9/14/14 Sepsis Jon Femling MD, PhD Department of Emergency Medicine University of New Mexico Disclosures No financial conflicts of interest I review cases of sepsis admiFed to the ICU from the ED I am a microbiologist and an ED aFending physician Objec0ves Define Sepsis and determinants requiring emergent intervenLon and treatment. Define fundamental tenants of treatment and current controversies. Discuss screening algorithms and future direcLons. 1 9/14/14 Defini0on Infec4on Systemic Inflammatory + Response Syndrome Number of Pa0ents at UNM / year # o f p a t ie n ts 2000 1500 ~ 24 / month 1000 500 0 AM I C VA T AP S e p s is Mortality Comparison 30 % M o r t a lit y 25 20 15 10 5 0 AM I C VA T AP S e p s is 2 9/14/14 Deaths per Year # o f p a t ie n ts 80 60 40 20 0 AM I C VA T AP S e p s is Sepsis is common and deadly “Old” Clinical Defini0on: Suspicion of Infec4on + 2 S.I.R.S. criteria Temperature > 38.3 oC or < 36 oC (>100.1 oF or <96.8 oF) Heart Rate > 90 Respiratory Rate >20 or PaCO2 <32 WBC > 12,000 or < 4,000 or > 10% bands 3 9/14/14 “New” Defini0on = “Diagnos0c Criteria” Surviving Sepsis Campaign: InternaLonal Guidelines for Management of Severe Sepsis and SepLc Shock, 2012: PMID: 23353941 Diagnos0c Criteria simplified General Fever / Hypothermia Tachycardia Tachypnea Edema Hyperglycemia Inflammatory Leukocytosis / Leukopenia Elevated C-‐reacLve protein Elevated Procalcitonin Hemodynamic / Perfusion variables Hypotension Hyperlactemia Decreased capillary refill or moFling Organ DysfuncLon variables Hypoxemia Altered Mental Status Oliguria / CreaLnine increase Coagulopathy Ileus Thrombocytopenia Hyperbilirubinemia Diagnos0c Criteria -‐ Inflammatory General Fever / Hypothermia Tachycardia Tachypnea Edema Hyperglycemia Defines the disease as Systemic Inflamma4on Inflammatory Leukocytosis / Leukopenia Elevated C-‐reacLve protein Elevated Procalcitonin 4 9/14/14 Diagnos0c Criteria -‐ Inflammatory General Fever / Hypothermia Tachycardia Tachypnea Edema Hyperglycemia Inflammatory S.I.R.S. criteria Temperature > 38.3 oC or < 36 oC Heart Rate > 90 Respiratory Rate >20 or PaCO2 <32 WBC > 12,000 or < 4,000 or > 10% bands Leukocytosis / Leukopenia Elevated C-‐reacLve protein Elevated Procalcitonin Diagnos0c Criteria -‐ Severity Hemodynamic / Perfusion variables Defines the Severity Hypotension Hyperlactemia Decreased capillary refill or moFling Organ DysfuncLon variables Hypoxemia Altered Mental Status Oliguria / CreaLnine increase Coagulopathy Ileus Thrombocytopenia Hyperbilirubinemia Diagnosis is important for ini0a0ng treatment 5 9/14/14 Prac0cal Considera0ons Surviving Sepsis Campaign: Interna4onal Guidelines for Management of Severe Sepsis and Sep4c Shock, 2012 “We recommend the protocolized, quanLtaLve resuscitaLon of paLents with sepsis -‐ induced Lssue hypoperfusion (defined in this document as hypotension persisLng ager iniLal fluid challenge or blood lactate concentra4on ≥4 mmol/L).” PMID: 23353941 BoMom Line Hypotension or Lactate ≥4 Ini4ate aggressive treatment Defining Severity Hemodynamic / Perfusion variables Hypotension Hyperlactemia Decreased capillary refill or moFling Organ DysfuncLon variables Hypoxemia