Sepsis

Sepsis is a condition where the body launches a large immune response to an infection that causes systemic inflammation and affects the functioning of the organs of the body.

 

Pathophysiology

The bacteria or other pathogens are recognised by macrophageslymphocytes and mast cells. These cells release vast amounts of cytokines like interleukins and tumor necrosis factor to alert the immune system of an invader. These cytokines activate other parts of the immune system. This immune activation leads to further release of chemicals such as nitrous oxide that causes vasodilation. This full immune response causes inflammation throughout the body.

Many of these cytokines cause the endothelial lining of blood vessels to become more permeable. This causes fluid to leak out of the blood and in to the extracellular space leading to oedema and a reduction in intravascular volume. The oedema around blood vessels creates a space between the blood and the tissues reducing the amount of oxygen that reaches the tissues.

Activation of the coagulation system leads to deposition of fibrin throughout the circulation further compromising organ and tissue perfusion. It also leads to consumption of platelets and clotting factors as they are being used up to form the clots within the circulatory system. This leads to thrombocytopeniahaemorrhages and an inability to form clots and stop bleeding. This is called disseminated intravascular coagulopathy (DIC).

Blood lactate rises due to hypoperfusion of tissues that starves the tissues of oxygen causing them to switch to anaerobic respiration. A waste product of anaerobic respiration is lactate.

 

Septic Shock

Septic shock is defined when arterial blood pressure drops and results in organ hypo-perfusion. This leads to a rise in blood lactate as the organs begin anaerobic respiration. This can be measured as either:

  • Systolic blood pressure less than 90 despite fluid resuscitation
  • Hyperlactaemia (lactate > 4 mmol/L)

This should be treated aggressively with IV fluids to improve the blood pressure and the tissue perfusion. If IV fluid boluses don’t improve the blood pressure and lactate level then they should be escalated to high dependency or intensive care where they can use medication called inotropes (such as noradrenalin) that help stimulate the cardiovascular system and improve blood pressure and tissue perfusion.

 

Severe Sepsis

Severe sepsis is defined when sepsis is present and results in organ dysfunction, for example:

  • Hypoxia
  • Oliguria
  • Acute Kidney Injury
  • Thrombocytopenia
  • Coagulation dysfunction
  • Hypotension
  • Hyperlactaemia (> 2 mmol/L)

 

Risk Factors

Any condition that impacts the immune system or makes the patient more frail or prone to infection is a risk factor for developing sepsis:

  • Very young or old patients (under 1 or over 75 years)
  • Chronic conditions such as COPD and diabetes
  • Chemotherapy, immunosuppressants or steroids
  • Surgery or recent trauma or burns
  • Pregnancy or peripartum
  • Indwelling medical devices such as catheters or central lines

 

Presentation

The National Early Warning Score (NEWS) is used in the UK to pick up the signs of sepsis. This involves checking physical observations and their consciousness level:

  • Temperature
  • Heart rate
  • Respiratory rate
  • Oxygen saturations
  • Blood pressure
  • Consciousness level

Other signs on examination:

  • Signs of potential sources such as cellulitis, discharge from a wound, cough or dysuria
  • Non-blanching rash can indicate meningococcal septicaemia
  • Reduced urine output
  • Mottled skin
  • Cyanosis
  • Arrhythmias such as new onset atrial fibrillation

There are a few key points worth being aware of:

  • High respiratory rate (tachypnoea) is often the first sign of sepsis
  • Elderly patients often present with confusion or drowsiness or simply “off legs”
  • Neutropenic or immunosuppressed patients may have normal observations and temperature despite being life threatening unwell

 

Investigations

Arrange blood tests for patients with suspected sepsis:

  • Full blood count to assess cell count including white cells and neutrophils
  • U&Es to assess kidney function and for acute kidney injury
  • LFTs to assess liver function and for possible source of infection
  • CRP to assess inflammation
  • Clotting to assess for disseminated intravascular coagulopathy (DIC)
  • Blood cultures to assess for bacteraemia
  • Blood gas to assess lactate, pH and glucose

Additional investigations can be helpful in locating the source of the infection:

  • Urine dipstick and culture
  • Chest xray
  • CT scan if intra-abdominal infection or abscess is suspected
  • Lumbar puncture for meningitis or encephalitis

 

Management

Every hospital will have a sepsis protocol and pathway that should be followed for patients with presumed sepsis.

NICE recommend risk stratifying patients into low, medium and high risk based on their presentation. High risk patients need urgent attention and management. Moderate risk patients may be managed in the community where the diagnosis is clear and it is safe to do so. Always remember safety-netting advice when managing patients in the community and giving clear instructions about when they need to seek help.

Patients should be assessed and treatment initiated within 1 hour of presenting with suspected sepsis. This involves performing the sepsis six. This involves three tests and three treatments.

Patients should also be escalated to the senior decision maker and the appropriate level of care such as HDU or ICU if needed.

  

Sepsis Six

Three Tests:

  • Blood lactate level
  • Blood cultures
  • Urine output

Three Treatments:

  • Oxygen to maintain oxygen saturations 94-98% (or 88-92% in COPD)
  • Empirical broad spectrum antibiotics
  • IV fluids

 

Neutropenic Sepsis

Neutropenic sepsis is a very important medical emergency. It is sepsis in a patient with a low neutrophil count of less than 1 x 109/L.

Low neutrophil counts are usually the consequence of anti-cancer or immunosuppressant treatment. Medication that may cause neutropenia include:

  • Anti-cancer chemotherapy
  • Clozapine (schizophrenia)
  • Hydroxychloroquine (rheumatoid arthritis)
  • Methotrexate (rheumatoid arthritis)
  • Sulfasalazine (rheumatoid arthritis)
  • Carbimazole (hyperthyroidism)
  • Quinine (malaria)
  • Infliximab (monoclonal antibody use for immunosuppression)
  • Rituximab (monoclonal antibody use for immunosuppression)

Have a low threshold for suspecting neutropenic sepsis in patients taking immunosuppressants or medications that may cause neutropenia. Treat any temperature above 38C as neutropenic sepsis in these patients until proven otherwise. They are at high risk of death from sepsis as their immune system cannot adequately fight the infection. They need emergency admission and careful management.

Each local hospital will have a neutropenic sepsis policy. Treatment is with immediate broad spectrum antibiotics such as piperacillin with tazobactam (tazocin). The other aspects of management are essentially the same as for sepsis however extra precaution needs to be taken. Time is precious so don’t delay antibiotics while waiting for investigation results.

 

Last updated March 2019
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