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Author: Dr. Lipeeka Parulekar,  MD (Gen. Med)

Sepsis, severe sepsis and septic shock are terms used to describe the body’s systemic response to infection.

Severe sepsis is one of the most important causes of morbidity, increased length of hospitalization as well as death at healthcare setups. An infection that is getting worse and is not treated can lead to sepsis. Health   care   providers   should   take   opportunities to prevent, identify and rapidly treat patients with sepsis. The mortality rate from sepsis is as high as between 15% and 30%.

The consensus committee of American experts developed a set of definitions in 1992.They proposed that even early systemic responses to infection, such as tachycardia, leukocytosis and fever are inflammatory and maybe used to define a systemic inflammatory response syndrome (SIRS). This definition has been arrived by applying a clinical and laboratory findings to a likely framework of pathogenesis.

Therefore SIRS is an abnormal generalized inflammatory reaction in organs remote from the initial insult.(1) When it occurs in patients with proven or suspected infection,SIRS is called sepsis. If sepsis is associated with hypotension or dysfunction of organs distant to the site of infection, it is known as Severe Sepsis. When sepsis is associated with hypotension and lactic acidosis or organ hypo perfusion and cannot be  reversed  by  the  administration  of  intravenous fluids it is Septic Shock.

Sepsis is a clinical syndrome caused by the body’s immune and coagulation systems being switched on by the presence of an infection (bacteria, viruses or fungi).


Term Definition Comment
Infection Presence of microorganism in a normally sterile site
Bacteremia Cultivable bacteria in the bloodstream Maybe transient;  inconsistent correlation with severe sepsis
Systemic inflammatory response syndrome Temp>38C/<36C Heart rate>96/m RR>20/min PaCo2<32mmHg WBC>12,000/<4000 cells/mm3>10%band  form
Sepsis The systemic response to infection. SIRS is called sepsis if proven or clinically suspected infection. With exception of leukopenia and hypothermia,  these changes are among the body’s normal systemic responses to infection.
Severe Sepsis Sepsis associated with organ dysfunction,  distant from the site of infection, hypoperfusion and hypotension Associated with lactic acidosis, oliguria, altered mental status and acute lung injury.  Hypotension should be reversible  by the administration  of fluids
Septic Shock Sepsis with hypotension that despite fluid resuscitation requires pressor therapy Septic Shock lasting >1 hour and does not respond to pressor administration  is referred to as Refractory  septic shock


The pathogenetic mechanism and physiologic changes associated with sepsis are exceedingly complex, but our understanding is evolving rapidly. The major pathophysiologic changes in patients with sepsis appears to be a disorder of tissue metabolism in which altered microcirculation and diffuse endothelial injury are the important factors .In addition there is an associated neuroendocrine derangement as tissue microcirculation is regulated via peripheral nerves and circulating hormones.

When bacterial pathogens invade previously healthy tissue, they initiate an extravascular tissue infection that activates local inflammation and may enhance systemic anti- inflammatory responses.The inability of local responses to kill the bacteria, triggers bacteremia and mediators of sepsis and septic shock.

On  the  other  hand,  microbes  can  invade  healthy people and cause bacteremia without eliciting extravascular inflammation and therefore  escape local innate immune defenses.If circulating antibody or complement are unable to contain them,these microbes can infect vascular endothelial cells  or  circulating  blood  cells  and  release  endotoxins that stimulate inflammation within the blood and various organs.The circulating microbes provoke both shock and profound coagulopathy that can result in hemorrhage or arterial thrombosis,or both.Examples include N.meningitis and Rickettsia rickettsii.Therefore the absence of an early proinflammatory host defense is an important key to their pathogenesis.

These  pathophysiologic  changes  play  a  central  role in the management of sepsis. The early management of patients with severe  sepsis and septic shock centers on the administration of antibiotics, IV fluids, and vasoactive agents, followed by source control. However, the specific approach to the resuscitation of patients with septic shock remains controversial.

Clinical Features

  1. Fever, hypothermia, tachycardia, tachypnea.
  2. Acute   Lung   Injury:   Hyper-ventilation   with respiratory alkalosiscan be an early manifestation of sepsis. A combination of arterial hypoxemia (PaO2/ FiO2<300) and bilateral pulmonary infiltrates on the chest radiograph in the absence of pneumonia or heart failure is indicative of Acute Lung Injury. When hypoxemia is severe (PaO2/FiO2<200), it is termed Acute Respiratory Distress Syndrome.
  3. Renal  Dysfunction:  Severe  sepsis  is  often accompanied by azotemia and oliguria. Hypotension can be followed by oliguria and may resolve with fluid resuscitation.
  4. Hepatic dysfunction: Sepsis may cause cholestatic jaundice characterized by elevations in conjugated and unconjugated bilirubin.There may be an elevation of the bilirubin, alkaline phosphatase, bilirubin and amino transferase levels.
  5. Mild cognitive derangement with confusion and altered cerebral functions especially in the elderly may be early manifestations of severe sepsis.Focal seizures and cranial nerve palsies and signs of encephalopathy are associated with poor prognosis.
  6. The systolic arterial blood pressure <90 mmHg or a mean arterial BP <60 mmHg or a fall of >40 mmHg below the baseline is significant.
  7. Cutaneous  Manifestations:  Wide  range  of  skin lesions can occur with severe sepsis. Hematogenous seeding of the skin or underlying soft tissue which could be petechiae, pustules, ecthyma gangrenosum (necrotic blister), cellulitis, diffuse eruptions caused by blood borne toxins and hemorrhagic or necrotic eruptions.
  8. Evidence of poor tissue perfusion determined by lactic acidosis, sudden fall in the urine output and dysfunction of one or more organs
  9. Any onset of sudden tachypnea, presence of icterus, changes in the mental state due to hypoper fusion and metabolic changes or presence of purpura or bleeding point to early organ dysfunction and may precede hypotension.

