Septic shock, updated presentation, including latest guidelines from Intensive care societies and how to approach to the diagnosis with few notes about Early Goal Directed Therapy and role of steroids

1. ‫الرحيم‬ ‫الرحمن‬ ‫هللا‬ ‫بسم‬

2. Management of Septic Shock
Dr. Ramadan Arafa; MSc, MRCPI
Physician; Fujairah Hospital

3. OVERVIEW
• Septic shock is the most common cause of
mortality in the intensive care units.
• An analysis of a large sample from major US
medical centers reported the incidence of severe
sepsis is 3 cases/1000 population and 2.26 cases
per 100 hospital discharges. Of these patients,
51.1% were admitted to ICU, and 17.3% were in
an intermediate care or CCU (Angus 2001).
• The incidence of severe sepsis doubled over a 6-
year period (2004-2009) (Gaieski 2013).

4. Etiology
Pathophysiology
How To Diagnose?
How To Manage?
Sepsis syndromes
Objectives

5. Sepsis syndromes
SIRS
Sepis
Severe sepsis-SIRS
Septic shock
MODS

6. (Systemic Inflammatory Response Syndrome)
is a systemic inflammatory response to non
specific insults.
SIRS
SIRS is either due to Infection or others
Clinically:
1. hyperthermia >38°C or hypothermia <36°C
2. tachycardia > 90 bpm
3. tachypnea > 20 r.p.m. or PaCO2 <4.3 kPa
4. neutrophilia >12000 or neutropenia <4000/uL or more
than 10% immature forms

7. Venn Diagram; Andre Kalil; septic shock 2015

8. Clinically?!
• Known or suspected infection, plus
• >2 SIRS Criteria.
Sepsis
The systemic inflammatory response to infection.
Severe sepsis-SIRS
• Severe sepsis resulting in at least one organ
failure
Clinically?!
• Sepsis plus >1 organ dysfunction.

9. Septic shock
•Sepsis induced shock with hypotension (SBP <90
mmHg or decreased > 40 mmHg from baseline
readings) despite adequate resuscitation plus;
presence of perfusion abnormalities which may
include lactic acidosis, oliguria, or an acute
alteration in mental status.

10. • Shock = inadequate tissue perfusion
–Decreased O2 delivery and decreased removal
of metabolites
• Tissue perfusion is determined by:
–Cardiac output (CO) = HR x SV
SV = function of preload, afterload,
contractility
–Systemic vascular resistance (SVR)

11. MODS
(multiple organ dysfunction syndrome)
The presence of altered organ function in an
acutely ill patient such that homeostasis cannot
be maintained without intervention.

12. SIRS
systemic
inflammatory
response
syndrome
SEPSIS
SIRS with a presumed or
confirmed infectious process
Severe sepsis
Sepsis with ≥1 sign of organ failure
Septic shock
SIRS + Infection + Organ Failure +
Refractory Hypotension

14. Etiology
Pathophysiology
How To Diagnose?
How To Manage?
Sepsis syndromes
Objectives

15. Etiology
Caustive
organisms
•Gram –ve the
commonest
•Staph
•Candida
Sources of
infection
• Endogenus source
1. Peritonitis
2. Perforated viscous
3. Gangrenous
bowel
4. Genitourinary
infection
• Exogenus source
 Infected CVP
Predisposing
factors
• Old age
• DM
• Corticosteroid
therpy
• Malignancy
• Major surgery

16. Etiology
Pathophysiology
How To Diagnose?
How To Manage?
Sepsis syndromes
Objectives

17. It is not precisely understood, but it involves a
complex interaction between the pathogen
and the host's immune system.
Physiological response to localized infection:
o Influx of activated PMN leukocytes &
monocytes  release of inflammatory
mediators
o Local vasodilatation & increased endothelial
permeability
o Activation of the coagulation cascade.
Pathophysiology

18. • The same occurs in septic shock but at
a systemic level.
1. Diffuse endothelial disruption
2. Increased vascular permeability
3. Vasodilatation
4. Thrombosis of end organ capillaries

19. Infection
Inflammatory
Mediators
Endothelial
Dysfunction
Vasodilation
Hypotension Vasoconstriction Edema
Maldistribution of Microvascular Blood Flow
Organ Dysfunction
Microvascular Plugging
Ischemia
Cell Death

