Sepsis, causes and management

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Sepsis is a clinical syndrome characterised by systemic inflammation (SIRS) due to infection. Although inflammation is an essential and beneficial host response, sepsis involves a dysregulation of the normal inflammatory process. The result is an uncontrolled release of pro-inflammatory mediators that, coupled with the release of bacterial toxins, induce widespread tissue injury. As this process invariably occurs within the vasculature, most of the damage is to the endothelium. The endothelium is not a passive surface, and is widely involved in maintenance of circulating volume and in coagulation and fibrinolysis.

A spectrum of clinical disease follows: when the infection produces multiple systemic symptoms, such as fever and increased respiratory or heart rate, the syndrome is referred to as sepsis; if the systemic response to infection progresses and causes evidence of organ dysfunction distant from the site of infection, patients are classified as having severe sepsis; septic shock is defined as severe organ dysfunction with hypotension or hypoperfusion not responsive to initial fluid resuscitation.

As sepsis progresses to septic shock, the risk of dying increases substantially. Where sepsis is usually reversible with early appropriate therapy, patients with septic shock have a mortality of 40 – 60% despite aggressive therapy.

Sepsis is a major challenge in hospitals, where it’s one of the leading causes of death. It’s also a main reason why people are readmitted to the hospital. Sepsis occurs unpredictably and can progress rapidly.

What causes sepsis?

Many types of microbes can cause sepsis, including bacteria, fungi, and viruses. However, bacteria are the most common cause.

Severe cases of sepsis often result from a body-wide infection that spreads through the bloodstream. In some cases, bloodstream infection cannot be detected, and doctors use other information such as body temperature and mental status to diagnose sepsis.

Sepsis often results from infections to the lungs, stomach, kidneys, or bladder. It’s possible for sepsis to begin with a small cut that gets infected or an infection that develops after surgery. Sometimes, sepsis can occur in people who didn’t know that they had an infection.

Risk factors

Anyone is at risk for sepsis. People who are at higher risk for sepsis include:

  • The elderly
  • People with diabetes
  • People on dialysis for kidney failure
  • People who have cancer, especially those getting chemotherapy
  • People who have had an organ transplant
  • People who have a weakened immune system or are taking medications that affect the immune system
  • People with severe or hard-to-treat infections on long-term antibiotics
  • People with severe burns or skin disorders
  • Anyone who has a history of sepsis in the past

Clinical manifestations of the septic response

Clinical manifestations are nonspecific and usually superimposed on the symptoms and signs of the patient’s underlying illness and primary infection. There are striking individual variations in presentation and the rate at which symptoms develop may differ from patient to patient.

Patients usually present with fever or hypothermia. A normal temperature on presentation is uncommon but may occur in neonates, the elderly, alcoholics and the severely immunosuppressed.

Early symptoms and signs may include hyperventilation and sometimes confusion or disorientation. Signs of encephalopathy are more common in the elderly and in individuals with preexisting neurological disorders. Focal neurological deficits are not usually a feature of sepsis, but existing deficits may become more prominent in the septic patient.


On occasion, skin lesions that suggest a specific pathogenic aetiology may be present at the sites of haematogenous seeding of organisms and/or toxins to the skin

Nausea, vomiting, diarrhoea and ileus are usually nonspecific manifestations of the septic response, but may suggest acute gastroenteritis as primary infection.


Early in the course of sepsis, increasing alveolar capillary permeability causes increased pulmonary water content, which interferes with oxygen exchange and results in ventilation perfusion mismatching and a fall in PO2. Progressive diffuse pulmonary infiltrates and arterial hypoxaemia (PaO2/FIO2 <200) indicate the development of ARDS. Failure (fatigue) of respiratory muscles further exacerbates hypoxaemia and hypercapnia. ARDS must be differentiated from fluid overload, cardiac failure, viral pneumonitis and pneumocystis pneumonia.

Sepsis-induced hypotension develops from general microcirculatory maldistribution of blood flow and blood volume, and from hypovolaemia due to capillary leakage of intravascular fluid. Dehydration secondary to insensible fluid losses, diarrhoea, vomiting and polyuria also contribute.

During early septic shock systemic vascular resistance is usually elevated and cardiac output decreased. After fluid repletion, cardiac output typically increases, but systemic vascular resistance falls. Increased or normal cardiac output and decreased systemic vascular resistance is the hallmark of septic shock. Other conditions that may cause this combination include anaphylaxis, liver cirrhosis, and an overdose of narcotics.

Depressed myocardial function (low ejection fraction) develops within 24 hours in most patients with severe sepsis. Cardiac output is, however, maintained because ventricular dilatation permits a normal stroke volume. Although myocardial dysfunction may contribute to hypotension, refractory hypotension is usually due to the low systemic vascular resistance.

Decreased urinary output is often present, but some patients may be inappropriately polyuric. Renal failure is usually due to acute tubular necrosis (ATN), induced by hypotension or capillary injury. ATN may be aggravated by giving hypovolaemic patients aminoglycoside antibiotics.

How is sepsis diagnosed?

Doctors will start by checking for the symptoms mentioned above. They may also test the person’s blood for an abnormal number of white blood cells or the presence of bacteria or other infectious agents. Doctors may also use a chest X-ray or a CT scan to locate an infection.

How is sepsis treated?

Doctors typically treat people with sepsis in hospital intensive care units. Doctors try to stop the infection, protect the vital organs, and prevent a drop in blood pressure. This almost always includes the use of antibiotic medications and fluids. More seriously affected patients might need a breathing tube, kidney dialysis, or surgery to remove an infection. Despite years of research, scientists have not yet developed a medicine that specifically targets the aggressive immune response seen with sepsis.

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