Amit Taneja

Nationwide Trends of Severe Sepsis in the 21st Century (2000–2007)

BACKGROUND Severe sepsis is common and often fatal. The expanding armamentarium of evidence-based therapies has improved the outcomes of persons with this disease. However, the existing national estimates of the frequency and outcomes of severe sepsis were made before many of the recent therapeutic advances. Therefore, it is important to study the outcomes of this disease in an aging US population with rising comorbidities. METHODS We used the Healthcare Costs and Utilization Projects Nationwide Inpatient Sample (NIS) to estimate the frequency and outcomes of severe sepsis hospitalizations between 2000 and 2007. We identified hospitalizations for severe sepsis using International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating the presence of sepsis and organ system failure. Using weights from NIS, we estimated the number of hospitalizations for severe sepsis in each year. We combined these with census data to determine the number of severe sepsis hospitalizations per 100,000 persons. We used discharge status to identify in-hospital mortality and compared mortality rates in 2000 with those in 2007 after adjusting for demographics, number of organ systems failing, and presence of comorbid conditions. RESULTS The number of severe sepsis hospitalizations per 100,000 persons increased from 143 in 2000 to 343 in 2007. The mean number of organ system failures during admission increased from 1.6 to 1.9 (P < .001). The mean length of hospital stay decreased from 17.3 to 14.9 days. The mortality rate decreased from 39% to 27%. However, more admissions ended with discharge to a long-term care facility in 2007 than in 2000 (35% vs 27%, P < .001). CONCLUSIONS An increasing number of admissions for severe sepsis combined with declining mortality rates contribute to more individuals surviving to hospital discharge. Importantly, this leads to more survivors being discharged to skilled nursing facilities and home with in-home care. Increased attention to this phenomenon is warranted.

Pulmonary Embolism: The Weekend Effect

BACKGROUND Pulmonary embolism is a common, often fatal condition that requires timely recognition and rapid institution of therapy. Previous studies have documented worse outcomes for weekend admissions for a variety of time-sensitive medical conditions. This phenomenon has not been clearly demonstrated for pulmonary embolism. METHODS We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the years 2000 to 2008 to identify people with a principal discharge diagnosis of pulmonary embolism. We classified admissions as weekend if they occurred between midnight Friday and midnight Sunday. We compared all-cause in-hospital mortality between weekend and weekday admissions and investigated the timing of inferior vena cava (IVC) filter placement and thrombolytic infusion as potential explanations for differences in mortality. RESULTS Unadjusted mortality was higher for weekend admissions than weekday admissions (OR, 1.19; 95% CI, 1.13-1.24). This increase in mortality remained statistically significant after controlling for potential confounding variables (OR, 1.17; 95% CI, 1.11-1.22). Among patients who received an IVC filter, a larger proportion of those admitted on a weekday than on the weekend received it on their first hospital day (38% vs 29%, P < .001). The timing of thrombolytic therapy did not differ between weekday and weekend admissions. CONCLUSIONS Weekend admissions for pulmonary embolism were associated with higher mortality than weekday admissions. Our finding that IVC filter placement occurred later in the hospital course for patients admitted on weekends with pulmonary embolism suggests differences in the timeliness of diagnosis and treatment between weekday and weekend admissions. Regardless of cause, physicians should be aware that weekend admissions for pulmonary embolism have a 20% increased risk of death and warrant closer attention than provided during the week.

Pulmonary embolism in patients with CKD and ESRD.

BACKGROUND AND OBJECTIVES CKD and ESRD are growing burdens. It is unclear whether these conditions affect pulmonary embolism (PE) risk, given that they affect both procoagulant and anticoagulant factors. This study examined the frequency and associated outcomes of PE in CKD and ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The Healthcare Cost and Utilization Projects Nationwide Inpatient Sample was used to estimate the frequency and outcomes of PE in adults with CKD and ESRD. Hospitalizations for the principal diagnosis of PE and presence of CKD or ESRD were identified using International Classification of Diseases, Ninth Revision codes. Data from the annual US Census and US Renal Data System reports were used to calculate the number of adults with CKD, ESRD, and normal kidney function (NKF) as well as the annual incidence of PE in each group. Logistic regression modeling was used to compare in-hospital mortality among persons admitted for PE who had ESRD or CKD to those without these conditions. RESULTS The annual frequency of PE was 527 per 100,000, 204 per 100,000, and 66 per 100,000 persons with ESRD, CKD, and NKF, respectively. In-hospital mortality was higher for persons with ESRD and CKD (P<0.001) compared with persons with NKF. Median length of stay was longer by 1 day in CKD and 2 days in ESRD than among those with NKF. CONCLUSIONS Persons with CKD and ESRD are more likely to have PE than persons with NKF. Once they have PE, they are more likely to die in the hospital.

