Robotic-Assisted In-Bed Mobilization in Ventilated ICU Patients With COVID-19: An Interventional, Randomized, Controlled Pilot Study (ROBEM II Study).

OBJECTIVES: The COVID-19 pandemic significantly impacted global healthcare systems, particularly in managing critically ill mechanically ventilated patients. This study aims to assess the feasibility of robotic-assisted mobilization in COVID-19 patients. DESIGN: Randomized controlled pilot study. SETTING: Four COVID-19 specialized ICUs at Charité-Universitätsmedizin Berlin (March 2021 to February 2022). PATIENTS: Twenty critically ill COVID-19 patients expected to require greater than 24 hours of ventilation. INTERVENTIONS: A 5-day intervention phase with bid robotic-assisted mobilization greater than or equal to 20 minutes and follow-up at day 180, compared with standard care. MEASUREMENTS AND MAIN RESULTS: Intervention sessions were conducted in 98.9% according to protocol, with one session missing due to staff shortage. Primary outcome was the mobilization level measured with the ICU Mobility Scale (IMS) and Surgical ICU Optimal Mobilization Score (SOMS), assessed until day 5 or extubation. Safety events were recorded during mobilization. The median IMS and SOMS were 0 (0-0.16) and 1 (1-1.03) in the intervention group, and 0 (0-0.15) ( p = 0.77) and 0.8 (0.65-1.20) ( p = 0.08) in the standard care group, respectively. Significant secondary outcomes included average number of mobilization sessions (intervention: 8.5 [7.75-10] vs. standard care: 4.5 [3.5-5]; p = 0.001), total mobilization time (intervention: 232.5 min [187.25-266.5 min] vs. standard care: 147.5 min [107.5-167.5 min]; p = 0.011), and healthcare providers per session (intervention: 2 [2-2] vs. standard care: 1 [1-1.4]; p = 0.001) during intervention. Four safety events (hypertension and agitation, n = 2 each) in the intervention group and none in the standard care group were reported. CONCLUSIONS: Robotic-assisted mobilization in mechanically ventilated COVID-19 patients appears to be safe and feasible.

Comparison of Different Ultrasound Methods to Assess Changes in Muscle Mass in Critically ill Patients.

BACKGROUND: Muscle ultrasound represents a promising approach to aid diagnoses of neuromuscular diseases in critically ill patients. Unfortunately, standardization of ultrasound measurements in clinical research is lacking, making direct comparisons between studies difficult. Protocols are required to assess qualitative muscle changes during an ICU stay in patients at high risk for the development of neuromuscular acquired weakness (ICUAW). METHODS: We conducted a retrospective, observational analysis comprised of three prospective observational studies with the aim of diagnosing muscle changes by ultrasound measurement of the quadriceps muscle. Different protocols were used in each of the three studies. In total, 62 surgical, neurocritical care and trauma intensive care patients were serially assessed by different ultrasound protocols during the first week of critical illness. The relative change in ultrasound measurements was calculated for all possible locations, methods and sides. Comparison was obtained using mixed effect models with the location, the height and the side as influencing variables and patients as fixed effect. The relationship between variables and outcomes was assessed by multivariable regression analysis. RESULTS: Ultrasound methods and measurement sites of the quadriceps muscles from all protocols were equally effective in detecting muscle changes. During the first week of an ICU stay, two groups were identified: patients with decreased muscle mass on ultrasound (n = 42) and a cohort with enlargement (n = 23). Hospital mortality was significantly increased in the cohort with muscle swelling (8 (19%) versus 12 (52%), p = .013). CONCLUSIONS: Different approaches of ultrasound measurement during critical-illness are equally able to detect muscle changes. While some patients have a decrease in muscle mass, others show swelling, which may result in a reduced probability of surviving the hospital stay. Causative reasons for these results still remain unclear.

Enhancing European Management of Analgesia, Sedation, and Delirium: A Multinational, Prospective, Interventional Before-After Trial.

