guidelines for managament of sepsis and septic shock with overview on pathophysiology

1. Sepsis and Septic
Shock

2. By
Nadia Ismail Abdulhameed
Lecturer of Internal Medicine and Critical Care
2

3. Objectives:
Tools For Identifying High
Risk: SOFA AND QSOFA
 DEFINITIONS
 Review the causes of septic
shock.
 Describe the
pathophysiology of septic
shock.
 Outline the treatment
options for septic shock.
3

4. “
▸ Sepsis and particularly septic shock should be
recognized as medical emergencies in which time
matters, as in stroke and acute myocardial infarction.
▸ Early recognition and rapid institution of resuscitative
measures are critical.
▸ But recognizing sepsis can be a challenge, and best
management practices continue to evolve.
4

5. DEFINITIONS HAVE EVOLVED:
▸ In 1991,Sepsis was first defined as a systemic inflammatory response
syndrome (SIRS) due to a suspected or confirmed infection with 2 or more
of the following criteria :
• Temperature below 36°C or above 38°C
• Heart rate greater than 90/minute
• Respiratory rate above 20/minute, or arterial partial pressure of carbon dioxide
less than 32 mm Hg
• White blood cell count less than 4 × 109 /L or greater than 12 × 109 /L, or
more than 10% bands.
5

6. DEFINITIONS HAVE EVOLVED:
▸ Severe sepsis was defined as the progression of sepsis to
organ dysfunction, tissue hypoperfusion, or hypotension.
▸ Septic shock was described as hypotension and organ
dysfunction that persisted despite volume resuscitation,
necessitating vasoactive medication, and with 2 or more of
the SIRS criteria listed above.
6

7. DEFINITIONS HAVE EVOLVED:
▸ In 2016, the Sepsis-3 committee issued the following new definitions:
▸ • Sepsis—A life-threatening condition caused by a dysregulated host
response to infection, resulting in organ dysfunction
▸ • Septic shock—Circulatory, cellular, and metabolic abnormalities in
septic patients, presenting as fluid-refractory hypotension requiring
vasopressor therapy with associated tissue hypoperfusion (lactate > 2
mmol/L).
▸ The classification of severe sepsis was eliminated.
7

8. Etiology of
Sepsis and
Septic Shock
8

9. ▸ Most cases of septic shock are caused
by hospital-acquired gram-negative bacilli or
gram-positive cocci and often occur in
immunocompromised patients and patients
with chronic and debilitating diseases.
▸ Rarely, it is caused by Candida or other
fungi.
▸ A postoperative infection (deep or
superficial) should be suspected as the
cause of septic shock in patients who have
recently had surgery.
▸ A unique, uncommon form of shock
caused by staphylococcal and streptococcal
toxins is called toxic shock syndrome.
▸ Predisposing factors include
1) Diabetes mellitus
2) Cirrhosis
3) Leukopenia (especially that associated with
cancer or treatment with cytotoxic drugs)
4) Invasive devices (including endotracheal
tubes, vascular or urinary catheters, drainage
tubes, and other foreign materials)
5) Prior treatment with antibiotics or
corticosteroids
6) Recent hospitalization (especially in an
intensive care unit)
9

10. Other Risk factors
Patient related
• <1 year of age
• >65 years of age
• Debilitated
• Malnourished
• Chronic health
problems
Treatment Related
• Invasive lines and
procedures
• Surgical procedures
• Treatment for burns
or traumatic wounds
• Immuno-suppression
Entry sites for septic
shock
• Most common - GU
Tract
• GI Tract
• Respiratory Tract
• Skin
10

11. Pathophysiology
of Sepsis and
Septic Shock
11

12. • Proinflammatory and procoagulation responses
dominate and lead to uncontrolled inflammation
and advanced coagulopathy
Three known problems:
• Excess Coagulation
• Exaggerated or malignant inflammation
• Impaired fibrinolysis
Balance of coagulation and fibrinolysis shifts
toward increased coagulation via the extrinsic
pathway
12

13. • Endotoxin (within the Gram Negative bacteria wall)
released into the blood during bacterial cell lysis
• Macrophages (Phagocytic cells found in the lung
interstitium and alveoli, liver, sinuses etc) Activated by
endotoxin to release cytokines ( Tumor necrosis factor,
Major endogenous toxin, Interleukin-1 and Interleukin-
2
• Endotoxins activates GRANULOCYTES
Releases toxic mediators e.g. platelet activating factor,
Oxygen derived free radicals, Proteolytic enzymes
• Endotoxins activate arachidonic acid cascade
Results in prostaglandin, leukotrienes, thromboxane A
effecting smooth muscle
13

