Sepsis
WHO
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Sepsis

26 August 2020

Key facts

  • Sepsis is a syndromic response to infection and is frequently a final common pathway to death from many infectious diseases worldwide
  • The global burden of sepsis is difficult to ascertain, although a recent scientific publication estimated that in 2017 there were 48.9 million cases and 11 million sepsis-related deaths worldwide, which accounted for almost 20% of all global deaths (1)
  • In 2017, almost half of all global sepsis cases occurred among children, with an estimated 20 million cases and 2.9 million global deaths in children under five years of age (1)
  • Significant regional disparities in sepsis incidence and mortality exist; approximately 85.0% of sepsis cases and sepsis-related deaths worldwide occurred in low- and middle-income countries (1)
  • Sepsis can be the clinical manifestation of infections acquired both in the community setting or in health care facilities. Health care-associated infections are one of, if not the most frequent type of adverse event to occur during care delivery and affect hundreds of millions of patients worldwide every year (2). Since these infections are often resistant to antibiotics, they can rapidly lead to deteriorating clinical conditions.

Background

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection (3). If not recognized early and managed promptly, it can lead to septic shock, multiple organ failure and death. It is most frequently a serious complication of infection, particularly in low- and middle-income countries where it represents a major cause of maternal and neonatal morbidity and mortality.

In the community setting, sepsis often presents as the clinical deterioration of common and preventable infections. Sepsis also frequently results from infections acquired in health care settings, which are one of the most frequent adverse events during care delivery and affect hundreds of millions of patients worldwide every year (2).

Healthcare-associated infections are often resistant to antibiotics and can rapidly lead to deteriorating clinical conditions. Antimicrobial resistance is a major factor determining clinical unresponsiveness to treatment and rapid evolution to sepsis and septic shock. Sepsis patients with resistant pathogens have been found to have a higher risk of hospital mortality.

Implementing preventive measures against infections, such as good hygiene practices, ensuring access to vaccination programmes, improved sanitation and water quality and availability, and other infection prevention and control best practices both in the community and health care settings, are key steps in reducing the occurrence of sepsis. Early diagnosis and timely and appropriate clinical management of sepsis, such as optimal antimicrobial use and fluid resuscitation, are crucial to increase the likelihood of survival. Even though the onset of sepsis can be acute and poses a short-term mortality burden, it can also be the cause of significant long-term morbidity requiring treatment and support. Thus, sepsis requires a multidisciplinary approach.

Who is at risk?

Anyone affected by an infection, severe injury, or serious non-communicable disease can progress to sepsis but vulnerable populations are at higher risk (4) including:

  • older persons,
  • pregnant or recently pregnant women,
  • neonates,
  • hospitalized patients,
  • patients in intensive care units,
  • people with HIV/AIDS,
  • people with liver cirrhosis,
  • people with cancer,
  • people with kidney disease,
  • people with autoimmune diseases,
  • and people with no spleen.

Signs and symptoms

Sepsis is a medical emergency and can present with various signs and symptoms at different times. Warning signs and symptoms include:

  • fever or low temperature and shivering,
  • altered mental status,
  • difficulty breathing/rapid breathing,
  • increased heart rate,
  • weak pulse/low blood pressure,
  • low urine output,
  • cyanotic or mottled skin,
  • cold extremities,
  • and extreme body pain or discomfort (5-7).

Suspecting sepsis is a first major step towards early recognition and diagnosis.

Common Causes

In 2017, the largest contributors to sepsis cases and sepsis-related mortality across all ages were diarrhoeal diseases (9.2 to 15 million annual cases) and lower respiratory infections (1.8-2.8 million annually) (1). However, non-communicable diseases are on the rise; one-third of sepsis cases and nearly half of all sepsis-related deaths in 2017 were due to an underlying injury or chronic disease (1). Maternal disorders were the most common non-communicable disease complicated by sepsis. Among children, the most common causes of sepsis-related deaths were neonatal disorders, lower respiratory infections, and diarrhoeal diseases (1). Group B streptococcus is the leading cause of both neonatal and maternal sepsis, though Escherichia coli is an emerging threat (8,9).  Both of these pathogens have displayed considerable resistance to  treatment and are considered priority pathogens for research and development (R&D) of new antibiotics.

