Sepsis

Sepsis is one of the leading causes of death worldwide but remains a little-known entity to the general public. Every year, around 245,000 people in the UK develop sepsis, and of those, over 48,000 die. The incidence of sepsis in the developed world is increasing by an alarming rate of 8-13% per year. It is now a commoner diagnosis than myocardial infarction and claims more lives annually than breast and bowel cancer combined. Sepsis is one of the most important and challenging problems facing the modern physician.

 

What is sepsis?

Sepsis occurs when the body’s response to an infection injures its own tissues and organs. It may lead to shock, multiple organ failure, and death, especially if not recognised early and treated promptly. A wide variety of infectious agents can cause it.  However, the vast majority of cases are caused by bacteria commonly encountered by most people on a day-to-day basis. It remains the primary cause of death from infection despite advances in modern medicine, including vaccines, antibiotics, and acute care, with hospital mortality rates between 30 and 60%.

Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection.” 

Septic shock is “a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to increase mortality.”

 

In essence, this means that septic shock is sepsis plus the following, despite adequate fluid resuscitation:

• Vasopressors required to maintain a MAP > 65 mmHg
• Serum lactate > 2 mmol/l

 

The Surviving Sepsis Campaign

The surviving sepsis campaign is a joint collaboration between the Society of Critical Care Medicine and the European Society of Intensive Care. It was initiated in 2002, and the first set of guidelines was published in 2004. In 2021, the guidelines were updated, including some notable changes from previous versions.

Initial recognition and response

Sepsis can present without fever and often with non-specific symptoms, especially in:

• Older adults
• Very young children
• Immunocompromised individuals
• Pregnant patients
• Patients with recent surgery, trauma, or indwelling devices

 

Always maintain a high index of suspicion in patients with signs of infection, particularly when presenting with hypotension, altered mental status, elevated respiratory rate or abnormal laboratory markers (e.g. high lactate, rising creatinine).

Key point: If in doubt, initiate treatment and escalate care early.

 

Initial resuscitation

Resuscitation should be started as soon as sepsis or septic shock is recognised.

Fluid resuscitation:

• Administer at least 30 mL/kg of IV crystalloid within the first 3 hours for patients with sepsis-induced hypoperfusion or elevated lactate.
• Use balanced crystalloids (e.g. Hartmann’s or Plasma-Lyte) over normal saline to reduce the risk of hyperchloraemic acidosis.
• Avoid starch-based fluids.
• Consider adding albumin if large volumes of crystalloids are required and the patient remains hypotensive.

 

Fluid responsiveness and monitoring

• Use dynamic indicators of fluid responsiveness (e.g. stroke volume variation, passive leg raise and capillary refill time) over static measures like central venous pressure (CVP).
• Aim to reduce elevated lactate levels, which serve as a marker of tissue hypoperfusion.
• Capillary refill time is recommended as an adjunct to guide resuscitation in adults with septic shock.

 

Mean arterial pressure (MAP):

• Target an initial MAP ≥65 mmHg in patients requiring vasopressors.
• Use invasive arterial blood pressure monitoring when available, and start as soon as practical.
• If hypotension persists despite fluids, initiate vasopressors without delay.

 

 

Vasopressor therapy

First-line agent: 

• Noradrenaline – should be used to restore and maintain adequate MAP.

 

If MAP remains low:

• Add vasopressin (up to 0.03 units/min) rather than escalating norepinephrine.
• If still refractory, add adrenaline.

 

In patients with cardiac dysfunction and persistent hypoperfusion despite adequate MAP:

• Consider dobutamine or epinephrine alone.

 

Terlipressin and levosimendan should be avoided in septic shock.

Key point: Peripheral administration of vasopressors can be initiated if central access is not yet available but should be switched to central lines as soon as possible.

