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Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis.

ABSTRACT: Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown.To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes.Prospective cohort study at 28 sites.We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (+/-SD) for circulating IL-6 and IL-10 concentrations were 6.9 (+/-1) pg/ml and 1.2 (+/-1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Gray's survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02-1.46, P < 0.0001, and for IL-10 were 1.17-1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95-1.27 and 1.07-1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008).Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.

SUBMITTER: Yende S

PROVIDER: S-EPMC2720087 | biostudies-other | 2008 Jun

REPOSITORIES: biostudies-other

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Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis.

Yende Sachin S D'Angelo Gina G Kellum John A JA Weissfeld Lisa L Fine Jonathan J Welch Robert D RD Kong Lan L Carter Melinda M Angus Derek C DC

American journal of respiratory and critical care medicine 20080327 11

<h4>Rationale</h4>Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown.<h4>Objectives</h4>To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes.<h4>Methods</h4>Prospective cohort study at 28 sites.<h4>Measurements and main results</h4>We used standa ...[more]

PMID: 18369199

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Project description:Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of proinflammatory and anti-inflammatory markers, are associated with severe sepsis and death.This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality.A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8-39.0) (P<.001).The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and mortality is highest when both proinflammatory and anti-inflammatory cytokine levels are high.

Project description:ImportanceEarly administration of intravenous fluids is recommended for all patients with sepsis, but the association of this treatment with mortality may depend on the patient's initial blood pressure.ObjectiveTo test the association between early administration of intravenous fluids by paramedics and in-hospital mortality among patients with sepsis, accounting for patients' initial blood pressure.Design, setting, and participantsCohort study in which multiple analyses were conducted using a 1-year (from April 1, 2015, to March 31, 2016) cohort of 1871 patients with sepsis who were transported to the hospital by paramedics from a large emergency medical services system in Alberta, Canada. Multivariable logistic regression and a propensity-matched analysis adjusting for baseline patient characteristics were used to minimize confounding by indication and test the association between early administration of intravenous fluids by paramedics and in-hospital mortality. Nonparametric additive regression was used to assess the association of early administration of intravenous fluids with prehospital and in-hospital treatment times.ExposuresIntravenous fluids administered by paramedics at the point of first contact and during transportation to the hospital.Main outcomes and measuresThe primary outcome was in-hospital mortality. Secondary outcomes included prehospital and emergency department treatment times.ResultsA total of 1871 patients with sepsis were identified (955 women and 916 men; median age, 77 years [interquartile range, 64-85 years]), with an overall in-hospital mortality of 28.2% (n = 528). More than half of patients (1015 [54.2%]) received intravenous fluids from paramedics; the median volume provided was 400 mL (interquartile range, 250-500 mL). The association of intravenous fluids with mortality depended on the patient's initial systolic blood pressure (range, 42-222 mm Hg; P < .001 for interaction). For example, in a typical patient with an initial systolic blood pressure of 100 mm Hg, intravenous fluids were associated with decreased mortality (odds ratio, 0.73; 95% CI, 0.56-0.95), but for a typical patient with the median initial systolic blood pressure of 125 mm Hg, intravenous fluids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.81-2.44). Similar results were obtained in the propensity-matched analysis. The administration of intravenous fluids was associated with increased prehospital time compared with patients who did not receive intravenous fluids (median difference, 3.2 minutes; 95% CI, 1.7-4.7 minutes) but was not associated with time to assessment in the emergency department (median difference, 2.4 minutes; 95% CI, -2.4 to 7.3 minutes).Conclusions and relevanceIntravenous fluids provided by paramedics were associated with reduced in-hospital mortality for patients with sepsis and hypotension but not for those with a higher initial systolic blood pressure.

