Active clinical trials for "Critical Illness"

This study is to determine whether accelerometry can be used to measure physical activity occurring during routine clinical care in a diverse population of patients with medical or surgical critical illness.

Intensive Care Unit-acquired weakness (ICU-AW) is a well-recognized, important and preventable sequelae of critical illness, affecting up to 60% of adult ICU patient. ICU-AW is associated with increased mortality and length of stay, and negatively impacts long-term functional outcomes and quality of life in affected patients and their caregivers. While delayed mobilization adversely affects clinical outcomes, early rehabilitation in the critically ill adult population is safe, feasible, cost effective, results in more ventilator free-days and better functional outcomes at hospital discharge. In contrast, there is a paucity of this research in pediatrics. Our research suggests that immobilization is common in critically ill children, and rehabilitation is delayed particularly in the sickest children who are arguably at highest risk of morbidity. It is unclear however, whether delayed rehabilitation leads to adverse outcomes in critically ill children, as has been demonstrated in adults. Our objectives of this study are to evaluate if immobilization and delayed rehabilitation negatively impacts short-term clinical outcomes and the time to functional recovery in critically ill children. The investigators hypothesize that the following factors may influence functional recovery and morbidity in critically ill children: Pre-morbid condition Age Time-to-initiation of acute rehabilitation Critical illness disease severity

To diagnose acid base disturbances using blood gas analysis, multiple approaches are currently in use. These include the classic Henderson-Hasselbach bicarbonate approach and the physiochemical approach by Stewart1. All have shown to be mathematically compatible2. Diagnosing the metabolic component of acid base disturbances relies on the assessment of the so called ion gaps: the anion gap for the classic acid-base approach and the strong ion difference (SID) for the Stewart approach. This gap may unveil unidentified anions to provide a more accurate diagnosis. In particular they allow differentiating between relative hyperchloremia and other strong ions such as lactate, ketones, salicylates, citrate and ethylene glycol3. The accuracy of both gaps relies on the estimation of the weak acid dissociation: A-. This A- is dependent on the total concentration of weak acids (Atot) of which albumin is the most important and the effective dissociation constant for these (Ka), which determines the dissociated fraction of the Atot. This dissociation fraction needs to be accounted for in the ion gaps. This is reflected in the recommendation to correct the anion gap for albumin and incorporated in the SID which includes a factor for albumin by design3,4. However, the correction factor for albumin is currently based on data from animals and healthy volunteers4-9. In the critically ill albumin and protein content are very different compared to healthy volunteers, most notably in sepsis. Further, it is unknown if subunit composition of albumin is different in these patients. In addition, different protein species may be either up or downregulated in the critically ill1,8,9.Therefore from a pathophysiological point of view Atot and Ka and thus A- may differ in the critically ill. However it has not been previously investigated if and to what extent these matters affect Atot and Ka and therefore A- in this population. In addition, previous studies looking into this values showed a higher than expected value of unmeasured anions from the gap calculations. Despite rigorous experimental effort including high performance liquid chromatography, the origin of these unmeasured anions have not yet been elucidated17-20. However if the assumptions made in the Stewarts approach would not be valid, the existence of these unknown anions may have to be questioned. Thus it is of great interest to experimentally determine the exact contribution of the weak acids and their dissociation in sepsis. This could have major implications for these patients because different assumptions will ultimately lead to alterations in their calculated anion gap or SID. This may reduce unnecessary diagnostic test, alter final diagnosis and hence alter therapy. In this study the investigators aim to experimentally determine the Atot and Ka and thus their dissociated fraction A- in critically ill septic patients admitted to the intensive care unit by using in vitro CO2 tonometry, plasma dialysis and Marquardt regression analysis. In addition, as a control the investigators will do the same for patients admitted to the intensive care after routine cardiac surgery. Furthermore Atot and Ka values for both groups will be compared to values obtained from human volunteers in a previous study4. To achieve this, the investigators will plot CO2 versus pH titration curves from plasma samples of these patients. The investigators will then use Marquardt nonlinear regression analysis to quantify Atot and Ka and the SID by simultaneously solving for these parameters21. To make the quantification for Atot and Ka more robust, the investigators will also perform the same experiments after dialyzing the obtained plasma samples against a crystalloid solution of known composition in order to eliminate errors related to estimation of the SID. Finally, Atot and Ka values for both groups will be compared to values obtained from human volunteers in a previous study4. For application in the bicarbonate and base excess centred frameworks, Atot and Ka values will be related to albumin and protein content to update the correction factor for the anion gap in critically ill.

