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

2. Introduction. What is shock?
Shock is a state of acute disruption of circulatory function, resulting in insufficiency of tissue utilization and cellular energy production.
“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. Organ dysfunction at time of severe sepsis recognition

9. 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

10. 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

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

12. Pathophysiology septic shock:
Shock is as inadequate circulating blood volume producing decreased peripheral vascular perfusion and cellular metabolic derangements.
Microcirculatory hypo-perfusion is the common all types of shock.
Septic shock is caused by an immunologic reaction characterized by a hyperdynamic state, which produces increased cardiac output and decreased peripheral resistance
This reaction is secondary to endotoxin-antibody complement complexing and leukocyte lysis that results in the production of histamine, serotonin, super-radicals, lysosomal enzymes, and kinins.
These substances induce a marked capillary permeability and a third space loss, leading to hypovolemia.
This is the hypodynamic state of septic shock, which is characterized by decreased cardiac output and increased peripheral resistance.

15. What’s the infection?
Pure isolates, total n = 444 pts, 61% micro documented

16. Where’s the infection ?

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

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

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

20. 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

21. Goals and principles of treatment
Start adequate antibiotic therapy (proper dosage and spectrum) as early as possible
Resuscitate the patient, using supportive measures to correct hypoxia, hypotension, and impaired tissue oxygenation (hypoperfusion)
Identify the source of infection, and treat with antimicrobial therapy, surgery, or both (source
control)
Maintain adequate organ system function, guided by cardiovascular monitoring, and interrupt the progression to multiple organ dysfunction syndrome(MODS)

22. Management.
IV access: peripheral vein.
If IV access fails: Interosseous line.
Fluid resuscitation: 20mL/Kg NS or RL as bolus, repeat up to 60 mL/Kg.
End point : Improved
perfusion.
Two means of death: 1. Shock. 2. Multi organ failure. Aims of treatment: 1. Assure perfusion of critical vascular beds. ( cerebral, coronary, renal) 2. Rx underlying cause. Prevent / correct hypoxemia: Supplement oxygen %.

23. Management Steps Improved perfusion => a. CF b. Warmth
c. Strong pulses
d. Mental status
e. Tachycardia
f. BP (ideal = 90 + age x 2; Min = 70+ age x 2)
g. Urine output.

24. 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)
Administer IV antibiotics
Ampicillin +
gentamicin or
Ampicillin+ Ceftriaxone/Cefataxime
Ceftriaxone or Cefotaxime alone or
Ampicillin + Chloramphenicol

25. 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)

26. 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)

27. 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.

28. 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

29. 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
No need for cosyntropin stimulation test
Wean Steroids QUICKLY once off vasopressors
2 Trials
Annane et al, JAMA 2002; 228:
Corticus Trial, NEJM 2008; 358:

30. 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

31. SUMMARY AND RECOMMENDATIONS
Therapeutic priorities include securing the airway,
correcting hypoxemia, and administering fluids and
antibiotics. Intubation and mechanical ventilation are
required in some patients
Common signs of hypoperfusion include warm,
vasodilated skin in early sepsis that progresses to
cool, vasoconstricted skin in late sepsis, tachycardia
>90 per min, obtundation or restlessness, oliguria or
anuria, and lactic acidosis.
For initial fluid replacement use a crystalloid solution
rather than albumin-containing solution

32. SUMMARY AND RECOMMENDATIONS
Those who remain hypotensive following
intravascular volume repletion, use vasopressors
Prompt identification and treatment of the site of
infection are essential.
Sputum and urine should be collected for Gram stain
and culture. Intra-abdominal fluid collections
should be percutaneously sampled.
Blood should be taken from 2 distinct venipuncture
sites and from indwelling vascular access devices and
cultured aerobically and anaerobically.

33. SUMMARY AND RECOMMENDATION
Antibiotics should be administered within six
hours of presentation, preferably after
appropriate cultures have been obtained.
Empiric broad spectrum antibiotics when a definite source of infection can not be identified
Glucocorticoid therapy, nutritional support,
glucose control, and investigational therapies are
additional considerations in the management of
patients with severe sepsis or septic shock

34. 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.