Project description:RationaleImmunosuppressive medical conditions are risk factors for mortality from severe infections. It is unknown whether hospital characteristics affect this risk.ObjectivesTo determine whether the odds of death for an immunosuppressed patient with sepsis relative to a nonimmunosuppressed patient with sepsis varies according to the hospital's yearly case volume of immunosuppressed patients with sepsis.MethodsPatients with sepsis at hospitals in the Vizient database were characterized as immunosuppressed or not immunosuppressed on the basis of diagnosis codes and medication use. Hospitals were grouped into quartiles based on their average volumes of immunosuppressed patients with sepsis per year. Multilevel logistic regression with clustering of patients by hospital was used to determine whether the odds of in-hospital death from sepsis owing to a suppressed immune state varied by hospital quartile.ResultsThere were 350,183 patients with sepsis at 60 hospitals in the Vizient database from 2010 to 2012. Immunosuppressed patients with sepsis at the 15 hospitals in the lowest quartile (64 to 224 immunosuppressed patients with sepsis per year) had an increased odds of in-hospital death relative to nonimmunosuppressed patients with sepsis at these hospitals (adjusted odds ratio, 1.38; 95% confidence interval, 1.27-1.50; P < 0.001). The odds of in-hospital death for immunosuppressed patients with sepsis relative to nonimmunosuppressed patients with sepsis was similar for patients at hospitals in the second, third, and fourth quartiles (225 to 1,056 immunosuppressed patients with sepsis per year). The adjusted odds of death from sepsis owing to a suppressed immune state of 1.21 (95% confidence interval, 1.18-1.25; P < 0.001) for patients at these 45 hospitals was significantly less than for patients at the 15 hospitals in the lowest quartile (P = 0.004 for difference).ConclusionsThe risk of death from sepsis owing to a suppressed immune state was greatest at hospitals with the lowest volume of immunosuppressed patients with sepsis. Further study is needed to determine whether this finding is related to differences in patient characteristics or in care delivery at hospitals with different amounts of exposure to immunosuppressed patients.

Project description:BackgroundHospital-acquired pneumonia (HAP) is the most common hospital-acquired infection in China with substantial morbidity and mortality. But no specific risk assessment model has been well validated in patients with HAP. The aim of this study was to investigate the published risk assessment models that could potentially be used to predict 30-day mortality in HAP patients in non-surgical departments.MethodsThis study was a single-center, retrospective study. In total, 223 patients diagnosed with HAP from 2012 to 2017 were included in this study. Clinical and laboratory data during the initial 24 hours after HAP diagnosis were collected to calculate the pneumonia severity index (PSI); consciousness, urea nitrogen, respiratory rate, blood pressure, and age ≥65 years (CURB-65); Acute Physiology and Chronic Health Evaluation II (APACHE II); Sequential Organ Failure Assessment (SOFA); and Quick Sequential Organ Failure Assessment (qSOFA) scores. The discriminatory power was tested by constructing receiver operating characteristic (ROC) curves, and the areas under the curve (AUCs) were calculated.ResultsThe all-cause 30-day mortality rate was 18.4% (41/223). The PSI, CURB-65, SOFA, APACHE II, and qSOFA scores were significantly higher in non-survivors than in survivors (all P < 0.001). The discriminatory abilities of the APACHE II and SOFA scores were better than those of the CURB-65 and qSOFA scores (ROC AUC: APACHE II vs. CURB-65, 0.863 vs. 0.744, Z = 3.055, P = 0.002; APACHE II vs. qSOFA, 0.863 vs. 0.767, Z = 3.017, P = 0.003; SOFA vs. CURB-65, 0.856 vs. 0.744, Z = 2.589, P = 0.010; SOFA vs. qSOFA, 0.856 vs. 0.767, Z = 2.170, P = 0.030). The cut-off values we defined for the SOFA, APACHE II, and qSOFA scores were 4, 14, and 1.ConclusionsThese results suggest that the APACHE II and SOFA scores determined during the initial 24 h after HAP diagnosis may be useful for the prediction of 30-day mortality in HAP patients in non-surgical departments. The qSOFA score may be a simple tool that can be used to quickly identify severe infections.

