good

1. Approach to sepsis
Hywet Engida M.D
Assist prof. Emergency Medicine ,
AAU

2. Objectives
• Understand the current nomenclature
• Understand the spectrum of presenting illness
• Get a handle on the basic treatment

3. Old Definitions
• Sepsis = SIRS + Infection
• SIRS = 2/4 of
• Temp >38 or <36 (febrile or hypothermic. Hypothermia as a manifestation of sepsis is
seen in paediatrics, especially neonates)
• HR >90
• Respiratory Rate >20 or PaCO2 <32 (4.3kPa)
• WBCC >12 or <4 or >10% bands (leucocytosis or leukopenia. Leukopenia is seen in
immunocompromised patients e.g., RVI, hematologic malignancies, post-chemotherapy,
on immunosuppressive drugs)
• Infection = either
• Bacteraemia (or viremia/fungaemia/protozoan)
• Septic focus (abscess / cavity / tissue mass)
• This definition has a limitation in that it might over-diagnose the
condition. For e.g., patient with pneumonia might be diagnosed as having
sepsis based on this definition.
• The definition of sepsis requires a deep cellular level understanding

4. • The new argument is that:
– To be defined as sepsis, the condition must be overwhelming. Normally, when
the body is infected, it has to manifest in some way. When an organ is
infected, it should not be dormant, rather it has to react. This is the body’s
own protective mechanism. Just like we react to entry of a foreign body in our
airway with a cough, our body has to react to an infection.
– But, always, during the reaction, pro-inflammatory and anti-inflammatory
factors have to be in balance. So, it is when this balance is lost that sepsis
occurs.
– For e.g., a patient with a lung infection (showing consolidation…) should not
be labeled as septic just because he/she has fever or tachypnea (fulfills SIRS).
BUT, when the body fails to contain the infection to the lungs and if for e.g.
the patient starts to become confused, then he/she can be diagnosed as
septic. Because, the body has become overwhelmed, could not contain the
infection to the lungs and another distant organ system has been affected
(brain). The same goes for other organs e.g. UTI.

5. Old Definitions Cont.
• Severe sepsis = Sepsis + Organ Dysfunction
• Organ Dysfunction = Any of
• SBP <90 or 40<usual or inotrope to get MAP 90 (the hypotension
should respond to fluid therapy. Otherwise it becomes septic shock)
(for patients with a higher baseline BP, shock definition is different for
e.g., hypertensive patients) (we must not wait until the BP becomes
<90, because cells can become hypo-perfused even with a higher BP)
• Lactate >2mmol/L (sepsis => hypo-perfusion => anaerobic metabolism
=> lactate)
• Oliguria <30ml/hr for 1 hour
• Creatinine >2mg/dL
• Confusional state
• FIO2 >0.4 and PEEP >5 for oxygenation (FiO2 from the atm is 21%.
When we put a patient on 1 litre O2, we increase the FiO2 by 3-4%. To
get an FiO2 of 40%:
 Subtract 21% from 40% and divide by 3 or 4% => at
least this amount (L) of O2 should be given.
PEEP (positive end expiratory pressure)

6. Old Definitions Cont.
• Septic Shock = Severe sepsis + Hypotension
• Severe sepsis + shock which is not responsive to
fluid management
• Hypotension = either
• SBP <90 or 40<usual
• Inotrope to get MAP >90

7. Sepsis: What Happened in 2016?
New Definitions : Why, How and What
• Sepsis is redefined as : “life-threatening organ
dysfunction caused by a dysregulated host
response to infection.”
• This definition lumps sepsis and severe sepsis
together from the old definition. With the
new definition, there is no more severe sepsis.

8. SOFA (sequential organ failure assessment) score. When we admit the patients, we have to
immediately acquire these baseline tests and do the P/Es. Then we follow the patients based on
the baseline results. For e.g., a patient is admitted, we do the tests and P/Es, acquire the baseline
score of the patient. Then after 3 days, if the patient starts to become more sick, we update the
initial investigations and examinations. If the score has increased from the baseline score by >/= 2
we label the patient as septic. This doesn’t work in the ED, because we don’t have the baseline
for the patients. But it is ideal for patients in ward and ICU. There are conditions where it is not
ideal.