Laboratory Features

Lecopenia or Leukocytosis

Coagulation may show Elevated Prothrombin Time, decreased platelet count, decreased fibrinogen increased Fibrinogen degradation products and increased prothrombin index which may be evidence of early disseminated intravascular coagulopathy. Thrombocytopenia may often occur without frank DIC

Sudden rise of serum glucose levels should also indicate impending sepsis, whereas hypoglycemia, raised serum bilirubin, rising serum amino transferases and alkaline phosphatases indicates hepatic dysfunction due to sepsis.

Principles of Management

  1. Identify the focus of infection.
  2. Start appropriate antibiotic after collection of blood for cultures. Invasive treatment of infection, eg. drainage of pus.
  3. Restore altered hemodynamics
    1. Volume PCWP >15 mmHg
    2. Inotropic support Noradrenaline, Dopamine,Restore altered hemodynamics dobutamine
    3. Non Invasive or Mechanical Ventilation
  4. Provide  nutritional  support  either  by  enteral  or parenteral route
  5. Metabolic support eg: correction of acidosis, blood sugar levels, electrolytes
  6. Prophylaxis for DVT and stress ulcers need to be given.

2012 Recommendation for Initial Resuscitation

During the first 6 hours of resuscitation, the goals of initial resuscitation should include all of the follow i n g as  a  part  of  a  treatment protocol:

  1. CVP 8–12 mm Hg
  2. MAP ≥ 65 mm Hg
  3. Urine output ≥ 5 mL/kg/hr
  4. Scvo2 ≥ 70%

Fluid resuscitation is the mainstay of hemodynamic support in patients with septic shock. Crystalloid is generally preferred over colloid. A reasonable aim is maintenance of mean arterial pressure of 60 mmHg. In most patients 4-6 litres of fluid is required.

A   Central   venous   catheter maybe useful for monitoring volume status,cardiac output, mixed venous oxygen saturation (Svo2). Svo2 can be used  assess  the adequacy of oxygen delivery. Values <70% suggest decreased systemic perfusion. Recent  studies  suggest that patients who received initial fluid, blood transfusion and pressor therapy  as  well  as  aggressively titrated to maintain a Svo2 >70% had significantly better survival than patients who received conventional resuscitation in an ICU.

Fig. 2: This figure explores the nuancing of initial administration of 30 ml/kg crystalloid for sepsis induced hypoperfusion based on patient characteristics. It also draws attention to reassessment tools following the initial fluid dose as an influence on further fluid administration or inotropic therapy.

Dopamine was considered as the drug of choice for restoring normotension in patients with septic shock. When used at low doses that is (<5mic/kg/min), it’s interaction with dopaminergic receptors was thought to produce renal and splanchnic vasodilation. However, recent trials have found that low dose dopamine infusion did not have any advantage for improved survival or prevention of renal failure in critically ill patients.(4)

Other Therapies

Recent  studies  suggest  a  potential  benefit of  a  trial of hydrocortisone (50-100mg) every 6 to 8 hourly intravenously in pressor dependent patients with septic shock. If there is a positive response (ability to maintain MAP of >65 mmHg without pressors) within the first

24 hours of the first dose of hydrocortisone, then it should be continued for 7 days.(5)

Avoiding hyperglycemia may prevent infection and sepsis in critically ill patients.

Nutritional and other supportive measures.

Enteral nutrition is supported by numerous studies. Prophylaxis for GI bleeding,deep vein thrombosis and decubitus ulcers should be a part of care in critically ill patients.

Prevention of Secondary Infections.

The risk of nosocomial pneumonia is highest in patients  who  have  received  mechanical  ventilation for longer than one week. A semirecumbent position reduces the risk the risk for nosocomial pneumonia, especially in patients who receive enteral nutrition.

It is also important to maintain an adequate intracuff pressure to prevent aspiration pneumonia.

Regular handwashing as well as barrier precautions while examining patients colonized with resistant bacteria reduces the risk of acquiring as well as transmitting Hospital Acquired Infections.


Severe sepsis and septic shock are associated with high mortality.The outcome is significantly influenced by the patients underlying disease. Prognostic scores based on bedside evaluations such as APACHE II and the Sequential Organ Assessments (SOFA) are more appropriate in the usual ICU settings and should be made a part of the critical care setup protocols.(6)


  1. American  College  of  Chest  Physicians  /  Society of Critical Care Medicine Consensus Conference Committee. Crt Care Med 1992:20:864-874
  2. Leroy  E.M.,   Baize S Volchkov V.E.,  etal.  Lancet 200; 355:2210-2215.
  3. Rivers E.,  Nguyen B., Havstad S.,  et al: Early goal directed therapy in the treatment of severe sepsis and septic shock. N Eng J Med. 2001; 345:1368-1377.
  4. Doughtery S.H.,  Flohr A.B., Simmons R.L. Break through enterococcal septicemia in surgical patients. Arch Surg. 1983; 118:232-238.
  5. Marik P.E.,  Zaloga GP, Adrenal insufficiency during septic shock. Crit  Care  Med. 2003; 31:141-145.
  6. Vincent J.L.,  deMendonca A,  Cantraine  F.,  et al. Use of the SOFA score to assess the incident of organ dysfunction /  failure in intensive care units:  Result of a multicenter, prospective study. Crit Care Med.1998; 26:1793-1800.