Examination of serial muscle ultrasounds and muscle sampling within the population of ICU patients who require mechanical ventilation for acute respiratory failure, will lead to the ability of investigators to link specific baseline comorbidities, drugs, or fluid administrations, to the onset and duration of architectural changes within muscle and correlate ultimately with muscle function. With this study, we will be better able to understand the relationships between the pattern of resolution of the muscle architectural abnormalities within the context of multiple other clinical abnormalities and therapies present and rendered to ICU patients.

Rationale: A higher citrate dose during continuous venovenous hemofiltration provides better anticoagulation but possibly a higher risk of citrate accumulation in case of metabolic limitations. A higher citrate dose also increases magnesium loss in ultrafiltrate, while a negative magnesium balance is unwanted. Objective: Aim of this study is to determine the magnesium balance of citrate-based continuous veno-venous hemofiltration (CVVH) and to determine whether and to which extent the magnesium balance depends on citrate dose. Study design and methods: A prospective randomized study conducted in critically ill patients with acute kidney injury (AKI), treated with CVVH, with either low dose citrate (2.5 mmol/L blood flow in the filter) or high dose citrate (4.5 mmol/L blood flow in the filter) as anti-coagulant, targeting a postfilter ionized Calcium (iCa) of resp. 1.3-1.6 mg/dL (0.325-0.4 mmol/L) and 0.8-1.1 mg/dL (0.2-0.275 mmol/L). Post-filter blood as well as effluent aliquots and bloodconcentrations in the patient are tested for the following variables: (0 , 2 , 4, 6, 12 and 24 hrs): Total Magnesium (tMg) and total Calcium (tCa), ionized Ca (iCa)(bloodgas analyzer). In addition, hematocrit, albumin, total protein, ureum and creatinine and parathormone (PTH) are determined in arterial blood at 0 and 24 hrs or at the time of protocol exit and citrate concentrations in postfilter and arterial blood at 1 and 24 hrs or at protocol exit. Sample sites: arterial line, postfilter port (after postdilution and calcium compensation), effluent sample. All flow rates to be noted. Study population: Twenty patients admitted to intensive care, requiring continuous renal replacement therapy (CRRT) for AKI. Intervention: Anti-coagulation with either low dose citraat (2.5 mmol/L blood flow) or high dose citraat (4.5 mmol/L blood flow) targeting postfilter iCa of resp. 1.3-1.6 and 0.8-1.1 mg/dL. Both regimens are within standard protocolled CVVH treatment in the intensive care department.

The care of critically ill patients in Intensive Care Units (ICUs) is an important part of modern health care systems. However, ICU care suffers from similar problems as the rest of the health care system. Powerful arguments support the concept that most of problems in complex systems, such as ICUs, relates to flaws in institutional systems and processes that hinder the ability of individuals to perform their jobs well. To fix these problems, the defective systems and processes must be redesigned in ways that make it easy for people to do their job well, and hard to make mistakes. Altering the structure of ICU care for the purpose of improving ICU performance is an example of Organizational Systems Engineering, alternatively called Total Quality Management. Another serious problem in ICU care is that after 2007 there will be a increasing shortage of physicians specializing in the care of the critically ill (Intensivists), with a 35% shortfall by 2030. One contributor to this shortage is that Intensivists retire at a younger age than do physicians in general, and often curtail their care of critically ill patients even before they retire. It is likely that the emotional and physical demands of this career choice leads Intensivists to "burn out" and leave the field prematurely. For these reasons it is important to find ways to make working as an Intensivist more sustainable so that the most experienced practitioners will continue in the field up to a normal retirement age. The way in which groups of Intensivists organize themselves to provide care in an ICU is highly variable. One potentially important way in which Intensivist staffing differs is in the degree of continuity of care. The more days in a row that the same physician cares for a patient the greater the continuity of care. While it is generally held that a higher continuity of care results in better care and better outcomes for patients, in fact there are no studies addressing this issue. On the other side of the coin however, it seems likely that working many days in a row increases the physical and emotional burdens on the Intensivist, increasing job distress and job burnout over time. A common pattern of Intensivist staffing, in which continuity of care is reduced, is when the Intensivist who is caring for ICU patients during the weekdays has the weekend off, during which one of his/her partners provides "cross-coverage". While it is reasonable to hypothesize that cross-coverage would lead to inefficient patient care, at the same time it may reduce the burdens on the Intensivists. This purpose of this study is to investigate the effects of weekend cross-coverage on both ICU patients and on Intensivists. This will be a multicenter study performed in 4 member institutions of the Midwest Critical Care Consortium: The University of Toledo, MetroHealth Medical Center, Ohio State University, and Indiana University. Five adult medical ICUs from the six institutions will participate in this study, with two ICUs from the Ohio State University site. To answer the research questions, each participating ICU will alternate between two common models of Intensivist staffing. In both models an Intensivist is responsible for ICU care for 14 days. In the Continuous model, a single Intensivist will be responsible for all 14 days. In the Discontinuous model, both weekends during the 14 days will be cross-covered by a colleague. Continuity of care is higher in the Continuous model, which has 2 physician transitions over a 4 week period, while the Discontinuous model has 8 transitions per 4 weeks. Each participating ICU will use one model for 12 weeks, then switch to the other model for 12 weeks, and finally revert back to the first model for the final 12 weeks of this 36 week study. To address problems of historical controls, seasonal differences, and to increase comparability of groups, the participating ICUs have been randomly assigned to begin the study either with the Continuous or Discontinuous model. Comparisons will be made between the two scheduling models in: (1) patient outcomes, specifically hospital mortality rate, ICU length of stay, and hospital length of stay, and (2) Intensivist outcomes, specifically job distress, job burnout, and the balance between work and home life. Since there is currently nothing known about whether weekend cross-coverage influences medical care, both models of care are common in ICUs. Thus the investigators expect that the findings of this study will have general relevance. While the patients admitted to the participating ICUs during this study would not be expected to benefit from this investigation, the results derived are expected to enable policy makers to make evidence-based decisions about this important aspect of ICU physician staffing and thus improve the performance and/or cost-effectiveness of ICU care, benefiting future ICU patients, and society.

