Anxiety and agitation in mechanically ventilated patients.

During an ethnography conducted in an intensive care unit (ICU), we found that anxiety and agitation occurred frequently and were important considerations in the care of 30 patients weaning from prolonged mechanical ventilation. We conducted a secondary analysis to (a) describe characteristics of anxiety and agitation experienced by mechanically ventilated patients, (b) explore how clinicians recognized and interpreted anxiety and agitation, and (c) describe strategies and interventions used to manage anxiety and agitation with mechanically ventilated patients. We constructed the Anxiety/Agitation in Mechanical Ventilation Model to illustrate the multidimensional features of symptom recognition and management. Patients' ability to interact with the environment served as a basis for identification and management of anxiety or agitation. Clinicians' attributions about anxiety or agitation, and "knowing the patient," contributed to their assessment of patient responses. Clinicians chose strategies to overcome either the stimulus or the patient's appraisal of risk of the stimulus. This article contributes to the body of knowledge about symptom recognition and management in the ICU by providing a comprehensive model to guide future research and practice.

Nitrogen-enriched discharges from a highly managed watershed intensify red tide (Karenia brevis) blooms in southwest Florida.

Karenia brevis blooms on Florida's Gulf Coast severely affect regional ecosystems, coastal economies, and public health, and formulating effective management and policy strategies to address these blooms requires an advanced understanding of the processes driving them. Recent research suggests that natural processes explain offshore bloom initiation and shoreward transport, while anthropogenic nutrient inputs may intensify blooms upon arrival along the coast. However, past correlation studies have failed to detect compelling evidence linking coastal blooms to watershed covariates indicative of anthropogenic inputs. We explain why correlation is neither necessary nor sufficient to demonstrate a causal relationship-i.e., a persistent pattern of interaction governed by deterministic rules-and pursue an empirical investigation leveraging the fact that systematic temporal patterns may reveal systematic cause-and-effect relationships. Using time series derived from in-situ sample data, we applied singular spectrum analysis-a non-parametric spectral decomposition method-to recover deterministic signals in the dynamics of K. brevis blooms and upstream water quality and discharge covariates in the Charlotte Harbor region between 2012 and 2021. Next, we applied causal analysis methods based on chaos theory-i.e., convergent cross-mapping and S-mapping-to detect and quantify persistent, state-dependent interaction regimes between coastal blooms and watershed covariates. We discovered that nitrogen-enriched Caloosahatchee River discharges have consistently intensified K. brevis blooms to varying degrees over time. River discharge was typically most influential at the earliest stages of blooms, while total nitrogen concentrations exerted the strongest influence during blooms' growth/maintenance stages. These results indicate that discharges and nitrogen inputs influence blooms through distinct yet synergistic causal mechanisms. Additionally, we traced this anthropogenic influence upstream to Lake Okeechobee (which discharges to the Caloosahatchee River) and the Kissimmee River basin (which drains into Lake Okeechobee), suggesting that watershed-scale nutrient management and modifications to Lake Okeechobee discharge protocols will likely be necessary to mitigate coastal blooms.

Understanding the potential role of statins in pneumonia and sepsis.

OBJECTIVE: To examine the association of statin use with clinical outcomes and circulating biomarkers in community-acquired pneumonia and sepsis. DESIGN: Multicenter inception cohort study. SETTING: Emergency departments of 28 U.S. hospitals. PATIENTS: A total of 1895 subjects hospitalized with community-acquired pneumonia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our approach consisted of two different comparison cohorts, each reflecting methods used in prior publications in this area. We first compared subjects with prior statin use (prior use cohort), defined as a history of statin use in the week before admission, with those with no prior use. We then compared prior statin users whose statins were continued inhospital (continued use cohort) with those with either no prior use or no inhospital use. We adjusted for patient characteristics, including demographics, comorbid conditions, and illness severity, and accounted for healthy user effect and indication bias using propensity analysis. We determined risk of severe sepsis and 90-day mortality. We measured markers inflammation (tumor necrosis factor, interleukin-6, interleukin-10), coagulation (antithrombin, factor IX, plasminogen activator inhibitor, d-dimer, thrombin antithrombin complex), and lymphocyte cell surface protein expression during the first week of hospitalization. There were no differences in severe sepsis risk between statin users and nonusers for prior (30.8% vs. 30.7%, p = .98) or continued statin use (30.2% vs. 30.8%, p = .85) in univariate analyses and after adjusting for patient characteristics and propensity for statin use. Ninety-day mortality was similar in prior statin users (9.2% vs. 12.0%, p = .11) and lower in continued statin users (7.9% vs. 12.1%, p = .02). After adjusting for patient characteristics and propensity for statin use, there was no mortality benefit for prior (odds ratio, 0.90 [0.63-1.29]; p = .57) or continued statin use (odds ratio, 0.73 [0.47-1.13]; p = .15). Only antithrombin activity over time was higher in statin subjects, yet the magnitude of the difference was modest. There were no differences in other coagulation, inflammatory, or lymphocyte cell surface markers. CONCLUSIONS: We found no evidence of a protective effect for statin use on clinical outcomes and only modest differences in circulating biomarkers in community-acquired pneumonia, perhaps as a result of healthy user effects and indication bias.