9. Sepsis: What Happened in 2016?
• qSOFA Score: A means of rapidly identifying ED
and hospital ward (non-ICU) patients with
suspected infection at increased risk. A short
version of SOFA. Takes into consideration the
basic vital organs that sepsis might affect (so as to
narrow the evaluation).
• At least 2 of 3 criteria:
– RR ≥ 22/min
– Altered mentation
– SBP ≤ 100 mmHg (hypotension that doesn’t
respond to fluid)

10. New sepsis definition
• Severe Sepsis: No longer used
• Sepsis:
– Suspected or documented infection and:
– Acute increase of ≥2 SOFA points (a proxy for organ
dysfunction) for inpatients or qSOFA for ED patients.
• Septic Shock: Sepsis and:
– Vasopressor therapy needed to elevate MAP ≥65
mm Hg (requirement of inotropy) and
– Lactate >2 mmol/L (18 mg/dL) despite adequate
fluid resuscitation

12. Issues with the old Definitions
• SIRS is an appropriate response to infection –
or any other stimulus that activates inflammation
(was considered as inappropriate and included in the criteria for
sepsis in the old definition)
• In the old definition patients with pneumothorax, pancreatitis,
trauma, … which might manifest with an appropriate SIRS were
labeled as sepsis. (over-diagnosis)

13. Issues with the old Definitions
Severe Sepsis
• Confusing
Most people say “sepsis” when they mean
“severe sepsis”
Is “severe sepsis” really needed ?
Should be incorporated in the definition of
sepsis.

14. How Good is SOFA?
Mortality rate of septic shock => 30-40% (around 70% in our setup). Studies show that
SOFA/qSOFA do not decrease the mortality rate of sepsis. As they are in early phase,
they have to be modified.

15. How Good is SOFA?

16. How Good is qSOFA?
•Retrospective review of
ED and ward patients
with suspected infection
•Compared SIRS, qSOFA
• Primary endpoint: in-
hospital mortality, and
combined endpoint of
mortality or ICU
admission

17. How Good is qSOFA?
Conclusions:
• qSOFA has a poor sensitivity (but has high specificity. Once we find
that a patient is septic, we can be sure that it is actually sepsis and
not other condition. But poor sensitivity to pick sepsis in the first
place.)
• qSOFA is a late indicator of deterioration (once patient develops
confusion, ARDS, or hypotension it is less likely that they are going
to reversed)
• qSOFA is inferior to the NEWS (national early warning score)
(despite the NEWS score being based on data which is equally easy
to obtain at the bedside) (used in the US for triage purpose; not
used in our setup).

19. How ?
• SCCM/ESICM Task Force to Re-Define Sepsis
• Third International Consensus :Definitions for
Sepsis and Septic Shock (Sepsis-3)

21. What ?
CONSENSUS :Task Force Decisions
1. Beyond the remit of the task force to define infection
2. Sepsis is not simply infection + two or more SIRS criteria
3. The host response is of key importance
4. Sepsis represents bad infection where
bad = infection leading to organ dysfunction
5. “Severe sepsis” is not helpful and should be eliminated

22. Key Distinctions
• Sepsis is life-threatening organ dysfunction
caused by a dysregulated host response to infection
So … “sepsis” now = the old “severe sepsis” (organ
dysfunction)
As opposed to the “regulated host response”
that characterizes the non-septic response to infection
(dysregulated)

23. The Definition of Septic Shock
More problematic
• Is septic shock sepsis where the dysfunctional organ is the cardiovascular system ?
Task force opinion – NO (we must not label a patient septic just because the myocardium is
affected and patient becomes hypotensive)
– Also involves cellular/metabolic abnormalities (there should be understanding at the cellular level – when
we understand at this level, we know that in sepsis, each and every cell of the body is in hypoperfusion
state)
• What distinguishes septic shock from sepsis ?
– Treatment ?
NO. Management is the same
Management of septic shock:
- Fluid – up to 30ml/kg bolus. F/U with U/O, mentation, RR and add fluid based on these.
- Early initiation of antibiotics (within 1 hour). Every hour delay => increased mortality by 10%.
- Vasopressors – if patient is not responding to fluid. With vasopressors, our primary intension is to
augment the myocardial contractility. The first choice is NE. After NE we use dopamine. Its action
depends on the dose. On lower doses it acts on beta receptors and on higher doses acts on alpha
receptors. We use epinephrine at last for refractory shock.
Most of the initial treatments of septic shock and sepsis are the same. So, their difference is not
management-wise.
– Pathobiology ?
Maybe … but at this time not known
– Their difference is that in septic shock there is hypoperfusion at the cellular level.