The ability to measure cardiac output (CO) accurately and reproducibly at frequent intervals remains elusive to the clinician caring for critically ill pediatric patients even though a large proportion of these children are known to have hemodynamic compromise as a result of their illness. Current techniques used in adults to measure CO are not suitable for routine use with pediatric patients. A new ultrasound dilution approach provides an opportunity to measure cardiac output and blood volumes in pediatric patients. The main aim of this study is to compare CO measured by the new method with the clinician's estimate and implied CO from the measurement of the arteriovenous oxygen content difference.

This study provides training opportunities for critical care specialists in evaluating and treating critically ill patients. Patients enrolled in the study receive standard tests and treatments. The study objectives are to: Provide additional training for staff of the NIH Clinical Center intensive care unit, including physicians, nurses, fellows, and other trainees so that they develop and maintain essential skills, Gather information about the natural history and outcomes of critical illness, accompanying conditions, and complications, Develop hypotheses about the medical problems involved in the illnesses and their treatment, and Identify critically ill patients who may be eligible for specific NIH research protocols. Critically ill patients 18 years of age and older who may benefit by transferring to the NIH Clinical Center for treatment may be eligible for this study. Patients will be transferred to the Clinical Center from another hospital only when the referring and accepting physicians in both institutions agree that the potential benefit of coming to the NIH outweighs the risk of transferring the patient. Participants are evaluated and treated at the Clinical Center. Patients provide a medical history and have a physical examination. They may also have various medical tests and procedures needed to evaluate their condition. These procedures may include blood work, placement of an intravenous (IV) line, x-rays and other imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI) and other procedures. Patients who are diagnosed with a specific condition may be offered treatment or may be referred to another study that is more appropriate for that particular problem.

The purpose of this study is to determine whether subcutaneous continuous glucose monitoring in critically ill patients is clinically feasible accurate and reliable.

An appropriate hypothalamic-pituitary-adrenal (HPA) axis response is required to survive critical illness. Primary adrenal insufficiency, relative adrenal insufficiency, tissue resistance to glucocorticoids, ACTH deficiency and immune-mediated inhibition of the HPA axis may impair the secretion or action of glucocorticoids in critically ill patients. Adrenal insufficiency is estimated to occur in up to 77% of critically ill patients, but currently, there is no consensus on the diagnostic criteria for adrenal insufficiency in this setting, and standard testing does not discriminate among the aforementioned factors. We will study the incidence and natural history of adrenal insufficiency in critically ill patients to further define adrenal insufficiency and provide data to develop diagnostic tests. Clinical features and outcomes will be correlated with laboratory measurements of hormones, cytokines and glucocorticoid action. Healthy volunteers will undergo cortrosyn tests with measurement of free cortisol levels to develop a normative range for this endpoint. <TAB> Previous glucocorticoid use, if prolonged and supraphysiologic, also inhibits the HPA and can result in adrenal insufficiency. Patients with short intermittent courses of glucocorticoid administration have not been studied well, and may also be at risk. To gain further information about this group, patients receiving pulse glucocorticoid doses as part of bone marrow transplant regimens at the Clinical Center will also be studied. ...