The Impact of Acute Organ Dysfunction on Long-Term Survival in Sepsis*

Schuler, Alejandro; Wulf, David A.; Lu, Yun; Iwashyna, Theodore J.; Escobar, Gabriel J.; Shah, Nigam H.; Liu, Vincent X

doi:10.1097/ccm.0000000000003023

Cited by 109 publications

(101 citation statements)

References 42 publications

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“…Research on more restricted patient populations in the ED, suspected infection or sepsis patients, has presented in-hospital mortality around 10%, 30-day mortality between 10% and 25% and 1-year mortality around 30%, and in parallel to the present study with mortality increasing by increasing number of organ failures 4 42 43. Furthermore, cerebral failure, as in our study, had the strongest association with short-term mortality, followed by respiratory and circulatory failure, the latter in contrast to our study, and hepatic and cerebral failure were associated with long-term mortality 14. In organ failure patients with positive blood culture, the highest in-hospital mortality was observed in patients with circulatory failure followed by respiratory and cerebral 15.…”

Section: Discussionsupporting

confidence: 83%

“…Organ failure was defined based on Sequential Organ Failure Assessment (SOFA) Score,24 25 which is used in the intensive care unit (ICU) setting. Due to research located in an ED, we used modified definitions that were based on SOFA criteria and with input from quick-SOFA (qSOFA)14 26–30:…”

Section: Methodsmentioning

confidence: 99%

“…Studies indicate a high prevalence of organ failure and in-hospital mortality 8–11. Furthermore, organ failure affects not only in-hospital prognosis but also long-term morbidity and mortality 12–14. In addition, different prevalences are described for different organ failures, and the mortality varies by organ failure and number of organ failures 15–17.…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of organ failure and mortality among patients in the emergency department: a population-based cohort study

et al. 2019

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ObjectivesThe aim was to describe population-based incidence and emergency department-based prevalence and 1-year all-cause mortality of patients with new organ failure present at arrival.DesignThis was a population-based cohort study of all citizens in four municipalities (population of 230 000 adults).SettingEmergency department at Odense University Hospital, Denmark.ParticipantsWe included all adult patients who arrived from 1 April 2012 to 31 March 2015.Primary and secondary outcome measuresOrgan failure was defined as a modified Sequential Organ Failure Assessment score≥2 within six possible organ systems: cerebral, circulatory, renal, respiratory, hepatic and coagulation.The primary outcome was prevalence of organ failure, and secondary outcomes were 0–7 days, 8–30 days and 31–365 days all-cause mortality.ResultsWe identified in total 175 278 contacts, of which 70 399 contacts were further evaluated for organ failure. Fifty-two per cent of these were women, median age 62 (IQR 42–77) years. The incidence of new organ failure was 1342/100 000 person-years, corresponding to 5.2% of all emergency department contacts.The 0–7-day, 8–30-day and 31–365-day mortality was 11.0% (95% CI: 10.2% to 11.8%), 5.6% (95% CI: 5.1% to 6.2%) and 13.2% (95% CI: 12.3% to 14.1%), respectively, if the patient had one or more new organ failures at first contact in the observation period, compared with 1.4% (95% CI: 1.3% to 1.6%), 1.2% (95% CI: 1.1% to 1.3%) and 5.2% (95% CI: 5.0% to 5.4%) for patients without. Seven-day mortality ranged from hepatic failure, 6.5% (95% CI: 4.9% to 8.6%), to cerebral failure, 33.8% (95% CI: 31.0% to 36.8%), the 8–30-day mortality ranged from cerebral failure, 3.9% (95% CI: 2.8% to 5.3%), to hepatic failure, 8.6% (95% CI: 6.6% to 10.8%) and 31–365-day mortality ranged from cerebral failure, 9.3% (95% CI: 7.6% to 11.2%), to renal failure, 18.2% (95% CI: 15.5% to 21.1%).ConclusionsThe study revealed an incidence of new organ failure at 1342/100 000 person-years and a prevalence of 5.2% of all emergency department contacts. One-year all-cause mortality was 29.8% among organ failure patients.

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Section: Discussionsupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prevalence of organ failure and mortality among patients in the emergency department: a population-based cohort study

et al. 2019

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“…Of note, sepsis-associated encephalopathy (SAE) is one of the most common etiological factors for febrile encephalopathy, especially in elderly people. Approximately 70% of patients with bacteremia develop neurological symptoms ranging from lethargy to coma, and over 80% suffer from abnormalities as measured by electroencephalogram (EEG) [3,4]. Moreover, it has been identified that SAE is critically involved in increased mortality, extensive in-hospital cost, and prolonged hospitalization, followed by persistent cognitive impairment and limitations in physical function [5,6].…”

Section: Introductionmentioning

confidence: 99%

Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Ren

Yao

Zhang

et al. 2020

J Neuroinflammation

159

131

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Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitaryadrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.

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“…The constant interest in sepsis research is justified by data showing an increased number of deaths despite a reduction in sepsis-associated mortality during the last four decades; the intra-hospital risk of death by sepsis is 10-20%, and increases to 40-80% in septic shock [1][2][3][4]. Sepsis associated mortality became higher due to the increased rates of diagnosis [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

et al. 2020

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Background: The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. Methods: We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A,-238G/A,-376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. Results: TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. Conclusions: TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

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The Impact of Acute Organ Dysfunction on Long-Term Survival in Sepsis*

Abstract: Acute sepsis-related neurologic dysfunction was the organ dysfunction most strongly associated with short- and long-term mortality and represents a key mediator of long-term adverse outcomes following sepsis.

Cited by 109 publications

References 42 publications

Prevalence of organ failure and mortality among patients in the emergency department: a population-based cohort study

Prevalence of organ failure and mortality among patients in the emergency department: a population-based cohort study

Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

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