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
“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 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 SIRS results from a variety of conditions
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 < 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 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 > 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 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. Protocol used in the NEJM 2001 early goal directed therapy group.

16. 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
ProCESS trial: 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

17. 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

18. Surviving Sepsis Guidelines 2012

19. Surviving Sepsis Guidelines 2012

20. 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

21. Delay in Antibiotics Kills

22. 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
If abdominal abscess found, preference for interventional radiology over open surgical intervention

23. Surviving Sepsis Guidelines 2012

24. Surviving Sepsis Guidelines 2012

25. 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

26. 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 units/min to norepinephrine did not lower mortality compared to norepinephrine alone

27. Surviving Sepsis Guidelines 2012
Basic take away message: Do not use corticosteroids in septic shock if the patient does not have a history of adrenal insufficiency.

28. 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

29. 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