Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain. METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation. RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group. CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

Comparison of muscle ultrasound and needle electromyography findings in neuromuscular disorders.

INTRODUCTION/AIMS: Needle electromyography (EMG) and muscle ultrasound can be used to evaluate patients with suspected neuromuscular disorders. The relation between muscle ultrasound pathology and the corresponding needle EMG findings is unknown. In this study we compared the results of concurrent ultrasound and needle EMG examinations in patients suspected of a neuromuscular disorder. METHODS: Retrospective data from 218 patients with pairwise ultrasound and EMG results of 796 muscles were analyzed. We compared overall quantitative and visual muscle ultrasound results to EMGs with neurogenic and myopathic abnormalities and assessed the congruency of both methods in the different clinical diagnosis categories. RESULTS: In muscles of patients with a neuromuscular disorder, abnormalities were found with EMG in 71.8%, and quantitative and visual muscle ultrasound results were abnormal in 19.3% and 35.4% respectively. In muscles with neurogenic EMG abnormalities, quantitative and visual muscle ultrasound results were abnormal in 18.9% versus 35.6%, increasing up to 43.7% versus 87.5% in muscles with the most pronounced signs of denervation. Congruency of EMG and ultrasound was better for more proximal and cranial muscles than for muscles in the hand and lower limb. DISCUSSION: Needle EMG and muscle ultrasound typically produce disparate results and identify different aspects of muscle pathology. Muscle ultrasound seems less suited for detecting mild neurogenic abnormalities. As the severity of neurogenic needle EMG abnormalities increased, muscle ultrasound abnormalities were also increasingly found. Visual analysis seems better suited than grayscale quantification for detecting neurogenic abnormalities.

Future directions for respiratory muscle training in neuromuscular disorders: a scoping review.

BACKGROUND: Respiratory muscle training (RMT) aims to improve inspiratory and/or expiratory muscle function in neuromuscular disorders (NMDs). A comprehensive overview of the available literature is lacking. This scoping review explores methodological characteristics, (adverse) effects, and adherence of RMT studies in NMDs. Moreover, it identifies limitations and research gaps in the literature, and provides future research directions. SUMMARY: Eligible studies were identified using MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases Three reviewers independently selected articles. Inclusion criteria were English language, original research articles on RMT using a device, patients with an NMD, and pulmonary function tests or respiratory muscle strength as outcome measures. We included NMDs with slow, intermediate and fast progression. Exclusion criteria were critically ill patients, weaning from mechanical ventilation, other neurological disorders, and RMT combined with non-respiratory interventions. One reviewer extracted the data on patients characteristics, methodological characteristics, results of outcome measures, adverse events, and patient adherence. Forty-five studies were identified. We found a large diversity in study designs and training protocols. The effects of RMT on respiratory muscle strength and/or endurance are variable. Patient adherence was high and no serious adverse events were reported. KEY MESSAGES: The diversity in studies across the available literature precludes definitive conclusions regarding effects of RMT on respiratory muscle function and clinically relevant outcomes in NMDs. Therefore, well-powered and -designed studies that focus on clinically relevant outcomes and assess whether RMT can improve or offset deterioration of respiratory muscle weakness in NMDs are needed.

Visual versus quantitative analysis of muscle ultrasound in neuromuscular disease.

INTRODUCTION/AIMS: Visual and quantitative muscle ultrasound are both valid diagnostic tools in neuromuscular diseases. To optimize muscle ultrasound evaluation and facilitate its use in neuromuscular disease, we examined the correlation between visual and quantitative muscle ultrasound analysis and their pitfalls. METHODS: Retrospective data from 994 patients with 13,562 muscle ultrasound images were analyzed. Differences in echogenicity z-score distribution per Heckmatt grade and corresponding correlation coefficients were calculated. RESULTS: Overall, there was a correlation of 0.60 between the two scoring systems, with a gradual increase in z-score with increasing Heckmatt grades and vice versa. Patients with a neuromuscular disorder had higher Heckmatt grades (p < 0.001) and z-scores (median z-score = 0.30, p < 0.001) than patients without. The highest Heckmatt grades and z-scores were found in patients with either a dystrophy or inflammatory myopathy (both median Heckmatt grade of 2 and median z score of 0.74 and 1.20, respectively). Discrepant scores were infrequent (<2%), but revealed important pitfalls in both grading systems. DISCUSSION: Visual and quantitative muscle ultrasound are complementary techniques to evaluate neuromuscular disease and have a moderate positive correlation. Importantly, we identified specific pitfalls for visual and quantitative muscle ultrasound and how to overcome them in clinical practice.

