What are the current trends in the epidemiology of sepsis?

Current Trends in the Epidemiology of Sepsis

The global incidence of sepsis is increasing, with over 1.7 million adults affected annually in the United States alone, resulting in more than 15% mortality and exceeding 30% in-hospital mortality rate. 1

Global Burden and Incidence

• Sepsis represents a significant global health burden, accounting for 5.2% of total US hospital costs, amounting to more than $20 billion in 2011 1
• The incidence continues to rise due to an aging population with more comorbidities 1
• In middle and low-income countries, sepsis represents a disproportionately high burden, with 90% of worldwide deaths from infections occurring in less developed regions 1
• Approximately 70% of the 9 million global deaths in neonates and infants are attributable to sepsis, with the majority occurring in Asia and sub-Saharan Africa 1
• The incidence of neonatal sepsis in middle-income countries has been reported to be up to 40 times higher than in high-income countries 1

Risk Factors and Demographics

• Key risk factors include immune compromise, chronic diseases such as malignancy, extremes of age (infants and elderly), male gender, and Black race 1
• Additional risk factors in resource-limited settings include high incidence of bacterial, parasitic, and HIV infections, low hygienic standards, limited vaccination rates, widespread malnutrition, and limited healthcare resources 1
• Maternal sepsis rates are increasing and now rank as the second leading cause of preventable maternal mortality 2

Common Sources of Infection

• Chest infections (pneumonia) are the most commonly identified source of sepsis, reported in 38.6% of patients 1
• Pulmonary and intra-abdominal infections are the most commonly associated sites of infection in patients suffering acute lung injury related to sepsis 1
• In neonatal sepsis in low and lower-middle-income countries, Gram-negative bacteria account for 60% of cases, with significant regional variations in pathogen types 1
• Intra-abdominal infections are the second leading cause of sepsis globally 2

Changing Definitions and Recognition

• The definition of sepsis has evolved from "systemic inflammatory response syndrome triggered by infection" (Sepsis-1) to "life-threatening organ dysfunction caused by a dysregulated host response to infection" (Sepsis-3) 2, 3
• The Sepsis-3 definition discontinued the recommendation for using systemic inflammatory response syndrome (SIRS) criteria for screening and classification of sepsis 2
• This evolution reflects growing knowledge of sepsis mechanisms and the success and failure of diagnostic and therapeutic interventions 3
• The changing definitions have implications for epidemiological tracking and comparisons over time 4

Healthcare Impact and Resource Utilization

• Sepsis accounts for a significant proportion of intensive care unit (ICU) admissions, varying from 10% in Switzerland to 64% in Portugal 1
• Countries with fewer ICU beds per capita show a greater proportion of beds occupied by sepsis patients 1
• The availability of ICU beds impacts sepsis care, with countries having fewer ICU beds showing delayed ICU admissions and potentially higher mortality rates 1
• Delayed ICU admission is associated with substantially longer time in hospital before ICU admission and higher mortality, even after adjustment for case-mix 1

Mortality Trends and Outcomes

• Overall hospital mortality from sepsis has shown improvement, decreasing from 29.7% in pre-implementation periods (2006-2008) to 21.1% after implementation of early recognition and response programs (2009-2014) 5
• Mortality in sepsis is most often due to unresolved sepsis or multisystem organ failure rather than progressive respiratory failure 1
• Factors affecting mortality include age, severity of illness, cause of infection, presence of multisystem organ failure, and preexisting comorbid conditions 1
• Hospitals with higher compliance to sepsis bundles demonstrate lower mortality rates, with overall hospital mortality decreasing 0.7% for every 3 months a hospital participated in the Surviving Sepsis Campaign 2

Early Recognition and Screening

• Early recognition and prompt intervention have been shown to save lives in sepsis 5, 6
• Performance improvement programs for sepsis are associated with improved patient outcomes 2
• Sepsis screening has been associated with decreased mortality in several studies 2
• The implementation of a core set of recommendations (bundles) has been a cornerstone of sepsis performance improvement programs 2
• A meta-analysis of 50 observational studies demonstrated that performance improvement programs were associated with a significant increase in compliance with the Surviving Sepsis Campaign bundles and a reduction in mortality (OR 0.66; 95% CI 0.61–0.72) 2

Challenges in Sepsis Management

• High rates of antimicrobial resistance are observed against WHO-recommended empirical antibiotics for neonatal sepsis in many low and lower-middle-income countries 1
• A major challenge in evaluating the host response in sepsis is to characterize what is protective and what is harmful 3
• The new criteria for recognition and diagnosis of sepsis were derived from robust databases restricted to developed countries, raising questions about their global applicability 3
• Clinicians should not be restricted to definition criteria when evaluating patients with infection and should use the broad array of information obtained by clinical observation 3

Emerging Concepts in Sepsis Pathophysiology

• Current conceptual models of sepsis outcomes reflect concurrent inflammatory and immunosuppressive responses 2
• Fewer patients are dying in the early period due to earlier recognition and better implementation of best clinical practices 2
• Some patients survive the early inflammatory response but experience chronic critical illness characterized by persistent inflammation, immunosuppression, and catabolism syndrome 2
• The late immunosuppressive effects of sepsis include mobilization of immunosuppressive immature polymorphonuclear leukocytes and myeloid-derived suppressor cells from the bone marrow 2