Intensive care unit renal support therapy volume is not associated with patient outcome.

OBJECTIVE: Evidence suggests that patients requiring high-risk procedures benefit from care at institutions providing a large volume of these procedures. Our objective was to determine whether there is a volume-outcome relationship among intensive care unit patients receiving renal support therapy in two different healthcare systems (France and the United States). DESIGN: Retrospective cohort study. SETTING: Two multicenter intensive care unit databases: CUB-Réa (France) and Project IMPACT (United States). PATIENTS: All nonsurgical adults requiring renal support therapy from 1997 to 2007 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed association of annual renal support therapy volume with intensive care unit and hospital mortality using multivariable modeling, accounting for clustering and adjusting for age, comorbidities, admitting diagnosis, illness severity, pre-intensive care unit length of stay, admission source, and hospital and intensive care unit characteristics. Our final cohorts were 9,449 patients treated in 32 intensive care units in CUB-Réa and 3,498 patients treated in 76 intensive care units in Project IMPACT. Patient demographics did not differ between cohorts. Renal support therapy delivery varied widely across intensive care units (3-129 patients per year in CUB-Réa, 1-66 in Project IMPACT). Overall intensive care unit and hospital mortality rates were 45% and 49% in CUB-Réa and 34% and 47% in Project IMPACT. After adjustment for patient, intensive care unit, and hospital characteristics, there was no association between renal support therapy volume and intensive care unit or hospital mortality whether we treated volume as a continuous measure or quartiles. Higher renal support therapy volume was associated with shorter length of stay only in CUB-Réa. CONCLUSIONS: There is a large variation in annual renal support therapy volume across intensive care units in France and the United States but no association of higher volumes with improved outcomes.

Toward an integrated research agenda for critical illness in aging.

Aging brings an increased predisposition to critical illness. Patients older than 65 years of age account for approximately half of all intensive care unit (ICU) admissions in the United States, a proportion that is expected to increase considerably with the aging of the population. Emerging research suggests that elderly survivors of intensive care suffer significant long-term sequelae, including accelerated age-related functional decline. Existing evidence-based interventions are frequently underused and their efficacy untested in older subjects. Improving ICU outcomes in the elderly will require not only better methods for translating sound science into improved ICU practice but also an enhanced understanding of the underlying molecular, physiological, and pathophysiological interactions of critical illness with the aging process itself. Yet, significant barriers to research for critical illness in aging exist. We review the state of knowledge and identify gaps in knowledge, research opportunities, and barriers to research, with the goal of promoting an integrated research agenda for critical illness in aging.

The epidemiology of mechanical ventilation use in the United States.