20. Inadequate
Resuscitation
Preoperative
Illness
Trauma or
Operation
Tissue Injury
optimal oxygen
delivery and
support
Recovery
Excessive
Inflammatory
Response
SIRS/MODS
Pathogenesis of SIRS/MODS in surgical
patients

21. Identifying Acute Organ Dysfunction
as a Marker of Severe Sepsis
Tachycardia
Hypotension
 CVP
 PAOP
Jaundice
 Enzymes
 Albumin
 PT
Altered
Consciousness
Confusion
Psychosis
Tachypnea
PaO2 <70 mm Hg
SaO2 <90%
PaO2/FiO2 300
Oliguria
Anuria
 Creatinine
 Platelets
 PT/APTT
 Protein C
 D-dimer
Rhabdomyolysis
Addison’s disease
Polyneuropathy

22. Etiology
Pathophysiology
How To Diagnose?
How To Manage?
Sepsis syndromes
Objectives

23. How To Diagnose?
• When you suspect sepsis in patient with
predisposing factors, do not wait for septic shock
• The diagnosis of sepsis requires the taking of an
EXCELLENT history, physical examination,
appropriate laboratory tests, and a close follow-
up of hemodynamic status
• Early recognition is live saving in such rapid
overwhelming situation

24. Hyperdynamic- Warm-
Early Septic Shock
Restlness & confusion
Vitals
1. fever more than 38
chills
2. Mild decrease ABP
3. Tachycardia
4. Tachypnea
Skin warm ,dry ,flushed
High cardiac output
Hypodynamic- Cold- Late
Septic Shock
 Semicomatosed
 Vitals
1. Temperature
decreased
2. Tachycardia
3. Tachypnea
4. SBP<90mmHg
 Oliguria & low COP
 Multiorgan failure start at
this stage

26. Work up…
Laboratory studies
o CBC
o Coagulation studies
o Blood, sputum, body fluids & urine cultures
o LFT, Renal and electrolytes
o Serum lactate
Imaging studies
o Chest radiography
o Abdominal radiography
o Others according to the suspected cause.

27. Complications of septic shock
• ARDS: starts 12-48 hours of the inciting event.
– Mild (mortality: 27%)
– moderate (mortality: 32%)
– severe (mortality: 45) (JAMA 2012)
• AKI: affects 40-70% of critically ill patients
• Chronic renal insufficiency
• DIC
• Mesentric ischemia
• Myocardial dysfunction and MI
• Liver failure

28. Etiology
Pathophysiology
How To Diagnose?
How To Manage?
Sepsis syndromes
Objectives

29. How To Manage?

30. How To Manage?
Goals:
Septic
•Identify and manage Infection
Source
Shock
•Adequate Resuscitation
MODS
•Support Dysfunctional
Systems & Monitoring

31. Management principles
• Early recognition
• Early and adequate antibiotic therapy
• Source control
• Early hemodynamic resuscitation and continued
support
• Proper ventilator management with low tidal
volume in patients with ARDS

32. General measures
• Venous access
• Crystalloid infusion
• Central venous line insertion ?
• Urinary catheterization
• Oxygenation and ventilation. Low tidal volume
ventilation is associated with better outcome

33. • Within 6 hours of presentation to ER, intensive
monitoring of specific circulatory parameters with
the aggressive management of 5 key parameters
to specified targets to optimise oxygen delivery to
tissues and maintain hemodynamic stability.
(Rivers 2001)
Early goal directed therapy
(EGDT)

34. Effective Sepsis Management for Quality
Patient Outcomes
• EGDT have been shown to be effective at
improving patient costs and outcomes,
including significant reductions in sepsis-
related mortality.
• EGDT with the PreSep oximetry catheter has
been shown to:
– Reduce sepsis-related mortality by 46%
– Reduce hospital length-of-stay by 5 days
– Reduce hospital charges by $5,882 per patient
– Guide therapy and enable early intervention

35. Continuous ScvO2 Monitoring, PreSep
Oximetry Catheter
The Vigileo monitor works with the
PreSep catheter
The PreSep catheter is a triple lumen
central venous oximetry catheter
with an added capability for
continuously monitoring ScvO2.

