Early Mobilization In the ICU Setting Survivors of critical illness commonly have muscle weakness and impairments in their physical function that may be severe and persist long after hospital ...discharge.1-3 The etiology of this weakness is likely multi-factorial and may include pre-existing weakness prior to hospitalization, neuromuscular dysfunction related to critical illness (eg, neuropathy, myopathy, atrophy, or a combination thereof), and other complications and deconditioning related to bed rest and immobility.4,5 Patients in ICU often are exposed to prolonged immobility,6 due not only to the nature of their critical illness but also to the deep sedation, lack of rehabilitation staffing, and perceived barriers by their ICU clinicians.7,8 ICU-acquired neuromuscular dysfunction is associated with a prolonged need for mechanical ventilation and increased ICU and hospital length of stay.5 A study by Herridge, et al,3 reported that patients who survived Acute Respiratory Distress Syndrome (ARDS) lost an average of 18% of their body weight in the ICU and were only able to walk at only 66% of their predicted value at 1 year after hospital discharge. ICU delirium is common in patients requiring mechanical ventilation and has been associated with prolonged hospitals stays and increased mortality rates.22,23 Similarly, patients requiring chronic mechanical ventilation also demonstrated increases in strength, functional status, and ability to liberate from mechanical ventilation after a program of whole body rehabilitation was initiated.24 At Johns Hopkins Hospital, a multidisciplinary quality improvement (QI) project was conducted to address sedation management, ICU delirium, and improved access to physical and occupational therapy for patients requiring mechanical ventilation ≥ 4 days.25, 26 Reduction in the use of deep sedation was promoted to enable more patients to participate in early physical medicine and rehabilitation (PM&R) activities.
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DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical ...efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis, with a focus on respiratory function.
The REFALS study is a randomised, double-blind, placebo-controlled phase 3 trial at 99 amyotrophic lateral sclerosis specialist centres in 14 countries worldwide. People with amyotrophic lateral sclerosis were eligible for participation if they were at least 18 years of age and had a sitting slow vital capacity (SVC) of 60–90% predicted. Participants were randomly assigned (2:1) by interactive web-response system to receive either levosimendan or placebo. The capsules for oral administration were identical in appearance to maintain blinding of participants and investigators. The primary endpoint was the change from baseline in supine SVC at 12 weeks, assessed as the percentage of predicted normal sitting SVC. The key secondary endpoint was the combined assessment of function and survival (CAFS) up to 48 weeks. Analyses were done in the intention-to-treat population, comprising all participants who were randomly assigned. This trial is registered at ClinicalTrials.gov (NCT03505021) and has been completed. An extension study (REFALS-ES; NCT03948178) has also been completed, but will be reported separately.
Between June 21, 2018, and June 28, 2019, 871 people were screened for the study, of whom 496 were randomly assigned either levosimendan (n=329) or placebo (n=167). Participants were followed up between June 27, 2018 and June 26, 2020, for a median duration of 50·1 (IQR 37·5–51·1) weeks. The median duration of treatment was 47·9 (IQR 26·4–48·1) weeks. Change from baseline in supine SVC at 12 weeks was –6·73% with levosimendan and –6·99% with placebo, with no significant difference between the treatments (estimated treatment difference 0·26%, 95% CI –2·03 to 2·55, p=0·83). Similarly, at week 48, CAFS did not differ between treatment groups (least squares mean change from baseline 10·69, 95% CI –15·74 to 37·12; nominal p value=0·43). The most frequent adverse events were increased heart rate (106 33% of 326 receiving levosimendan vs 12 7% of 166 receiving placebo), fall (85 26% vs 48 29%), headache (93 29% vs 36 22%), and dyspnoea (59 18% vs 32 19%). 33 (10%) participants allocated levosimendan and 20 (12%) assigned placebo died during the trial, mainly due to respiratory failure or progression of amyotrophic lateral sclerosis.
Levosimendan was not superior to placebo in maintaining respiratory function in a broad population with amyotrophic lateral sclerosis. Although levosimendan was generally well tolerated, increased heart rate and headache occurred more frequently with levosimendan than with placebo. The possibility of a clinically relevant subgroup of responsive individuals requires further evaluation.
Orion Corporation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To review the literature on retention strategies in follow-up studies and their relevance to critical care and to comment on the Toronto experience with the acute respiratory distress syndrome (ARDS) ...and severe acute respiratory syndrome (SARS) follow-up studies.
Literature review and two cohort studies in a tertiary care hospital in Toronto, Canada.
ARDS and SARS patients.
Review articles from the social sciences and medicine are summarized and our own experience with two longitudinal studies is drawn upon to elucidate strategies that can be successfully used to attenuate participant drop-out from longitudinal studies. Three key areas for retention of subjects are identified from the literature: (a) respect for patients: respect for their ideas and their time commitment to the research project; (b) tracking: collect information on many patient contacts at the initiation of the study and outline tracking procedures for subjects lost to follow-up; and (c) study personnel: interpersonal skills must be reinforced, flexible working hours mandated, and support offered. Our 5-year ARDS and 1-year SARS study retention rates were 86% and 91%, respectively, using these methods.
Strategies to reduce patient attrition are time consuming but necessary to preserve internal and external validity. When the follow-up system is working effectively, researchers can acquire the necessary data to advance knowledge in their field and patients are satisfied that they have an important role to play in the research project.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
