Hallie C. Prescott

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis

BACKGROUND In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. METHODS We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3‐hour bundle of care for patients with sepsis (i.e., blood cultures, broad‐spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3‐hour bundle and risk‐adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. RESULTS Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3‐hour bundle completed within 3 hours. The median time to completion of the 3‐hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3‐hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk‐adjusted in‐hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). CONCLUSIONS More rapid completion of a 3‐hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk‐adjusted in‐hospital mortality. (Funded by the National Institutes of Health and others.)

Late mortality after sepsis: propensity matched cohort study

Objectives To determine whether late mortality after sepsis is driven predominantly by pre-existing comorbid disease or is the result of sepsis itself. Deign Observational cohort study. Setting US Health and Retirement Study. Participants 960 patients aged ≥65 (1998-2010) with fee-for-service Medicare coverage who were admitted to hospital with sepsis. Patients were matched to 777 adults not currently in hospital, 788 patients admitted with non-sepsis infection, and 504 patients admitted with acute sterile inflammatory conditions. Main outcome measures Late (31 days to two years) mortality and odds of death at various intervals. Results Sepsis was associated with a 22.1% (95% confidence interval 17.5% to 26.7%) absolute increase in late mortality relative to adults not in hospital, a 10.4% (5.4% to 15.4%) absolute increase relative to patients admitted with non-sepsis infection, and a 16.2% (10.2% to 22.2%) absolute increase relative to patients admitted with sterile inflammatory conditions (P<0.001 for each comparison). Mortality remained higher for at least two years relative to adults not in hospital. Conclusions More than one in five patients who survives sepsis has a late death not explained by health status before sepsis.

Obesity and 1-year outcomes in older Americans with severe sepsis.

Objectives:Although critical care physicians view obesity as an independent poor prognostic marker, growing evidence suggests that obesity is, instead, associated with improved mortality following ICU admission. However, this prior empirical work may be biased by preferential admission of obese patients to ICUs, and little is known about other patient-centered outcomes following critical illness. We sought to determine whether 1-year mortality, healthcare utilization, and functional outcomes following a severe sepsis hospitalization differ by body mass index. Design:Observational cohort study. Setting:U.S. hospitals. Patients:We analyzed 1,404 severe sepsis hospitalizations (1999–2005) among Medicare beneficiaries enrolled in the nationally representative Health and Retirement Study, of which 597 (42.5%) were normal weight, 473 (33.7%) were overweight, and 334 (23.8%) were obese or severely obese, as assessed at their survey prior to acute illness. Underweight patients were excluded a priori. Interventions:None. Measurements and Main Results:Using Medicare claims, we identified severe sepsis hospitalizations and measured inpatient healthcare facility use and calculated total and itemized Medicare spending in the year following hospital discharge. Using the National Death Index, we determined mortality. We ascertained pre- and postmorbid functional status from survey data. Patients with greater body mass indexes experienced lower 1-year mortality compared with nonobese patients, and there was a dose-response relationship such that obese (odds ratio = 0.59; 95% CI, 0.39–0.88) and severely obese patients (odds ratio = 0.46; 95% CI, 0.26–0.80) had the lowest mortality. Total days in a healthcare facility and Medicare expenditures were greater for obese patients (p < 0.01 for both comparisons), but average daily utilization (p = 0.44) and Medicare spending were similar (p = 0.65) among normal, overweight, and obese survivors. Total function limitations following severe sepsis did not differ by body mass index category (p = 0.64). Conclusions:Obesity is associated with improved mortality among severe sepsis patients. Due to longer survival, obese sepsis survivors use more healthcare and result in higher Medicare spending in the year following hospitalization. Median daily healthcare utilization was similar across body mass index categories.

