Rahul Nanchal

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.

Liberation From Mechanical Ventilation in Critically Ill Adults: An Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline: Inspiratory Pressure Augmentation During Spontaneous Breathing Trials, Protocols Minimizing Sedation, and Noninvasive Ventilation Immediately After Extubation.

Background An update of evidence‐based guidelines concerning liberation from mechanical ventilation is needed as new evidence has become available. The American College of Chest Physicians (CHEST) and the American Thoracic Society (ATS) have collaborated to provide recommendations to clinicians concerning liberation from the ventilator. Methods Comprehensive evidence syntheses, including meta‐analyses, were performed to summarize all available evidence relevant to the guideline panel’s questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, and the results were summarized in evidence profiles. The evidence syntheses were discussed and recommendations developed and approved by a multidisciplinary committee of experts in mechanical ventilation. Results Recommendations for three population, intervention, comparator, outcome (PICO) questions concerning ventilator liberation are presented in this document. The guideline panel considered the balance of desirable (benefits) and undesirable (burdens, adverse effects, costs) consequences, quality of evidence, feasibility, and acceptability of various interventions with respect to the selected questions. Conditional (weak) recommendations were made to use inspiratory pressure augmentation in the initial spontaneous breathing trial (SBT) and to use protocols to minimize sedation for patients ventilated for more than 24 h. A strong recommendation was made to use preventive noninvasive ventilation (NIV) for high‐risk patients ventilated for more than 24 h immediately after extubation to improve selected outcomes. The recommendations were limited by the quality of the available evidence. Conclusions The guideline panel provided recommendations for inspiratory pressure augmentation during an initial SBT, protocols minimizing sedation, and preventative NIV, in relation to ventilator liberation.

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.

Structural and functional alterations in the rat lung following whole thoracic irradiation with moderate doses: injury and recovery

Purpose: To characterize structural and functional injuries following a single dose of whole-thorax irradiation that might be survivable after a nuclear attack/accident. Methods: Rats were exposed to 5 or 10 Gy of X-rays to the whole thorax with other organs shielded. Non-invasive measurements of breathing rate and arterial oxygen saturation, and invasive evaluations of bronchoalveolar lavage fluid, (for total protein, Clara cell secretory protein), vascular reactivity and histology were conducted for at least 6 time points up to 52 weeks after irradiation. Results: Irradiation with 10 Gy resulted in increased breathing rate, a reduction in oxygen saturation, an increase in bronchoalveolar lavage fluid protein and attenuation of vascular reactivity between 4–12 weeks after irradiation. These changes were not observed with the lower dose of 5 Gy. Histological examination revealed perivascular edema at 4–8 weeks after exposure to both doses, and mild fibrosis beyond 20 weeks after 10 Gy. Conclusions: Single-dose exposure of rat thorax to 10 but not 5 Gy X-irradiation resulted in a decrease in oxygen uptake and vasoreactivity and an increase in respiratory rate, which paralleled early pulmonary vascular pathology. Vascular edema resolved and was replaced by mild fibrosis beyond 20 weeks after exposure, while lung function recovered.

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.

Chronic Kidney Disease and End-Stage Renal Disease Predict Higher Risk of Mortality in Patients with Primary Upper Gastrointestinal Bleeding

Background: The outcome of gastrointestinal bleeding in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients is difficult to discern from the literature. Many publications are small, single-center series or are from an era prior to advanced interventional endoscopy, widespread use of proton pump inhibitors or treatment for Helicobacter pylori infections. In this study, we quantify the role of CKD and ESRD as independent predictors of mortality in patients admitted to the hospital with a principal diagnosis of primary upper gastrointestinal bleeding (UGIB). Methods: We used the Nationwide Inpatient Sample that contains data on approximately 8 million admissions in 1,000 hospitals chosen to approximate a 20% stratified sample of all US facilities. Patients discharged with the principal diagnosis of primary UGIB, CKD or ESRD were identified through the ninth revision of the International Classification of Diseases, clinical modification (ICD-9-CM) codes. The outcome variables included frequency and in-hospital mortality of UGIB in CKD and ESRD patients as compared to non-CKD patients and were analyzed using logistic regression modeling. Results: In 2007, out of a total of 398,213 admissions with a diagnosis of primary UGIB, 35,985 were in CKD, 14,983 in ESRD, and 347,245 in non-renal disease groups. The OR for primary UGIB hospitalization in CKD and ESRD was 1.30 (95% CI 1.17–1.46) and 1.84 (95% CI 1.61–2.09), respectively. The corresponding all-cause mortality OR was 1.47 (95% CI 1.21–1.78) and 3.02 (95% CI 2.23–4.1), respectively. Conclusion: Patients with CKD or ESRD admitted with primary UGIB have up to three times higher risk of all-cause in-hospital mortality, warranting heightened vigilance by their clinicians.

Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit

Objectives: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. Design: Observational cohort study. Setting: Seven hundred and thirty ICUs in 84 countries. Patients: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. Measurements and Main Results: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (–90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (–951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock. Conclusions: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.

Cotton dust lung diseases.

Purpose of review Although, in the industrialized world, there is a significant decline in the prevalence of cotton dust lung diseases, studies show an increasing incidence in the developing world. With rapid industrialization of the developing world, cotton dust-induced lung diseases are poised to become a global health problem. Discovery of other vegetable dusts causing similar conditions and appreciation of a wider variety of clinical features also make this an opportune time to review this topic. Recent findings In addition to chronic exposure-related byssinosis and less common forms of acute byssinosis, recent reports describe the rare occurrence of cotton dust-induced pulmonary fibrosis. New data also relate long-term cotton dust exposure to symptoms and physiologic changes of chronic obstructive pulmonary disease. There have also been new developments relating the pathogenesis of cotton dust airway disease to endotoxin lipopolysaccharide found in cotton dust and bract extracts. Summary Establishment of an association between prolonged exposure to cotton and other vegetable dusts and symptoms of chronic obstructive pulmonary disease widens the clinical implication of cotton dust exposure. In addition, accumulating knowledge of endotoxins will bring about promising new developments reshaping industrial safety standards and measures to prevent cotton dust exposure.

Being Overweight Is Associated With Greater Survival in ICU Patients : Results From the Intensive Care Over Nations Audit

Objective:To assess the effect of body mass index on ICU outcome and on the development of ICU-acquired infection. Design:A substudy of the Intensive Care Over Nations audit. Setting:Seven hundred thirty ICUs in 84 countries. Patients:All adult ICU patients admitted between May 8 and 18, 2012, except those admitted for less than 24 hours for routine postoperative monitoring (n = 10,069). In this subanalysis, only patients with complete data on height and weight (measured or estimated) on ICU admission in order to calculate the body mass index were included (n = 8,829). Interventions:None. Measurements and Main Results:Underweight was defined as body mass index less than 18.5 kg/m2, normal weight as body mass index 18.5–24.9 kg/m2, overweight as body mass index 25–29.9 kg/m2, obese as body mass index 30–39.9 kg/m2, and morbidly obese as body mass index greater than or equal to 40 kg/m2. The mean body mass index was 26.4 ± 6.5 kg/m2. The ICU length of stay was similar among categories, but overweight and obese patients had longer hospital lengths of stay than patients with normal body mass index (10 [interquartile range, 5–21] and 11 [5–21] vs 9 [4–19] d; p < 0.01 pairwise). ICU mortality was lower in morbidly obese than in normal body mass index patients (11.2% vs 16.6%; p = 0.015). In-hospital mortality was lower in morbidly obese and overweight patients and higher in underweight patients than in those with normal body mass index. In a multilevel Cox proportional hazard analysis, underweight was independently associated with a higher hazard of 60-day in-hospital death (hazard ratio, 1.32; 95% CI, 1.05–1.65; p = 0.018), whereas overweight was associated with a lower hazard (hazard ratio, 0.79; 95% CI, 0.71–0.89; p < 0.001). No body mass index category was associated with an increased hazard of ICU-acquired infection. Conclusions:In this large cohort of critically ill patients, underweight was independently associated with a higher hazard of 60-day in-hospital death and overweight with a lower hazard. None of the body mass index categories as independently associated with an increased hazard of infection during the ICU stay.

An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests

Background: Interventions that lead to earlier liberation from mechanical ventilation can improve patient outcomes. This guideline, a collaborative effort between the American Thoracic Society and the American College of Chest Physicians, provides evidence‐based recommendations to optimize liberation from mechanical ventilation in critically ill adults. Methods: Two methodologists performed evidence syntheses to summarize available evidence relevant to key questions about liberation from mechanical ventilation. The methodologists appraised the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach and summarized the results in evidence profiles. The guideline panel then formulated recommendations after considering the balance of desirable consequences (benefits) versus undesirable consequences (burdens, adverse effects, and costs), the certainty in the evidence, and the feasibility and acceptability of various interventions. Recommendations were rated as strong or conditional. Results: The guideline panel made four conditional recommendations related to rehabilitation protocols, ventilator liberation protocols, and cuff leak tests. The recommendations were for acutely hospitalized adults mechanically ventilated for more than 24 hours to receive protocolized rehabilitation directed toward early mobilization, be managed with a ventilator liberation protocol, be assessed with a cuff leak test if they meet extubation criteria but are deemed high risk for postextubation stridor, and be administered systemic steroids for at least 4 hours before extubation if they fail the cuff leak test. Conclusions: The American Thoracic Society/American College of Chest Physicians recommendations are intended to support healthcare professionals in their decisions related to liberating critically ill adults from mechanical ventilation.