20201118 sepsis and septic shock

1. Sepsis and septic shock
2020.11.18
EM F. 박희수

2. 1992 Definitions for Sepsis and Organ Failure and
Guidelines for the Use of Innovative Therapies in
Sepsis

3. Systemic Inflammatory Response
Syndrome
• Temperature > 38℃ or < 36℃
• Heart rate >90 /minute
• Respiratory rate >20 /minute or PaCO2 <32 mm Hg
• White blood cell count >12,000, <4,000, or >10%
immature (band) forms.

4. 1992 Definitions for Sepsis and Organ Failure and
Guidelines for the Use of Innovative Therapies in
Sepsis
• Severe Sepsis : sepsis + organ dysfunction or hypoperfusion
(lactic acidosis, oliguria, alteration of mental status), hypotension
• Septic Shock : severe sepsis despite adequate fluid resuscitation

5. 2001 SCCM/ESICM/ACCP/ATS/SIS International
Sepsis Definitions Conference
Infection
a
Documented or suspected and some of the following
b
:
General parameters
Fever (core temperature >38.3°C)
Hypothermia (core temperature <36°C
Heart rate >90 bpmor >2 SD above the normal value for age
Tachypnea: >30 bpm
Altered mental status
Significant edema or positive fluid balance (>20 ml/kg over 24 h)
Hyperglycemia (plasma glucose >110 mg/dl or 7.7 mM/l) in the absence of diabetes
Inflammatory parameters
Leukocytosis (white blood cell count >12,000/µl)
Leukopenia (white blood cell count <4,000/µl)
Normal white blood cell count with >10% immature forms
Plasma C reactive protein>2 SD above the normal value
Plasma procalcitonin >2 SD above the normal value
Hemodynamic parameters
Arterial hypotension
b
(systolic blood pressure <90 mmHg, mean arterial pressure <70, or a systolic blood pressure decrease >40 mmHg
in adults or <2 SD below normal for age)
Mixed venous oxygen saturation >70%
b
Cardiac index >3.5 l min
−1
m
−2c,d

6. 2001 SCCM/ESICM/ACCP/ATS/SIS International
Sepsis Definitions Conference
Organ dysfunction parameters
Arterial hypoxemia (PaO2/FIO2 <300)
Acute oliguria (urine output <0.5 ml kg
−1
h
−1
or 45 mM/l for at least 2 h)
Creatinine increase ≥0.5 mg/dl
Coagulation abnormalities (international normalized ratio >1.5 or activated partial thromboplastin time >60 s)
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count <100,000/µl)
Hyperbilirubinemia (plasma total bilirubin >4 mg/dl or 70 mmol/l)
Tissue perfusion parameters
Hyperlactatemia (>3 mmol/l)
Decreased capillary refill or mottling
1.aDefined as a pathological process induced by a micro-organism
2.bValues above 70% are normal in children (normally 75–80%) and should therefore not be used as a sign of sepsis in newborns or children
3.cValues of 3.5–5.5 are normal in children and should therefore not be used as a sign of sepsis in newborns or children
4.dDiagnostic criteria for sepsis in the pediatric population is signs and symptoms of inflammation plus infection with hyper- or hypothermia
(rectal temperature >38.5°C or <35°C), tachycardia (may be absent in hypothermic patients) and at least one of the following indications of
altered organ function: altered mental status, hypoxemia, elevated serum lactate level, and bounding pulses