Association of diaphragm thickness and echogenicity with age, sex, and body mass index in healthy subjects.

INTRODUCTION/AIMS: Diaphragm ultrasound is increasingly used in the diagnosis of diaphragm dysfunction and to guide respiratory management in patients with neuromuscular disorders and those who are critically ill. However, the association between diaphragm ultrasound variables and demographic factors like age, sex, and body mass index (BMI) are understudied. Such relationships are important for correct interpretation of normative values and comparison with selected patients groups. The aim of this study was to determine the associations between diaphragm ultrasound variables and subject characteristics. METHODS: B-mode ultrasound was used to image the diaphragm at the zone of apposition in 83 healthy subjects. Diaphragm thickness at resting end-expiration (Tend-exp ), diaphragm thickness at maximal end-inspiration (Tmax-insp ), diaphragm thickening ratio (Tmax-insp /Tend-exp ), and diaphragm echogenicity were measured. Multivariate linear regression was used to explore the associations between diaphragm ultrasound variables and subject characteristics. RESULTS: Tend-exp , Tmax-insp , and thickening ratio do not change with age whereas diaphragm echogenicity increases with age. The thickening ratio had a weak negative association with BMI, while Tend-exp was positively associated with BMI. Men had a larger Tend-exp and Tmax-insp than women (Tend-exp 1.6 ± 0.5 and 1.4 ± 0.3 mm; p = .011, Tmax-insp 3.8 ± 1.0 and 3.2 ± 0.9 mm; p = .004), but similar thickening ratios. DISCUSSION: Diaphragm thickness, thickening, and echogenicity measured with ultrasound are associated with factors such as age, BMI, and sex. Therefore, subject characteristics should be considered when interpreting diaphragm ultrasound measurements. In the absence of normative values, matched control groups are a prerequisite for research and in clinical practice.

Muscle ultrasound is a sensitive biomarker in oculopharyngeal muscular dystrophy.

INTRODUCTION/AIMS: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, progressive muscle disease. Quantitative muscle ultrasound (QMUS) assesses structural changes in muscles and is a sensitive biomarker in neuromuscular disorders. Our aim of this study was to determine whether QMUS can detect muscle pathology and can be used as longitudinal imaging biomarker in OPMD. METHODS: Genetically confirmed OPMD patients, recruited by their treating physicians or from the national neuromuscular database, were examined twice, 20 months apart, using QMUS of orofacial and limb muscles, and measurements of functional capacity and muscle strength. Absolute echo intensity (AEI) and muscle thickness of all muscles were analyzed and correlated with clinical data. RESULTS: The tongue, deltoid, iliopsoas, rectus femoris, and soleus muscles showed increased AEI at baseline compared with normal values in 43 OPMD patients, with the rectus femoris being most often affected (51%).The AEI and muscle thickness of 9 of 11 muscles correlated significantly with the motor function measure, 10-step stair test, swallowing capacity, dynamometry, Medical Research Council grade, tongue strength, and bite force (r = 0.302 to -0.711). Between baseline and follow-up, deterioration in AEI was found for the temporalis, tongue, and deltoid muscles, and decreased muscle thickness was detected for the temporalis, masseter, digastric, tongue, deltoid, iliopsoas, and soleus muscles (P < .05). No relation was found between the change in AEI and repeat length or disease duration. DISCUSSION: QMUS detected muscle pathology and disease progression in OPMD over 20 months. We conclude that QMUS should be considered as a biomarker in treatment trials.

Respiratory muscle imaging by ultrasound and MRI in neuromuscular disorders.

