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, normal-weight patients 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.

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.

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 .

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 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.

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.

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.

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.

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.

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.

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.

Due to an Editorial Office error during processing, a number of male and female symbols were incorrectly shown in the pdf version of the manuscript [...].

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.

Sex-Specific Aspects of Skeletal Muscle Metabolism in the Clinical Context of Intensive Care Unit-Acquired Weakness.

(1) Background: Female sex is considered a risk factor for Intensive Care Unit-Acquired Weakness (ICUAW). The aim is to investigate sex-specific aspects of skeletal muscle metabolism in the context of ICUAW. (2) Methods: This is a sex-specific sub-analysis from two prospectively conducted trials examining skeletal muscle metabolism and advanced muscle activating measures in critical illness. Muscle strength was assessed by Medical Research Council Score. The insulin sensitivity index was analyzed by hyperinsulinemic-euglycemic (HE) clamp. Muscular metabolites were studied by microdialysis. M. vastus lateralis biopsies were taken. The molecular analysis included protein degradation pathways. Morphology was assessed by myocyte cross-sectional area (MCSA). Multivariable linear regression models for the effect of sex on outcome parameters were performed. (3) Results: n = 83 (♂n = 57, 68.7%; ♀n = 26, 31.3%) ICU patients were included. ICUAW was present in 81.1%♂ and in 82.4%♀ at first awakening (p = 0.911) and in 59.5%♂ and in 70.6%♀ at ICU discharge (p = 0.432). Insulin sensitivity index was reduced more in women than in men (p = 0.026). Sex was significantly associated with insulin sensitivity index and MCSA of Type IIa fibers in the adjusted regression models. (4) Conclusion: This hypothesis-generating analysis suggests that more pronounced impairments in insulin sensitivity and lower MCSA of Type IIa fibers in critically ill women may be relevant for sex differences in ICUAW.

Impact of protocol-based physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients.

BACKGROUND: The impact of physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients is not well understood. METHODS: This pooled analysis investigates the impact of different physiotherapeutic strategies on insulin sensitivity in critically ill patients. We pooled data from two previous trials in adult patients with sequential organ failure assessment score (SOFA)≥ 9 within 72 h of intensive care unit (ICU) admission, who received hyperinsulinaemic euglycaemic (HE) clamps. Patients were divided into three groups: standard physiotherapy (sPT, n = 22), protocol-based physiotherapy (pPT, n = 8), and pPT with added muscle activating measures (pPT+, n = 20). Insulin sensitivity index (ISI) was determined by HE clamp. Muscle metabolites lactate, pyruvate, and glycerol were measured in the M. vastus lateralis via microdialysis during the HE clamp. Histochemical visualization of glucose transporter-4 (GLUT4) translocation was performed in surgically extracted muscle biopsies. All data are reported as median (25th/75th percentile) (trial registry: ISRCTN77569430 and ISRCTN19392591/ethics approval: Charité-EA2/061/06 and Charité-EA2/041/10). RESULTS: Fifty critically ill patients (admission SOFA 13) showed markedly decreased ISIs on Day 17 (interquartile range) 0.029 (0.022/0.048) (mg/min/kg)/(mU/L) compared with healthy controls 0.103 (0.087/0.111), P < 0.001. ISI correlated with muscle strength measured by medical research council (MRC) score at first awakening (r = 0.383, P = 0.026) and at ICU discharge (r = 0.503, P = 0.002). Different physiotherapeutic strategies showed no effect on the ISI [sPT 0.029 (0.019/0.053) (mg/min/kg)/(mU/L) vs. pPT 0.026 (0.023/0.041) (mg/min/kg)/(mU/L) vs. pPT+ 0.029 (0.023/0.042) (mg/min/kg)/(mU/L); P = 0.919]. Regardless of the physiotherapeutic strategy metabolic flexibility was reduced. Relative change of lactate/pyruvate ratio during HE clamp is as follows: sPT 0.09 (-0.13/0.27) vs. pPT 0.07 (-0.16/0.31) vs. pPT+ -0.06 (-0.19/0.16), P = 0.729, and relative change of glycerol concentration: sPT -0.39 (-0.8/-0.12) vs. pPT -0.21 (-0.33/0.07) vs. pPT+ -0.21 (-0.44/-0.03), P = 0.257. The majority of ICU patients showed abnormal localization of GLUT4 with membranous GLUT4 distribution in 37.5% (3 of 8) of ICU patients receiving sPT, in 42.9% (3 of 7) of ICU patients receiving pPT, and in 53.8% (7 of 13) of ICU patients receiving pPT+ (no statistical testing possible). CONCLUSIONS: Our data suggest that a higher duration of muscle activating measures had no impact on insulin sensitivity or metabolic flexibility in critically ill patients with sepsis-related multiple organ failure.