7. The PIRO system
Domain Present Future Rationale
Predisposition Premorbid illness with reduced pr
obability of short tem survival. Cu
ltural or religious beliefs, age, gen
der
Genetic polymorphisms in components o
f inflammatory response (e.g., Toll-like re
ceptor, tumor necrosis factor, interleukin
1, CD14); enhanced understanding of sp
ecific interactions between pathogens an
d host diseases
At the present, premorbid factors impact on the p
otential attributable morbidity and mortality of an
acute insult; deleterious consequences of insult de
pend heavily on genetic predisposition (future)
Insult
(infection)
Culture and sensitivity of infecting
pathogens; detection of disease a
menable to source control
Assay of microbial products (lipopolysacc
haride, mannan, bacterial DNA); gene tra
nscript profiles
Specific therapies directed against inciting insult r
equire demonstration and characterization of that
insult
Response SIRS, other signs of sepsis, shock,
C-reactive protein
Nonspecific markers of activated inflamm
ation (e.g., procalcitonin or interleukin 6)
or impaired host responsiveness (e.g., HL
A-DR); specific detection of target of ther
apy (e.g., protein C, tumor necrosis factor
, platelet-activating factor)
Both mortality risk and potential to respond to th
erapy vary with nonspecific measures of disease s
everity (e.g., shock); specific mediator-targeted the
rapy is predicated on presence and activity of me
diator
Organ
dysfunction
Organ dysfunction as number of f
ailing organs or composite score (
e.g.,multiple-organ dysfunction sy
ndrome, logistic organ dysfunctio
n system, Sequential Organ Failur
e Assessment, Pediatric Multiple
Organ Dysfunction, Pediatric Logis
tic Organ Dysfunction)
Dynamic measures of cellular response t
o insult – apoptosis, cytopathic hypoxia,
cell stress
Response to preemptive therapy (e.g., targeting m
icro-organism or early mediator) not possible if d
amage already present; therapies targeting the inj
urious cellular process require that it be present

8. The Third International Consensus Definitions
for Sepsis and Septic Shock (Sepsis-3) : 2016
2001 sepsis-2 2016 sepsis-3
Sepsis
Severe Sepsis Sepsis
Septic Shock Septic Shock
• SIRS: unhelpful
• SOFA score: helpful

9. Organ dysfunction
• Sequential Organ Failure Assessment score(SOFA)
SOFA score Mortality risk
0 - 6 <10%
7 - 9 15 - 20%
10 - 12 40 - 50%
13 - 14 50 - 60%
15 >80%
16 - 24 >90%
Vincent JL, et al. Intensive Care Med
1996;22:707-10

10. The Third International Consensus Definitions
for Sepsis and Septic Shock (Sepsis-3)
Sepsis
• Life threatening organ dysfunction caused by a dysregulated host
response to infection
• SOFA score variation >+2
Septic shock
• persisting hypotension requiring vasopressors to maintain MAP ≥65
mm Hg and serum lactate level >2 mmol/L (18 mg/dL) despite
adequate volume resuscitation.

11. Surviving Sepsis Campaign guidelines for
management of severe sepsis and septic shock
Early Goal Directed Therapy(EGDT)
• Central venous pressure (CVP) 8–12 mmHg
• Mean arterial pressure (MAP) ≥65 mmHg
• Urine output ≥0.5 ml/kg h−1
• Central venous (superior vena cava) or mixed venous oxygen
saturation ≥70%.

12. SSC bundle (2012 SSC)
Dellinger RP, et al. Crit Care Med 2013;41:580-637

13. SSC bundle (2016 SSC)
Rhodes A, et al. Crit Care Med 2017;45:486-552

15. SSC bundle update (2018 SSC)

16. SSC 2016 guideline

17. Initial resuscitation
• Sepsis and septic shock are medical emergencies,
and we recommend that treatment and resuscitation begin
immediately.
• We recommend that, in the resuscitation from sepsis-induced
hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given
within the first 3h.
• We recommend that, following initial fluid resuscitation, additional
fluids be guided by frequent reassessment of hemodynamic
status.

18. Initial resuscitation
• 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.
• We suggest that dynamic over static variables be used to predict
fluid responsiveness, where available.
• We recommend an initial target mean arterial pressure (MAP) of 65
mmHg in patients with septic shock requiring vasopressors.

19. Initial resuscitation
• We suggest guiding resuscitation to normalize lactate in
patients with elevated lactate levels as a marker of tissue
hypoperfusion.
Intensive Care Medicine 41, 1862-1863(2015)

20. Diagnosis
• We recommend that appropriate routine microbiologic cultures
(including blood) be obtained before starting antimicrobial therapy
in patients with suspected sepsis or septic shock if doing so results in
no substantial delay in the start of antimicrobials.
Antimicrobial therapy
• 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.

