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Evidence has accumulated that respiratory muscle dysfunction develops in critically ill patients and contributes to prolonged weaning from mechanical ventilation. Accordingly, it seems highly appropriate to monitor the respiratory muscles in these patients. Today, we are only at the beginning of routinely monitoring respiratory muscle function. Indeed, most clinicians do not evaluate respiratory muscle function in critically ill patients at all. In our opinion, however, practical issues and the absence of sound scientific data for clinical benefit should not discourage clinicians from having a closer look at respiratory muscle function in critically ill patients. This perspective discusses the latest developments in the field of respiratory muscle monitoring and possible implications of monitoring respiratory muscle function in critically ill patients.

Background Diaphragm dysfunction develops frequently in ventilated intensive care unit (ICU) patients. Both disuse atrophy (ventilator over-assist) and high respiratory muscle effort (ventilator under-assist) seem to be involved. A strong rationale exists to monitor diaphragm effort and titrate support to maintain respiratory muscle activity within physiological limits. Diaphragm electromyography is used to quantify breathing effort and has been correlated with transdiaphragmatic pressure and esophageal pressure. The neuromuscular efficiency index (NME) can be used to estimate inspiratory effort, however its repeatability has not been investigated yet. Our goal is to evaluate NME repeatability during an end-expiratory occlusion (NMEoccl) and its use to estimate the pressure generated by the inspiratory muscles (Pmus). Methods This is a prospective cohort study, performed in a medical-surgical ICU. A total of 31 adult patients were included, all ventilated in neurally adjusted ventilator assist (NAVA) mode with an electrical activity of the diaphragm (EAdi) catheter in situ. At four time points within 72 h five repeated end-expiratory occlusion maneuvers were performed. NMEoccl was calculated by delta airway pressure (ΔPaw)/ΔEAdi and was used to estimate Pmus. The repeatability coefficient (RC) was calculated to investigate the NMEoccl variability. Results A total number of 459 maneuvers were obtained. At time T  = 0 mean NMEoccl was 1.22 ± 0.86 cmH 2 O/μV with a RC of 82.6%. This implies that when NMEoccl is 1.22 cmH 2 O/μV, it is expected with a probability of 95% that the subsequent measured NMEoccl will be between 2.22 and 0.22 cmH2O/μV. Additional EAdi waveform analysis to correct for non-physiological appearing waveforms, did not improve NMEoccl variability. Selecting three out of five occlusions with the lowest variability reduced the RC to 29.8%. Conclusions Repeated measurements of NMEoccl exhibit high variability, limiting the ability of a single NMEoccl maneuver to estimate neuromuscular efficiency and therefore the pressure generated by the inspiratory muscles based on EAdi.

ObjectSurgery of tumours in the cerebellopontine angle (CPA) can lead to loss of facial nerve function. Different methods of intra-operative nerve monitoring (IOM) (including free-running EMG, direct nerve stimulation and transcranial motor evoked potentials (TcMEP)) have been used to predict facial nerve outcome during surgery. Recent research has shown TcMEP threshold increase and the occurrence of A-trains on the EMG to have great potential in doing so. This study compares these two methods and correlates them to House-Brackmann (HB) scores post-op in patients with tumours in the cerebellopontine angle.MethodForty-three patients (one was operated twice) with large CPA tumours treated surgically in the Radboud University Medical Center between 2015 and 2019 were included in this study. During surgery, TcMEP threshold increases and A-train activity were measured. Because our treatment paradigm aims at facial nerve preservation (accepting residual tumour), TcMEP threshold increase of over 20 mA or occurrence of A-trains were considered as warning signs and used as a guide for terminating surgery. HB scores were measured post-op, at 6 weeks, 6 months and 1 year after surgery. Spearman’s correlation was calculated between the IOM-values and the HB scores for a homogeneous subgroup of 30 patients with vestibular schwannoma (VS) without neurofibromatosis type II (NF-II) and all patients collectively.ResultsTcMEP threshold was successfully measured in 39 (90.7%) procedures. In the homogeneous VS non-NFII group, we found a statistically significant moderate-to-strong correlation between TcMEP threshold increase and House Brackmann score immediately post-op, at 6 weeks, 6 months and 1 year after surgery (Spearman’s rho of 0.79 (p < 0.001), 0.74 (p < 0.001), 0.64 (p < 0.001) and 0.58 (p = 0.002), respectively). For A-trains, no correlation was found. Similar results were found when including all patients with CPA tumours. A threshold increase of < 20 mA was a predictor of good facial nerve outcome.ConclusionThese results show that TcMEP threshold increases are strongly correlated to post-operative HB scores, while A-trains are not. This suggests TcMEP threshold increases can be a valuable predictor for facial nerve outcome in patients with large tumours when facial nerve preservation is prioritized over total resection. In this study, we found no use for A-trains to prevent facial nerve deficits.

