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SEPSIS Intern Bootcamp Scott Denstaedt, PGYIII Sepsis /ˈsɛpsɨs/; from the Greek σῆψις: the state of putrefaction and decay Background • local inflammation systemic inflammatory response tissue hypoperfusion and multiorgan failure DEATH – release of specific toxins eg. Gram Negative Bacteria lipid A, Staph. aureus TSST-1 – Host cytokine response eg. TNF-alpha • Septic shock with multi-organ failure is most common cause of death in ICU • >750000 cases/year, mortality rate of 1 in 4 ***Sepsis is a spectrum of illness that requires early intervention to prevent complications and progression*** Definitions • Systemic Inflammatory Response Syndrome (SIRS) criteria – – – – – – response to infectious and non-infectious insults 2 criteria needed to meet SIRS Temp >38, <36 HR >90 RR >20, PaCO2 <32 (differs depending on textbook) WBC >12k or <4k or 10% bands • *NO BLOOD PRESSURE IN SIRS CRITERIA Definitions • Sepsis – 2 SIRS criteria + source of infection (you don’t necessarily need concrete evidence – high level of clinical suspicion is enough) Definitions • Severe Sepsis – Sepsis with organ dysfunction (don’t memorize the list below) • Sepsis-induced hypotension • Lactate above upper limits laboratory normal • Urine output <0.5 mL kg/h for more than 2 h despite adequate fluid resuscitation • Acute lung injury with Pa /Fi <250 in the absence of pneumonia as infection source • Acute lung injury with Pa /Fi <200 in the presence of pneumonia as infection source • Creatinine[2.0 mg/dL (176.8 lmol/L) • Bilirubin[2 mg/dL (34.2 lmol/L) • Platelet count <100,000 lL • Coagulopathy (INR >1.5) O2 O2 O2 O2 Definitions • Septic Shock – Sepsis induced hypotension despite adequate fluid resuscitation • Sepsis induced hypotension = SBP <90mmhg or 40mmhg change from baseline • Each term describes the the intensity of infectious insult • Increase in # of SIRS criteria associated with decreased interval to progression of severe sepsis and septic shock ***CAVEATS*** • Elderly, uremic, and patients with end-stage liver disease or those receiving corticosteroids may NOT have fevers. • SIRS Criteria are entirely non-specific – EG. Everyone met SIRS criteria on day one of intern year • Clinical picture must be taken into account Rivers et. al 2001 • Initial 6 hours of resuscitation in ED • ~1-1.5 hours to identification of sepsis on avg. Early Goal Directed Therapy Outcomes • Severe Sepsis and Septic Shock – Randomized to standard therapy (iv fluids, abx) v. Early Goal Directed Therapy • RESULTS (Patients with EGDT): – Elevated CVP, MAP, Scv02 – Decreased Lactate – Improved Mortality (almost 50% reduction in mortality compared to standard therapy!!) Surviving Sepsis Campaign • Global initiative to reduce mortality from sepsis • Evidence based guidelines for the management of sepsis • Evidence graded based on LEVEL OF RECOMMENDATION (strong v. weak) and QUALITY OF EVIDENCE (ABCD) • First published 2003, revised 2008, revised again 2012 • Diagnosis: – 2 sets of blood cultures from separate sites (culture ALL vascular devices unless <48 hours old) BEFORE antibiotics (1C) – Imaging studies promptly performed to confirm potential source (UG) • Antimicrobial Therapy: – Administration of effective antimicrobials within 1 hour of recognition of septic shock (1B) or severe sepsis (1C) – Initial empiric therapy against all likely pathogens and that penetrate adequately into tissue presumed to be the source of sepsis (1B) – DAILY reassessment for de-escalation (1B) • Source Control: – seek and diagnose a source - if possible remove it within 12 hours (1C) • Initial resuscitation: – Protocolized resuscitation (Early Goal Directed therapy) during first 6 hours (1C) – Abnormal lactate should be re-checked, and normalization sought (2B) – Crystalloids initial fluid of choice (1B) – Hydroxyethyl starches for fluid resuscitation should not be used (1B) – Albumin in severe sepsis and septic shock in patients who require substantial amounts of crystalloid (2C) – Initial fluid challenge = 30ml/kg (1C) – Continue fluid challenge technique as along as there is hemodynamic improvement (UG) • Vasopressors: – Norepinephrine initial pressor (1B) – Epinephrine added to or as substitute for norepinephrine (2B) – Vasopressin 0.03 added to NE to reach MAP or decrease dosage of NE (UG) – Dopamine