1. Septic shock is a life-threatening condition that occurs when sepsis leads to dangerously low blood pressure and organ dysfunction. It is caused by an uncontrolled immune response to infection that damages the cardiovascular system. 2. Early and aggressive treatment of septic shock is crucial and involves rapid administration of broad-spectrum antibiotics, controlling the infection source, and fluid resuscitation along with vasopressors to maintain adequate blood pressure over the first six hours. 3. The goals of fluid resuscitation in septic shock are to restore adequate tissue perfusion as indicated by targets such as a mean arterial pressure over 65 mmHg, urine output over 0.5 ml/kg/hr, and normalization of lactate

1. SEPTIC SHOCK
DR. LANDO ELVIS
PKH-IMED

2. Overview: Normal Response to
Infection
• Local infection
• Non-specific inflammatory response
• 3 phases
– Vasodilation - increased blood flow to site, infusion of antibodies and cells to
fight infection
– Vessel permeability - antibodies and cells exit bloodstream and enter infected
tissue
– Once infection is controlled, tissue repairs itself

3. Overview: Pathophysiology of Sepsis
• Uncontrolled, exaggerated immune response
• Endothelium damage, cell mediator activation, disruption of
coagulation system homeostasis
• Vasodilation and capillary permeability
• Systemic inflammatory response
• End-organ damage, death

4. DEFINITIONS : SIRS
• Systemic Inflammatory Response Syndrome(SIRS): Is a
nonspecific inflammatory response to an insult that
results in activation of the immune system. This
inflammatory response is the body’s way of attempting to
maintain homeostasis.
• Requires ≥ 2 of the following:
• Temperature > 38°C or < 36°C
• Respiratory rate > 20/min, or PaCO2 < 32 mmHg
• Heart rate > 90 bpm
• WBC count >12,000 or <4,000 cells/µL, or > 10% bands
• Sepsis: ≥ 2 SIRS criteria + evidence of infection
ACCP/SCCM Consensus Conference. Crit Care Med 1992;20(6):864–74.

5. DEFINITIONS: Severe Sepsis
• Sepsis + new organ dysfunction = severe sepsis
• Sepsis-induced tissue hypoperfusion or organ dysfunction (any
of the following):
• Hypotension (SBP < 90 mmHg, MAP < 70 mmHg, or SBP of 40 mmHg
below baseline)
• Elevated lactate
• UOP < 0.5 mL/kg/hr x 2 hours, despite adequate IVF
• Creatinine > 2 mg/dL
• PaO2/FIO2 < 250 in absence of PNA as source
• PaO2/FIO2 < 200 in presence of PNA as source
• Bilirubin > 2 mg/dL
• Platelets < 100,000/µL
• Coagulopathy (INR > 1.5)
Levy MM, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis
Definitions Conference. Crit Care Med 2003;31:1250-1256.

6. • Severe sepsis + refractory hypotension OR lactate ≥ 4 mmol/L =
septic shock
• Shock in general is a state of cellular and tissue hypoxia due to:
1. Reduced O2 delivery (e.g. anemia, hypoxemia);
2. Outstripped O2 consumption (e.g. thyrotoxicosis); and/or
3. Impaired utilization (e.g. mitochondrial dysfunction)
• Septic shock commonly manifests with #1 and #3 concurrently in a
patient
• Most common clinical definition of septic shock is presence of
severe sepsis + hypotension refractory to intravenous fluids alone
• i.e. the patient requires vasopressors
• generally hypotension is mean arterial pressure (MAP) < 65 mmHg
• Watch out for shock in a chronically hypertensive patient with “normal BP”
that is significantly below baseline
• Some argue presence of elevated lactate (>4 mmol/L) also indicates
shock regardless of MAP
DEFINITIONS: Septic shock