21. Crit Care Med 34, 1589-96 (June 2015) Crit Care Med 42,1749-55 (Aug 2014)

22. Antimicrobial therapy
• We recommend empiric broad-spectrum therapy with one or
more antimicrobials for patients presenting with sepsis or septic
shock to cover all likely pathogens (including bacterial and
potentially fungal or viral coverage).
• We recommend that empiric antimicrobial therapy be narrowed
once pathogen identification and sensitivities are established
and/or adequate clinical improvement is noted.
• We recommend against sustained systemic antimicrobial
prophylaxis in patients with severe inflammatory states of
noninfectious origin (e.g., severe pancreatitis, burn injury)

23. Antimicrobial therapy
• We suggest empiric combination therapy (using at least two
antibiotics of different antimicrobial classes) aimed at the
most likely bacterial pathogen(s) for the initial management
of septic shock.
• We suggest that combination therapy not be routinely
used for ongoing treatment of most other serious infections,
including bacteremia and sepsis without shock
• We recommend against combination therapy for the
routine treatment of neutropenic sepsis/bacteremia.

24. Antimicrobial therapy
• If combination therapy is initially used for septic shock, we
recommend de-escalation with discontinuation of
combination therapy within the first few days in response
to clinical improvement and/ or evidence of infection
resolution. This applies to both targeted (for culture-positive
infections) and empiric (for culture-negative infections)
combination therapy.

25. Antimicrobial therapy
• We suggest that an antimicrobial treatment duration of 7–10
days is adequate for most serious infections associated with
sepsis and septic shock.
• We suggest that longer courses are appropriate in patients who
have a slow clinical response, undrainable foci of infection,
bacteremia with S. aureus, some fungal and viral infections, or
immunologic deficiencies, including neutropenia.
• We recommend daily assessment for de-escalation of
antimicrobial therapy in patients with sepsis and septic shock.

26. Antimicrobial therapy
• We suggest that measurement of procalcitonin levels can
be used to support shortening the duration of
antimicrobial therapy in sepsis patients.

27. 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.
• We recommend prompt removal of intravascular access
devices that are a possible source of sepsis or septic shock
after other vascular access has been established

28. Fluid therapy
• We recommend that a fluid challenge technique be applied
where fluid administration is continued as long as
hemodynamic factors continue to improve.
• We recommend crystalloids as the fluid of choice for initial
resuscitation and subsequent intravascular volume
replacement in patients with sepsis and septic shock.
• We suggest using either balanced crystalloids or
saline for fluid resuscitation of patients with sepsis or septic
shock.

31. Fluid therapy
• We suggest using albumin in addition to crystalloids for initial
resuscitation and subsequent intravascular volume replacement in
patients with sepsis and septic shock when patients require
substantial amounts of crystalloids.
• We recommend against using hydroxyethyl starches (HESs) for
intravascular volume replacement in patients with sepsis or septic
shock.
• We suggest using crystalloids over gelatins when resuscitating
patients with sepsis or septic shock.

32. Vasoactive medications
• We recommend norepinephrine as the first choice vasopressor.
• We suggest adding either vasopressin (up to 0.03 U/min) or
epinephrine to norepinephrine with the intent of raising MAP to
target, or adding vasopressin (up to 0.03 U/min) to decrease
norepinephrine dosage.
• We suggest using dopamine as an alternative vasopressor agent
to norepinephrine only in highly selected patients (e.g., patients
with low risk of tachyarrhythmias and absolute or relative
bradycardia).

33. Vasoactive medications
• We recommend against using low-dose dopamine for renal
protection.
• We suggest using dobutamine in patients who show
evidence of persistent hypoperfusion despite adequate fluid
loading and the use of vasopressor agents.
• We suggest that all patients requiring vasopressors have an
arterial catheter placed as soon as practical if resources are
available.

34. Corticosteroid
• We suggest against using IV hydrocortisone to treat septic
shock patients if adequate fluid resuscitation and
vasopressor therapy are able to restore hemodynamic
stability.
• If this is not achievable, we suggest IV hydrocortisone at a
dose of 200 mg per day.