24. • What tangibly differentiates septic shock from
sepsis ?
MORTALITY
Septic shock is “really bad” sepsis
Septic shock is a really bad sepsis with bad outcome. There is hypoperfusion at the cellular level
because of a gross hypotension. Septic shock is basically a sepsis where early management was
not started resulting in hypoperfusion at the cellular level and a bad outcome (increased MR).

25. As a conclusion
• Clinical criteria for sepsis
– Infection plus 2 or more SOFA points (above
baseline)
• Prompt outside the ICU to consider sepsis
– Infection plus 2 or more qSOFA points

26. As a conclusion about septic shock
Definition
• Septic shock is defined as a subset of sepsis in which
underlying circulatory, cellular and metabolic abnormalities are associated with a greater risk
of mortality than sepsis alone
Clinical criteria
• Hypotension requiring use of vasopressors to maintain MAP ≥65 mmHg and having a serum
lactate >2 mmol/l persisting despite adequate fluid resuscitation
Limitations:
- Pediatrics
- Lactate level determination – it is not done here at all and in westerns it is done in only
some setups. So, it is not suitable to put it as 1 criteria.
- Generally, because outcome is bad, it is better to over-diagnose than underdiagnose.

27. A pragmatic offering
• there is no absolute biomarker (yet) for sepsis or
septic shock
– Generalizability - readily measurable identifiers that
best capture conceptualization of ‘sepsis’
– objectivity, reproducibility – speak same language
– ease of use
• qSOFA - rapid bedside measure
• SOFA - clinical measures and lab tests performed routinely in
any sick patient

28. • SIRS has its place
.. though not for diagnosing sepsis
– white count, temperature etc.. still useful in
helping to form a provisional diagnosis of infection
– SIRS is an appropriate - but not necessarily
dysregulated - host response to infection

29. Reality
• Sepsis is (often) diagnosed in retrospect …
• infection usually confirmed belatedly (or not in
~30-50%) … yet still often treated if suspected
• same with sepsis .. start treating patient and
modify as more data become available ..
• identifying patient as being ‘septic’ should not
affect treatment other than
prompting/confirming that the patient is at high
risk for a poor outcome

30. Out with the Old , In with the New

31. Rivers Protocol
Potential for RBC
and Inotropes
Therapy
titrated to
CVP, MAP
and ScvO2
With central venous pressure we determine the right ventricular pressure. Based on this, we
indirectly estimate the left ventricular pressure. As a patient goes into shock the left ventricle
stiffens and loses its flexibility => its pressure becomes high. The CVP should be <8. If we cannot
measure the CVP alternatively we can use:
- BP
- Urine output – we can estimate whether the CO is good/not
MAP
ScvO2 (central venous O2 saturation)
The old algorithm

32. New Guideline: Surviving Sepsis
Campaign 2016
• EGDT (end-goal directed therapy) is done as a
specific recommendation
• Guide additional fluid by frequent reassessment of
hemodynamic status
• If clinical examination dose not lead to clear
diagnosis of volume status, use additional
hemodynamic measures
• Use dynamic rather than static variables to predict
fluid responsiveness, where available

33. New Guideline: Surviving Sepsis
Campaign 2016
• Optimize antimicrobial dosing based on accepted
pharmacokinetic/ pharmacodynamics principles and
particular drug properties in patients with sepsis/septic
shock
• 7-10 days of antimicrobial therapy for most serious
infections, but shorter duration for some (rapid clinical
resolution after intra-abdominal source control, urinary
sepsis, uncomplicated pyelonephritis)

34. Sepsis and septic shock are
medical emergencies and we
recommend that treatment and
resuscitation begin immediately.
Best Practice Statement

35. Source Control
• We recommend that a specific anatomic
diagnosis of infection requiring emergent
source control be identified or excluded as
rapidly as possible in patients with sepsis
or septic shock, and that any required
source control intervention be
implemented as soon as medically and
logistically practical after the diagnosis is
made.
(Best Practice Statement).

36. Antibiotics
• We recommend that administration of IV antimicrobials be initiated as soon as
possible after recognition and within 1 h for both sepsis and septic shock.
(strong recommendation, moderate quality of evidence).
• We recommend empiric broad-spectrum therapy with one or more antimicrobials
to cover all likely pathogens.
(strong recommendation, moderate quality of evidence).
The number of antibiotics to use depends on the patient, the source/focus of
infection, and where patient acquired the infection. For e.g., if patient was at hospital,
we think of pseudomonas, MERSA, VERSA, which are not covered by our routine
antibiotics.
Especially in tertiary hospitals like TAH, because the patients come from primary
hospitals or health centers and have already been exposed to routine antibiotics, we
have to start them with higher antibiotics.
We usually initiate them with ceftazidime and vancomycin. Or we can initiate with
ampicillin and gentamycin (if patient is antibiotic-naïve. If patient was on Augmentin
previously, this is not going to work).
Meanwhile, it is important to do culture.