BACKGROUND: The objective of this study was to analyze the impact of a structured educational intervention on the implementation of guideline-recommended pain, agitation, and delirium (PAD) assessment. METHODS: This was a prospective, multinational, interventional before-after trial conducted at 12 intensive care units from 10 centers in Germany, Austria, Switzerland, and the UK. Intensive care units underwent a 6-week structured educational program, comprising online lectures, instructional videos, educational handouts, and bedside teaching. Patient-level PAD assessment data were collected in three 1-day point-prevalence assessments before (T1), 6 weeks after (T2), and 1 year after (T3) the educational program. RESULTS: A total of 430 patients were included. The rate of patients who received all three PAD assessments changed from 55% (107/195) at T1 to 53% (68/129) at T2, but increased to 73% (77/106) at T3 (p = 0.003). The delirium screening rate increased from 64% (124/195) at T1 to 65% (84/129) at T2 and 77% (82/106) at T3 (p = 0.041). The pain assessment rate increased from 87% (170/195) at T1 to 92% (119/129) at T2 and 98% (104/106) at T3 (p = 0.005). The rate of sedation assessment showed no signficiant change. The proportion of patients who received nonpharmacological delirium prevention measures increased from 58% (114/195) at T1 to 80% (103/129) at T2 and 91% (96/106) at T3 (p < 0.001). Multivariable regression revealed that at T3, patients were more likely to receive a delirium assessment (odds ratio [OR] 2.138, 95% confidence interval [CI] 1.206-3.790; p = 0.009), sedation assessment (OR 4.131, 95% CI 1.372-12.438; p = 0.012), or all three PAD assessments (OR 2.295, 95% CI 1.349-3.903; p = 0.002) compared with T1. CONCLUSIONS: In routine care, many patients were not assessed for PAD. Assessment rates increased significantly 1 year after the intervention. Clinical trial registration ClinicalTrials.gov: NCT03553719.

Mobilisation of critically ill patients receiving norepinephrine: a retrospective cohort study.

BACKGROUND: Mobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation. METHODS: We conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs. RESULTS: A total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI - 0.09, - 0.05; p ≤ 0.001) and early mobilisation (adjusted OR 0.83; 95% CI 0.76, 0.90; p ≤ 0.001), while a higher norepinephrine dose corresponded to a lower chance to be mobilised out-of-bed (adjusted OR 0.01; 95% CI 0.00, 0.04; p ≤ 0.001). Mobilisation with norepinephrine did not significantly affect mortality (p > 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice (p > 0.1). We identified that mobilisation was safe with up to 0.20 µg/kg/min norepinephrine for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0-1) mobilisation. CONCLUSIONS: Mobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 µg/kg/min for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0-1) mobilisation.

Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients.

BACKGROUND: The objective was to investigate the role of gene expression and plasma levels of the muscular protein myostatin in intensive care unit-acquired weakness (ICUAW). This was performed to evaluate a potential clinical and/or pathophysiological rationale of therapeutic myostatin inhibition. METHODS: A retrospective analysis from pooled data of two prospective studies to assess the dynamics of myostatin plasma concentrations (day 4, 8 and 14) and myostatin gene (MSTN) expression levels in skeletal muscle (day 15) was performed. Associations of myostatin to clinical and electrophysiological outcomes, muscular metabolism and muscular atrophy pathways were investigated. RESULTS: MSTN gene expression (median [IQR] fold change: 1.00 [0.68-1.54] vs. 0.26 [0.11-0.80]; p = 0.004) and myostatin plasma concentrations were significantly reduced in all critically ill patients when compared to healthy controls. In critically ill patients, myostatin plasma concentrations increased over time (median [IQR] fold change: day 4: 0.13 [0.08/0.21] vs. day 8: 0.23 [0.10/0.43] vs. day 14: 0.40 [0.26/0.61]; p < 0.001). Patients with ICUAW versus without ICUAW showed significantly lower MSTN gene expression levels (median [IQR] fold change: 0.17 [0.10/0.33] and 0.51 [0.20/0.86]; p = 0.047). Myostatin levels were directly correlated with muscle strength (correlation coefficient 0.339; p = 0.020) and insulin sensitivity index (correlation coefficient 0.357; p = 0.015). No association was observed between myostatin plasma concentrations as well as MSTN expression levels and levels of mobilization, electrophysiological variables, or markers of atrophy pathways. CONCLUSION: Muscular gene expression and systemic protein levels of myostatin are downregulated during critical illness. The previously proposed therapeutic inhibition of myostatin does therefore not seem to have a pathophysiological rationale to improve muscle quality in critically ill patients. TRIAL REGISTRATION: ISRCTN77569430 -13th of February 2008 and ISRCTN19392591 17th of February 2011.