[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.

The Functional Trajectory in Frail Compared With Non-frail Critically Ill Patients During the Hospital Stay.

Background: Long-term outcome is determined not only by the acute critical illness but increasingly by the reduced functional reserve of pre-existing frailty. The patients with frailty currently account for one-third of the critically ill, resulting in higher mortality. There is evidence of how frailty affects the intrahospital functional trajectory of critically ill patients since prehospital status is often missing. Methods: In this prospective single-center cohort study at two interdisciplinary intensive care units (ICUs) at a university hospital in Germany, the frailty was assessed using the Clinical Frailty Scale (CFS) in the adult patients with critical illness with an ICU stay >24 h. The functional status was assessed using the sum of the subdomains "Mobility" and "Transfer" of the Barthel Index (MTB) at three time points (pre-hospital, ICU discharge, and hospital discharge). Results: We included 1,172 patients with a median age of 75 years, of which 290 patients (25%) were frail. In a propensity score-matched cohort, the probability of MTB deterioration till hospital discharge did not differ in the patients with frailty (odds ratio (OR) 1.3 [95% CI 0.8-1.9], p = 0.301), confirmed in several sensitivity analyses in all the patients and survivors only. Conclusion: The patients with frailty have a reduced functional status. Their intrahospital functional trajectory, however, was not worse than those in non-frail patients, suggesting a rehabilitation potential of function in critically ill patients with frailty.

Outcomes in Critically Ill Patients Sedated with Intravenous Lormetazepam or Midazolam: A Retrospective Cohort Study.

The benzodiazepine, midazolam, is one of the most frequently used sedatives in intensive care medicine, but it has an unfavorable pharmacokinetic profile when continuously applied. As a consequence, patients are frequently prolonged and more deeply sedated than intended. Due to its distinct pharmacological features, including a cytochrome P450-independent metabolization, intravenous lormetazepam might be clinically advantageous compared to midazolam. In this retrospective cohort study, we compared patients who received either intravenous lormetazepam or midazolam with respect to their survival and sedation characteristics. The cohort included 3314 mechanically ventilated, critically ill patients that received one of the two drugs in a tertiary medical center in Germany between 2006 and 2018. A Cox proportional hazards model with mortality as outcome and APACHE II, age, gender, and admission mode as covariates revealed a hazard ratio of 1.75 [95% CI 1.46-2.09; p < 0.001] for in-hospital mortality associated with the use of midazolam. After additionally adjusting for sedation intensity, the HR became 1.04 [95% CI 0.83-1.31; p = 0.97]. Thus, we concluded that excessive sedation occurs more frequently in critically ill patients treated with midazolam than in patients treated with lormetazepam. These findings require further investigation in prospective trials to assess if lormetazepam, due to its ability to maintain light sedation, might be favorable over other benzodiazepines for sedation in the ICU.

Assessment of magnetic flux density properties of electromagnetic noninvasive phrenic nerve stimulations for environmental safety in an ICU environment.

Diaphragm weakness affects up to 60% of ventilated patients leading to muscle atrophy, reduction of muscle fiber force via muscle fiber injuries and prolonged weaning from mechanical ventilation. Electromagnetic stimulation of the phrenic nerve can induce contractions of the diaphragm and potentially prevent and treat loss of muscular function. Recommended safety distance of electromagnetic coils is 1 m. The aim of this study was to investigate the magnetic flux density in a typical intensive care unit (ICU) setting. Simulation of magnetic flux density generated by a butterfly coil was performed in a Berlin ICU training center with testing of potential disturbance and heating of medical equipment. Approximate safety distances to surrounding medical ICU equipment were additionally measured in an ICU training center in Bern. Magnetic flux density declined exponentially with advancing distance from the stimulation coil. Above a coil distance of 300 mm with stimulation of 100% power the signal could not be distinguished from the surrounding magnetic background noise. Electromagnetic stimulation of the phrenic nerve for diaphragm contraction in an intensive care unit setting seems to be safe and feasible from a technical point of view with a distance above 300 mm to ICU equipment from the stimulation coil.