OBJECTIVE: Few contemporary population-based data exist about the incidence, patient characteristics, and outcomes of mechanical ventilation in acute care hospitals. We sought to describe the epidemiology of mechanical ventilation use in the United States. DESIGN: Retrospective cohort study using year 2005 hospital discharge records from six states. National projections were generated from age-, race-, and sex-specific rates in the cohort. SETTING: Nonfederal acute care hospitals. PATIENTS: All discharges that included invasive mechanical ventilation identified using International Classification of Diseases, 9th Revision, Clinical Modification procedure codes (96.7x). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 6,469,674 hospitalizations in the six states, 180,326 (2.8%) received invasive mechanical ventilation. There was a wide age distribution with 52.2% of patients <65 yrs of age. A total of 44.6% had at least one major comorbid condition. The most common comorbidities included diabetes (13.2%) and pulmonary disease (13.2%). Inhospital mortality was 34.5%, and only 30.8% of patients were discharged home from the hospital. Almost all patients received care in urban (73.5%) or suburban (23.6%) hospitals vs. rural hospitals (2.9%). Patients in urban hospitals experienced a higher number of organ dysfunctions, more dialysis and tracheostomies, and higher mortality compared with patients in rural hospitals. Projecting to national estimates, there were 790,257 hospitalizations involving mechanical ventilation in 2005, representing 2.7 episodes of mechanical ventilation per 1000 population. Estimated national costs were $27 billion representing 12% of all hospital costs. Incidence, mortality, and cumulative population costs rose significantly with age. CONCLUSIONS: Mechanical ventilation use is common and accounts for a disproportionate amount of resource use, particularly in urban hospitals and in elderly patients. Mortality for mechanically ventilated patients is high. Quality improvement and cost-reduction strategies targeted at these patients are warranted.

Do hospitals provide lower quality of care to black patients for pneumonia?

OBJECTIVES: Recent studies reported lower quality of care for black vs. white patients with community-acquired pneumonia and suggested that disparities persist at the individual hospital level. We examined racial differences in emergency department and intensive care unit care processes to determine whether differences persist after adjusting for case-mix and variation in care across hospitals. DESIGN: Prospective, observational cohort study. SETTING: Twenty-eight U.S. hospitals. PATIENTS: Patients with community-acquired pneumonia: 1738 white and 352 black patients. INTERVENTIONS: None. MEASUREMENTS: We compared care quality based on antibiotic receipt within 4 hrs and adherence to American Thoracic Society antibiotic guidelines, and intensity based on intensive care unit admission and mechanical ventilation use. Using random effects and generalized estimating equations models, we adjusted for case-mix and clustering of racial groups within hospitals and estimated odds ratios for differences in care within and across hospitals. MAIN RESULTS: Black patients were less likely to receive antibiotics within 4 hrs (odds ratio, 0.55; 95% confidence interval, 0.43-0.70; p < .001) and less likely to receive guideline-adherent antibiotics (odds ratio, 0.72; 95% confidence interval, 0.57-0.91; p = .006). These differences were attenuated after adjusting for casemix (odds ratio, 0.59; 95% confidence interval; 0.46-0.76 and 0.84; 95% confidence interval, 0.66 -1.09). Within hospitals, black and white patients received similar care quality (odds ratio, 1; 95% confidence interval, 0.97-1.04 and 1; 95% confidence interval, 0.97-1.03). However, hospitals that served a greater proportion of black patients were less likely to provide timely antibiotics (odds ratio, 0.84; 95% confidence interval, 0.78-0.90). Black patients were more likely to receive mechanical ventilation (odds ratio, 1.57; 95% confidence interval, 1.02-2.42; p = .042). Again, within hospitals, black and white subjects were equally likely to receive mechanical ventilation (odds ratio, 1; 95% confidence interval, .94-1.06) and hospitals that served a greater proportion of black patients were more likely to institute mechanical ventilation (odds ratio, 1.13; 95% confidence interval, 1.02-1.25). CONCLUSIONS: Black patients appear to receive lower quality and higher intensity of care in crude analyses. However, these differences were explained by different case-mix and variation in care across hospitals. Within the same hospital, no racial differences in care were observed.

The prevalence of anemia and its association with 90-day mortality in hospitalized community-acquired pneumonia.

BACKGROUND: The prevalence of anemia in the intensive care unit is well-described. Less is known, however, of the prevalence of anemia in hospitalized patients with lesser illness severity or without organ dysfunction. Community-acquired pneumonia (CAP) is one of the most frequent reasons for hospitalization in the United States (US), affecting both healthy patients and those with comorbid illness, and is typically not associated with acute blood loss. Our objective was to examine the development and progression of anemia and its association with 90d mortality in 1893 subjects with CAP presenting to the emergency departments of 28 US academic and community hospitals. METHODS: We utilized hemoglobin values obtained for clinical purposes, classifying subjects into categories consisting of no anemia (hemoglobin >13 g/dL), at least borderline (

Prevalence and significance of coagulation abnormalities in community-acquired pneumonia.