7. Cont..
• Septic shock is a distributive shock
• Cytokine release leads to a large-scale inflammatory response
• Massive vasodilation
• Increased capillary permeability
• Decreased systemic vascular resistance
• Blood clots form in the microvasculature
• Hypotension reduces tissue perfusion causing tissue hypoxia

8. DEFINITIONS: Multiple Organ Dysfunction
Syndrome (MODS)
MODS is altered organ function in an acutely ill patient requiring medical intervention to
achieve homeostasis. Can be the end result of septic shock.
Sepsis-related organ dysfunction → No organ system is immune
• Respiratory failure
• Liver failure
• Kidney failure
• Heart failure
• Gut permeability
• DIC (disseminated intravascular coagulation)
• Altered mental status
• Brain death

9. SIRS
Sepsis
Severe
Sepsis
Septic
Shock
MODS
Linear model of sepsis Progression
Early identification and treatment
It is crucial to identify septic patients and initiate treatment as early along the continuum as
possible and treat them to avoid developing organ damage or shock.
SIRS + Infection
Sepsis + End Organ Damage
Severe Sepsis + Refractory (unresponsive) hypotension
Temp. > 38 C or < 36 C, HR > 90, RR > 20 or PaCO2 < 32,
WBCs > 12,000 or < 4,000 or > 10% bands
Goal:
early identification
here Death can result
©2019 CHA

10. Singer M, et al. Sepsis-3. JAMA. 2016;315(8):801-10.
• In 2016, the Society of Critical Care Medicine and European Society of
Intensive Care Medicine released a consensus statement redefining the
sepsis syndrome.
• “SIRS” and “severe sepsis” were eliminated
• “Septic shock” was redefined as hypotension despite adequate IVF
requiring vasopressors to maintain MAP > 65 mmHg, and serum lactate > 2
mmol/L.
New Definitions of Sepsis?

11. • Emphasis was placed on organ failure (SOFA score),
especially the “quick SOFA” or qSOFA score:
• Presence of altered mental status
• Systolic blood pressure ≤100 mmHg
• Respiratory rate ≥ 22/minute
• A score of ≥ 2 reflects high risk for organ failure and
mortality and should prompt appropriate intervention
New Definitions of Sepsis?
Singer M, et al. Sepsis-3. JAMA. 2016;315(8):801-10.

12. • While these definitions may prove to be clinically
useful, they are not yet validated, so should be used
cautiously.
• For example, while SIRS sacrifices specificity for
sensitivity, qSOFA is likely under-sensitive, which is
problematic for a screening test because it may miss
septic patients.
New Definitions of Sepsis?
Singer M, et al. Sepsis-3. JAMA. 2016;315(8):801-10.
Additional reading on Sepsis-3 definitions:
Simpson SQ. New Sepsis Criteria: A Change We
Should Not Make. Chest. 2016;149(5):1117-8.

13. Risk Factors for Sepsis
• Extremes of age (old and young)
– Can’t communicate, need careful assessment
– Patients with developmental delay
– Cerebral Palsy
• Recent surgery, invasive procedure, illness, childbirth/pregnancy
termination/miscarriage
• Reduced immunity

14. Increased Risk for Sepsis
• DIABETES, DIABETES, DIABETES
• Liver cirrhosis
• Autoimmune diseases (lupus, rheumatoid arthritis)
• HIV/AIDS
• Para/quadriplegics
• Sickle cell disease
• Splenectomy patients
• Compromised skin (chronic wounds, burns, ulcers)

15. Increased Risk for Sepsis
• Chemotherapy
• Post-organ transplant (bone marrow, solid organ)
• Chronic steroid use
• Recent antibiotic use
• Indwelling catheters of any kind (dialysis, Foley, IV, PICC, PEG
tubes, etc)

16. Signs/Symptoms of Sepsis
• Symptoms of sepsis are often nonspecific and include the
following:
– Fever = most common (elderly patients often do NOT mount
a febrile response)
– Flu-like symptoms
– Chills/shaking (mistaken for seizure)
– Nausea/vomiting
– Mental status changes/fatigue/lethargy
Patient often does NOT
appear acutely ill