[Mobilization of Intensive Care Unit Patients: How Can the ICU Rooms and Modern Medical Equipment Help?] / Mobilisation auf Intensivstationen: Intensivpflegezimmer und Medizintechnik können helfen.

Intensive Care Unit patients frequently develop physical impairments, mainly weakness, during their ICU stay. Early mobilization is a central therapeutic element in patients on an intensive care unit to prevent and treat these physical sequelae to conserve independence. Different barriers such as lacking patient motivation, insufficient staffing and fear of dislocating vascular access or the airway led to insufficient implementation of current guideline recommendation. Integration of modern medical equipment as well as the adequate ICU room concepts is a promising option to overcome those barriers.Allowing for sufficient free floor area when planning an ICU - maybe through the integration of mobile elements - is likely to ease early mobilization and should be thoroughly considered when building or remodeling an ICU. Furthermore, wireless monitoring has been deemed necessary and could potentially decrease the fear regarding dislocation due to less cable or lines that need to be managed during mobilization.Virtual reality is a rapidly evolving field and while in ICU patients it could so far only show to reduce stress level it has been shown to improve rehabilitation in stroke patients. It is imaginable that its integration in mobilization on the ICU will boost patients' motivation. Trials are still outstanding.Robotics integrated in the ICU bed or in form of exoskeletons are currently being piloted in critically ill patients with many expected benefits due to the ability to support patients tailored to their individual needs, reduce staff requirements as the robotics will cover support function and improved duration and intensity of mobilization as for example the patient can be ambulated without ever leaving the bed, which also translates into potentially reduced fear regarding dislocation of the airway or vascular access.Currently, evidence on the benefits regarding the integration of ICU rooms as well as modern medical technology into the process of (early) mobilization is lacking but especially in the sector of robotics a huge potential is to be suspected.

[Blended Learning in Critical Care to Improve Quality of Care the ERIC-Training]. / Blended-Learning-Konzepte in der Intensivmedizin am Beispiel des ERIC-Trainings.

Communication and teamwork skills are, besides clinical knowledge, key components of high quality care in modern intensive care units. In light of high staff fluctuations among intensive care unit teams and disparities in clinical experience, an ongoing training is essential to ensure optimal performance in stressfull situations. Further, when implementing new procedures, an adequate concept for staff education is of utmost importance. Blended learning is a novel approach, combining autonomous web-based education and on-site workshops in order to improve the training process. Enhanced Recovery after Intensive Care (ERIC) is a newly developed telemedical intervention targeted at improving evidence-based practice in critical care, guided by quality indicators defined by the German Interdisciplinary Society of Emergency and Critical Care Medicine (DIVI). This telemedical intervention is supplemented with a blended-learning concept combining an e-learning website, simulator-based workshops and on-site training in order to expand the knowledge and practical skills regarding adherence to the quality indicators.

Differential contractile response of critically ill patients to neuromuscular electrical stimulation.

BACKGROUND: Neuromuscular electrical stimulation (NMES) has been investigated as a preventative measure for intensive care unit-acquired weakness. Trial results remain contradictory and therefore inconclusive. As it has been shown that NMES does not necessarily lead to a contractile response, our aim was to characterise the response of critically ill patients to NMES and investigate potential outcome benefits of an adequate contractile response. METHODS: This is a sub-analysis of a randomised controlled trial investigating early muscle activating measures together with protocol-based physiotherapy in patients with a SOFA score ≥ 9 within the first 72 h after admission. Included patients received protocol-based physiotherapy twice daily for 20 min and NMES once daily for 20 min, bilaterally on eight muscle groups. Electrical current was increased up to 70 mA or until a contraction was detected visually or on palpation. Muscle strength was measured by a blinded assessor at the first adequate awakening and ICU discharge. RESULTS: One thousand eight hundred twenty-four neuromuscular electrical stimulations in 21 patients starting on day 3.0 (2.0/6.0) after ICU admission were included in this sub-analysis. Contractile response decreased from 64.4% on day 1 to 25.0% on day 7 with a significantly lower response rate in the lower extremities and proximal muscle groups. The electrical current required to elicit a contraction did not change over time (day 1, 50.2 [31.3/58.8] mA; day 7, 45.3 [38.0/57.5] mA). The electrical current necessary for a contractile response was higher in the lower extremities. At the first awakening, patients presented with significant weakness (3.2 [2.5/3.8] MRC score). When dividing the cohort into responders and non-responders (> 50% vs. ≤ 50% contractile response), we observed a significantly higher SOFA score in non-responders. The electrical current necessary for a muscle contraction in responders was significantly lower (38.0 [32.8/42.9] vs. 54.7 [51.3/56.0] mA, p < 0.001). Muscle strength showed higher values in the upper extremities of responders at ICU discharge (4.4 [4.1/4.6] vs. 3.3 [2.8/3.8] MRC score, p = 0.036). CONCLUSION: Patients show a differential contractile response to NMES, which appears to be dependent on the severity of illness and also relevant for potential outcome benefits. TRIAL REGISTRATION: ISRCTN ISRCTN19392591 , registered 17 February 2011.