Background Respiratory muscle weakness is common in critically ill children. Changes in respiratory muscle structure play pivotal role in the development of weakness. Echogenicity is a non-invasive marker to detect structural changes in skeletal muscles. In this study, we evaluated respiratory muscle echogenicity in critically ill ventilated children at PICU admission compared to a control group and its change over time. Secondary, we explored its association with clinical parameters and outcome. Methods Two cohorts were studied: a secondary analysis of a prospective longitudinal observational cohort study in mechanically ventilated children ( n  = 32) and a prospective control group ( n  = 13) for obtaining reference values. Ultrasound images of the diaphragm and expiratory muscles were analysed. Muscle echogenicity, muscle thickness, muscle thickening fraction, clinical parameters (inflammation, fluid balance and protein intake) and clinical outcome measurements (ventilation free days, extubation failure and 28-day mortality) were collected. Results The analysis included 174 diaphragm ultrasounds and 144 expiratory respiratory muscles ultrasounds. Echogenicity at PICU admission was not different from controls; for the diaphragm: 27.3 [20.0–32.0] vs 26.3 [19.3–29.3] ( P  = 0.488), m. obliquus externus: 32.2 [25.5–37.9] vs 34.0 [28.0–51.3] ( P  = 0.166), m. obliquus interna: 29.8 [25.8–38.8] vs 33.0 [27.8–39.3] ( P  = 0.390), m. transversus: 30.0 [20.8–38.8] vs 32.3 [24.7–37.0] ( P  = 0.762), respectively. There was no increase in respiratory muscle echogenicity after four days of mechanical ventilation, though a substantial interindividual variation existed. No correlation was found between changes in echogenicity and changes in muscle thickness, thickening fraction and echogenicity on day four of mechanical ventilation, or clinical outcome. The intra-observer repeatability of the echogenicity for all the respiratory muscles was excellent (all ≥ 0.97). Conclusion In critically ill children, four days of mechanical ventilation does not result in an increase in respiratory muscle echogenicity. Our findings suggest that short periods of mechanical ventilation with relatively low ventilator setting in moderate critically ill children do not lead to large structural changes in the respiratory muscles.

Motor cortex stimulation (MCS) was introduced as a last-resort treatment for chronic neuropathic pain. Over the years, MCS has been used for the treatment of various pain syndromes but long-term follow-up is unknown. This paper reports the results of MCS from 2005 until 2012 with a 3-year follow-up. Patients who suffered from chronic neuropathic pain treated with MCS were studied. The analgesic effect was determined as successful by decrease in pain-intensity on the visual analog scale (VAS) of at least 40%. The modifications in drug regimens were monitored with use of the medication quantification scale (MQS). Stimulation parameters and complications were also noted. Interference of pain with quality of life (QoL), the Quality of Life Index (QLI), was determined with use of a specific subset of questions from the MPQ-DLV score. Eighteen patients were included. Mean pre-operative VAS changed from 89.4 ± 11.2 to 53.1 ± 25.0 after three years of follow-up (P < 0.0001). A successful outcome was achieved in seven responders (38.9%). All patients in the responder group suffered from pain caused by a central lesion. With regard to all the patients with central pain lesions (n = 10) and peripheral lesions (n = 8), a significant difference in response to MCS was noticed (P = 0.002). MQS scores and QLI-scores diminished during the follow-up period (P = 0.210 and P = 0.007, respectively). MCS seems a promising therapeutic option for patients with refractory pain syndromes of central origin.

Background Spinocerebellar ataxia type 3 (SCA3) is the most common subtype among the autosomal dominant cerebellar ataxias, a group of neurodegenerative disorders for which currently no disease-specific therapy is available. Evidence-based options for symptomatic treatment of ataxia are also limited. Recent investigations in a heterogeneous group of hereditary and acquired ataxias showed promising, prolonged effects of a two-week course with daily sessions of cerebellar anodal transcranial direct current stimulation (tDCS) on ataxia severity, gait speed, and upper limb dexterity. The aim of the SCA3-tDCS study is to further examine whether tDCS improves ataxia severity and various (cerebellar) non-motor symptoms in a homogeneous cohort of SCA3 patients and to explore the time course of these effects. Methods/design An investigator-initiated, double-blind, randomized, sham-controlled, single-center trial will be conducted. Twenty mildly to moderately affected SCA3 patients (Scale for the Assessment and Rating of Ataxia score between 3 and 20) will be included and randomly assigned in a 1:1 ratio to either cerebellar anodal tDCS or sham cerebellar tDCS. Patients, investigators, and outcome assessors are unaware of treatment allocation. Cerebellar tDCS (20 min, 2 mA, ramp-up and down periods of 30 s each) will be delivered over ten sessions, distributed in two groups of five consecutive days with a two-day break in between. Outcomes are assessed after a single session of tDCS, after the tenth stimulation (T1), and after three, six, and twelve months. The primary outcome measure is the absolute change of the SARA score between baseline and T1. In addition, effects on a variety of other motor and neuropsychological functions in which the cerebellum is known to be involved will be evaluated using quantitative motor tests, static posturography, neurophysiological measurements, cognitive assessment, and questionnaires. Discussion The results of this study will inform us whether repeated sessions of cerebellar anodal tDCS benefit SCA3 patients and whether this form of non-invasive stimulation might be a novel therapeutic approach to consider in a neurorehabilitation setting. Combined with two earlier controlled trials, a positive effect of the SCA3-tDCS study will encourage implementation of this intervention and stimulate further research in other SCAs and heredodegenerative ataxias. Trial registration NL7321 , registered October 8, 2018.