14. Want big impact? Use big image.
14

15. Want big impact? Use big image.
15

16. Hemodynamic alterations of septic
shock
16
Hemodynamics
•Profound Vasodilation
•Systemic vascular resistance is decreased
•Blood Pressure falls
•Intravascular pooling in the venous capacitance
system
•Increased capillary permeability
•Microembolization
•Decreased ejection fraction

17. Clinical Manifestations.
Recognition of Septic Shock:
▸ Inflammatory triad-
▹ Fever
▹ Tachycardia
▹ flushed skin Warm Shock
▸ Hypoperfusion
▹ Altered sensorium
▹ Urine output
▹ Wide pulse pressure.......bounding pulses

18. Clinical Manifestations.
▸ Hypotension
▹ Cold and clammy skin
▹ Mottling
▹ Tachycardia Cold shock
▹ Cyanosis
▹ Narrow pulse pressure
▹ Hypoxemia
▹ Acidosis.

19. ▸ Many patients with severe sepsis develop
relative adrenal insufficiency (ie, normal or
slightly elevated baseline cortisol levels that
do not increase significantly in response to
further stress or exogenous
adrenocorticotropic hormone [ACTH]).
19

20. .
Staging of Septic Shock:
I. Compensated / Preshock / Hyperdynamic
II.Decompensated / Organ hypoperfusion
III. End organ failure / Irreversible
Staging of Septic Shock:

21. DIAGNOSIS
There is no gold-standard method for determining whether a pt is
septic.
Sepsis is suspected when a patient with a known infection develops
systemic signs of inflammation or organ dysfunction.
21

22. 22
 Clinical manifestations
 Blood pressure (BP), heart rate, and oxygen monitoring
 Complete blood count (CBC) with differential, electrolyte panel and creatinine,
lactate levels.
 Invasive central venous pressure (CVP), PaO2, and central venous oxygen
saturation (ScvO2) readings
 Cultures of blood, urine, and other potential sites of infection, including
wounds in surgical patients

23. 23
• In patients with a suspected surgical or occult cause
of sepsis, ultrasonography, CT, or MRI may be
required, depending on the suspected source.
• Blood levels of C-reactive protein and procalcitonin
are often elevated in severe sepsis and may
facilitate diagnosis, but they are not specific.
Ultimately, the diagnosis is clinical.
• Other causes of shock (eg, hypovolemia, myocardial
infarction [MI]) should be ruled out via history,
physical examination, ECG, and serum cardiac
markers.

24. Lab Derangement In Septic Shock
 Hyperglycemia (glucose more than 120
mg/dL)
 Leukocytosis (WBC more than
12,000/mm3) or leukopenia (WBC less
than 4000/mm3)
 Bandemia (more than 10%)
 C-reactive protein or procalcitonin more
than 2 SD above normal
 Mixed venous saturation of more than
70%
 PaO2: FiO2 less than 300
 Pre-renal azotemia
 Coagulopathy, INR more than 1.5
or PTT more than 60 sec
 Thrombocytopenia (platelets less
than 100,000/mL)
 Hyperbilirubinemia (total bilirubin
more than 4 mg/dL)
 Lactic acidosis (more than 2
mmol/L)
24

25. Tools For Identifying High Risk: SOFA AND
qSOFA

26. 26
It is important to detect organ dysfunction as early as possible.
A number of scoring systems have been devised, but the sequential organ
failure assessment score (SOFA score) and the quick SOFA score (qSOFA)
have been validated with respect to mortality risk and are relatively simple to
use.
The qSOFA score is based on the blood pressure, respiratory rate, and
the Glasgow coma scale and does not require waiting for lab results. For
patients with a suspected infection who are not in the intensive care unit (ICU),
the qSOFA score is a better predictor of inpatient mortality than the systemic
inflammatory response syndrome (SIRS) and SOFA score. For patients with a
suspected infection who are in the intensive care unit (ICU), the SOFA score is
a better predictor of in-patient mortality than the systemic inflammatory
response syndrome (SIRS) and qSOFA score.

