Sachin Yende

Epidemiology of severe sepsis

Severe sepsis is a leading cause of death in the United States and the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Respiratory tract infections, particularly pneumonia, are the most common site of infection, and associated with the highest mortality. The type of organism causing severe sepsis is an important determinant of outcome, and gram-positive organisms as a cause of sepsis have increased in frequency over time and are now more common than gram-negative infections. Recent studies suggest that acute infections worsen pre-existing chronic diseases or result in new chronic diseases, leading to poor long-term outcomes in acute illness survivors. People of older age, male gender, black race, and preexisting chronic health conditions are particularly prone to develop severe sepsis; hence prevention strategies should be targeted at these vulnerable populations in future studies.

Effect of clopidogrel on bleeding after coronary artery bypass surgery.

Objective Platelet dysfunction is a common cause of bleeding after coronary artery bypass graft surgery. This study explores the effects of clopidogrel on bleeding complications after coronary artery bypass graft surgery. Design Prospective observational study of patients undergoing coronary artery bypass graft. Setting Tertiary care center. Patients A total of 247 patients undergoing coronary artery bypass graft surgery. Interventions None. Measurements Primary end point was need for reexploration secondary to bleeding. Secondary end points included need for transfusion of blood products and chest tube output. Main results Eight (3.3%) of 247 patients required reexploration secondary to bleeding. Clopidogrel recipients had higher incidence of reexploration for bleeding (9.8 vs. 1.6, p = .01) with an odds ratio of 6.9 (95% confidence interval, 1.6–30). Clopidogrel also increased the percentage of patients receiving packed red blood cell transfusion (72.6 vs. 51.6%, p = .007), the number of packed red blood cell units (3 vs. 1.6, p =0.0004), and the number of cryoprecipitate units (2.4 vs. 1.2, p = .04) transfused after coronary artery bypass graft surgery. Among clopidogrel recipients, a trend for increased transfusion of platelet units (4.3 vs. 1.7, p = .05) and fresh frozen plasma units (1.1 vs. 0.6, p = .08) also was found. Conclusions Preoperative use of clopidogrel in combination with aspirin is associated with increased need for surgical reexploration as well as risk of packed red blood cell and cryoprecipitate transfusions after coronary artery bypass graft surgery.

Inflammatory Markers at Hospital Discharge Predict Subsequent Mortality after Pneumonia and Sepsis

RATIONALE 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. OBJECTIVES To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes. METHODS Prospective cohort study at 28 sites. MEASUREMENTS AND MAIN RESULTS 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 Grays 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). CONCLUSIONS Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects

Background: Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. Methods: The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70–79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD). Results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H2O v 74.2 cm H2O, p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p<0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL-6 (adjusted regression coefficients (β) = −5.3 (95% CI −9.1 to−1.5) and −3.1 (95% CI −4.3 to −1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (β = −6.4 (95% CI −12.8 to −0.03) and −3.4 (95% CI −5.4 to −1.3), respectively, for IL-6 and β = −10.1 (95% CI −18.7 to −1.5) and −3.8 (95% CI −7 to −0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. Conclusions: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity.

Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival

While sepsis is a leading cause of acute kidney injury in critically ill patients, the relationship between immune response and acute kidney injury in less severely ill patients with infection is not known. Here we studied the epidemiology, 1-year mortality, and immune response associated with acute kidney injury in 1836 hospitalized patients with community-acquired severe and non-severe pneumonia. Acute kidney injury developed in 631 patients of whom 329 had severe and 302 had non-severe sepsis. Depending on the subgroup classification, 16-25% of the patients with non-severe pneumonia also developed acute kidney injury. In general, patients with acute kidney injury were older, had more comorbidity, and had higher biomarker concentrations (interleukin-6, tumor necrosis factor, D-dimer) even among patients without severe sepsis. The risk of death associated with acute kidney injury varied when assessed by Grays survival model and after adjusting for differences in age, gender, ethnicity, and comorbidity. This risk was significantly higher immediately after hospitalization but gradually fell over time in the overall cohort and in those with non-severe pneumonia. A significantly higher risk of death (hazard ratio 1.29) was also present in those never admitted to an intensive care unit. Hence acute kidney injury is common even among patients with non-severe pneumonia and is associated with higher immune response and an increased risk of death.

Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis

CONTEXT Severe sepsis, defined as infection complicated by acute organ dysfunction, occurs more frequently and leads to more deaths in black than in white individuals. The optimal approach to minimize these disparities is unclear. OBJECTIVE To determine the extent to which higher severe sepsis rates in black than in white patients are due to higher infection rates or to a higher risk of acute organ dysfunction. DESIGN, SETTING, AND PARTICIPANTS Analysis of infection-related hospitalizations from the 2005 hospital discharge data of 7 US states and infection-related emergency department visits from the 2003-2007 National Hospital Ambulatory Care Survey. MAIN OUTCOME MEASURE Age- and sex-standardized severe sepsis and infection hospitalization rates and the risk of acute organ dysfunction. RESULTS Of 8,661,227 non-childbirth-related discharges, 2,261,857 were associated with an infection, and of these, 381,787 (16.8%) had severe sepsis. Black patients had a 67% higher age- and sex-standardized severe sepsis rate than did white patients (9.4; 95% confidence interval [CI], 9.3-9.5 vs 5.6; 95% CI, 5.6-5.6 per 1000 population; P < .001) and 80% higher standardized mortality (1.8, 95% CI, 1.8-1.9 vs 1.0, 95% CI, 1.0-1.1 per 1000 population; P < .001). The higher severe sepsis rate was explained by both a higher infection rate in black patients (47.3; 95% CI, 47.1-47.4 vs 34.0; 95% CI, 33.9-34.0 per 1000 population; incidence rate ratio, 1.39; P < .001) and a higher risk of developing acute organ dysfunction (age- and sex-adjusted odds ratio [OR], 1.29; 95% CI, 1.27-1.30; P < .001). Differences in infection presented broadly across different sites and etiology of infection and for community- and hospital-acquired infections and occurred despite a lower likelihood of being admitted for infection from the emergency department (adjusted OR, 0.70; 95% CI, 0.64-0.76; P < .001). The higher risk of organ dysfunction persisted but was attenuated after adjusting for age, sex, comorbid conditions, poverty, and hospital effect (OR, 1.14; 95% CI, 1.13-1.16; P < .001). Racial disparities in infection and severe sepsis incidence and mortality rates were largest among younger adults (eg, the proportion of invasive pneumococcal disease occurring in adults < 65 years was 73.9% among black patients vs 44.5% among white patients, P < .001). CONCLUSION Racial differences in severe sepsis are explained by both a higher infection rate and a higher risk of acute organ dysfunction in black than in white individuals.

Association Between Hospitalization for Pneumonia and Subsequent Risk of Cardiovascular Disease

IMPORTANCE The risk of cardiovascular disease (CVD) after infection is poorly understood. OBJECTIVE To determine whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD. DESIGN, SETTINGS, AND PARTICIPANTS We examined 2 community-based cohorts: the Cardiovascular Health Study (CHS, n = 5888; enrollment age, ≥65 years; enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15,792; enrollment age, 45-64 years; enrollment period, 1987-1989). Participants were followed up through December 31, 2010. We matched each participant hospitalized with pneumonia to 2 controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching. We estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for demographics, CVD risk factors, subclinical CVD, comorbidities, and functional status. EXPOSURES Hospitalization for pneumonia. MAIN OUTCOMES AND MEASURES Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease). RESULTS Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. CVD risk after pneumonia was highest in the first year. CVD occurred in 54 cases and 6 controls in the first 30 days (HR, 4.07; 95% CI, 2.86-5.27); 11 cases and 9 controls between 31 and 90 days (HR, 2.94; 95% CI, 2.18-3.70); and 22 cases and 55 controls between 91 days and 1 year (HR, 2.10; 95% CI, 1.59-2.60). Additional CVD risk remained elevated into the tenth year, when 4 cases and 12 controls developed CVD (HR, 1.86; 95% CI, 1.18-2.55). In ARIC, of 680 pneumonia cases, 112 had CVD over 10 years after hospitalization. CVD occurred in 4 cases and 3 controls in the first 30 days (HR, 2.38; 95% CI, 1.12-3.63); 4 cases and 0 controls between 31 and 90 days (HR, 2.40; 95% CI, 1.23-3.47); 11 cases and 8 controls between 91 days and 1 year (HR, 2.19; 95% CI, 1.20-3.19); and 8 cases and 7 controls during the second year (HR, 1.88; 95% CI, 1.10-2.66). After the second year, the HRs were no longer statistically significant. CONCLUSIONS AND RELEVANCE Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD.

Influence of Comorbid Conditions on Long-Term Mortality After Pneumonia in Older People

OBJECTIVES: To test the hypothesis that increased long‐term mortality after hospitalization for community‐acquired pneumonia (CAP) is independent of comorbid conditions.

The Epidemiology of Chronic Critical Illness in the United States

Objectives:The epidemiology of chronic critical illness is not well characterized. We sought to determine the prevalence, outcomes, and associated costs of chronic critical illness in the United States. Design:Population-based cohort study using data from the United States Healthcare Costs and Utilization Project from 2004 to 2009. Setting:Acute care hospitals in Massachusetts, North Carolina, Nebraska, New York, and Washington. Patients:Adult and pediatric patients meeting a consensus-derived definition for chronic critical illness, which included one of six eligible clinical conditions (prolonged acute mechanical ventilation, tracheotomy, stroke, traumatic brain injury, sepsis, or severe wounds) plus at least 8 days in an ICU. Interventions:None. Measurements and Main Results:Out of 3,235,741 admissions to an ICU during the study period, 246,151 (7.6%) met the consensus definition for chronic critical illness. The most common eligibility conditions were prolonged acute mechanical ventilation (72.0% of eligible admissions) and sepsis (63.7% of eligible admissions). Among patients meeting chronic critical illness criteria through sepsis, the infections were community acquired in 48.5% and hospital acquired in 51.5%. In-hospital mortality was 30.9% with little change over the study period. The overall population-based prevalence was 34.4 per 100,000. The prevalence varied substantially with age, peaking at 82.1 per 100,000 individuals 75–79 years old but then declining coincident with a rise in mortality before day 8 in otherwise eligible patients. Extrapolating to the entire United States, for 2009, we estimated a total of 380,001 cases; 107,880 in-hospital deaths and

Understanding the potential role of statins in pneumonia and sepsis

26 billion in hospital-related costs. Conclusions:Using a consensus-based definition, the prevalence, hospital mortality, and costs of chronic critical illness are substantial. Chronic critical illness is particularly common in the elderly although in very old patients the prevalence declines, in part because of an increase in early mortality among potentially eligible patients.