 

Antimicrobial therapy

Timing and selection:

• In patients with possible septic shock or a high likelihood of sepsis, administer broad-spectrum antimicrobials within 1 hour of recognition.
• In patients with possible sepsis without shock, perform a rapid assessment to determine the likelihood of infection:
• If infection is still suspected, administer antimicrobials within 3 hours.
• If there is a low suspicion of infection and no shock, defer antibiotics but closely monitor.

 

Empirical coverage:

• Choose broad-spectrum agents that cover likely pathogens based on:
• Source of infection
• Local resistance patterns
• Patient risk factors (e.g. recent hospitalisation, immunosuppression)
• Cover MRSA empirically in high-risk patients
• For patients at risk of multidrug-resistant (MDR) organisms, consider two antimicrobials with Gram-negative coverage.
• Avoid double Gram-negative coverage once susceptibilities are known.

 

Special situations:

• In patients at high risk of fungal infection, empiric antifungal therapy is recommended.
• In patients at low risk of fungal infection, avoid empiric antifungal therapy.
• No firm recommendation on antiviral therapy due to insufficient evidence.

 

Antibiotic stewardship and source control:

• Perform daily assessment of the need for ongoing antibiotics and de-escalate as appropriate.
• Use shorter courses of therapy in patients with adequate source control and clinical improvement.
• If the optimal duration of therapy is uncertain, use procalcitonin with clinical judgment to guide discontinuation.
• Promptly identify and treat the source of infection, including surgical or interventional source control.
• Remove any intravascular devices that may be the source of infection once alternate access is secured.

 

Intensive Care Unit (ICU) admission

Rapid ICU admission is vital for patients in septic shock:

• Patients with sepsis or septic shock who require organ support should be admitted to ICU within 6 hours of recognition.
• Early ICU admission improves survival, particularly when there is evidence of ongoing shock, respiratory failure, or deteriorating organ function.

 

Respiratory support and ARDS management

In adults with sepsis-induced hypoxaemia, consider high-flow nasal oxygen (HFNO) over non-invasive ventilation (NIV).

For sepsis-induced ARDS:

• Use low tidal volume ventilation (6 mL/kg) of predicted body weight
• Maintain plateau pressure ≤30 cm H₂O
• Use higher levels of PEEP in moderate-to-severe ARDS
• Prone positioning for ≥12 hours/day in moderate-to-severe ARDS is recommended
• Use intermittent NMBA boluses instead of continuous infusions
• Avoid routine use of recruitment manoeuvres; do not use incremental PEEP strategies
• Consider VV-ECMO in centres with expertise for refractory cases

 

Additional therapeutic measures

Corticosteroids:

• Use IV corticosteroids (e.g. hydrocortisone 200 mg/day) in septic shock patients requiring vasopressors who remain hypotensive despite fluid resuscitation.

 

Renal replacement therapy (RRT):

• Use either continuous or intermittent RRT as clinically appropriate.
• Do not initiate RRT without a clear indication (e.g. fluid overload, severe acidosis, electrolyte disturbances).

 

Blood glucose management:

• Initiate insulin therapy when blood glucose is ≥10 mmol/L (180 mg/dL), targeting ≤10 mmol/L.

 

Gastrointestinal protection:

• Provide stress ulcer prophylaxis in patients at risk (e.g. mechanical ventilation, coagulopathy).

 

VTE prophylaxis:

• Use low molecular weight heparin (LMWH) unless contraindicated.
• Do not add mechanical VTE prophylaxis to pharmacological prophylaxis unless pharmacological prophylaxis is contraindicated.

 

Nutrition:

• Initiate enteral nutrition within 72 hours in patients who can be fed enterally.

 

Think sepsis: The clinical mindset:

• Always consider sepsis in patients with new-onset deterioration and possible infection.
• Remember, sepsis can present subtly and is frequently missed in its early stages.
• Act immediately with fluids and antibiotics.
• Escalate care if unsure.
• Awareness and early intervention save lives.

 

Reference:

Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2021. Intensive Care Med. 2021;47(11):1181–1247.

 

Header image used on licence from Shutterstock

Thank you to the joint editorial team of MRCEM Exam Prep for this article.