Innovative ICU Solutions to Prevent and Reduce Delirium and Post-Intensive Care Unit Syndrome.

Delirium, the most common form of acute brain dysfunction affecting up to 80% of intensive care unit (ICU) patients, has been shown to predict long-term cognitive impairment, one of the domains in "Post-ICU Syndrome" (PICS). The ICU environment affects several potentially modifiable risk factors for delirium, such as disorientation and disruption, of the sleep-wake cycle. Innovative solutions aim to transform standard concepts of ICU room design to limit potential stressors, and utilizing the patient care space as a treatment tool, exerting positive, therapeutic effects. The main areas affected by most architectural and interior design modifications are sound environment, light control, floor planning, and room arrangement. Implementation of corresponding solutions is challenging considering the significant medical and technical demands of ICUs. This article discusses innovative concepts and promising approaches in ICU design that may be used to prevent stress and to support the healing process of patients, potentially limiting the impact of delirium and PICS.

[Positioning therapy for intensive care patients]. / Lagerungstherapie bei Intensivpatienten.

The current S3 guideline, "Positioning Therapy and Mobilization of Critically Ill Patients in Intensive Care Units", introduces methodological changes and substantive updates compared to the previous version. Additionally, new evidence-based insights with specified PICO questions have been integrated, aiming for a more precise application of recommendations in clinical practice and thus enhancing the care of critically ill patients.A notable aspect is the more nuanced approach to early mobilization, which is recommended to commence within the first 72 hours of ICU admission. A staged concept and score-based mobilization schema facilitate improved patient rehabilitation. Mobilization should be standard of care, i.e., immobilization should be ordered by the physician. The guideline provides suggestions for the duration and additional mobilization measures to ensure patients stand, transfer actively from bed to chair, or walk as frequently as possible. These recommendations apply even during ECMO therapy, highlighting the importance of early mobilization.Further updates include semi-recumbent positions of at least 40° in intubated patients, with careful consideration of potential side effects. Continuous lateral rotation therapy (CLRT) is not advised due to the progress in intensive care therapy, shifting from deep sedation toward responsive patient management.Prone positioning (PP) involves rotating the patient 180° onto the ventral side. It is recommended as a therapeutic option for invasively ventilated patients with ARDS and impaired arterial oxygenation (PaO2/FiO2 <150mmHg), with a recommended minimum duration of 12 hours, ideally 16 hours. Special recommendations apply, for example, to COVID-19 patients with acute hypoxemic respiratory failure, where awake proning should be considered.Additionally, new chapters have been introduced focusing on assistive devices and neuromuscular electrical stimulation.

Noninvasive Electromagnetic Phrenic Nerve Stimulation in Critically Ill Patients: A Feasibility Study.