36. • Parameters
– CVP 8-12 mmHg
– MAP > 65mmHg and / or SBP > 90 mmHg
– Urine output > 0.5 ml/kg/hr
– Mixed venous oxygen saturation >65% / ScvO2 >70%
– Haematocrit >30%
• Interventions
– Reduce work of breathing by early use of mech. Vent
– Fluid resuscitation
– Use of vasoactive agents: noradrenaline, dobutamine
– Transfusion

37. ScvO2
O2 delivery
Cardiac
output
HR SV
preload
Bleeding
Fluid shift
afterload
Vascular
resistance
contractility
Heart
disease
Hb
Bleeding
Hemodilution
Anemia
Oxygenation
SaO2
FiO2
Vent
O2
consumption
Metabolic
demands
Fever
Anxiety
Pain
Shivering
Muscle
activitySt joseph 2008

38. • In critically ill patients, it is crucial to
maintain the balance between
oxygen consumption and oxygen
delivery

41. International guidelines for
management of severe sepsis and
septic shock 2012
The Society of Critical Care Medicine
The European Society of Intensive
Care Medicine 2013

42. Initial Resuscitation and Infection Issues
A. Initial Resuscitation:
1. We recommend the protocolized, quantitative
resuscitation of patients with sepsis- induced tissue
hypoperfusion (defined in this document as
hypotension persisting after initial fluid challenge or
blood lactate concentration ≥ 4 mmol/L).
This protocol should be initiated as soon as
hypoperfusion is recognized and should not be delayed
pending ICU admission.

43. During the first 6 hr of resuscitation, the goals of initial
resuscitation of sepsis-induced hypoperfusion should
include all of the following (grade 1C):
a) CVP 8–12 mm Hg
b) MAP ≥ 65 mm Hg
c) Urine output ≥ 0.5 mL/kg/hr
d) ScvO2 or SvO2 70% or 65%, respectively.
2. We suggest targeting resuscitation to normalize
lactate in patients with elevated lactate levels

44. B. Screening for Sepsis and Performance
Improvement
1. Routine screening of potentially infected
seriously ill patients for severe sepsis to allow
earlier implementation of therapy (grade 1C).
2. Hospital–based performance improvement
efforts in severe sepsis (UG).

45. C. Diagnosis
1. Cultures as clinically appropriate before
antimicrobial therapy if no significant delay (> 45
mins) in the start of antimicrobial(s) (grade 1C). At
least 2 sets of blood cultures to be obtained
before antimicrobial therapy with at least 1 drawn
percutaneously and 1 drawn through each
vascular access device, unless the device was
recently (<48 hrs) inserted (grade 1C).
2. Invasive candidiasis should be in differential
diagnosis of cause of infection.
3. Imaging studies performed promptly to confirm a
potential source of infection (UG).

46. D. Antimicrobial Therapy
1. Administration of effective IV antimicrobials within
the first hour of recognition of septic shock (grade
1B) and severe sepsis without septic shock (grade
1C) as the goal of therapy.
2. - 2a. Initial empiric anti-infective therapy of one or
more drugs that have activity against all likely
pathogens (bacterial and/or fungal or viral) and that
penetrate in adequate concentrations into tissues
presumed to be the source of sepsis (grade 1B).
– 2b. Antimicrobial regimen should be
reassessed daily for potential de-escalation
(grade 1B).

47. 3. Use of low procalcitonin levels or similar biomarkers to
assist the clinician in the discontinuation of empiric antibiotics
in patients who initially appeared septic, but have no
subsequent evidence of infection (grade 2C).
4a. Combination empirical therapy for neutropenic patients
with severe sepsis (grade 2B) and for patients with difficult-to-
treat, multi-drugresistant bacterial pathogens such as
Acinetobacter and Pseudomonas spp. (grade 2B).
For patients with severe infections associated with respiratory
failure and septic shock, combination therapy with an
extended spectrum beta-lactam and either an aminoglycoside
or a fluoroquinolone is for P. aeruginosa bacteremia (grade
2B).
A combination of beta-lactam and macrolide for patients with
septic shock from bacteremic Streptococcus pneumoniae
infections (grade 2B).

48. 4b. Empiric combination therapy should not be administered
for more than 3–5 days. De-escalation to the most
appropriate single therapy should be performed as soon as
the susceptibility profile is known (grade 2B).
5. Duration of therapy typically 7–10 days; longer courses
may be 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 (grade 2C).
6. Antiviral therapy initiated as early as possible in patients
with severe sepsis or septic shock of viral origin (grade 2C).
7. Antimicrobial agents should not be used in patients with
severe inflammatory states determined to be of
noninfectious cause (UG).