17. Multiple Organ System Dysfunction
Cardiovascular
Tachycardia
Hypotension
Renal
Oliguria
Anuria
Renal failure
Hematologic
Consumptive coagulopathy
Petechiae
Purpura
CNS
Altered mental status
Respiratory
Tachypnea
Hypoxia
Hepatic
Jaundice
Liver inflammation
Coagulopathy
Metabolic
Lactic acidosis

18. APROACH IN MANAGING SEPSIS
.
Lactate
Blood
cultures x2
before
antibiotics
Give
antibiotics
Give fluids at
30 mL/kg if:
initial
hypotension,
lactate ≥ 4, or
septic shock
Reperfusion
assessment
©2019 CHA

19. 1.Lactate
• With sepsis, lactate is viewed as a marker of global tissue perfusion.
• Lactate has some predictive use:
• Sustained > 6 hours, an elevated lactate foreshadows increased mortality
• Mortality increases as lactate levels increase
Lactate Level Mortality
0-2.5 mmol/L 4.9 percent mortality
2.5-4.0 mmol/L 9.0 percent mortality
> 4.0 mmol/L 28.4 percent mortality
(Nguyen, et al., 2004; Shapiro, et al., 2005)
©2019 CHA

20. 2.Blood Cultures
Source control: identify and stop the infection
Why two sets of blood cultures?
• Corroboration of matching sets confirms treatment of a true pathogen versus a
contaminate
The goal is to prevent culture negative severe sepsis (CNSS) and septic shock
• Of 6.8 million severe sepsis admissions, 47 percent were culture negative
• CNSS was seen as a statistically significant independent predictor of death
©2019 CHA

21. 3. The Rapid Choice of the Right Antibiotic(s)
Morell MR et al. The Management of Severe Sepsis and Septic Shock
Infectious Disease Clinics of North America 23 (3): 485-501, 2009
Early, broad-spectrum antibiotics are absolutely critical. Failure to treat up front
with the right antibiotics increases mortality by 10-20 percentage points.
• Every hour antibiotic initiation is delayed increases the risk for mortality by more
than eight percent.
• Antibiotics should be given as soon as possible after blood cultures are drawn.
o Preferably after the second set of cultures; however, if the second set is going to be
delayed more than 30 minutes, antibiotics should be started after the first set.
• If more than one antibiotic is ordered, give the broadest-spectrum antibiotic first.
Infuse multiple antibiotics concurrently, if appropriate.

22. 1. The Rapid Choice of the Right Antibiotics
• Review of risk factors for certain infections
• E.g., recent bowel surgery should make you think about gram-negatives, anaerobes, and Candida.
• Identification of source(s) or suspected source(s)
• E.g., comprehensive work-up based on risk factors, history, physical, laboratory, and imaging
studies
• Correct stratification of patients as hospital-acquired, health-care associated, or
community-acquired
• E.g., recent hospitalization, SNF patient, etc.
• Review of prior infection history and prior microbiological cultures and sensitivities
• E.g., urine culture from 2 months ago grew Zosyn-resistant E. coli
• Early (within 60 minutes of diagnosis) delivery of antibiotics
What does this look like in action?
3. The Rapid Choice of the Right Antibiotic(s)

23. 1. The Rapid Choice of the Right Antibiotics
• This means EARLY involvement of procedural and surgical colleagues for adequate
source control:
• E.g. inserting chest tubes for empyemas, biliary tubes for biliary obstructions, nephrostomy tubes
for obstructing kidney stones, joint wash-out for septic arthritis, ex-laps for bowel perfs, etc.
• One caveat – patients much be stabilized for these procedures, which means they
need to be fluid resuscitated first (see next slide).
• It is also common for patients to transiently worsen following source control
procedure (classically drainage of liver abscess) due to “stirring up infection”.
Anticipate this and stay on top of it with fluids and vasopressors!
• Consider inadequate source control in a patient who fails to improve with fluids and
antibiotics alone
Antibiotics will not effectively penetrate
undrained abscesses
4. Achieve Adequate Source Control