BACKGROUND: Electromagnetic stimulation of the phrenic nerve induces diaphragm contractions, but no coils for clinical use have been available. We recently demonstrated the feasibility of ventilation using bilateral transcutaneous noninvasive electromagnetic phrenic nerve stimulation (NEPNS) before surgery in lung-healthy patients with healthy weight in a dose-dependent manner. RESEARCH QUESTION: Is NEPNS feasible in critically ill patients in an ICU setting? STUDY DESIGN AND METHODS: This feasibility nonrandomized controlled study aimed to enroll patients within 36 h of intubation who were expected to remain ventilated for ≥ 72 h. The intervention group received 15-min bilateral transcutaneous NEPNS bid, whereas the control group received standard care. If sufficient, NEPNS was used without pressure support to ventilate the patient; pressure support was added if necessary to ventilate the patient adequately. The primary outcome was feasibility, measured as time to find the optimal stimulation position. Further end points were sessions performed according to the protocol or allowing a next-day catch-up session and tidal volume achieved with stimulation reaching only 3 to 6 mL/kg ideal body weight (IBW). A secondary end point was expiratory diaphragm thickness measured with ultrasound from days 1 to 10 (or extubation). RESULTS: The revised European Union regulation mandated reapproval of medical devices, prematurely halting the study. Eleven patients (five in the intervention group, six in the control group) were enrolled. The median time to find an adequate stimulation position was 23 s (interquartile range, 12-62 s). The intervention bid was executed in 87% of patients, and 92% of patients including a next-day catch-up session. Ventilation with 3 to 6 mL/kg IBW was achieved in 732 of 1,701 stimulations (43.0%) with stimulation only and in 2,511 of 4,036 stimulations (62.2%) with additional pressure support. A decrease in diaphragm thickness was prevented by bilateral NEPNS (P = .034) until day 10. INTERPRETATION: Bilateral transcutaneous NEPNS was feasible in the ICU setting with the potential benefit of preventing diaphragm atrophy during mechanical ventilation. NEPNS ventilation effectiveness needs further assessment. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05238753; URL: www. CLINICALTRIALS: gov.

Guideline on positioning and early mobilisation in the critically ill by an expert panel.

A scientific panel was created consisting of 23 interdisciplinary and interprofessional experts in intensive care medicine, physiotherapy, nursing care, surgery, rehabilitative medicine, and pneumology delegated from scientific societies together with a patient representative and a delegate from the Association of the Scientific Medical Societies who advised methodological implementation. The guideline was created according to the German Association of the Scientific Medical Societies (AWMF), based on The Appraisal of Guidelines for Research and Evaluation (AGREE) II. The topics of (early) mobilisation, neuromuscular electrical stimulation, assist devices for mobilisation, and positioning, including prone positioning, were identified as areas to be addressed and assigned to specialist expert groups, taking conflicts of interest into account. The panel formulated PICO questions (addressing the population, intervention, comparison or control group as well as the resulting outcomes), conducted a systematic literature review with abstract screening and full-text analysis and created summary tables. This was followed by grading the evidence according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence and a risk of bias assessment. The recommendations were finalized according to GRADE and voted using an online Delphi process followed by a final hybrid consensus conference. The German long version of the guideline was approved by the professional associations. For this English version an update of the systematic review was conducted until April 2024 and recommendation adapted based on new evidence in systematic reviews and randomized controlled trials. In total, 46 recommendations were developed and research gaps addressed.

Insulin signaling in skeletal muscle during inflammation and/or immobilisation.

BACKGROUND: The decline in the downstream signal transduction pathway of anabolic hormone, insulin, could play a key role in the muscle atrophy and insulin resistance observed in patients with intensive care unit acquired weakness (ICUAW). This study investigated the impact of immobilisation via surgical knee and ankle fixation and inflammation via Corynebacterium parvum injection, alone and in combination, as risk factors for altering insulin transduction and, therefore, their role in ICUAW. RESULTS: Muscle weight was significantly decreased due to immobilisation [estimated effect size (95% CI) - 0.10 g (- 0.12 to - 0.08); p < 0.001] or inflammation [estimated effect size (95% CI) - 0.11 g (- 0.13 to - 0.09); p < 0.001] with an additive effect of both combined (p = 0.024). pAkt was only detectable after insulin stimulation [estimated effect size (95% CI) 85.1-fold (76.2 to 94.0); p < 0.001] irrespective of the group and phosphorylation was not impaired by the different perturbations. Nevertheless, the phosphorylation of GSK3 observed in the control group after insulin stimulation was decreased in the immobilisation [estimated effect size (95% CI) - 40.2 (- 45.6 to - 34.8)] and inflammation [estimated effect size (95% CI) - 55.0 (- 60.4 to - 49.5)] groups. The expression of phosphorylated GS (pGS) was decreased after insulin stimulation in the control group and significantly increased in the immobilisation [estimated effect size (95% CI) 70.6-fold (58.8 to 82.4)] and inflammation [estimated effect size (95% CI) 96.7 (85.0 to 108.5)] groups. CONCLUSIONS: Both immobilisation and inflammation significantly induce insulin resistance, i.e., impair the insulin signaling pathway downstream of Akt causing insufficient GSK phosphorylation and, therefore, its activation which caused increased glycogen synthase phosphorylation, which could contribute to muscle atrophy of immobilisation and inflammation.

