Sepsis is one of the leading causes of death worldwide but remains a little known entity to the general public. Every year, around 150,000 people in the UK develop sepsis and, of those, over 40,000 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 arises 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 recognized early and treated promptly. It can be caused by a wide variety of infectious agents, but the vast majority of cases are caused by bacteria that are 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%.

 

The definition of sepsis is that it is “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. Recently in 2021, an updated version of the guidelines was released, and they included some notable changes from previous versions.

The key aspects of the current surviving sepsis recommendations are summarised below:

 

Initial resuscitation:

  • Sepsis and septic shock are medical emergencies, and treatment and resuscitation should begin immediately.
  • In the resuscitation of patients with sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid should be given within the first 3 hours.
  • Dynamic over static variables should be used to predict fluid responsiveness, where available.
  • Resuscitation should aim to decrease lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion.
  • The use of capillary refill time to guide resuscitation as an adjunct to other measures of perfusion is recommended for adults in septic shock. (New recommendation)

 

Mean arterial pressure:

  • An initial target mean arterial pressure (MAP) of 65 mm Hg is recommended in patients with septic shock requiring vasopressors.

 

Admission to intensive care:

  • Admission within 6 hours is recommended for adults with sepsis or septic shock requiring ICU admission.

 

Infection:

  • For adults with suspected sepsis or septic shock but unconfirmed infection, continuous re-evaluation and searching for alternative diagnoses is recommended. Empiric antimicrobials should be discontinued if an alternative cause of illness is demonstrated or strongly suspected.
  • For adults with possible septic shock or a high likelihood for sepsis, it is recommended that antimicrobials are administered immediately, ideally within 1 hour of recognition.
  • For adults with possible sepsis without shock, rapid assessment of the likelihood of infectious versus non-infectious causes of acute illness is recommended.
  • For adults with possible sepsis without shock, a time-limited course of rapid investigation is recommended, and if concern for infection persists, the administration of antimicrobials should occur within 3 hours from the time when sepsis was first recognised. (New recommendation)
  • For adults with a low likelihood of infection and without shock, deferring antimicrobials while continuing to closely monitor the patient is suggested. (New recommendation)
  • For adults with suspected sepsis or septic shock, the guidelines suggest against using procalcitonin plus clinical evaluation to decide when to start antimicrobials, as compared to clinical evaluation alone.
  • For adults with sepsis or septic shock at high risk of MRSA, the use of empiric antimicrobials with MRSA coverage over using antimicrobials without MRSA coverage is recommended. (New recommendation)
  • For adults with sepsis or septic shock and high risk for multidrug-resistant (MDR) organisms, the use of two antimicrobials with gram-negative coverage for empiric treatment over one gram-negative agent is suggested.
  • For adults with sepsis or septic shock and low risk for multidrug-resistant (MDR) organisms, using two gram-negative agents for empiric treatment, as compared to one gram-negative agent, is suggested.
  • For adults with sepsis or septic shock, using double gram-negative coverage once the causative pathogen and the susceptibilities are known is not recommended.
  • For adults with sepsis or septic shock at high risk of fungal infection, the use of empiric antifungal therapy over no antifungal therapy is suggested. (New recommendation)
  • For adults with sepsis or septic shock at low risk of fungal infection, the empiric use of antifungal therapy is not suggested. (New recommendation)
  • No recommendation is made on the use of antiviral agents.
  • For adults with sepsis or septic shock, the use of a prolonged infusion of beta-lactams for maintenance (after an initial bolus) over conventional bolus infusion is recommended.
  • For adults with sepsis or septic shock, the guidelines recommend optimising dosing strategies of antimicrobials based on accepted pharmacokinetic/pharmacodynamic (PK/PD) principles and specific drug properties.
  • For adults with sepsis or septic shock, the guidelines recommend rapidly identifying or excluding a specific anatomical diagnosis of infection that requires emergent source control and implementing any required source control intervention as soon as medically and logistically practical.
  • For adults with sepsis or septic shock, the prompt removal of intravascular access devices that are a possible source of sepsis or septic shock after other vascular access has been established is recommended.
  • For adults with sepsis or septic shock, the guidelines suggest daily assessment for de-escalation of antimicrobials over using fixed durations of therapy without daily reassessment for de-escalation.
  • For adults with an initial diagnosis of sepsis or septic shock and adequate source control, the guidelines suggest using a shorter over a longer duration of antimicrobial therapy.
  • For adults with an initial diagnosis of sepsis or septic shock and adequate source control where the optimal duration of therapy is unclear, the guidelines suggest using procalcitonin AND clinical evaluation to decide when to discontinue antimicrobials over clinical evaluation alone.

 

Haemodynamic management:

  • For adults with sepsis or septic shock, crystalloids are recommended as the first-line fluid for resuscitation.
  • For adults with sepsis or septic shock, the guidelines suggest using balanced crystalloids instead of normal saline for resuscitation.
  • For adults with sepsis or septic shock, the guidelines suggest using albumin in patients who received large volumes of crystalloids.
  • For adults with sepsis or septic shock, the guidelines recommend against using starches for resuscitation.
  • For adults with septic shock, it is recommended that norepinephrine (noradrenaline) is used as the first-line agent over other vasopressors.
  • For adults with septic shock on norepinephrine with inadequate mean arterial pressure levels, the guidelines suggest adding vasopressin instead of escalating the dose of norepinephrine.
  • For adults with septic shock and inadequate mean arterial pressure levels despite norepinephrine and vasopressin, the guidelines suggest adding epinephrine (adrenaline).
  • For adults with septic shock, the guidelines suggest against using terlipressin.
  • For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, the guidelines suggest either adding dobutamine to norepinephrine or using epinephrine alone.
  • For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, the guidelines suggest against using levosimendan. (New recommendation)
  • For adults with septic shock, the guidelines suggest invasive monitoring of arterial blood pressure over non-invasive monitoring as soon as practical and if resources are available.
  • For adults with septic shock, the guidelines suggest starting vasopressors peripherally to restore mean arterial pressure rather than delaying initiation until central venous access is secured. (New recommendation)
  • There is insufficient evidence to make a recommendation on the use of restrictive versus liberal fluid strategies in the first 24 hours of resuscitation in patients with sepsis and septic shock who still have signs of hypoperfusion and volume depletion after the initial resuscitation. (New recommendation)