27. 27
Patients with ≥ 2 of the following criteria meet criteria for SIRS and should have further clinical
and laboratory investigation:
 Temperature > 38° C (100.4° F) or < 36° C 96.8° F
 Heart rate > 90 beats per minute
 Respiratory rate > 20 breaths per minute or PaCO2 < 32 mm Hg
 White blood cell count > 12,000/mcL (12 × 109/L), < 4,000/mcL (4 × 109/L) or > 10%
immature (band) forms
Patients with ≥ 2 of the following qSOFA criteria should have further clinical and laboratory
investigation:
 Respiratory rate ≥ 22 breaths per minute
 Altered mentation
 Systolic blood pressure ≤ 100 mm Hg
The SOFA score is somewhat more robust in the ICU setting, but requires laboratory testing.

28. 28
PaO2
FIO2
Ventilatory Support Yes (1)
No (0)
Platelets
Total Bilirubin
Blood Pressure Hypotension absent (0)
Mean arterial pressure <70 mmHg (1)
On Dopamine ≤5 mcg/kg/min or any Dobutamine (2)
On Dopamine >5 mcg/kg/min, Epinephrine <=0.1 mcg/kg/min
or Norepinephrine <=0.1 mcg/kg/min (3)
On Dopamine >15 mcg/kg/min or Epinephrine >0.1
mcg/kg/min or Norepinephrine >0.1 mcg/kg/min (4)
Glasgow Coma Score
Creatinine
Urine Output mL/day
 The SOFA score helps predict morbidity rather than mortality, though individuals with a
score of 15 or more had a mortality rate of 90%.

29. 29
• The quickSOFA (qSOFA) score is a simpler
algorithm that can be computed at the bedside.
• Pts are given 1 point each for systolic
hypotension (≤100 mmHg), tachypnea (≥22
breaths/min), or altered mentation.
• A qSOFA score of ≥2 has a predictive value for
sepsis similar to that of the SOFA score.
2 to 3 points: High risk
0 to 1 point: Not high risk

30. MEDS Score: Mortality in ER Sepsis
▸ Terminal illness with possible death in 1 month (6 points)
▸ Hypoxia or tachypnea (3 points)
▸ Shock from sepsis (3 points)
▸ Platelet count below 150,000 (3 points)
▸ Granulocytic bands >5% of WBC (3 points)
▸ Patient older than 65 years old (3 points)
▸ Mental status is altered (2 points)
▸ Patient is from a nursing home (2 points)
▸ Lower respiratory infection (2 points) 30

31. 31
Mortality risk
0 to 4 points: 0.9 - 1.1%
5 to 7 points: 2 - 4.4%
8 to 12 points: 7.8 - 9.3%
12 to 15 points: 16.1 - 20.2%
16 to 27 points: 38 - 50%

32. Multiple Organ Dysfunction Score
(MODS)
▸ PaO2
▸ FIO2
▸ Central Venous
Pressure
▸ Mean Arterial Pressure
▸ Heart Rate
▸ Platelets
▸ Bilirubin
▸ Creatinine
▸ Glasgow Coma Score
32

33. 33
MODS Score
0 points: ICU Mort 0%, Hosp Mort 0%, ICU Stay 2 Days
1 to 4 points: ICU Mort 1-2%, Hosp Mort 7%, ICU Stay 3 Days
5 to 8 points:
ICU Mort 3-5%, Hosp Mort 16%, ICU Stay 6
Days
9 to 12 points:
ICU Mort 25%, Hosp Mort 50%, ICU Stay 10
Days
13 to 16 points:
ICU Mort 50%, Hosp Mort 70%, ICU Stay 17
Days
17 to 20 points:
ICU Mort 75%, Hosp Mort 82%, ICU Stay 21
Days
21 to 24 points: ICU Mort 100%, Hosp Mort 100%

34. Clinical Management
Sepsis is a multifaceted disease, and its
management is complex
34

35. Goals of Treatment:
▸ Measures most
effective if achieved
within the first six hours
of diagnosis
▸ Restore central venous
pressure (CVP) to 8
mmHg to 12 mmHg
▸ Restore mean arterial
pressure (MAP) greater
than 65 mmHg
▸ Restore superior vena
cava saturation to 70% or
mixed venous saturation to
65%
▸ Fluid resuscitation with
crystalloid (NS or albumin)
and colloid (blood
products) up to 80 ml/kg
▸ Mechanical ventilation to
reduce metabolic demand
▸ First-line vasoactive agents
(epinephrine in cold shock
versus norepinephrine in
warm shock) when fluid-
refractory shock developed
▸ Note: dopamine as a first-
line agent has fallen out of
favor given its inhibitory
effect on the HPA axis,
namely prolactin and
growth hormone, which can
confer immunologic
dysfunction
35