Transcranial magnetic stimulation (TMS) of the motor cortex can be used during a voluntary contraction to inhibit corticospinal drive to the muscle and consequently induce involuntary muscle relaxation. Our aim was to evaluate the reproducibility and the effect of varying experimental conditions (robustness) of TMS‐induced muscle relaxation. Relaxation of deep finger flexors was assessed in 10 healthy subjects (5 M, 5 F) using handgrip dynamometry with normalized peak relaxation rate as main outcome measure, that is, peak relaxation rate divided by (voluntary plus TMS‐evoked)force prior to relaxation. Both interday and interrater reliability of relaxation rate were high with intraclass correlation coefficient of 0.88 and 0.92 and coefficient of variation of 3.8 and 3.7%, respectively. Target forces of 37.5% of maximal voluntary force or higher resulted in similar relaxation rate. From 50% of maximal stimulator output and higher relaxation rate remained the same. Only the most lateral position (>2 cm from the vertex) rendered lower relaxation rate (mean ± SD: 11.1 ± 3.0 s−1, 95% CI: 9.0–13.3 s−1) compared to stimulation at the vertex (12.8 ± 1.89 s−1, 95% CI: 11.6–14.1 s−1). Within the range of baseline skin temperatures, an average change of 0.5 ± 0.2 s−1 in normalized peak relaxation rate was measured per 1°C change in skin temperature. In conclusion, interday and interrater reproducibility and reliability of TMS‐induced muscle relaxation of the finger flexors were high. Furthermore, this technique is robust with limited effect of target force, stimulation intensity, and coil position. Muscle relaxation is strongly affected by skin temperature; however, this effect is marginal within the normal skin temperature range. We deem this technique well suited for clinical and scientific assessment of muscle relaxation. Transcranial magnetic stimulation (TMS) can be used to assess muscle relaxation during a voluntary contraction by abruptly halting neural drive to the muscle. Our results show that this technique has high interday and interrater reproducibility and reliability. Furthermore, generated results are robust with limited effect of target force, stimulation intensity, coil position, and skin temperature on relaxation rate. TMS‐induced muscle relaxation appears well suited for clinical and scientific assessment of muscle relaxation rate.

This review highlights the latest advancements in imaging techniques for monitoring respiratory muscles in critically ill patients. At the bedside, conventional ultrasound has been widely adopted to measure diaphragm thickness, thickening and excursion. It has also been used to assess extradiaphragmatic respiratory muscles, including parasternal intercostal and abdominal muscles. Advanced ultrasound-derived techniques have expanded its applications, enabling the evaluation of tissue velocity (tissue Doppler imaging), stiffness (shear wave elastography), and local tissue displacement (speckle tracking). Facility-based imaging modalities such as magnetic resonance imaging and chest tomography provide complementary insights into respiratory muscles structure and function, offering valuable information for evaluating the effects of therapeutic interventions. Finally, imaging techniques have emerged as valuable tools for evaluating the metabolic demands of respiratory muscles, with advanced methods such as positron emission tomography and contrast-enhanced ultrasound showing significant potential.

Purpose Respiratory muscle weakness frequently develops in critically ill patients and is associated with adverse outcome, including difficult weaning from mechanical ventilation. Today, no drug is approved to improve respiratory muscle function in these patients. Previously, we have shown that the calcium sensitizer levosimendan improves calcium sensitivity of human diaphragm muscle fibers in vitro and contractile efficiency of the diaphragm in healthy subjects. The main purpose of this study is to investigate the effects of levosimendan on diaphragm contractile efficiency in mechanically ventilated patients. Methods In a double-blind randomized placebo-controlled trial, mechanically ventilated patients performed two 30-min continuous positive airway pressure (CPAP) trials with 5-h interval. After the first CPAP trial, study medication (levosimendan 0.2 µg/kg/min continuous infusion or placebo) was administered. During the CPAP trials, electrical activity of the diaphragm (EA di ), transdiaphragmatic pressure ( P di ), and flow were measured. Neuromechanical efficiency (primary outcome parameter) was calculated. Results Thirty-nine patients were included in the study. Neuromechanical efficiency was not different during the CPAP trial after levosimendan administration compared to the CPAP trial before study medication. Tidal volume and minute ventilation were higher after levosimendan administration (11 and 21%, respectively), whereas EA di and P di were higher in both groups in the CPAP trial after study medication compared to the CPAP trial before study medication. Conclusions Levosimendan does not improve diaphragm contractile efficiency.