only in highly selected patients (due to risk of arrhythmia) (2C) – Pheynlephrine only if arrhythmia with NE or as a salvage therapy (1C) – Low dose dopamine for renal protection should not be used (1A) – All patients on vasopressors should receive arterial catheters (UG) • Steroids: – NO STEROIDS if initial resuscitation (fluid/pressors) adequate. If this is not achievable, we suggest intravenous hydrocortisone alone at a dose of 200 mg per day (2C). • Blood product administration: – transfuse only when Hgb <7g/dl to target of 7-9 in the absence of extenuating cricumstances (1B) – FFP should not be used to correct coagulopathy in the absence of bleeding or planned procedure (2D) – transfuse prophylactically when platelets <10k or <20k if significant risk of bleeding, goal of >50k if active bleeding, surgery or invasive procedure (2D) • Mechanical ventilation (ARDS) – another lecture all together • Sedation: – minimize sedation and titrate to sepcific endpoints 1B – Neuromuscular blocking agents avoided if possible if no ARDS 1C • Glucose control: – initialize protocolized glucose management when 2 blood glucose levels >180 (insulin gtt), target goal <180 1A • DVT prophy and Stress ulcer prophy: – LMWH when possible in severe sepsis 1B, Dalteparin if CrCl <30 – PPI or H2RA in severe sepsis, septic shock 1B • Nutrition: – enteral or oral feeding as tolerated in first 48 hours 2C • Goals of care: – set goals of care 1B – address as early as feasibile, no later than 72 hours after admission 2C 2008 compared to 2012 • • • • • Crystalloid initial fluid of choice Epinephrine 2nd pressor of choice Dopamine no longer recommended Activated protein C no longer recommended Normalization of lactate as an endpoint in sepsis induced hypoperfusion • Use of 1,3-B-D Glucan and antigalactomannan antibodies if concern for invasive candidal infection Your Septic Patient: H+P • age • infectious review of systems: fever/chills, fatigue, myalgias, cognition, HA, sensitivity to light, rhinorrhea, sore throat, neck stiffness, cough, sob, cp, n/v/d, abdominal pain, back pain, dysuria, frequency, skin changes or wounds, recent sick contacts, recent antibiotics • medical comorbidities (chronic diseases etc.) • medications: immunosuppressants Your Septic Patient: Exam • vitals Temp, HR, RR, BP (stable or not) • head and neck (meningeal signs, oropharynx, sinuses), cardiac (murmurs!), respiratory (signs of consolidation), back (CVA, spinal/paraspinal) tenderness, abdomen, ascites, skin exam for wounds, feet! Your Septic Patient: Labs • • • • • • • • WBC - %PMN, %bands Hgb and Plt (important for sepsis and DIC) BUN/Cr Anion Gap LFT (Hyperbilirubinemia in sepsis, also shock liver) INR (to assess for DIC) Lactate if hypotension, anion gap, ill appearing ABG if anion gap, hypoxic, obtunded (pH <7.2-7.25 --> patient belongs in ICU) • U/A, Urine culture • Blood cultures from two different sites • Culture other sites as necessitated by history and exam Your Septic Patient: Imaging • CXR • Other imaging depending on your clinical suspicion (usually CT with contrast) Your Septic Patient: Treatment • Empiric therapy based on suspected source of infection • Supportive Care – Early Goal Directed Therapy – Surviving Sepsis Campaign, update 2012 Clinical Method • Identify your septic patient (based on the definitions) • Triage level of care (Floor v ICU) • Work-up and treat their underlying infection • Resuscitate according to EGDT and Surviving Sepsis Campaign – Initial fluid resuscitation 30mL/kg as fast as possible, unless CHF/low EF • If in MICU place central line, arterial line Clinical Pearls • Managing Sepsis on the floor: – Use defined endpoints for fluid resuscitation • U/O >0.5cc/kg/hr • MAP >65 • Normalization of lactate • • • • KNOW the patients Ejection Fraction and renal function Fluid resuscitation is the priority!!! Start pressors if MAP <65, even if CVP not yet known Transfer to MICU: – Hypotension resistant to fluid resuscitation (Septic shock) – usually after 4-6L fluid – Severe lactic acidosis (pH 7.2-7.25) – Severe or acutely worsening hypoxia or obtundation Sources • Rivers et. al Early Goal Directed Therapy, NEJM 2001 • Dellinger et. al Surviving Sepsis Campaign 2012, Intensive Care Med 2013 • Current Diagnosis and Treatment: Critical Care, 3rd Edition • http://www.youtube.com/watch?v=MceGURf XdR0