So I say again what do I do on the wards and in the ED????

Sepsis Suspicion!! Suspicion!! Suspicion!!

3 hour bundle Surviving Sepsis Campaign Measure lactate level Obtain blood cultures prior to administration of antibiotics Administer broad spectrum antibiotics Administer 30ml/kg crystalloid for hypotension or lactate 4mmol/L or higher

6 hour bundle SSC 2012 Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain MAP 65mmHg or higher If persistent hypotension after initial fluid administration (MAP <65) or if initial lactate was equal to or more than 4mmol/L, reassess volume status and tissue perfusion according to the following: repeat focused exam: VS, cardiopulmonary, capillary refill, skin findings, pulse OR CVP, ScvO2, echocardiogram, or passive leg raise/fluid challenge

Surviving Sepsis Campaign 2012 Level 1 recommendations Early quantitative resuscitation during the first 6 hours after recognition Blood cultures obtained before antibiotic therapy Broad spectrum antibiotics within 1 hour of recognition of septic shock and severe sepsis as the goal of therapy De-escalation of antibiotic therapy as appropriate Infection source control within 12 hours of diagnosis Initial fluid resuscitation with crystalloid 30mL/kg crystalloid rapidly if sepsis induced hypoperfusion initially

Level 1 recommendations Avoidance of hetastarch Norepinephrine as first choice of vasopressor Dobutamine if myocardial dysfunction or adequate fluid/map and evidence of ongoing hypoperfusion Hemoglobin target of 7-9g/dL absent ischemic CAD/acute hemorrhage Low tidal volume strategy (6cc/kg PBW) Limitation of plateau pressures At least a minimal amount of PEEP (PEEP tables)

Level 1 recommendations Head of bed elevated 30 degrees unless contraindicated Conservative fluid strategy if ARDS without hypoperfusion Protocols for weaning and sedation Minimize sedation/target specific endpoints Avoidance of neuromuscular blockers in patients without ARDS Protocolized glucose management DVT prophylaxis/stress ulcer prophylaxis in at risk patients Address goals of care