1. Septic shock
Dr. M. A. Sofi MD; FRCP (London); FRCPEdin; FRCSEdin

2. What is shock?
Shock is a state of acute circulatory failure characterized by persistent arterial hypotension despite adequate fluid resuscitation or by tissue hypoperfusion (manifested by a lactate concentration >4 mg/dL) unexplained by other causes.
“Sepsis is a clinical syndrome characterized by systemic inflammation due to infection. There is a continuum of severity ranging from sepsis to severe sepsis and septic shock”
Septic shock refers to sepsis with cardiovascular dysfunction (i.e., hypotension, reliance on administration of vasoactive drug to maintain a normal blood pressure, or two of the following:
“prolonged capillary refill, oliguria, metabolic acidosis, or elevated arterial lactate) that persists despite the administration of ≥40 mL/kg of isotonic fluid in one hour.”

3. Organ dysfunction secondary to Sepsis.
Terminology
Severe Sepsis
Organ dysfunction secondary to Sepsis.
e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy.
Septic Shock
Hypotension secondary to Sepsis that is resistant to adequate fluid administration and associated with hypoperfusion.
Systemic Inflammatory Response Syndrome (SIRS)
Temp > 38 or < 36
HR > 90
RR > 20 or PaCO2 < 32
WBC > 12 or < 4 or Bands > 10%
Sepsis
The systemic inflammatory response to infection.
Two out of four criteria
acute change from baseline

5. Comparable global Epidemiology
SSC
The incidence of sepsis syndrome is between 51 – 95 cases per 100,000 in several countries
 Over 1,665,000 cases of sepsis occur in the United States each year, with a mortality rate up to 50 percent .
Even with optimal treatment, mortality due to severe sepsis or septic shock is approximately 40 percent and can exceed 50 percent in the sickest patients
September 2005
Comparable global Epidemiology
The increased incidence of sepsis syndrome is a global phenomenon with a documented incidence between 51 – 95 cases per 100,000 in several countries.

6. SIRS SIRS – systemic inflammatory response syndrome
Must have at least 2 of the following:
Temperature >38.5ºC or <36ºC
Heart rate >90 beats/min
Respiratory rate >20 breaths/min or PaCO2 <32 mmHg
WBC >12,000 cells/mm3, <4000 cells/mm3, or >10 % immature (band) forms
SIRS is the body’s response to infection, inflammation, stress.
Definitions according to the American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM) in 1992

7. Sepsis and Severe Sepsis
Sepsis – SIRS + suspected or confirmed infection (documented via cultures or visualized via physical exam/imaging)
Severe Sepsis – Sepsis + at least one sign of organ hypo-perfusion or dysfunction
Areas of mottled skin
Disseminated intravascular coagulation
Capillary refill > 3 secs
AKI
UOP < 0.5cc/kg /hr
ARDS or acute lung injury (ALI)
Lactate > 2mmol /L
Cardiac dysfunction on echo
Altered mental status
Plt < 100
Abnormal EEG
Troponin Leak

8. Septic Shock
Septic Shock - Severe sepsis plus one of the following conditions:
MAP <60 mm Hg (<80 mm Hg if previous hypertension) after adequate fluid resuscitation
Need for vasopressors to maintain BP after fluid resuscitation
Adequate fluid resuscitation = 40 to 60 mL/kg saline solution (NS 5L- 10L)
Lactate > 4mmol /L
HIGHEST RISK OF MORTALITY

9.  26-year-old woman developed rapidly progressive shock associated with purpura and signs of meningitis.

10. Sepsis Pathogenesis
An incompletely understood pathogenesis: hallmarks are microvascular thrombosis, vasodilation, free radical damage, Capillary Leak
Unbalanced Immune Reaction
Mediators of
Inflammation
Tissue Factor
An incompletely understood pathogenesis: hallmarks are microvascular thrombosis, vasodilation, free radical damage, Capillary Leak
Procoagulant State
ROS
Microvascular
Thrombosis
Vasodilation
CapillaryLeak

12. Shock Classification, Terminology, and Staging
Hypovolemic shock results from the loss of blood volume caused by GI bleeding, extravasation of plasma, major surgery, trauma
Obstructive shock from an intrinsic or extrinsic obstruction of circulation. PE embolism and pericardial tamponade.
Distributive shock is caused by excessive vasodilation and impaired distribution of blood flow.  Patients have hyperdynamic shock with high cardiac output, hypotension.
Cardiogenic shock is caused by primary myocardial dysfunction. The patients have cool clammy extremities,

13. Clinical Manifestations.
Staging of Septic Shock:
I. Compensated / Pre-shock / Hyperdynamic
II. Decompensated / Organ hypoperfusion
III. End organ failure / Irreversible

14. Clinical Manifestations.
Recognition of Septic Shock:
Early compensated, hyperdynamiic state
Clinical signs
Warm extremities
Bounding pulses
Tachycardia Warm shock
tachypnoea
confusion
flushed skin
Decreased systemic vascular resistance