36. Steps of Management:
FLUID RESUSCITATION ANTIMICROBIAL
THERAPY
ROLE OF
CORTICOSTEROIDS IS
QUESTIONED
36
EARLY SOURCE
CONTROL
RESTORING BLOOD
PRESSURE

37. 37
Early treatment of sepsis and septic shock is best summarized by
two “bundles” of care:
1. Within 3 h of presentation (ideally within the first hour), the pt
should be given appropriate broad-spectrum antibiotics. with
collection of blood for culture before antibiotic administration and
measurement of serum lactate levels. – For every 1-h delay in the
initiation of antibiotic administration to pts with sepsis, there is a 3–
7% increase in the odds of in-hospital death.
2. Within 6 h of presentation, the pt should receive an IV fluid bolus
and treatment with vasopressors for persistent hypotension or shock,
and serum lactate levels should be re-measured. – More than 30% of
pts with severe sepsis require source control, mainly for abdominal,
urinary, and soft-tissue infections.

38. Fluid Resuscitation
▸ Fluid Administration
▸ • To restore adequate ventricular preload
▸ • Colloids vs. crystalloids • Colloids my cause movement of
fluid into interstitial space because of the capillary permeability
▸ • If ineffective, may need Dopamine and Dobutamine
▸ A crystalloid bolus of 30 mL/kg is recommended within 3 hours
of detecting severe sepsis or septic shock.
▸ Assess volume with dynamic measures (The passive leg-raise
test has excellent sensitivity and specificity for determining
fluid responsiveness)
▸ Lactate level as a resuscitation guide
38

39. 39

40. ANTIMICROBIAL THERAPY
▸ Appropriate antimicrobials should be started within an hour of recognizing sepsis
▸ Delay in giving appropriate antibiotics is associated with a significant increase
in mortality rate
▸ The initial antimicrobial drugs should be broad-spectrum, covering all likely
pathogens.
▸ Multidrug regimens are favored to ensure sufficient coverage, especially in
septic shock.
▸ Antifungals should be considered for patients at risk, such as those who have
had total parenteral nutrition, recent broad-spectrum antibiotic exposure,
perforated abdominal viscus, or immunocompromised status, or when clinical
suspicion of fungal infection is high.
40

41. ▸ A robust antimicrobial de-escalation
strategy needs to balance an initial broad-
spectrum approach.
▸ Antibiotic de-escalation should be
discussed daily.
41

42. Role Of Corticosteroids Is
Questioned
▸ The evidence is not conclusive that giving
corticosteroids for sepsis improves clinical
outcomes or survival, and so they are not
recommended in sepsis or severe sepsis if fluid
resuscitation and vasopressors are sufficient to
restore hemodynamic stability. Rather, they can
be added as adjunctive therapy for patients
requiring higher doses of vasopressors.
42

43. ▸ If corticosteroids are used in septic shock, current
guidelines recommend hydrocortisone 200 mg per
day intravenously as a continuous drip or 50 mg
bolus in 4 divided doses for at least 3 days, based
on a systematic review showing a longer course of
low-dose steroids is associated with a lower
mortality rate.
▸ In most cases, steroids are stopped after cessation
of vasopressors.
43

44. ▸ Patients with sepsis have a high metabolism and
thus prolonged starvation should be avoided. Early
nutrition can help protect gut mucosa and prevent
the translocation of organisms from the GI tract
into the systemic circulation.
44

45. Key Points
 Sepsis and septic shock are increasingly severe
clinical syndromes of life-threatening organ
dysfunction caused by a dysregulated response
to infection.
 Tools such as the Systemic Inflammatory
Response Syndrome criteria and the quick
version of the Sequential Organ Failure
Assessment can help with early diagnosis and
triage.
45

46. Key Points
 An important component is critical reduction in
tissue perfusion, which can lead to acute
failure of multiple organs, including the lungs,
kidneys, and liver.
46

47. Key Points
 Early recognition and treatment is the key to
improved survival.
 Resuscitate with intravenous fluids and
sometimes vasopressors titrated to optimize
central venous oxygen saturation (ScvO2) and
preload, and to lower serum lactate levels.
47

48. Key Points
 Control the source of infection by removing
catheters, tubes, and infected and/or necrotic
tissue and by draining abscesses.
 Give empiric broad-spectrum antibiotics
directed at most likely organisms and switch
quickly to more specific drugs based on culture
and sensitivity results.
48

49. Thank you