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Sepsis

This article discusses the importance of ICU care and early goal-directed therapy in the evaluation and treatment of sepsis. It covers the definition of SIRS and sepsis, Surviving Sepsis Guidelines 2012, CVP and MAP goals, choice of vasopressors, source identification and control, and the use of corticosteroids.

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Sepsis

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  1. Sepsis

  2. Outline • ICU Care involves evaluation and re-evaluation • Assessment of your diagnosis and treatments • Definition of SIRS and Sepsis • Surviving Sepsis Guidelines 2012 • CVP goal • MAP goal • Early goal directed therapy and new evidence • Choice of vasopressors • Source identification and control • Use of corticosteroids

  3. ICU Care • ICU Care involves continual assessment and re-assessment • Assessment • “What is going on?” • Treatment in a timely manner • “Am I working fast enough?” • Monitor efficacy of treatment • “Is what I’m doing working?” • Re-assessment • “Is the treatment doing what it’s supposed to do?” • “If not, why? Am I missing something?”

  4. Sepsis Highlights • Early resuscitation is beneficial • Goals of resuscitation • ScVO2 > 70% • Lactate clearance > 10% within the 1st six hours • Use norepinephrine as first line vasopressor • Can add low dose vasopressin 1.8-2.4 units/hr if needed • Antibiotics within the 1st hour • Cultures should be drawn before antibiotics if possible • Re-evaluate after initial survey and resuscitation • Look for other sources of infection

  5. Definitions • Systemic inflammatory response syndrome (SIRS) • Two or more of the following • Temperature > 38.5 oC or temperature < 35 oC • Heart rate > 90 beats/min • Respiratory rate > 20 breaths/min or PaCO2 < 32 mmHg • WBC > 12,000 cells/mm3, WBC < 4000 cells/mm3, or > 10% immature (band) forms • SIRS results from a variety of conditions • Autoimmune disorders, pancreatitis, thromboembolism, burns, or surgery

  6. Definitions • Sepsis • SIRS in response to documented infection • Culture or Gram stain of blood, sputum, urine, or normally sterile body fluid positive for pathogenic microorganism • Focus of infection identified by visual inspection • Ruptured bowel with free air or bowel contents found in abdomen at surgery, wound with purulent discharge

  7. Definitions • Severe sepsis • Sepsis plus at least one organ dysfunction • Areas of mottled skin • Capillary refilling requires 3 seconds or longer • Urine output < 0.5 mL/kg/hr or on renal replacement therapy • Lactate > 2 mmol/L • Abrupt change in mental status • Abnormal EEG • Platelets < 100,000 platelets/mL • Disseminated intravascular coagulation • Acute lung injury or acute respiratory distress syndrome • Cardiac dysfunction, as defined by echocardiography or direct measurement of the cardiac index

  8. Definitions • Septic shock • Severe sepsis plus one or both of the following • Systemic mean blood pressure < 60 mmHg (or < 80 mmHg if history of baseline hypertension) despite adequate fluid resuscitation • Maintaining systemic mean blood pressure > 60 mmHg (or > 80 mmHg if history of baseline hypertension) requires dopamine > 5 mcg/kg/min, norepinephrine < 0.25 mcg/kg/min, or epinephrine < 0.25 mcg/kg/min • Adequate fluid resuscitation • 40-60 mL/kg of saline solution • 20-30 mL/kg of starch • Measured pulmonary capillary wedge pressure of 12-20 mmHg

  9. Definitions • Refractory septic shock • Maintaining systemic mean blood pressure > 60 mmHg (or > 80 mmHg if history of baseline hypertension) requires dopamine > 15 mcg/kg/min, norepinephrine > 0.25 mcg/kg/min, or epinephrine > 0.25 mcg/kg/min despite adequate fluid resuscitation

  10. Surviving Sepsis Guidelines 2012

  11. Initial Resuscitation after Identification of Sepsis • Initial resuscitation should be rapid and sufficient • Intravenous fluids with goal CVP 8-12 mmHg • Vasopressors if needed with MAP goal of 65 mmHg • Initial resuscitation should be toward a physiological goal • Early goal-directed protocol (central venous saturation goal of 70%) • However, there is evidence that early goal directed therapy may be equivalent to usual care. ProCESS trial NEJM 2014, ARISE NEJM 2014 and ProMISe trial NEJM 2015 • Lactate clearance by at least 10% within 6 hours

  12. Initial Resuscitation after Identification of Sepsis • Resuscitation ensures vital organ perfusion but does not treat underlying etiology • Need to initiate antibiotics within 1 hour of identification of sepsis • Preferably cultures (blood, urine and respiratory) are obtained prior to initiation of antibiotics • However, obtaining cultures should not delay the timely initiation of antibiotics • Need to look for a source of infection • If found, preference is for least invasive amount of source control in patients that are hemodynamically unstable • E.g., interventional radiology for drain placement into abdominal abscess rather than open surgery

  13. Early Goal-Directed Therapy • Ensure adequate perfusion of vital organs • Brain, heart, kidneys • Assess adequacy of early goal-directed therapy • ScVO2 • Needs proper placement of central venous catheter in superior vena cava and right atrium junction • Goal: ScVO2 > 70% • Lactate clearance (10% lactate clearance within initial 6 hours of resuscitation) • Lactate clearance by 6 hours associated with better outcome • Less invasive than ScVO2 monitoring • Results are equivalent as long as both goals are met