Respiratory muscle weakness is common in neuromuscular disorders (NMDs) and leads to significant respiratory difficulties. Therefore, reliable and easy assessment of respiratory muscle structure and function in NMDs is crucial. In the last decade, ultrasound and magnetic resonance imaging (MRI) have emerged as promising imaging techniques to assess respiratory muscle structure and function. Respiratory muscle imaging directly measures the respiratory muscles and, in contrast to pulmonary function testing, is independent of patient effort. This makes respiratory muscle imaging suitable to use as a tool in clinical respiratory management and as an outcome parameter in upcoming drug trials for NMDs, particularly in children. In this narrative review, we discuss the latest studies and technological developments in imaging of the respiratory muscles by ultrasound and MRI, and its clinical application and limitations. We aim to increase understanding of respiratory muscle imaging and facilitate its use as an outcome measure in daily practice and clinical trials.

Natural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENON-related myopathy in children and adults: protocol of the LAST STRONG study.

BACKGROUND: SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness. METHODS: LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient's age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed. DISCUSSION: Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up. CONCLUSION: Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD. TRIAL REGISTRATION: This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017-3911) and is registered at ClinicalTrial.gov ( NCT04478981 ).

Ultrasound can differentiate inclusion body myositis from disease mimics.

INTRODUCTION: The diagnosis of inclusion body myositis (IBM) can be challenging, and its presentation can be confused with other forms of myositis or neuromuscular disorders. In this study we evaluate the ability of quantitative muscle ultrasound to differentiate between IBM and mimicking diseases. METHODS: Patients 50 years of age and older were included from two specialty centers. Muscle echogenicity and muscle thickness of four characteristically involved muscles in IBM were measured and compared with polymyositis (PM)/dermatomyositis (DM), other neuromuscular disorders, and healthy controls. RESULTS: Echogenicity was higher and muscle thickness generally lower in all four muscles in IBM compared with PM/DM and normal controls. When comparing IBM with the comparator groups, the flexor digitorum profundus was the most discriminative muscle. DISCUSSION: Ultrasound appears to be a good test to differentiate established IBM from PM/DM and neuromuscular controls, with value as a diagnostic tool for IBM.

TcMEP threshold change is superior to A-train detection when predicting facial nerve outcome in CPA tumour surgery.

OBJECT: Surgery 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. METHOD: Forty-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. RESULTS: TcMEP 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. CONCLUSION: These 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.

Coherence of jaw and neck muscle activity during sleep bruxism.

BACKGROUND: Studies have shown co-contraction of jaw and neck muscles in healthy subjects during (sub) maximum voluntary jaw clenching, indicating functional inter-relation between these muscles during awake bruxism. So far, coherence of jaw and neck muscles has not been evaluated during either awake or sleep bruxism. OBJECTIVE: The objective of this study was to evaluate the coherence between jaw and neck muscle activity during sleep bruxism. METHODS: In a cross-sectional observational design, the electromyographic activity of jaw (masseter, temporalis) and neck (sternocleidomastoid, trapezius) muscles in individuals with "definite" sleep bruxism was measured using ambulatory polysomnography (PSG). Coherence for masseter-temporalis, masseter-sternocleidomastoid and masseter-trapezius was measured during phasic and mixed rhythmic masticatory muscle activity episodes using coherence-analysing software. Outcome measures were as follows: presence or absence of significant coherence per episode (in percentages), frequency of peak coherence (FPC) per episode and sleep stage. RESULTS: A total of 632 episodes within 16 PSGs of eight individuals were analysed. Significant coherence was found between the jaw and neck muscles in 84.9% of the episodes. FPCs of masseter-temporalis were significantly positively correlated with those of masseter-sternocleidomastoid or masseter-trapezius (P < .001). Sleep stages did not significantly influence coherence of these muscular couples. CONCLUSION: During sleep bruxism, jaw and neck muscle activation is significantly coherent. Coherence occurs independently of sleep stage. These results support the hypothesis of bruxism being a centrally regulated phenomenon.

Cerebellar transcranial direct current stimulation in spinocerebellar ataxia type 3 (SCA3-tDCS): rationale and protocol of a randomized, double-blind, sham-controlled study.

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.