Outcomes in critically ill patients after diaphragmatic stimulation on ventilator-induced diaphragmatic dysfunction: a systematic review.

INTRODUCTION: Mechanical ventilation (MV) is a lifesaving procedure for critically ill patients. Diaphragm activation and stimulation may counteract side effects, such as ventilator-induced diaphragm dysfunction (VIDD). The effects of stimulation on diaphragm atrophy and patient outcomes are reported in this systematic review. EVIDENCE ACQUISITION: Studies investigating diaphragmatic stimulation versus standard of care in critically ill patients and evaluating clinical outcomes were extracted from a Medline database last on January 23, 2023, after registration in Prospero (CRD42021259353). Selected studies included the investigation of diaphragmatic stimulation versus standard of care in critically ill patients, an evaluation of the clinical outcomes. These included muscle atrophy, VIDD, weaning failure, mortality, quality of life, ventilation time, diaphragmatic function, length of stay in the Intensive Care Unit (ICU), and length of hospital stay. All articles were independently evaluated by two reviewers according to their abstract and title and, secondly, a full texts evaluation by two independent reviewers was performed. To resolve diverging evaluations, a third reviewer was consulted to reach a final decision. Data were extracted by the reviewers following the Oxford 2011 levels of evidence guidelines and summarized accordingly. EVIDENCE SYNTHESIS: Seven studies were extracted and descriptively synthesized, since a metanalysis was not feasible. Patients undergoing diaphragm stimulation had moderate evidence of higher maximal inspiratory pressure (MIP), less atrophy, less mitochondrial respiratory dysfunction, less oxidative stress, less molecular atrophy, shorter MV time, shorter ICU length of stay, longer survival, and better SF-36 scores than control. CONCLUSIONS: Evidence of the molecular and histological benefits of diaphragmatic stimulation is limited. The results indicate positive clinical effects of diaphragm activation with a moderate level of evidence for MIP and a low level of evidence for other outcomes. Diaphragm activation could be a therapeutic solution to avoid diaphragm atrophy, accelerate weaning, shorten MV time, and counteract VIDD; however, better-powered studies are needed to increase the level of evidence.

The optimal dose of mobilisation therapy in the ICU: a prospective cohort study.

BACKGROUND: This study aimed to assess the impact of duration of early mobilisation on survivors of critical illness. The hypothesis was that interventions lasting over 40 min, as per the German guideline, positively affect the functional status at ICU discharge. METHODS: Prospective single-centre cohort study conducted in two ICUs in Germany. In 684 critically ill patients surviving an ICU stay > 24 h, out-of-bed mobilisation of more than 40 min was evaluated. RESULTS: Daily mobilisation ≥ 40 min was identified as an independent predictor of an improved functional status upon ICU discharge. This effect on the primary outcome measure, change of Mobility-Barthel until ICU discharge, was observed in three different models for baseline patient characteristics (average treatment effect (ATE), all three models p < 0.001). When mobilisation parameters like level of mobilisation, were included in the analysis, the average treatment effect disappeared [ATE 1.0 (95% CI - 0.4 to 2.4), p = 0.16]. CONCLUSIONS: A mobilisation duration of more than 40 min positively impacts functional outcomes at ICU discharge. However, the maximum level achieved during ICU stay was the most crucial factor regarding adequate dosage, as higher duration did not show an additional benefit in patients with already high mobilisation levels. TRIAL REGISTRATION: Prospective Registry of Mobilization-, Routine- and Outcome Data of Intensive Care Patients (MOBDB), NCT03666286. Registered 11 September 2018-retrospectively registered, https://classic. CLINICALTRIALS: gov/ct2/show/NCT03666286 .

Corrigendum: The functional trajectory in frail compared with non-frail critically ill patients during the hospital stay.

[This corrects the article DOI: 10.3389/fmed.2021.748812.].

First non-invasive magnetic phrenic nerve and diaphragm stimulation in anaesthetized patients: a proof-of-concept study.