Coagulation abnormalities are common in severe pneumonia and sepsis, yet little is known about the presence of coagulopathy or its significance in patients with lesser illness severity. We examined coagulation abnormalities in 939 subjects hospitalized with community-acquired pneumonia (CAP) in 28 US hospitals, hypothesizing that abnormalities would increase with illness severity and poor outcomes. We measured plasma coagulation markers (D-dimer, plasminogen activator inhibitor [PAI], antithrombin, factor IX, and thrombin-antithrombin complex [TAT]) at the time of patient presentation to the emergency department and daily during the first wk of hospitalization. Day-1 clinical laboratory test results for international normalized ratio, activated partial thromboplastin time, and platelet count were recorded from the medical record. In our cohort, 32.5% of patients developed severe sepsis and 11.1% died by d 90. Day-1 coagulation abnormalities were common, especially for D-dimer (80.6%) and TAT (36.0%), and increased with illness severity and poor outcomes. However, abnormalities also occurred in those patients who never developed organ dysfunction and differences between groups were modest. The proportion of patients with abnormalities changed over time, yet the magnitude of change was small and not always in the direction of normality. Many patients remaining in the hospital continued to manifest coagulation abnormalities on d 7, especially for D-dimer (86.5%) and TAT (36.9%). In conclusion, coagulation abnormalities were common and persistent in CAP patients, even among the least ill. These findings underscore the complexity of the coagulation response to infection and may offer insights into coagulation-based therapeutics in clinical sepsis trials.

Differences in immune response may explain lower survival among older men with pneumonia.

OBJECTIVE: Lower life expectancy in men is generally attributed to higher likelihood of risky behavior and because men develop chronic conditions earlier. If sex-related differences in survival are independent of preinfection chronic health and health behavior, it would suggest that survival differences may occur because of sex differences in quality of care and biological response to infection, and these differences may contribute to sex differences in life expectancy. We assessed if sex-related survival difference following community-acquired pneumonia (CAP) is due to differences in clinical characteristics, quality of care, or immune response. DESIGN, SETTING, AND SUBJECTS: Prospective observational cohort of 2183 subjects with CAP. MEASUREMENTS AND MAIN RESULTS: Mean age was 64.9 years. Men were more likely to smoke and had more comorbidity compared with women. At emergency department presentation, men had different biomarker patterns, as evidenced by higher inflammation (tumor necrosis factor, interleukin [IL]-6, and IL-10) and fibrinolysis (d-dimer), and lower coagulation biomarkers (antithrombin-III and factor IX) (p < 0.05). Small differences in favor of men were seen in care quality, including antibiotic timing and compliance with American Thoracic Society guidelines. Men had lower survival at 30, 90, and 365 days. The higher 1-year mortality was not attenuated when adjusted for differences in demographics, smoking, resuscitation, insurance, and vaccination status, comorbidity, hospital characteristics, and illness severity (unadjusted hazard ratio [HR] = 1.35, p = 0.003; and adjusted HR = 1.29, p = 0.004). HR was no longer statistically significant when additionally adjusted for differences in emergency department concentrations of tumor necrosis factor, IL-6, IL-10, d-dimer, antithrombin-III, and factor IX (adjusted HR = 1.27, p = 0.17). Patterns of biomarkers observed in men were associated with worse survival for 1 year. CONCLUSIONS: Lower survival among men following CAP was not explained by differences in chronic diseases, health behaviors, and quality of care. Patterns of inflammatory, coagulation, and fibrinolysis biomarkers among men may explain reduced short-term and long-term survival.

Growth of intensive care unit resource use and its estimated cost in Medicare.