Acute Myocardial Infarction: A National Analysis of the Weekend Effect Over Time

Previous work has shown that persons admitted over the weekend for certain time-sensitive acute conditions, including acute myocardial infarction (AMI), have increased mortality risk compared with similar counterparts admitted on weekdays [(1)][1]. This excess mortality risk for AMI has been partly

Utilization of Mechanical Ventilation for Asthma Exacerbations — Analysis of a National Database

BACKGROUND: The current frequency of noninvasive (NIV) and invasive mechanical ventilation use in asthma exacerbations (AEs) and the relationship to outcomes are unknown. METHODS: We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample to identify patients discharged with a principal diagnosis of AE. For each discharge, we determined whether NIV or invasive mechanical ventilation was initiated during the first 2 hospital days. Using multivariate logistic regression to adjust for potential confounders, we determined whether use of mechanical ventilation and in-hospital mortality changed between 2000 and 2008. RESULTS: The number of AEs increased by 15.8% from 2000 to 2008. The proportion of admissions for which invasive mechanical ventilation was used during the first 2 days decreased from 1.4% in 2000 to 0.73% in 2008, whereas NIV use increased from 0.34% to 1.9%. The adjusted mortality from AEs requiring NIV or invasive mechanical ventilation was unchanged from 2000 to 2008. The hospital stay was also unchanged. CONCLUSIONS: There was a substantial increase in the use of mechanical ventilation, accompanied by a shift from invasive mechanical ventilation to NIV. Although we could not determine the clinical reasons for this increase, hospital stay and mortality were unchanged. A randomized trial is needed to determine whether NIV can improve outcomes in AEs before widespread adoption makes it impossible to conduct such a trial.

The association of lacking insurance with outcomes of severe sepsis: retrospective analysis of an administrative database*.

Objective:Patients with severe sepsis have high mortality that is improved by timely, often expensive, treatments. Patients without insurance are more likely to delay seeking care; they may also receive less intense care. Design:We performed a retrospective analysis of administrative database—Healthcare Costs and Utilization Project’s Nationwide Inpatient Sample—to test whether mortality is more likely among uninsured patients hospitalized for severe sepsis. Patients:None. Interventions:We used International Classification of Diseases—9th Revision, Clinical Modification, codes indicating sepsis and organ system failure to identify hospitalizations for severe sepsis among patients aged 18–64 between 2000 and 2008. We excluded patients with end-stage renal disease or solid organ transplants because very few are uninsured. We performed multivariate logistic regression modeling to examine the association of insurance status and in-hospital mortality, adjusted for patient and hospital characteristics. We performed subgroup analysis to examine whether the impact of insurance status varied by geographical region; by patient age, sex, or race; or by hospital characteristics such as teaching status, size, or ownership. We used similar methods to examine the impact of insurance status on the use of certain procedures, length of stay, and discharge destination. Measurements and Main Results:There were 1,600,269 discharges with severe sepsis from 2000 through 2008 in the age group 18–64 years. Uninsured people, who accounted for 7.5% of admissions with severe sepsis, had higher adjusted odds of mortality (odds ratio, 1.43; 95% CI, 1.37–1.47) than privately insured people. The higher mortality in uninsured was present in all subgroups and was similar in each year from 2000 to 2008. After adjustment, uninsured individuals had a slightly shorter length of stay than insured people and were less likely to receive five of the six interventions we examined. They were also less likely to be discharged to skilled nursing facilities or with home healthcare after discharge. Conclusions:Uninsured are more likely to die following admission for severe sepsis than patients with insurance, even after adjusting for potential confounders. This was not due to a hospital effect or demographic or clinical factors available in our administrative database. Further research should examine the mechanisms that lead to this association.