Project description:ImportanceThe Affordable Care Act has led to US national reductions in hospital 30-day readmission rates for heart failure (HF), acute myocardial infarction (AMI), and pneumonia. Whether readmission reductions have had the unintended consequence of increasing mortality after hospitalization is unknown.ObjectiveTo examine the correlation of paired trends in hospital 30-day readmission rates and hospital 30-day mortality rates after discharge.Design, setting, and participantsRetrospective study of Medicare fee-for-service beneficiaries aged 65 years or older hospitalized with HF, AMI, or pneumonia from January 1, 2008, through December 31, 2014.ExposureThirty-day risk-adjusted readmission rate (RARR).Main outcomes and measuresThirty-day RARRs and 30-day risk-adjusted mortality rates (RAMRs) after discharge were calculated for each condition in each month at each hospital in 2008 through 2014. Monthly trends in each hospital's 30-day RARRs and 30-day RAMRs after discharge were examined for each condition. The weighted Pearson correlation coefficient was calculated for hospitals' paired monthly trends in 30-day RARRs and 30-day RAMRs after discharge for each condition.ResultsIn 2008 through 2014, 2 962 554 hospitalizations for HF, 1 229 939 for AMI, and 2 544 530 for pneumonia were identified at 5016, 4772, and 5057 hospitals, respectively. In January 2008, mean hospital 30-day RARRs and 30-day RAMRs after discharge were 24.6% and 8.4% for HF, 19.3% and 7.6% for AMI, and 18.3% and 8.5% for pneumonia. Hospital 30-day RARRs declined in the aggregate across hospitals from 2008 through 2014; monthly changes in RARRs were -0.053% (95% CI, -0.055% to -0.051%) for HF, -0.044% (95% CI, -0.047% to -0.041%) for AMI, and -0.033% (95% CI, -0.035% to -0.031%) for pneumonia. In contrast, monthly aggregate changes across hospitals in hospital 30-day RAMRs after discharge varied by condition: HF, 0.008% (95% CI, 0.007% to 0.010%); AMI, -0.003% (95% CI, -0.005% to -0.001%); and pneumonia, 0.001% (95% CI, -0.001% to 0.003%). However, correlation coefficients in hospitals' paired monthly changes in 30-day RARRs and 30-day RAMRs after discharge were weakly positive: HF, 0.066 (95% CI, 0.036 to 0.096); AMI, 0.067 (95% CI, 0.027 to 0.106); and pneumonia, 0.108 (95% CI, 0.079 to 0.137). Findings were similar in secondary analyses, including with alternate definitions of hospital mortality.Conclusions and relevanceAmong Medicare fee-for-service beneficiaries hospitalized for heart failure, acute myocardial infarction, or pneumonia, reductions in hospital 30-day readmission rates were weakly but significantly correlated with reductions in hospital 30-day mortality rates after discharge. These findings do not support increasing postdischarge mortality related to reducing hospital readmissions.

Project description:BACKGROUND: Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST). METHODS: We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where appropriate. For interventions with biological plausibility but low quality evidence, a Delphi process was undertaken to estimate effectiveness. RESULTS: Searches of 2876 titles identified 7 studies. Among these, 4 evaluated oral antibiotics for neonatal pneumonia in non-randomised, concurrently controlled designs. Meta-analysis suggested reductions in all-cause neonatal mortality (RR 0.75 95% CI 0.64- 0.89; 4 studies) and neonatal pneumonia-specific mortality (RR 0.58 95% CI 0.41- 0.82; 3 studies). Two studies (1 RCT, 1 observational study), evaluated community-based neonatal care packages including injectable antibiotics and reported mortality reductions of 44% (RR = 0.56, 95% CI 0.41-0.77) and 34% (RR = 0.66, 95% CI 0.47-0.93), but the interpretation of these results is complicated by co-interventions. A third, clinic-based, study reported a case-fatality ratio of 3.3% among neonates treated with injectable antibiotics as outpatients. No studies were identified evaluating injectable antibiotics alone for neonatal pneumonia. Delphi consensus (median from 20 respondents) effects on sepsis-specific mortality were 30% reduction for oral antibiotics, 65% for injectable antibiotics and 75% for injectable antibiotics on pneumonia-specific mortality. No trials were identified assessing effect of hospital management for neonatal infections and Delphi consensus suggested 80%, and 90% reductions for sepsis and pneumonia-specific mortality respectively. CONCLUSION: Oral antibiotics administered in the community are effective for neonatal pneumonia mortality reduction based on a meta-analysis, but expert opinion suggests much higher impact from injectable antibiotics in the community or primary care level and even higher for facility-based care. Despite feasibility and low cost, these interventions are not widely available in many low income countries. FUNDING: This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US.

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Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis.

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Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis.

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