Sepsis Prevention

There are two main steps to preventing sepsis:

  1. Prevention of microbial transmission and infection
  2. Prevention of an infection evolving into sepsis

Prevention of infection in the community involves using effective hygiene practices, such as hand washing, and safe preparation of food, improving sanitation and water quality and availability, providing access to vaccines, particularly for those at high risk, as well as appropriate nutrition, including breastfeeding for newborns.

Prevention of infection in health care facilities mainly relies on having functioning infection prevention and control (IPC) programmes and teams, effective hygiene practices and precautions, including hand hygiene, along with a clean, well-functioning environment and equipment.

Prevention of the evolution to sepsis in both community and health care facilities requires the appropriate antibiotic treatment of infection, including reassessment for optimization, prompt seeking of medical care, and early detection of sepsis signs and symptoms.

Diagnosis and Clinical Management

Identifying and not underestimating the signs and symptoms listed above, along with the detection of some biomarkers (such as C reactive protein and procalcitonin), are crucial elements for early diagnosis of sepsis and the timely establishment of its appropriate clinical management. After early recognition, diagnostics to help identify a causal pathogen of infection leading to sepsis are important to guide targeted antimicrobial treatment. Once the source of infection is determined, source control, such as drainage of an abscess, is critical. Antimicrobial resistance (AMR) can jeopardize clinical management of sepsis because empirical antibiotic treatment is often required.  Early fluid resuscitation to improve volume status is also important in the initial phase of sepsis management. In addition, vasopressors may be required to improve and maintain tissue perfusion. Repeated exams and assessments, including monitoring vital signs, guide the appropriate management of sepsis over time.

Sepsis and the Sustainable Development Goals

Sepsis is a significant cause of maternal, neonatal and child mortality. Consequently, combating sepsis will contribute to achievement of Sustainable Development Goals (SDGs) targets 3.8 on quality of care, and 3.1 and 3.2 by improving mortality rates in these vulnerable populations. Sepsis can also ultimately lead to death in patients affected by HIV, tuberculosis, malaria, and other infectious diseases that are included in target 3.3. The prevention and/or appropriate diagnosis and management of sepsis is also linked to adequate vaccine coverage, quality universal health coverage, capacity to comply with the International Health Regulations, preparedness, and water and sanitation services. The challenge, however, remains how to achieve universal prevention, diagnosis and management of sepsis.

WHO Sepsis Response

To combat this important global health threat, WHO responded with a WHO Secretariat Report and, in May 2017, the Seventieth World Health Assembly adopted Resolution WHA70.7 on Improving the prevention, diagnosis and clinical management of sepsis. The key pillars of Resolution WHA 70.7 are to:

  1. Develop WHO guidance on sepsis prevention and management
  2. Draw attention to public health impacts of sepsis and estimate the global burden of sepsis
  3. Support Member States to define and implement standards and establish guidelines, infrastructure, laboratory capacity, strategies, and tools for identifying, reducing incidence of, and morbidity and mortality due to sepsis
  4. Collaborate with UN organizations, partners, international organizations, and stakeholders to enhance sepsis treatment and infection prevention and control including vaccinations

In collaboration and coordination with WHO regional offices, Member States and other stakeholders, several WHO headquarters programmes are currently working on the public health impact of sepsis and providing guidance and country support on sepsis prevention, early and appropriate diagnosis, and timely and appropriate clinical management.

References

(1)   Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet (London, England). 2020;395(10219):200-11.

(2)   World Health Organization. WHO Report on the burden of endemic health care-associated infection worldwide. 2017-11-21 15:11:22 2011.

(3)   Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801-10.

(4)   Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. British Medical Journal 2016.

(5)   United States Centers for Disease Control and Prevention. Healthcare Professional (HCP) Resources : Sepsis. Updated August 27, 2019. T06:23:15Z. https://www.cdc.gov/sepsis/get-ahead-of-sepsis/hcp-resources.html (accessed 25 February 2020).

(6)   Global Sepsis Alliance. Toolkits. https://www.world-sepsis-day.org/toolkits/ (accessed 25 February 2020).

(7)   UK Sepsis Trust. Education. 2018. https://sepsistrust.org/education/ (accessed 25 February 2020).

(8)   Lawn JE, Bianchi-Jassir F, Russell NJ, Kohli-Lynch M, Tann CJ, Hall J, et al. Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates? Clin Infect Dis. 2017;65(suppl_2):S89-S99.

(9)   Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics. 2011;127(5):817-26.