36. NEJM 1,378(9); 809-818. (2018 Mar)

37. Blood product
• We recommend that RBC transfusion occur only when
hemoglobin concentration decreases to <7.0 g/dL in
adults in the absence of extenuating circumstances, such as
myocardial ischemia, severe hypoxemia, or acute hemorrhage.
• We recommend against the use of erythropoietin for
treatment of anemia associated with sepsis.

38. Blood product
• We suggest against the use of fresh frozen plasma to correct
clotting abnormalities in the absence of bleeding or planned invasive
procedures.
• We suggest prophylactic platelet transfusion when counts are
<10,000/mm3 in the absence of apparent bleeding and when counts
are <20,000/mm3 if the patient has a significant risk of bleeding.
Higher platelet counts [≥50,000/mm3 (50 × 109/L)] are advised for
active bleeding, surgery, or invasive procedures.

39. Glucose control
• We recommend a protocolized approach to blood glucose
management in ICU patients with sepsis, commencing insulin dosing
when two consecutive blood glucose levels are >180 mg/dL. This
approach should target an upper blood glucose level ≤180 mg/dL
rather than an upper target blood glucose level ≤110 mg/dL.
• We recommend that blood glucose values be monitored every 1–2 h
until glucose values and insulin infusion rates are stable, then every
4h thereafter in patients receiving insulin infusions.
• We suggest the use of arterial blood rather than capillary blood for
point-of-care testing using glucose meters if patients have arterial
catheters.

40. Renal replacement therapy
• We suggest that either continuous RRT (CRRT) or
intermittent RRT be used in patients with sepsis and acute
kidney injury.
• We suggest using CRRT to facilitate management of fluid
balance in hemodynamically unstable septic patients
• We suggest against the use of RRT in patients with sepsis
and acute kidney injury for increase in creatinine or oliguria
without other definitive indications for dialysis.

41. Bicarbonate therapy
• We suggest against the use of sodium bicarbonate therapy
to improve hemodynamics or to reduce vasopressor
requirements in patients with hypoperfusion-induced lactic
acidemia with pH ≥ 7.15.

42. Nutrition
• We recommend against the administration of early parenteral
nutrition alone or parenteral nutrition in combination with enteral
feedings (but rather initiate early enteral nutrition) in critically ill
patients with sepsis or septic shock who can be fed enterally.
• We recommend against the administration of parenteral nutrition
alone or in combination with enteral feeds (but rather to initiate IV
glucose and advance enteral feeds as tolerated) over the first 7 days
in critically ill patients with sepsis or septic shock for whom early
enteral feeding is not feasible.

43. Nutrition
• We suggest the early initiation of enteral feeding rather
than a complete fast or only IV glucose in critically ill
patients with sepsis or septic shock who can be fed enterally.
• We suggest either early trophic/hypocaloric or early full
enteral feeding in critically ill patients with sepsis or septic
shock; if trophic/hypocaloric feeding is the initial strategy,
then feeds should be advanced according to patient
tolerance.

44. Nutrition
• We suggest against routinely monitoring gastric residual
volumes (GRVs) in critically ill patients with sepsis or septic shock.
However, we suggest measurement of gastric residuals in
patients with feeding intolerance or who are considered to be
at high risk of aspiration.
• We suggest the use of prokinetic agents in critically ill patients
with sepsis or septic shock and feeding intolerance.
• We suggest placement of post-pyloric feeding tubes in critically
ill patients with sepsis or septic shock with feeding intolerance or
who are considered to be at high risk of aspiration.

45. Reference
• Bone RC, Balk PA et al (1992), Definitions for sepsis and organ failure and guidelines
for the use of innovative therapies in sepsis. Chest, 101(6):1644-55.
• Mitchell M Levy, Mitchell P Fink et al (2003), 2001 SCCM/ESICM/ACCP/ATS/SIS
International Sepsis Definitions Conference, Intensive Care Med, 29(4):530-8.
• Andrew Rhodes, Laura E. Evans (2017), Surviving Sepsis Campaign: International
Guidelines for Management
of Sepsis and Septic Shock: 2016 , Intensive Care Med, 43: 304-377