The association of serum bilirubin levels on the outcomes of severe sepsis

Purpose: Admission serum bilirubin levels have been incorporated into severity of illness scoring systems in critical illness as a marker of liver dysfunction. The purpose of our study is to determine the independent association of serum bilirubin with mortality in severe sepsis and septic shock. Methods: We conducted a retrospective study of adult patients admitted with severe sepsis and septic shock. We excluded patients with a prior history of liver disease. We identified the highest serum bilirubin within 72 hours of admission and stratified bilirubin levels into ≤1 mg/dL (normal), 1.1 to 2 mg/dL (abnormal up to 2 mg/dL), and >2 mg/dL. We sought to determine the independent association of hyperbilirubinemia with mortality and length of intensive care unit stay in persons with severe sepsis and septic shock. Results: A total of 251 patients met criteria for severe sepsis. In all, 200 patients had a bilirubin of <1 mg/dL, and 51 had a bilirubin of >1 mg/dL. Of these 51, 12 had a bilirubin >2 mg/dL. Mortality was 12%, 24%, and 42% in persons with a bilirubin ≤1, 1.1 to 2, and >2 mg/dL, respectively. Compared to those with a bilirubin ≤ 1 mg/dL, adjusted odds of mortality in patients were 3.85 (95% confidence interval [CI] 1.21-12.2) and 9.85 (95% CI 1.92-50.5) times higher in persons with bilirubin levels between 1.1 and 2 and >2 mg/dL, respectively. Conclusion: After multivariable adjustment for potential confounding factors, elevated serum bilirubin levels within 72 hours of admission are associated with an increased risk of mortality in patients with severe sepsis and septic shock. Prospective studies are warranted to further validate our findings.

Outcomes of morbidly obese patients receiving invasive mechanical ventilation: a nationwide analysis.

BACKGROUND Critically ill, morbidly obese patients (BMI≥40 kg/m2) are at high risk of respiratory failure requiring invasive mechanical ventilation (IMV). It is not clear if outcomes of critically ill, obese patients are affected by obesity. Due to limited cardiopulmonary reserve, they may have poor outcomes. However, literature to this effect is limited and conflicted. METHODS We used the Nationwide Inpatient Sample from 2004 to 2008 to examine the outcomes of morbidly obese people receiving IMV and compared them to nonobese people. We identified hospitalizations requiring IMV and morbid obesity using International Classification of Diseases, 9th Revision, Clinical Modification codes. Primary outcomes studied were inhospital mortality, rates of prolonged mechanical ventilation (≥96 h), and tracheostomy. Multivariable logistic regression was used to adjust for potential confounding variables. We also examined outcomes stratified by number of organs failing. RESULTS Of all hospitalized, morbidly obese people, 2.9% underwent IMV. Mean age, comorbidity score, and severity of illness were lower in morbidly obese people. The adjusted mortality was not significantly different in morbidly obese people (OR 0.89; 95% CI, 0.74-1.06). When stratified by severity of disease, there was a stepwise increase in risk for mortality among morbidly obese people relative to nonobese people (range: OR, 0.77; 95% CI, 0.58-1.01 for only respiratory failure, to OR, 4.14; 95% CI, 1.11-15.3 for four or more organs failing). Rates of prolonged mechanical ventilation were similar, but rate of tracheostomy (OR 2.19; 95% CI, 1.77-2.69) was significantly higher in patients who were morbidly obese. CONCLUSIONS Morbidly obese people undergoing IMV have a similar risk for death as nonobese people if only respiratory failure is present. When more organs fail, morbidly obese people have increased risk for mortality compared with nonobese people.