Readmission Diagnoses After Hospitalization for Severe Sepsis and Other Acute Medical Conditions

Readmission Diagnoses After Hospitalization for Severe Sepsis and Other Acute Medical Conditions Patients are frequently rehospitalized within 90 days after having severe sepsis.1 Little is known, however, about the reasons for readmission and whether they can be reduced. We sought to determine the most common readmission diagnoses after hospitalization for severe sepsis, the extent to which readmissions may be potentially preventable by posthospitalization ambulatory care, and whether the pattern of readmission diagnoses differs compared with that of other acute medical conditions.

Hospitalization Type and Subsequent Severe Sepsis.

RATIONALE Hospitalization is associated with microbiome perturbation (dysbiosis), and this perturbation is more severe in patients treated with antimicrobials. OBJECTIVES To evaluate whether hospitalizations known to be associated with periods of microbiome perturbation are associated with increased risk of severe sepsis after hospital discharge. METHODS We studied participants in the U.S. Health and Retirement Study with linked Medicare claims (1998-2010). We measured whether three hospitalization types associated with increasing severity of probable dysbiosis (non-infection-related hospitalization, infection-related hospitalization, and hospitalization with Clostridium difficile infection [CDI]) were associated with increasing risk for severe sepsis in the 90 days after hospital discharge. We used two study designs: the first was a longitudinal design with between-person comparisons and the second was a self-controlled case series design using within-person comparison. MEASUREMENTS AND MAIN RESULTS We identified 43,095 hospitalizations among 10,996 Health and Retirement Study-Medicare participants. In the 90 days following non-infection-related hospitalization, infection-related hospitalization, and hospitalization with CDI, adjusted probabilities of subsequent admission for severe sepsis were 4.1% (95% confidence interval [CI], 3.8-4.4%), 7.1% (95% CI, 6.6-7.6%), and 10.7% (95% CI, 7.7-13.8%), respectively. The incidence rate ratio (IRR) of severe sepsis was 3.3-fold greater during the 90 days after hospitalizations than during other observation periods. The IRR was 30% greater after an infection-related hospitalization versus a non-infection-related hospitalization. The IRR was 70% greater after a hospitalization with CDI than an infection-related hospitalization without CDI. CONCLUSIONS There is a strong dose-response relationship between events known to result in dysbiosis and subsequent severe sepsis hospitalization that is not present for rehospitalization for nonsepsis diagnoses.

Hospital readmission and healthcare utilization following sepsis in community settings

BACKGROUND Sepsis, the most expensive cause of hospitalization in the United States, is associated with high morbidity and mortality. However, healthcare utilization patterns following sepsis are poorly understood. OBJECTIVE To identify patient-level factors that contribute to postsepsis mortality and healthcare utilization. DESIGN, SETTING, PATIENTS A retrospective study of sepsis patients drawn from 21 community-based hospitals in Kaiser Permanente Northern California in 2010. MEASUREMENTS We determined 1-year survival and use of outpatient and facility-based healthcare before and after sepsis and used logistic regression to identify the factors that contributed to early readmission (within 30 days) and high utilization (≥ 15% of living days spent in facility-based care). RESULTS Among 6344 sepsis patients, 5479 (86.4%) survived to hospital discharge. Mean age was 72 years with 28.9% of patients aged <65 years. Postsepsis survival was strongly modified by age; 1-year survival was 94.1% for <45 year olds and 54.4% for ≥ 85 year olds. A total of 978 (17.9%) patients were readmitted within 30 days; only a minority of all rehospitalizations were for infection. After sepsis, adjusted healthcare utilization increased nearly 3-fold compared with presepsis levels and was strongly modified by age. Patient factors including acute severity of illness, hospital length of stay, and the need for intensive care were associated with early readmission and high healthcare utilization; however, the dominant factors explaining variability-comorbid disease burden and high presepsis utilization-were present prior to sepsis admission. CONCLUSION Postsepsis survival and healthcare utilization were most strongly influenced by patient factors already present prior to sepsis hospitalization.