OBJECTIVE: The past 10-15 yrs brought significant changes in the United States healthcare system. Effects on Medicare intensive care unit use and costs are unknown. Intensive care unit costs are estimated using the Russell equation with a ratio of intensive care unit to floor cost per day, or "R value," of 3, which may no longer be valid. We sought to determine contemporary Medicare intensive care unit resource use, costs, and R values; whether these vary by patient and hospital characteristics; and the impact of updated values on estimated intensive care unit costs. DESIGN: Retrospective analysis of Medicare Inpatient Prospective Payment System hospitalizations from 1994 to 2004 using Medicare Provider Analysis and Review files. SETTING: All nonfederal acute care US hospitals paid through the Inpatient Prospective Payment System. SUBJECTS: Inpatient prospective payment system hospitalizations from 1994 to 2004 (n = 121,747, 260). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined resource use and costs (adjusted to y2004$), calculating intensive care unit and floor costs directly and using these to generate year-specific R values. By 2004, 33% of Medicare hospitalizations had intensive care unit or coronary care unit care, with more than half of the increase in total hospitalizations because of additional intensive care unit hospitalizations. Adjusted intensive care unit cost per day remained stable ($2,616 vs. $2,575; 1994 vs 2004), yet adjusted floor cost per day rose substantially ($1,027 vs. $1,488) driven by decreased floor length of stay. Annual adjusted Medicare intensive care unit costs increased 36% to $32.3B, largely because of increased utilization. R values decreased progressively from 2.55 to 1.73, were lower for surgical vs. medical admissions and survivors vs. nonsurvivors, but varied little by hospital characteristics. An R value of 3 overestimated Medicare intensive care unit costs by 17.6% ($5.7 billion) in 2004. CONCLUSIONS: Medicare intensive care unit use is rising rapidly and will likely continue to do so. Despite significant healthcare system changes, adjusted daily critical care costs remained stable, yet care outside the intensive care unit became more expensive. To track intensive care unit cost over time, year-specific R values should be used.

Bench-to-bedside review: critical illness-associated cognitive dysfunction--mechanisms, markers, and emerging therapeutics.

Cognitive dysfunction is common in critically ill patients, not only during the acute illness but also long after its resolution. A large number of pathophysiologic mechanisms are thought to underlie critical illness-associated cognitive dysfunction, including neuro-transmitter abnormalities and occult diffuse brain injury. Markers that could be used to evaluate the influence of specific mechanisms in individual patients include serum anticholinergic activity, certain brain proteins, and tissue sodium concentration determination via high-resolution three-dimensional magnetic resonance imaging. Although recent therapeutic advances in this area are exciting, they are still too immature to influence patient care. Additional research is needed if we are to understand better the relative contributions of specific mechanisms to the development of critical illness-associated cognitive dysfunction and to determine whether these mechanisms might be amenable to treatment or prevention.

Predicting late anemia in critical illness.

INTRODUCTION: Identifying critically ill patients most likely to benefit from pre-emptive therapies will become increasingly important if therapies are to be used safely and cost-effectively. We sought to determine whether a predictive model could be constructed that would serve as a useful decision support tool for the pre-emptive management of intensive care unit (ICU)-related anemia. METHODS: Our cohort consisted of all ICU patients (n = 5,170) admitted to a large tertiary-care academic medical center during the period from 1 July 2000 to 30 June 2001. We divided the cohort into development (n = 3,619) and validation (n = 1,551) sets. Using a set of demographic and physiologic variables available within six hours of ICU admission, we developed models to predict patients who either received late transfusion or developed late anemia. We then constructed a point system to quantify, within six hours of ICU admission, the likelihood of developing late anemia. RESULTS: Models showed good discrimination with receiver operating characteristic curve areas ranging from 0.72 to 0.77, although predicting late transfusion was consistently less accurate than predicting late anemia. A five-item point system predicted likelihood of late anemia as well as existing clinical trial inclusion criteria but resulted in pre-emptive intervention more than two days earlier. CONCLUSION: A rule-based decision support tool using information available within six hours of ICU admission may lead to earlier and more appropriate use of blood-sparing strategies.

Stress in mangrove forests: Early detection and preemptive rehabilitation are essential for future successful worldwide mangrove forest management.

Mangrove forest rehabilitation should begin much sooner than at the point of catastrophic loss. We describe the need for "mangrove forest heart attack prevention", and how that might be accomplished in a general sense by embedding plot and remote sensing monitoring within coastal management plans. The major cause of mangrove stress at many sites globally is often linked to reduced tidal flows and exchanges. Blocked water flows can reduce flushing not only from the seaward side, but also result in higher salinity and reduced sediments when flows are blocked landward. Long-term degradation of function leads to acute mortality prompted by acute events, but created by a systematic propensity for long-term neglect of mangroves. Often, mangroves are lost within a few years; however, vulnerability is re-set decades earlier when seemingly innocuous hydrological modifications are made (e.g., road construction, blocked tidal channels), but which remain undetected without reasonable large-scale monitoring.