Acute Kidney Injury Requiring Dialysis in Severe Sepsis

RATIONALE Understanding the changing incidence and impact of acute kidney injury requiring dialysis in patients with severe sepsis will allow better risk stratification, design of clinical trials, and guide resource allocation. OBJECTIVES To assess the longitudinal incidence of acute kidney injury requiring dialysis and its impact on mortality in patients with severe sepsis. METHODS Retrospective cohort study of adults (≥20 yr) hospitalized with severe sepsis from 2000 to 2009 in the United States using a nationally representative database. MEASUREMENTS AND MAIN RESULTS We calculated the incidences of acute kidney injury requiring dialysis and mortality over time. We used linear regression to assess temporal trends. We used logistic regression to estimate the odds of acute kidney injury requiring dialysis and mortality. Of the estimated 5,257,907 hospitalizations with severe sepsis, 6.1% had acute kidney injury requiring dialysis. The odds of acquiring acute kidney injury requiring dialysis increased by 14% in 2009 compared with 2000. Mortality in patients with acute kidney injury requiring dialysis was higher (43.6% vs. 24.9%; P < 0.001). After multivariable adjustment, odds of mortality declined 61% by the year 2009. Acute kidney injury requiring dialysis remained an independent predictor of mortality in patients with severe sepsis, although its influence on mortality declined with time. CONCLUSIONS Incidence of acute kidney injury requiring dialysis in patients with severe sepsis has increased over time; conversely, associated mortality has declined. The likelihood of demise from acute kidney injury requiring dialysis in patients with severe sepsis has also declined.

Severe sepsis in hematopoietic stem cell transplant recipients

Objective:Severe sepsis requires timely management and has high mortality if care is delayed. Hematopoietic stem cell transplant recipients are more likely to be immunocompromised and are predisposed to serious infections. Reports of outcomes of severe sepsis in this population are limited to data from single, tertiary care centers, and national outcomes data are missing. Design:Retrospective analysis of an administrative database. Setting:Twenty percent of community hospitals in United States, excluding federal hospitals. Subject:Patients with severe sepsis. Intervention:None. Measurements and Main Results:We used International Classification of Diseases, 9th Edition, Clinical Modification codes indicating the presence of sepsis and organ system failure to identify hospitalizations for severe sepsis between 2000 and 2008. We also used International Classification of Diseases, 9th Edition, Clinical Modification codes to identify hematopoietic stem cell transplant recipients. We compared outcomes of hematopoietic stem cell transplant recipients with severe sepsis during engraftment and subsequent admissions with a non–hematopoietic stem cell transplant cohort and excluded solid-organ transplantation from this cohort. We used mixed effect, multivariate logistic regression modeling with propensity score adjustment to examine factors associated with mortality of severe sepsis in hematopoietic stem cell transplant recipients. A total of 21,898 hematopoietic stem cell transplant recipients with severe sepsis were identified. The frequency of severe sepsis in hematopoietic stem cell transplant recipients was five times higher when compared with the non–hematopoietic stem cell transplant cohort. The unadjusted mortality was 32.9% in non–hematopoietic stem cell transplant cohort, which was similar to autologous hematopoietic stem cell transplant recipients (30.1%) and those who did not develop graft-versus-host disease (35%). Mortality was significantly higher in allogeneic transplants (55.1%, p < 0.001) and in those who developed graft-versus-host disease (47.9%, p < 0.001). After adjustment, during engraftment admission, the odds of in-hospital mortality in allogeneic hematopoietic stem cell transplant (odds ratio, 3.81; 95% CI, 2.39–6.07) and autologous hematopoietic stem cell transplant (odds ratio, 1.28; 95% CI, 1.06–1.53) recipients was significantly higher than non–hematopoietic stem cell transplant patients. Similarly, in subsequent admissions, hematopoietic stem cell transplant recipients with graft-versus-host disease (odds ratio, 2.14; 95% CI, 1.88–2.45) and without graft-versus-host disease (odds ratio, 1.35; 95% CI, 1.19–1.54) had significantly higher odds of mortality than non–hematopoietic stem cell transplant patients. Among patients with hematopoietic stem cell transplant, persons with autologous hematopoietic stem cell transplant and those without graft-versus-host disease fared better as compared with their allogeneic and graft-versus-host disease counterparts. Conclusions:Hematopoietic stem cell transplant recipients are more likely to develop severe sepsis and die following a severe sepsis episode than nontransplant patients. Autologous hematopoietic stem cell transplant recipients and those who do not develop graft-versus-host disease have significantly better outcomes than allogeneic and graft-versus-host disease patients.