  14. Early Goal Directed Therapy (EGDT) • Based on Rivers et al. NEJM 2001 trial that showed using EGDT showed decreased mortality • Involved placement of central venous catheter to measure continuous superior venous catheter oxygen saturation (ScVO2) after the initial goals of CVP 8-12 mmHg and MAP 65 mmHg were met • If CVP goals and MAP were met but ScVO2 < 70% • If hematocrit < 30%, then transfusion with packed red blood cells increased ScVO2 > 70% • If ScVO2 was still < 70% after transfusion of packed red blood cells, then dobutamine was initiated to increase ScVO2 > 70% • EGDT protocol on next page

  15. EGDT: New Evidence • EGDT has been controversial with limited adoption of its protocol given that it was a single center study • New evidence suggest that monitoring of ScVO2 is not associated with improved mortality compared to usual care • ProCESStrial: NEJM 2014 • United States: 31 emergency departments • ARISE trial: NEJM 2014 • Australia primarily with New Zealand: 51 centers • ProMISe trial: NEJM 2015 • England: 56 hospitals

  16. Lactate Clearance • Lactate clearance by at least 10% in the first 6 hours is associated with decreased mortality • Lactate clearance by at least 10% was equivalent to the Rivers et al EGDT NEJM 2001 trial • Jones et al. JAMA 2010 • Persistent elevated lactate at 24 hours and 48 hours is associated with increased mortality

  17. Surviving Sepsis Guidelines 2012

  18. Surviving Sepsis Guidelines 2012

  19. Antibiotics in Sepsis • Antibiotics must be administered within the 1st hour after identification of septic shock • Delay in administration of antibiotics is associated with increased mortality • Antibiotics must be appropriate for the suspected infection • Example: Community acquired pneumonia versus Healthcare associated pneumonia • Antibiotics must be according to local antibiogram • Example: Pseudomonas aeruginosa at UCLA MICU has very different sensitivities to a smaller community hospital

  20. Delay in Antibiotics Kills

  21. Source Identification and Control • Attempt to identify the source of infection within the first 12 hours after identification of sepsis • Additional imaging maybe needed • Example: • CT abdomen/pelvis looking for abdominal abscess if initial blood cultures, urine cultures and chest x-ray do not identify a source of infection • If a source of infection is found, need to perform source control with the least invasive procedure • Example: • If abdominal abscess found, preference for interventional radiology over open surgical intervention

  22. Surviving Sepsis Guidelines 2012

  23. Surviving Sepsis Guidelines 2012

  24. Choice of Vasopressor • Vasopressors are used for a goal MAP of 65 mmHg • Norepinephrine is the first choice for vasopressor in septic shock • Previously in Surviving Sepsis 2008, dopamine was given the same standing as norepinephrine however there are studies that demonstrate dopamine has worse outcomes especially in patients with cardiac disease • Patel et al Shock 2010 • In septic shock, dopamine was associated with increased sinus tachycardia and cardiac arrhythmias • De Backer et al NEJM 2010 • In cardiogenic shock, dopamine associated with more arrhythmias and increased mortality

  25. Choice of Vasopressor • Concern for tachycardia is not a reason to not use norepinephrine as the vasopressor in septic shock • Patients in shock already have tachycardia • Unless the patient has shown evidence of serious arrhythmias while on norepinephrine, norepinephrine should be the vasopressor of choice • If the patient is tachycardic and there is concern that norepinephrine will worsen it, can initiate a fixed dose of vasopressin at 0.03 units/min (1.8 units/hr) • This dose is a fixed, non-titrable dose • However, addition of vasopressin to norepinephrine did decrease the dose of norepinephrine, thus potentially lowering risk of tachycardia • Based on VASST trial NEJM 2008 that noted addition of vasopressin at 0.03 units/min to norepinephrine did not lower mortality compared to norepinephrine alone

  26. Surviving Sepsis Guidelines 2012

  27. Use of Corticosteroids in Septic Shock • In general, do not start corticosteroids in septic shock if fluids and vasopressors are sufficient to stabilize the patient’s hemodynamics. • Of course, this precludes patients that are adrenally insufficient or patients that are on chronic doses of corticosteroids • Several studies suggest no mortality benefit to starting corticosteroids in septic shock • Sprung et al Hydrocortisone Therapy for Patients with Septic Shock NEJM Jan 2008 • Annane et al Corticosteroid Treatment and Intensive Insulin Therapy for Septic Shock in Adults JAMA Jan 2010 • Use of hydrocortisone 50 mg IV q 6hr did not decrease mortality in septic shock

  28. Use of Corticosteroids in Septic Shock • If however, the patient is maxed out on vasopressors and has been sufficiently fluid resuscitated, corticosteroids can be used if absolutely necessary • Use of corticosteroids should then be hydrocortisone 200 mg over a 24 hour period • This recommendation is based on older evidence (Anane et al JAMA 200) that suggests that in very sick septic shock patients, addition of corticosteroids have mortality benefit • Again, this is more controversial nowadays as recent studies suggest no benefit to corticosteroids in septic shock

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