24. Hypotension (SBP < 90, MAP < 65) or lactate > 4 mmol/L:
initial fluid bolus 20-40 ml of crystalloid (or colloid equivalent) per kg of body weight.
• The Society of Critical Care Medicine suggests isotonic saline (normal saline) or balanced salt
solutions (lactated Ringers) for initial fluid resuscitation.
• Sepsis and severe sepsis without hypotension:
• For most patients, the provider will likely order a fluid bolus based on their assessment, but there is no
specific requirement
• Severe sepsis with hypotension or lactate ≥ 4 mmol/L:
• 30 mL/kg of actual body weight for patients with a BMI < 30
• 30 mL/kg of ideal body weight for patients with a BMI > 30
• Provider must document that they are using ideal body weight if BMI over 30
“Goal Directed Therapy” for sepsis, which targeted physiologic endpoints once
patients arrived in the ICU but not before.
5. Septic shock – Fluid therapy

25. 5. Fluid resuscitation: Central tenet of therapy
• 2012 Surviving Sepsis Campaign recommends
specific physiologic goals for fluid resuscitation:
• MAP > 65 mmHg
• CVP 8-12 mmHg (or 12-15 during mechanical vent)
• Central venous O2 sat > 65% or Mixed venous > 70%
• Urine output > 0.5 ml/kg/h
• Normalization of lactate
• It is important to note that these goals are for the first
6 hours of sepsis therapy

26. • First-line: Norepinephrine (dose: 0.01 - 1 µg/kg/min)
• Increases MAP mainly by vasoconstriction, but also is a mild inotrope which is
important for sepsis-mediated cardiac stunning
• Low doses improve cardiac output, and cerebral, renal, and splanchnic blood
flow
• Compared to dopamine: Less tachycardia, fewer arrhythmias, lower RR of
death (0.91; 0.83–0.99)
• Second-line: Vasopressin (dose: 0.01 – 0.04 units/min)
• Goal is to decrease dose of NE
• Reasonable to start when NE dose gets to 0.2 µg/kg/min
• Some say dose is “fixed” at 0.04, but in reality you can adjust.
6. Maintain Blood Pressure Support

27. • Third-line: Epinephrine (dose: 0.01 - 1 µg/kg/min)
• Same dosing regimen as norepinephrine
• FYI on Epinephrine:
• If patient is dead, the dose is 1 mg IV q3min.
• If patient is alive but hypotensive, the dose is 10 mcg IV (or 1 ml of 1:100,000
concentration) q1min prn. Don’t give 1 mg!
• Can use Phenylephrine infusion in certain situations, e.g. avoidance of beta-
adrenergic activation if patient has rapid Afib.
6. Maintain Blood Pressure Support

28. Summary
• The 3 most important components of sepsis care are:
1. Rapid administration of the right antibiotic(s)
2. Source control within first hospital day
3. Aggressive resuscitation with IVF, pressors, etc. during first 6 hours of care
• How do you judge fluid responsiveness? By all of these: Physical exam, straight leg raise,
IVC ultrasound, CVP, MAP, urine output (UOP), lactate, Central venous oxyhemoglobin
saturation (ScvO2), trial and error, etc. etc.
No single test will tell you what to do!

29. Summary
• Fluids should be administered as long as the patient is fluid responsive, to
a point.
• Avoid fluid overload (edema worsens O2 delivery due to increasing distance needed
for O2 diffusion)
• Conversely, using high dose vasopresors in a hypovolemic patient will cause digital
necrosis
• So the take home message is give enough fluids up front to fill the tank
(~4-5 L may be sufficient) but not too much to cause significant fluid
overload…

30. END
.