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

2. Septic Shock
Septic shock- once a uniformly fatal condition with 100% mortality.
Present recovery rates are up to 50%.
Significance: Frequent occurrence and high mortality.

3. Septic Shock Introduction. II. Pathophysiology
III. Clinical Manifestations
IV. Management

4. 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 (ie, hypotension, reliance on vasoactive drug administration 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.

5. Systemic Inflammatory Response Syndrome (SIRS) Temp > 38 or < 36
Terminology
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.
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.
TWO out of four criteria
acute change from baseline

6. Infection, SIRS & Sepsis

7. Comparable global Epidemiology
SSC
Comparable global Epidemiology
September 2005
95 cases per 100,000
2 week surveillance
206 French ICUs
3 month survey
23 Australian/New Zealand ICUs
51 cases per 100,000
England, Wales and Northern Ireland.
 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
The increased incidence of sepsis syndrome is a global phenomenon with a documented incidence between 51 – 95 cases per 100,000 in several countries.

8. 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

9. 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

10. 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 pressors 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

11. 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

12. Pathophysiology The nidus of infection:
Localized infections ( otitis, pneumonia, meningitis etc.,)
Colonization of mucosal and invasion (meningococci)
Occult bacteremia ( 3mo to 3 years )
Nosocomial : ‘at risk patients’

13. Pathophysiology The Pathogen:
Neonates: GBHS, enterobacteriacae, listeria, Staph aureus, HSV.
Infants: Hib, Strep pneumoniae, Staph aureus.
Children: Strep pneumoniae, N. meningitidis, S. aureus, enterobacteriacae, Hib.
Immunocompromised: Enterobacteria, Staph, Pseudomonas, Candida.

14. Pathophysiology What ‘type of shock’ is septic shock?
Septic shock has features of :
Hypovolemic shock
Cardiac shock
Distributive shock.

15. Sepsis Pathogenesis ROS
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

16. Sepsis-induced hypotension
Severe sepsis
Severe sepsis refers to sepsis-induced tissue hypo-perfusion or organ dysfunction with any of the following thought to be due to the infection
Sepsis-induced hypotension
Lactate above upper limits of laboratory normal
Urine output <0.5 mL/kg/hr for more than two hours despite adequate fluid resuscitation
Acute lung injury with PaO2/FIO2 <250 in the absence of pneumonia as infection source
Acute lung injury with PaO2/FIO2 <200 in the presence of pneumonia as infection source
Creatinine>2 mg/dL (176.8 micromol/L)
Bilirubin>4 mg/dL (34.2 micromol/L)
Platelet count <100,000 micromol/L
Coagulopathy (INR >1.5)

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:
Inflammatory triad-
Fever
Tachycardia
flushed skin
Hypoperfusion Warm Shock
Altered sensorium
Urine output
>CFT
Wide pulse pressure....bounding pulses

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

20. Management Prevention: 1. Immunization
2. Prompt treatment of local infections
3. Hospitalized patient: look out for nidus of infection- IV lines, catheters, E. tubes

21. Management Recognize septic shock early:
Remember- Inflammatory triad Signs of hypoperfusion
Do not wait for the BP to fall !
Lower limit for systolic BP = 70 +( age x 2)

22. Management. 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.

23. Management STEPS
1. Prevent / correct hypoxemia: Supplement oxygen %.
2. IV access: peripheral vein.
3. If IV access fails: Interosseous line.
4. Fluid resuscitation: 20mL/Kg NS or RL
as bolus, repeat up to 60 mL/Kg.
End point : Improved perfusion.

24. Management STEPS Improved perfusion => a. CFT 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.

25. Management STEPS
5. Establish a 2nd IV line for Dopamine infusion (Draw blood for culture)
6. Administer IV antibiotics
<2 mo: Ampicillin + gentamicin
or Ampicillin+ Ceftriaxone/Cefataxime
>2mo: Ceftriaxone or Cefotaxime alone or
Ampicillin + Chloramphenicol

26. Fluid therapy 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 !!

27. Management STEPS Metabolic acidosis.
7. Correct metabolic derangement:
Metabolic acidosis.
Hyper or hypoglycemia : always correct hypoglycemia.

28. Management STEPS
8. 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

29. Management STEPS 9. Recognize and manage organ failure:
a. Cardiovascular support:
Rate & rhythm- correct 02, acidosis, Ca, Mg, K variations
Stroke volume - fluid correction & replace losses
Inotrope support.

30. Management STEPS 9. Recognize and manage organ failure:
b. Renal: Volume replacement
Low dose dopamine
?diuretic with volume expansion
Indications for dialysis:
Hyperkalemia
Refractory metabolic acidosis
Anuria despite diuresis
BUN>100mg%

31. Management STEPS 9. Recognize and manage organ failure:
c. Respiratory support:
Supplement 02,
Early intubation and PPV ( PEEP)
d. GI: Antacids, sucralfate, early enteral nutrition.

32. 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
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.

33. 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 pressors
2 Trials
Annane et al, JAMA 2002; 228:
Corticus Trial, NEJM 2008; 358:

34. 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

35. 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.

36. 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 usea crystalloid solution rather than albumin-containing solution
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 two distinct venipuncture sites and from indwelling vascular access devices and cultured aerobically and anaerobically.

37. SUMMARY AND RECOMMENDATIONS
Severe sepsis and septic shock that are refractory to intravenous fluid and vasopressor + notropic therapy and blood transfusions, are administered based on individual assessment. Blood transfusion for patients with a hemoglobin level <7 g per deciliter.
Antibiotics should be administered within six hours of presentation, preferably after appropriate cultures have been obtained. We recommend empiric broad spectrum antibiotics when a definite source of infection can not be identified
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

38. KEY TAKE HOME POINTS Recongnize Sepsis EARLY and determine SEVERITY
EARLY Antibiotics are critical to resolution of shock
RESUSCITATE severe sepsis and septic shock ASAP
EARLY GOAL DIRECTED THERAPY