Respiratory Muscle Effort during Expiration in Successful and Failed Weaning from Mechanical Ventilation.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Respiratory muscle weakness in critically ill patients is associated with difficulty in weaning from mechanical ventilation. Previous studies have mainly focused on inspiratory muscle activity during weaning; expiratory muscle activity is less well understood. The current study describes expiratory muscle activity during weaning, including tonic diaphragm activity. The authors hypothesized that expiratory muscle effort is greater in patients who fail to wean compared to those who wean successfully. METHODS: Twenty adult patients receiving mechanical ventilation (more than 72 h) performed a spontaneous breathing trial. Tidal volume, transdiaphragmatic pressure, diaphragm electrical activity, and diaphragm neuromechanical efficiency were calculated on a breath-by-breath basis. Inspiratory (and expiratory) muscle efforts were calculated as the inspiratory esophageal (and expiratory gastric) pressure-time products, respectively. RESULTS: Nine patients failed weaning. The contribution of the expiratory muscles to total respiratory muscle effort increased in the "failure" group from 13 ± 9% at onset to 24 ± 10% at the end of the breathing trial (P = 0.047); there was no increase in the "success" group. Diaphragm electrical activity (expressed as the percentage of inspiratory peak) was low at end expiration (failure, 3 ± 2%; success, 4 ± 6%) and equal between groups during the entire expiratory phase (P = 0.407). Diaphragm neuromechanical efficiency was lower in the failure versus success groups (0.38 ± 0.16 vs. 0.71 ± 0.36 cm H2O/µV; P = 0.054). CONCLUSIONS: Weaning failure (vs. success) is associated with increased effort of the expiratory muscles and impaired neuromechanical efficiency of the diaphragm but no difference in tonic activity of the diaphragm.

Estimation of the diaphragm neuromuscular efficiency index in mechanically ventilated 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 cmH2O/µV with a RC of 82.6%. This implies that when NMEoccl is 1.22 cmH2O/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.

Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes.

RATIONALE: Controlled mechanical ventilation is used to deliver lung-protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm activity, partial support ventilation modes may be incompatible with lung-protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high-dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung-protective ventilation under partial support modes. OBJECTIVES: To investigate whether partial neuromuscular blockade can facilitate lung-protective ventilation while maintaining diaphragm activity under partial ventilatory support. METHODS: In a proof-of-concept study, we enrolled 10 patients with lung injury and a Vt greater than 8 ml/kg under pressure support ventilation (PSV) and under sedation. After baseline measurements, rocuronium administration was titrated to a target Vt of 6 ml/kg during neurally adjusted ventilatory assist (NAVA). Thereafter, patients were ventilated in PSV and NAVA under continuous rocuronium infusion for 2 hours. Respiratory parameters, hemodynamic parameters, and blood gas values were measured. MEASUREMENTS AND MAIN RESULTS: Rocuronium titration resulted in significant declines of Vt (mean ± SEM, 9.3 ± 0.6 to 5.6 ± 0.2 ml/kg; P < 0.0001), transpulmonary pressure (26.7 ± 2.5 to 10.7 ± 1.2 cm H2O; P < 0.0001), and diaphragm electrical activity (17.4 ± 2.3 to 4.5 ± 0.7 µV; P < 0.0001), and could be maintained under continuous rocuronium infusion. During titration, pH decreased (7.42 ± 0.02 to 7.35 ± 0.02; P < 0.0001), and mean arterial blood pressure increased (84 ± 6 to 99 ± 6 mm Hg; P = 0.0004), as did heart rate (83 ± 7 to 93 ± 8 beats/min; P = 0.0004). CONCLUSIONS: Partial neuromuscular blockade facilitates lung-protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury.

Safety of needle electromyography of the diaphragm: Anterior lung margins in quietly breathing healthy subjects.

INTRODUCTION: Controversy persists as to whether the lung interposes on the needle electrode insertion path during diaphragm electromyography (EMG). METHODS: Using high-resolution ultrasonography, we measured the distances between the medial recess of the intercostal spaces (ICSs) around the mid-clavicular line (MCL) and the lung margin. We performed measurements bilaterally during quiet breathing in the seated and supine positions. RESULTS: We studied 10 young healthy men and found that, in the first ICS with the medial recess clearly (i.e., several cm) lateral to MCL (usually the eighth ICS), the distance between the recommended insertion site and the lung margin varied from 7.5 to 17 cm. The distance was slightly larger on the right side and in the supine position. CONCLUSIONS: This study confirms that properly conducted "trans-intercostal" needle EMG of the diaphragm is generally safe in healthy subjects. Muscle Nerve 54: 54-57, 2016.

Strategies to optimize respiratory muscle function in ICU patients.