 

Ventilation:

  • There is insufficient evidence to make a recommendation on the use of conservative oxygen targets in adults with sepsis-induced hypoxemic respiratory failure.
  • For adults with sepsis-induced hypoxemic respiratory failure, the guidelines suggest the use of high flow nasal oxygen over non-invasive ventilation. (New recommendation)
  • There is insufficient evidence to make a recommendation on the use of non-invasive ventilation in comparison to invasive ventilation for adults with sepsis-induced hypoxemic respiratory failure.
  • For adults with sepsis-induced ARDS, the guidelines recommend using a low tidal volume ventilation strategy (6 mL/kg) over a high tidal volume strategy (> 10 mL/kg).
  • For adults with sepsis-induced severe ARDS, the guidelines recommend using an upper limit goal for plateau pressures of 30 cm H2O over higher plateau pressures.
  • For adults with moderate to severe sepsis-induced ARDS, the guidelines suggest using higher PEEP over lower PEEP.
  • For adults with sepsis-induced respiratory failure (without ARDS), the guidelines suggest using low tidal volume as compared with high tidal volume ventilation.
  • For adults with sepsis-induced moderate-severe ARDS, the guidelines suggest using traditional recruitment manoeuvres.
  • When using recruitment manoeuvres, the guidelines recommend against using incremental PEEP titration/strategy.
  • For adults with sepsis-induced moderate-severe ARDS, the guidelines recommend using prone ventilation for greater than 12 hours daily.
  • For adults with sepsis-induced moderate-severe ARDS, the guidelines suggest using intermittent NMBA boluses over NMBA continuous infusion.
  • For adults with sepsis-induced severe ARDS, the guidelines suggest using venovenous (VV) ECMO when conventional mechanical ventilation fails in experienced centres with the infrastructure in place to support its use. (New recommendation)

 

Additional therapies:

  • For adults with septic shock and an ongoing requirement for vasopressor therapy, the guidelines suggest using IV corticosteroids.
  • For adults with sepsis or septic shock, the guidelines suggest against using polymyxin B hemoperfusion. (New recommendation)
  • There is insufficient evidence to make a recommendation on the use of other blood purification techniques.
  • For adults with sepsis or septic shock the guidelines recommend using a restrictive (over liberal) transfusion strategy.
  • For adults with sepsis or septic shock, the guidelines suggest against using IV immunoglobulins.
  • For adults with sepsis or septic shock and who have risk factors for gastrointestinal bleeding, the guidelines suggest using stress ulcer prophylaxis.
  • For adults with sepsis or septic shock, pharmacologic venous thromboembolism (VTE) prophylaxis is recommended unless a contraindication to such therapy exists.
  • For adults with sepsis or septic shock, the guidelines recommend using low molecular weight heparin over unfractionated heparin for VTE prophylaxis
  • For adults with sepsis or septic shock, the guidelines suggest against using mechanical VTE prophylaxis, in addition to pharmacological prophylaxis, over pharmacologic prophylaxis alone.
  • In adults with sepsis or septic shock and AKI, the guidelines suggest using either continuous or intermittent renal replacement therapy.
  • In adults with sepsis or septic shock and AKI, with no definitive indications for renal replacement therapy, the guidelines suggest against using renal replacement therapy.
  • For adults with sepsis or septic shock, the guidelines recommend initiating insulin therapy at a glucose level of ≥180 mg/dL (10 mmol/L).
  • For adults with sepsis or septic shock, the guidelines suggest against using IV vitamin C. (New recommendation)
  • For adults with septic shock and hypoperfusion-induced lactic acidemia, the guidelines suggest against using sodium bicarbonate therapy to improve hemodynamics or reduce vasopressor requirements.
  • For adults with septic shock and severe metabolic acidemia (pH ≤7.2) and acute kidney injury (AKIN score 2 or 3), the guidelines suggest using sodium bicarbonate therapy
  • For adult patients with sepsis or septic shock who can be fed enterally, the guidelines suggest early (within 72 hr) initiation of enteral nutrition.

 

Think Sepsis

It is clearly very important to remain up-to-date with guideline changes but perhaps the most important thing to remember is that sepsis is a killer and that we should all “think sepsis” in any patient that presents with a suspected infection. It should be at the forefront of all our minds during day-to-day practice.

Sepsis can present without fever and with non-specific symptoms and signs. A high index of suspicion should be maintained in the very young and very old, immunocompromised and pregnant patients, patients with a history of recent surgery or trauma, and those that have indwelling catheters and devices.

When a diagnosis of sepsis is suspected act quickly and without delay. Refer to departmental and regional guidance, start fluids and antibiotics early, and if unsure whether your patient could have sepsis seek senior help immediately. Sepsis awareness saves lives.

 


Thank you to the joint editorial team of www.mrcemexamprep.net for this article.

Header image used on licence from Shutterstock

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