BACKGROUND: Mechanical ventilation has side effects such as ventilator-induced diaphragm dysfunction, resulting in prolonged intensive care unit length of stays. Artificially evoked diaphragmatic muscle contraction may potentially maintain diaphragmatic muscle function and thereby ameliorate or counteract ventilator-induced diaphragm dysfunction. We hypothesized that bilateral non-invasive electromagnetic phrenic nerve stimulation (NEPNS) results in adequate diaphragm contractions and consecutively in effective tidal volumes. RESULTS: This single-centre proof-of-concept study was performed in five patients who were 30 [IQR 21-33] years old, 60% (n = 3) females and undergoing elective surgery with general anaesthesia. Following anaesthesia and reversal of muscle relaxation, patients received bilateral NEPNS with different magnetic field intensities (10%, 20%, 30%, 40%); the stimulation was performed bilaterally with dual coils (connected to one standard clinical magnetic stimulator), specifically designed for bilateral non-invasive electromagnetic nerve stimulation. The stimulator with a maximal output of 2400 Volt, 160 Joule, pulse length 160 µs at 100% intensity was limited to 50% intensity, i.e. each single coil had a maximal output of 0.55 Tesla and 1200 Volt. There was a linear relationship between dosage (magnetic field intensity) and effect (tidal volume, primary endpoint, p < 0.001). Mean tidal volume was 0.00, 1.81 ± 0.99, 4.55 ± 2.23 and 7.43 ± 3.06 ml/kg ideal body weight applying 10%, 20%, 30% and 40% stimulation intensity, respectively. Mean time to find an initial adequate stimulation point was 89 (range 15-441) seconds. CONCLUSIONS: Bilateral non-invasive electromagnetic phrenic nerve stimulation generated a tidal volume of 3-6 ml/kg ideal body weight due to diaphragmatic contraction in lung-healthy anaesthetized patients. Further perspectives in critically ill patients should include assessment of clinical outcomes to confirm whether diaphragm contraction through non-invasive electromagnetic phrenic nerve stimulation potentially ameliorates or prevents diaphragm atrophy.

Mobilisation practices during the SARS-CoV-2 pandemic: A retrospective analysis (MobiCOVID).

BACKGROUND: Corona Virus Disease 2019 (COVID-19) patients display risk factors for intensive care unit acquired weakness (ICUAW). The pandemic increased existing barriers to mobilisation. This study aimed to compare mobilisation practices in COVID-19 and non-COVID-19 patients. METHODS: This retrospective cohort study was conducted at Charité-Universitätsmedizin Berlin, Germany, including adult patients admitted to one of 16 ICUs between March 2018, and November 2021. The effect of COVID-19 on mobilisation level and frequency, early mobilisation (EM) and time to active sitting position (ASP) was analysed. Subgroup analysis on COVID-19 patients and the ICU type influencing mobilisation practices was performed. Mobilisation entries were converted into the ICU mobility scale (IMS) using supervised machine learning. The groups were matched using 1:1 propensity score matching. RESULTS: A total of 12,462 patients were included, receiving 59,415 mobilisations. After matching 611 COVID-19 and non-COVID-19 patients were analysed. They displayed no significant difference in mobilisation frequency (0.4 vs. 0.3, p = 0.7), maximum IMS (3 vs. 3; p = 0.17), EM (43.2% vs. 37.8%; p = 0.06) or time to ASP (HR 0.95; 95% CI: 0.82, 1.09; p = 0.44). Subgroup analysis showed that patients in surge ICUs, i.e., temporarily created ICUs for COVID-19 patients during the pandemic, more commonly received EM (53.9% vs. 39.8%; p = 0.03) and reached higher maximum IMS (4 vs. 3; p = 0.03) without difference in mobilisation frequency (0.5 vs. 0.3; p = 0.32) or time to ASP (HR 1.15; 95% CI: 0.85, 1.56; p = 0.36). CONCLUSION: COVID-19 did not hinder mobilisation. Those treated in surge ICUs were more likely to receive EM and reached higher mobilisation levels.

Correction: Engelhardt et al. Sex-Specific Aspects of Skeletal Muscle Metabolism in the Clinical Context of Intensive Care Unit-Acquired Weakness. J. Clin. Med. 2022, 11, 846.

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