Respiratory muscle dysfunction may develop rapidly in critically ill ventilated patients and is associated with increased morbidity, length of intensive care unit stay, costs, and mortality. This review briefly discusses the pathophysiology of respiratory muscle dysfunction in intensive care unit patients and then focuses on strategies that prevent the development of muscle weakness or, if weakness has developed, how respiratory muscle function may be improved. We propose a simple strategy for how these can be implemented in clinical care.

Assessment of dead-space ventilation in patients with acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: Physiological dead space (VD/VT) represents the fraction of ventilation not participating in gas exchange. In patients with acute respiratory distress syndrome (ARDS), VD/VT has prognostic value and can be used to guide ventilator settings. However, VD/VT is rarely calculated in clinical practice, because its measurement is perceived as challenging. Recently, a novel technique to calculate partial pressure of carbon dioxide in alveolar air (PACO2) using volumetric capnography (VCap) was validated. The purpose of the present study was to evaluate how VCap and other available techniques to measure PACO2 and partial pressure of carbon dioxide in mixed expired air (PeCO2) affect calculated VD/VT. METHODS: In a prospective, observational study, 15 post-cardiac surgery patients and 15 patients with ARDS were included. PACO2 was measured using VCap to calculate Bohr dead space or substituted with partial pressure of carbon dioxide in arterial blood (PaCO2) to calculate the Enghoff modification. PeCO2 was measured in expired air using three techniques: Douglas bag (DBag), indirect calorimetry (InCal), and VCap. Subsequently, VD/VT was calculated using four methods: Enghoff-DBag, Enghoff-InCal, Enghoff-VCap, and Bohr-VCap. RESULTS: PaCO2 was higher than PACO2, particularly in patients with ARDS (post-cardiac surgery PACO2 = 4.3 ± 0.6 kPa vs. PaCO2 = 5.2 ± 0.5 kPa, P < 0.05; ARDS PACO2 = 3.9 ± 0.8 kPa vs. PaCO2 = 6.9 ± 1.7 kPa, P < 0.05). There was good agreement in PeCO2 calculated with DBag vs. VCap (post-cardiac surgery bias = 0.04 ± 0.19 kPa; ARDS bias = 0.03 ± 0.27 kPa) and relatively low agreement with DBag vs. InCal (post-cardiac surgery bias = -1.17 ± 0.50 kPa; ARDS mean bias = -0.15 ± 0.53 kPa). These differences strongly affected calculated VD/VT. For example, in patients with ARDS, VD/VTcalculated with Enghoff-InCal was much higher than Bohr-VCap (VD/VT Enghoff-InCal = 66 ± 10 % vs. VD/VT Bohr-VCap = 45 ± 7 %; P < 0.05). CONCLUSIONS: Different techniques to measure PACO2 and PeCO2 result in clinically relevant mean and individual differences in calculated VD/VT, particularly in patients with ARDS. Volumetric capnography is a promising technique to calculate true Bohr dead space. Our results demonstrate the challenges clinicians face in interpreting an apparently simple measurement such as VD/VT.

The differential diagnosis for failure to wean from mechanical ventilation.

PURPOSE OF REVIEW: In this review, we discuss the causes for a failed weaning trial and specific diagnostic tests that could be conducted to identify the cause for weaning failure. We briefly highlight treatment strategies that may enhance the chance of weaning success. RECENT FINDINGS: Impaired respiratory mechanics, respiratory muscle dysfunction, cardiac dysfunction, cognitive dysfunction, and metabolic disorders are recognized causes for weaning failure. In addition, iatrogenic factors may be at play. Most studies have focused on respiratory muscle dysfunction and cardiac dysfunction. Recent studies demonstrate that both ultrasound and electromyography are valuable tools to evaluate respiratory muscle function in ventilated patients. Sophisticated ultrasound techniques and biomarkers such as B-type natriuretic peptide, are valuable tools to identify cardiac dysfunction as a cause for weaning failure. Once a cause for weaning failure has been identified specific treatment should be instituted. Concerning treatment, both strength training and endurance training should be considered for patients with respiratory muscle weakness. Inotropes and vasodilators should be considered in case of heart failure. SUMMARY: Understanding the complex pathophysiology of weaning failure in combination with a systematic diagnostic approach allows identification of the primary cause of weaning failure. This will help the clinician to choose a specific treatment strategy and therefore may fasten liberation from mechanical ventilation.