Altered Mental Status Oliguria / CreaLnine increase Coagulopathy Ileus Thrombocytopenia Hyperbilirubinemia 6 9/14/14 Sepsis Severity -‐ specifics Surviving Sepsis Campaign: InternaLonal Guidelines for Management of Severe Sepsis and SepLc Shock, 2012: PMID: 23353941 c e lls x 1 0 E 3 20 Sepsis Severity -‐ specifics Mean with 95% confidence interval 15 Above = Severe Sepsis 10 Normal Range 5 Below = Severe Sepsis 0 W h it e B lo o d C e ll C o u n t Sepsis Severity -‐ specifics 6 20 50 400 2 10 5 0 W h it e B lo o d C e ll C o u n t L a c ta te 1 .5 100 0 .5 0 0 .0 G lu c o s e 200 100 0 P la t e le t c o u n t 7 .4 5 2 .5 7 .4 0 1 .0 50 300 H e m a t o c r it 3 .0 B iliru b in 2 .0 150 m g /d L m g /d L 200 20 0 2 .5 250 30 10 1 0 p la t e le t s x 1 0 E 3 3 40 15 2 .0 pH 4 p e rc e n t c e lls x 1 0 E 3 m m o l/L 5 1 .5 7 .3 5 1 .0 7 .3 0 0 .5 0 .0 C r e a t in in e 7 .2 5 B ilir u b in pH 7 9/14/14 Severity: Common Problems Lactates elevated Glucose elevated (in the absence of Diabetes) Kidney injury Liver injury AcidoLc Treatment Surviving Sepsis Campaign: InternaLonal Guidelines for Management of Severe Sepsis and SepLc Shock, 2012: PMID: 23353941 Treatment simply Hypotension or Lactate ≥4 Lactate Cultures Fluids An4bio4cs Pressors Central Venous Pressure 8 9/14/14 In Reality Hypotension An4bio4cs + Central Line + Intensive Care Unit and/or Intuba4on and/or Lactate ≥4 80 p t d e a t h s /y e a r a t U N M Importance of Time 60 40 20 0 AM I C VA Cath lab < 90 minutes TPA < 3 hours T AP S e p s is An4bio4cs < 60 minutes Trauma team < 0 minutes Patient Mortality by time of Antibiotic delivery Faster AnLbioLcs saves lives % Mortality 40 30 20 25% 28% 38% 24% 2 hrs 3 hrs > 3 hrs 24% 13% 13% 10 0 1 hr Percent of patients 50% 9 9/14/14 M o r t a lit y f r o m S e v e r e S e p s i s a t U N M 35 30 % m o r t a lit y Decreasing 4me to an4bio4cs decreases mortality 25 20 15 10 5 0 2010 2011 2012 2013 2014 Y ear Fluids, Resuscita0ve Monitoring, and Goals of Treatment Treatment Surviving Sepsis Campaign: InternaLonal Guidelines for Management of Severe Sepsis and SepLc Shock, 2012: PMID: 23353941 10 9/14/14 Treatment Guidelines Lactate Cultures Fluids An4bio4cs Pressors Central Venous Pressure Treatment Guidelines – Well Accepted Lactate Cultures An4bio4cs Pressors Treatment Guidelines -‐ Controversial Fluids Central Venous Pressure 11 9/14/14 Fluid and Central line problems Most agree fluids are important Few agree how much and how to tell if you’ve given enough Fluid status for heart and kidney failure paLents is difficult to measure Central lines require effort to place and have some risk Central Venous Pressures are not super reliable or well validated PubMed PMID: 24635773 Goal was to determine what parts of Early Goal Directed Therapy were necessary “Usual Care” Early Goal Directed Early Goal Directed Therapy Therapy Strictly as wriFen Central Line opLonal Important Caveats M o r t a lit y f r o m S e v e r e S e p s i s a t U N M 35 % m o r t a lit y 30 25 20 15 10 5 0 2010 2011 2012 Y ear 2013 2014 Surviving Sepsis Bundles are now standard of care Much beFer recogniLon Study done at high performing sites 12 9/14/14 