Analysis of Culture-Dependent versus Culture-Independent Techniques for Identification of Bacteria in Clinically Obtained Bronchoalveolar Lavage Fluid

ABSTRACT The diagnosis and management of pneumonia are limited by the use of culture-based techniques of microbial identification, which may fail to identify unculturable, fastidious, and metabolically active viable but unculturable bacteria. Novel high-throughput culture-independent techniques hold promise but have not been systematically compared to conventional culture. We analyzed 46 clinically obtained bronchoalveolar lavage (BAL) fluid specimens from symptomatic and asymptomatic lung transplant recipients both by culture (using a clinical microbiology laboratory protocol) and by bacterial 16S rRNA gene pyrosequencing. Bacteria were identified in 44 of 46 (95.7%) BAL fluid specimens by culture-independent sequencing, significantly more than the number of specimens in which bacteria were detected (37 of 46, 80.4%, P ≤ 0.05) or “pathogen” species reported (18 of 46, 39.1%, P ≤ 0.0001) via culture. Identification of bacteria by culture was positively associated with culture-independent indices of infection (total bacterial DNA burden and low bacterial community diversity) (P ≤ 0.01). In BAL fluid specimens with no culture growth, the amount of bacterial DNA was greater than that in reagent and rinse controls, and communities were markedly dominated by select Gammaproteobacteria, notably Escherichia species and Pseudomonas fluorescens. Culture growth above the threshold of 104 CFU/ml was correlated with increased bacterial DNA burden (P < 0.01), decreased community diversity (P < 0.05), and increased relative abundance of Pseudomonas aeruginosa (P < 0.001). We present two case studies in which culture-independent techniques identified a respiratory pathogen missed by culture and clarified whether a cultured “oral flora” species represented a state of acute infection. In summary, we found that bacterial culture of BAL fluid is largely effective in discriminating acute infection from its absence and identified some specific limitations of BAL fluid culture in the diagnosis of pneumonia. We report the first correlation of quantitative BAL fluid culture results with culture-independent evidence of infection.

Cell-associated bacteria in the human lung microbiome

BackgroundRecent studies have revealed that bronchoalveolar lavage (BAL) fluid contains previously unappreciated communities of bacteria. In vitro and in vivo studies have shown that host inflammatory signals prompt bacteria to disperse from cell-associated biofilms and adopt a virulent free-living phenotype. The proportion of the lung microbiota that is cell-associated is unknown.ResultsForty-six BAL specimens were obtained from lung transplant recipients and divided into two aliquots: ‘whole BAL’ and ‘acellular BAL,’ the latter processed with a low-speed, short-duration centrifugation step. Both aliquots were analyzed via bacterial 16S rRNA gene pyrosequencing. The BAL specimens represented a wide spectrum of lung health, ranging from healthy and asymptomatic to acutely infected. Bacterial signal was detected in 52% of acellular BAL aliquots, fewer than were detected in whole BAL (96%, p ≤ 0.0001). Detection of bacteria in acellular BAL was associated with indices of acute infection [BAL neutrophilia, high total bacterial (16S) DNA, low community diversity, p < 0.01 for all] and, independently, with low relative abundance of specific taxonomic groups (p < 0.05). When whole and acellular aliquots from the same bronchoscopy were directly compared, acellular BAL contained fewer bacterial species (p < 0.05); whole and acellular BAL similarity was positively associated with evidence of infection and negatively associated with relative abundance of several prominent taxa (p < 0.001). Acellular BAL contained decreased relative abundance of Prevotella spp. (p < 0.05) and Pseudomonas fluorescens (p < 0.05).ConclusionsWe present a novel methodological and analytical approach to the localization of lung microbiota and show that prominent members of the lung microbiome are cell-associated, potentially via biofilms, cell adhesion, or intracellularity.

Longitudinal Changes in Icu Admissions Among Elderly Patients in the United States.