49. E. Source Control
1. A specific anatomical diagnosis of infection
requiring consideration for emergent source control
be sought and diagnosed or excluded as rapidly as
possible, and intervention be undertaken for source
control within the first 12 hr after the diagnosis is
made, if feasible (grade 1C).
2. When infected peripancreatic necrosis is
identified as a potential source of infection,
definitive intervention is best delayed until
adequate demarcation of viable and nonviable
tissues has occurred (grade 2B).

50. 3. When source control in a severely septic patient
is required, the effective intervention associated
with the least physiologic insult should be used (eg,
percutaneous rather than surgical drainage of an
abscess) (UG).
4. If intravascular access devices are a possible
source of severe sepsis or septic shock, they should
be removed promptly after other vascular access
has been established (UG).

51. F. Infection Prevention
1a. Selective oral decontamination and selective digestive
decontamination should be introduced and investigated as a
method to reduce the incidence of VAP; This infection
control measure can then be instituted in health care
settings and regions where this methodology is found to be
effective (grade 2B).
1b. Oral chlorhexidine gluconate be used as a form of
oropharyngeal decontamination to reduce the risk of VAP in
ICU patients with severe sepsis (grade 2B).

52. G. Fluid Therapy of Severe Sepsis
1. We recommend against using hydroxymethyl
starch for fluid resuscitation in severe sepsis and
septic shock (grade1B).
2. We suggest the use of albumin in the fluid
resuscitation of severe sepsis and septic shock
when patients require substantial amounts of
crystalloids (grade 2C).

53. 4. Initial fluid challenge in a minimum of 30 mL/kg
of crystalloids (a portion of this may be albumin
equivalent). More rapid administration and greater
amounts of fluid may be needed in some patients
(grade 1C).
5. Fluid challenge technique be applied wherein
fluid administration is continued as long as there is
hemodynamic improvement either based on
dynamic or static variables (UG).

54. H. Vasopressors
1. Vasopressor therapy initially to target a MAP of 65 mm Hg
(grade 1C).
2. Norepinephrine as the first choice vasopressor (grade 1B).
3. Epinephrine (added to and potentially substituted for
norepinephrine) when an additional agent is needed to
maintain adequate blood pressure (grade 2B).
4. Vasopressin 0.03 units/minute can be added to
norepinephrine (NE) with intent of either raising MAP or
decreasing NE dosage (UG).

55. 5. Low dose vasopressin is not recommended as the
single initial vasopressor for treatment of sepsis-
induced hypotension and vasopressin doses higher than
0.03-0.04 units/minute should be reserved for salvage
therapy (failure to achieve adequate MAP with other
vasopressor agents) (UG).
6. Dopamine as an alternative vasopressor agent to
norepinephrine only in highly selected patients (eg,
patients with low risk of tachyarrhythmias and absolute
or relative bradycardia) (grade 2C).

57. 7. Phenylephrine is not recommended in the
treatment of septic shock except in circumstances
where (a) norepinephrine is associated with serious
arrhythmias, (b) cardiac output is known to be high
and blood pressure persistently low or (c) as salvage
therapy when combined inotrope/vasopressor
drugs and low dose vasopressin have failed to
achieve MAP target (grade 1C).

58. 8. Low-dose dopamine should not be used for
renal protection (grade 1A).
9. All patients requiring vasopressors have an
arterial catheter placed as soon as practical if
resources are available (UG).

59. I. Inotropic Therapy
1. Dobutamine infusion up to 20 mcg/kg/min be
administered or added to vasopressor (if in use) in
the presence of (a) myocardial dysfunction as
suggested by elevated cardiac filling pressures and
low cardiac output, or (b) ongoing signs of
hypoperfusion, despite achieving adequate
intravascular volume and adequate MAP (grade 1C).

60. J. Corticosteroids
1. Not using IV hydrocortisone to treat adult septic
shock patients if adequate fluid resuscitation and
vasopressor therapy are able to restore hemodynamic
stability . In case this is not achievable, we suggest IV
hydrocortisone at a dose of 200 mg/ day (grade 2C).
2. Not using the ACTH stimulation test to identify adults
with septic shock who should receive hydrocortisone
(grade 2B).