37. Initial Resuscitation
• We recommend that in the resuscitation from sepsis-induced
hypoperfusion, at least 30ml/kg of intravenous crystalloid fluid
be given within the first 3 hours.
(Strong recommendation; low quality of evidence)
• We recommend that following initial fluid resuscitation,
additional fluids be guided by frequent reassessment of
hemodynamic status.
(Best Practice Statement)
Every septic patient requires resuscitation with fluid. We should
not wait until their BP drops or become tachycardic.
If Hgb <10 or Hct <30 => blood.

38. Fluid Therapy
• We recommend crystalloids as the fluid of choice for
initial resuscitation and subsequent intravascular
volume replacement in patients with sepsis and
septic shock
(Strong recommendation, moderate quality of evidence).
• We suggest using albumin in addition to crystalloids
when patients require substantial amounts of
crystalloids (not available in our setup)
(weak recommendation, low quality of evidence).

39. We recommend an initial target mean arterial pressure of
65 mmHg in patients with septic shock requiring
vasopressors.
(Strong recommendation; moderate quality of evidence)

40. Vasoactive agents
• We recommend norepinephrine as the first choice
vasopressor (2-10 µg/min)
(strong recommendation, moderate quality of evidence).
• Dopamine is the second line vasopressor . (5-20
µg/kg/min) (>10 => alpha effect starts)
(>20ug/kg/min is not recommended)
The beta effect is more preferred than the alpha because
the beta effect causes inotropy. And the alpha effect causes
vasoconstriction which can lead to renal hypoperfusion =>
activation of RAAS => vicious cycle. The vasoconstriction
can also cause peripheral gangrene (especially seen in
adrenaline use for few days)
• Adrenaline is recommended as a last resort for refractory
shock not responsive to the above vasopressors.

41. If shock is not resolving quickly…..
• We recommend further hemodynamic assessment
(such as assessing cardiac function) to determine the
type of shock if the clinical examination does not lead
to a clear diagnosis.
(Best Practice Statement)
• We suggest that dynamic over static variables be used
to predict fluid responsiveness, where available.
(Weak recommendation; low quality of evidence)

42. Lactate can help guide resuscitation
• We suggest guiding resuscitation to normalize lactate
in patients with elevated lactate levels as a marker of
tissue hypo-perfusion.
(Weak recommendation; low quality of evidence)

43. • What are the goals of initial resuscitation of
sepsis or septic shock?

44. What are the goals of initial resuscitation of
sepsis or septic shock?
a) CVP 8–12 mm Hg
b) MAP ≥ 65 mm Hg
c) Urine output ≥ 0.5 mL/kg/hr
d) Scvo2(central venous o2) ≥ 70%.

46. • Fortunately or unfortunately, because patients in our setup come
late to clinical setting, it is easy to pick sepsis with SOFA or qSOFA
(they are confused, tachypneic, SBP<100).
• But if patient comes early, we use the SIRS criteria to screen but we
don’t rush to aggressive management, rather we do qSOFA and
additional investigations. (If it is just SIRS with infection and we
think that we have time we do workup and we won’t be as
aggressive as sepsis – for e.g., if we suspect just pneumonia we may
start with ceftriaxone and azithromycin and follow for 24 hours. But
if we find out that this patient is septic with focus as pneumonia,
we cannot just f/u with ceftriaxone/azithromycin. We have to have
a broader management – fluid, invasive follow ups, …).
Generally: for screening => SIRS
for decision of aggressive management => qSOFA

47. Some of the concerns…
• ‘SIRS is vital to diagnose sepsis and to treat patients early
• ‘SOFA won’t be measured daily on every patient’
• ‘do I need to measure SOFA twice to measure change’
• ‘lactate should be in the sepsis criteria’
• ‘lactate should go from the septic shock criteria’
• ’80% of the world cannot measure lactate’
• ‘why not shock = hyperlactatemia OR hypotension?’
• ‘patients will die if we wait until qSOFA hits ≥2 before
treating’
• ‘why don’t we just use qSOFA to diagnose sepsis?’
• ‘what about children?’ …