PubMed PMID: 24635773 No StaLsLcal Difference! PubMed PMID: 24635773 InterpretaLon free for all “we are doing great, keep up the good work” “usual care was fine so I don’t need a protocol” “central lines are not indicated” Fluids Interpreta0on All sites were part of the surviving sepsis campaign and had protocols in place already. In other words, “Usual Care” was at a preFy high level. PaLents received ~30 ml/kg fluid bolus BEFORE randomizaLon 13 9/14/14 Fluids and Central Line Interpreta0on Within the 6 hours ager randomizaLon paLents received another 2 to 3 Liters of IV fluids. Over half of those not required to have a central line received central lines. Take home points Protocols help Over 75% of all paLents received anLbioLcs before randomizaLon Most paLents received ~ 5+ liters between arrival and within the first 6 hours ager randomizaLon The big unknown How to guide fluid resuscitaLon. Current best guess: CVP or “clinical judgment” 14 9/14/14 Screening and early iden0fica0on Simplified algorithm Hypotension and/or Intuba4on and/or Lactate ≥4 An4bio4cs + Fluids + Intensive Care Unit Pa0ent Characteris0cs Hypotension and/or Intuba4on and/or Lactate ≥4 Typically Obvious Can be Occult 15 9/14/14 Hyperlactemia is a sign of shock! R e l a t i o n s h i p o f P r e s e n t in g c h a r a c t e r is t ic s t o m o r t a lit y In t u b a t io n + H y p e r la c t e m ia + H y p o t e n s io n In t u b a t io n + H y p e r la c t e m ia H y p e r la c t e m ia + H y p o t e n s io n In t u b a t io n a lo n e In t u b a t e d + H y p o t e n s io n H y p o t e n s io n a lo n e H y p e r la c t e m ia a lo n e none 0 10 20 30 40 % mortality 51 44 33 27 25 24 23 0 50 60 % m o r t a lit y Our Triage Guidelines: Goal is to iden0fy occult shock earlier Typically Obvious Easily iden4fiable Risk Criteria Prac0cal Considera0ons – Time of day 16 9/14/14 Prac0cal Considera0ons – Key characteris0cs % o f p a t ie n t s ( n = 6 0 7 ) 25 E D p a tie n ts 20 15 10 5 0 10 20 30 40 50 60 70 80 90 100 Age % o f p a t ie n t s ( n = 4 0 0 ) 30 S e v e r e S e p s is 20 10 0 10 20 30 40 50 60 70 80 90 100 Age Key Pa0ent Characteris0cs Older Tachycardic Tachypneic Step 2: Severity Tes4ng 17 9/14/14 T im e t o A n t ib io t ic s No POC tes4ng leads to long delays in care 300 M in u te s 240 180 120 60 0 no PO C Mortality P O C t e s t in g 23% T im e t o A n t ib io t ic s Point of care tes4ng leads to faster delivery of an4bio4cs and fewer deaths 300 M in u te s 240 180 120 60 0 no PO C Mortality 23% P O C t e s t in g 10% End-‐Tidal Carbon Dioxide Tes0ng Prehospital measurement predicts mortality and acidosis PMID: 24332900 Can be non-‐invasively and conLnuously monitored May be an easy adjunct for measuring fluid responsiveness 18 9/14/14 Our ED protocol Early Iden4fica4on Severity Tes4ng Treatment Disposi4on Future Direc0ons Sepsis care metrics used for payment Rapid Pathogen IdenLficaLon – target anLmicrobial therapy Non-‐invasive hemodynamic monitoring – guide fluid resuscitaLon Prehospital and Triage point of care screening – idenLfy occult shock Ques0ons? 19 9/14/14 Thanks! 20
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