61. 3. In treated patients hydrocortisone tapered when
vasopressors are no longer required (grade 2D).
4. Corticosteroids not be administered for the
treatment of sepsis in the absence of shock (grade 1D).
5. When hydrocortisone is given, use continuous flow
(grade 2D).
6. Steroids may be indicated in the presence of a
history of steroid therapy or adrenal dysfunction !!

62. K. Blood Product Administration
1. Once tissue hypoperfusion has resolved and in the
absence of extenuating circumstances, such as
myocardial ischemia, severe hypoxemia, acute
hemorrhage, or ischemic coronary artery disease,
we recommend that RBCs transfusion occur when
the Hb concentration decreases to < 7.0 g/dL to
target a Hb concentration of 7.0 to 9.0 g/dL in adults
(grade 1B).

63. 2. We recommend not using erythropoietin as a
specific treatment of anemia associated with severe
sepsis (grade 1B).
3. We suggest that FFP not be used to correct
laboratory clotting abnormalities in the absence of
bleeding or planned invasive procedures (grade 2D).
No studies suggest that correction of more severe
coagulation abnormalities benefits patients who are
not bleeding.
4. We recommend against antithrombin
administration for the treatment of severe sepsis
and septic shock (grade 1B).

64. 5. In patients with severe sepsis, we suggest that
platelets be administered prophylactically when:
– counts are ≤ 10,000/mm3 in the absence of apparent
bleeding
– counts are ≤ 20,000/mm3 if the patient has a
significant risk of bleeding.
– platelet counts ≥ 50,000/mm3 if the patient has active
bleeding, surgery, or invasive procedures (grade 2D).

65. L. Immunoglobulins
1. We suggest not using IV immunoglobulins in
adult patients with severe sepsis or septic
shock (grade 2B). Large RCTs found no benefit
M. Recombinant activated protein C
1. It is no longer available for treating patients
with severe sepsis or septic shock

66. N. Glucose Control
1. We recommend a protocolized approach to
blood glucose management in ICU patients with
severe sepsis, commencing insulin dosing when
two consecutive RBS levels are > 180 mg/dL. This
approach should target an upper blood glucose
level ≤ 180 mg/dL rather than an upper target
blood glucose ≤ 110 mg/dL (grade 1A).
2. We recommend blood glucose values be
monitored every 1-2 hrs until glucose values and
insulin infusion rates are stable, then every 4 hrs
thereafter (grade 1C).

67. 3. We recommend that capillary glucose levels to be
interpreted with caution, as such measurements
may not accurately estimate arterial blood or
plasma glucose values (UG).

68. O. Renal Replacement Therapy
1. Continuous RRT and intermittent hemodialysis are
equivalent in patients with severe sepsis and acute
renal failure (grade 2B).
2. Use continuous therapies to facilitate management
of fluid balance in hemodynamically unstable septic
patients (grade 2D).
P. Bicarbonate Therapy
1. Not using sodium bicarbonate therapy for the
purpose of improving hemodynamics or reducing
vasopressor requirements in patients with
hypoperfusion-induced lactic acidemia with pH
≥7.15 (grade 2B).

69. Q. Deep Vein Thrombosis Prophylaxis
1. Patients with severe sepsis receive daily
pharmacoprophylaxis against VTE (grade 1B).
Daily SC LMWH is more preferred than twice
daily UFH or three times daily UFH. If creatinine
clearance is <30 mL/min, use dalteparin (grade
1A) or another form of LMWH that has a low
degree of renal metabolism (grade 2C) or UFH
(grade 1A).
2. Patients with severe sepsis be treated with a
combination of pharmacologic therapy and
intermittent pneumatic compression devices
whenever possible (grade 2C).

70. 3. Septic patients who have a contraindication for
heparin use not receive pharmacoprophylaxis
(grade 1B), but receive mechanical prophylactic
treatment, such as graduated compression stockings
or intermittent compression devices (grade 2C),
unless contraindicated. When the risk decreases
start pharmacoprophylaxis (grade 2C).

71. R. Stress Ulcer Prophylaxis
1. Stress ulcer prophylaxis using H2 blocker or PPI
be given to patients with severe sepsis/septic
shock who have bleeding risk factors (grade 1B).
2. When stress ulcer prophylaxis is used, PPIs rather
than H2RA (grade 2D)
3. Patients without risk factors do not receive
prophylaxis (grade 2B).

72. Thank you

73. Questions ???