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

16. Where is infection?

17. Noninfectious mimics of sepsis
Acute myocardial infarction
Overzealous diuresis
Acute pulmonary embolus
Transfusion reactions
Acute pancreatitis
Adverse drug reactions
Fat emboli syndrome
Procedure-related transient bacteremia
Acute adrenal insufficiency
Amniotic fluid embolism
Acute gastrointestinal hemorrhage

18. Investigations
Sepsis work up:
CBC, ABG, Lactate
PCT, CRP
Metabolic panel/Electrolytes
Coagulation profile
Urine, Sputum, Blood, Stools, Throat swab
cultures
Viral cultures
Gastric aspirate/ET aspirate
CIE/Latex agglutination
Imaging:
CXR, CT, MRI, PET Scan, Echo. Ultrasound

19. Goals and principles of treatment
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 acute respiratory distress syndrome (ARDS)
Pharmacotherapy
Alpha-/beta-adrenergic agonists (eg, dopamine, dobutamine, epinephrine)
Isotonic crystalloids
Volume expanders
Antibiotics (eg, cefotaxime, piperacillin-tazobactam, ceftriaxone, ciprofloxacin, levofloxacin, vancomycin)
Corticosteroids (hydrocortisone, dexsamethasone)

20. Management Steps
Central Line Access (Fluid hydration +/- pressor)
1st line therapy – fluids, fluids, fluids!
Crystalloid equivalent to colloid
Initial 1-2 Liters (20mg /kg) crystalloid or 500 ml colloid
Careful in CHF patients !!
Establish a 2nd IV line for Dopamine infusion (Draw blood for culture)
IV antibiotics
Ampicillin +
gentamicin or
Ampicillin+ Ceftriaxone/Cefataxime
Ceftriaxone or Cefotaxime alone or
Ampicillin + Chloramphenicol

21. Correct metabolic derangement: Metabolic acidosis. Hyperglycemia
Management Steps
DIC: Restoration of normovolemia:
Reverses abnormal activation.
‘Component replacement’
(Goal - Normal PT, PTT, fibrinogen, PC = 40,000 to /cu mm.)
a. FFP - most beneficial in early stages.
b. Cryo- consider 1 unit/3 units of FFP transfused.
c. Platelet concentrate
Correct metabolic derangement:
Metabolic acidosis.
Hyperglycemia
hypoglycemia (always correct hypoglycemia)

22. Management Steps
Gastrointestinal:
Antacids, sucralfate, early enteral nutrition
Renal:
Volume replacement
Low dose dopamine
?diuretic with volume expansion
Indications for dialysis:
Hyperkalemia
Refractory metabolic acidosis
Anuria despite diuresis
BUN>100mg%
Recognize and manage organ failure: Cardiovascular support: Rate & rhythm- correct 02, acidosis, Ca, Mg, K variations Stroke volume - fluid correction & replace losses Inotrope support. Respiratory support: Supplement 02, Early intubation and PPV (PEEP)

23. Antibiotics Cultures / Antibiotics / Labs
Cultures PRIOR to Antibiotics ( 2 Sets, one peripheral and one from any line older than 48hrs)
IV Abx within 3 hrs in the ED, within 1 hr in the ICU
Broad Spectrum, combination therapy for neutropenic and patients with pseudomonas risk factors
Vancomycin PLUS Zosyn (Piperacillin and tazobactam)
Consider need for Source Control !
Drainage of abscess or cholangitis, removal of infected catheters, debridement or amputation of osteomyelitis
Stress importance of early cultures and IV antibiotics (BROAD).
Think Source control if relevant for your patient and possible need for surgery evaluation.

24. Vasopressor agents used in septic shock
Typical intravenous dose range
Dopamine
6 – 25 µg/Kg/min
Epinephrine
1 – 10 µg/min
Norepinephrine
1 – 30 µg/min
Phenylpherine
40 – 180 µg/min
Vasopressin
0.01 – 0.04 units/min

25. Corticosteroids
Use in Septic Shock, if NO response to vasopressors and fluids
HYDROCORTISONE 200mg -300mg / day Divided doses (Q6hrs)
Initial Dose 100mg IV x1
Consider for patients who received etomidate
Wean Steroids QUICKLY once off vasopressors
2 Trials
Annane et al, JAMA 2002; 228:
Corticus Trial, NEJM 2008; 358:

26. Parameters for monitoring organ system function in patients with sepsis
Respiratory system
PaO2/FiO2 ratio
Renal system
Urine output and serum creatinine
Hematologic system
Platelet count
Central nervous system
Glasgow coma score
Hepatobiliary system
Serum bilirubin and liver enzymes
Cardiovascular system
Blood pressure, arterial lactate
Gastrointestinal system
Gastric intramucosal pH (pHi), ileus, blood in nasogastric aspirate

27. Management- summary. Five important points
1. ABC, supplement 02 always.
2. IV or IO access and fluid resuscitation up to 60 mL/Kg.
3. Early dopamine
4. Empirical antibiotic.
5. Frequent monitoring.

28. THANK
YOU
FOR
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