Objectives: Changes in population demographics and comorbid illness prevalence, improvements in medical care, and shifts in care delivery may be driving changes in the composition of patients admitted to the ICU. We sought to describe the changing demographics, diagnoses, and outcomes of patients admitted to critical care units in the U.S. hospitals. Design: Retrospective cohort study. Setting: U.S. hospitals. Patients: There were 27.8 million elderly (age, > 64 yr) fee-for-service Medicare beneficiaries hospitalized with an intensive care or coronary care room and board charge from 1996 to 2010. Interventions: None. Measurements and Main Results: We aggregated primary International Classification of Diseases, 9th Revision, Clinical Modification discharge diagnosis codes into diagnoses and disease categories. We examined trends in demographics, primary diagnosis, and outcomes among patients with critical care stays. Between 1996 and 2010, we found significant declines in patients with a primary diagnosis of cardiovascular disease, including coronary artery disease (26.6 to 12.6% of admissions) and congestive heart failure (8.5 to 5.4% of admissions). Patients with infectious diseases increased from 8.8% to 17.2% of admissions, and explicitly labeled sepsis moved from the 11th-ranked diagnosis in 1996 to the top-ranked primary discharge diagnosis in 2010. Crude in-hospital mortality rose (11.3 to 12.0%), whereas discharge destinations among survivors shifted, with an increase in discharges to hospice and postacute care facilities. Conclusions: Primary diagnoses of patients admitted to critical care units have substantially changed over 15 years. Funding agencies, physician accreditation groups, and quality improvement initiatives should ensure that their efforts account for the shifting epidemiology of critical illness.

Enhancing Recovery From Sepsis: A Review

Importance Survival from sepsis has improved in recent years, resulting in an increasing number of patients who have survived sepsis treatment. Current sepsis guidelines do not provide guidance on posthospital care or recovery. Observations Each year, more than 19 million individuals develop sepsis, defined as a life-threatening acute organ dysfunction secondary to infection. Approximately 14 million survive to hospital discharge and their prognosis varies. Half of patients recover, one-third die during the following year, and one-sixth have severe persistent impairments. Impairments include development of an average of 1 to 2 new functional limitations (eg, inability to bathe or dress independently), a 3-fold increase in prevalence of moderate to severe cognitive impairment (from 6.1% before hospitalization to 16.7% after hospitalization), and a high prevalence of mental health problems, including anxiety (32% of patients who survive), depression (29%), or posttraumatic stress disorder (44%). About 40% of patients are rehospitalized within 90 days of discharge, often for conditions that are potentially treatable in the outpatient setting, such as infection (11.9%) and exacerbation of heart failure (5.5%). Compared with patients hospitalized for other diagnoses, those who survive sepsis (11.9%) are at increased risk of recurrent infection than matched patients (8.0%) matched patients (P < .001), acute renal failure (3.3% vs 1.2%, P < .001), and new cardiovascular events (adjusted hazard ratio [HR] range, 1.1-1.4). Reasons for deterioration of health after sepsis are multifactorial and include accelerated progression of preexisting chronic conditions, residual organ damage, and impaired immune function. Characteristics associated with complications after hospital discharge for sepsis treatment are not fully understood but include both poorer presepsis health status, characteristics of the acute septic episode (eg, severity of infection, host response to infection), and quality of hospital treatment (eg, timeliness of initial sepsis care, avoidance of treatment-related harms). Although there is a paucity of clinical trial evidence to support specific postdischarge rehabilitation treatment, experts recommend referral to physical therapy to improve exercise capacity, strength, and independent completion of activities of daily living. This recommendation is supported by an observational study involving 30 000 sepsis survivors that found that referral to rehabilitation within 90 days was associated with lower risk of 10-year mortality compared with propensity-matched controls (adjusted HR, 0.94; 95% CI, 0.92-0.97, P < .001). Conclusions and Relevance In the months after hospital discharge for sepsis, management should focus on (1) identifying new physical, mental, and cognitive problems and referring for appropriate treatment, (2) reviewing and adjusting long-term medications, and (3) evaluating for treatable conditions that commonly result in hospitalization, such as infection, heart failure, renal failure, and aspiration. For patients with poor or declining health prior to sepsis who experience further deterioration after sepsis, it may be appropriate to focus on palliation of symptoms.