Model-based control of neuromuscular block using mivacurium: design and clinical verification

BACKGROUND: Short-acting agents for neuromuscular block (NMB) require frequent dosing adjustments for individual patient's needs. In this study, we verified a new closed-loop controller for mivacurium dosing in clinical trials. METHODS: Fifteen patients were studied. T1% measured with electromyography was used as input signal for the model-based controller. After induction of propofol/opiate anaesthesia, stabilization of baseline electromyography signal was awaited and a bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal intubation. Closed-loop infusion was started thereafter, targeting a neuromuscular block of 90%. Setpoint deviation, the number of manual interventions and surgeon's complaints were recorded. Drug use and its variability between and within patients were evaluated. RESULTS: Median time of closed-loop control for the 11 patients included in the data processing was 135 [89-336] min (median [range]). Four patients had to be excluded because of sensor problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither manual interventions nor complaints from the surgeons were recorded. Mean necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1. Intrapatient variability of mean infusion rates over 30-min interval showed high differences up to a factor of 1.8 between highest and lowest requirement in the same patient. CONCLUSIONS: Neuromuscular block can precisely be controlled with mivacurium using our model-based controller. The amount of mivacurium needed to maintain T1% at defined constant levels differed largely between and within patients. Closed-loop control seems therefore advantageous to automatically maintain neuromuscular block at constant levels.

Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. In contrast to other confirmed risk factors that predispose to a higher morbidity and mortality, the particular risk of a preexisting neuromuscular impairment (NMI) in hospitalized children with RSV infection has not been prospectively studied in a multicenter trial. METHODS: The DMS RSV Paed database was designed for the prospective multicenter documentation and analysis of all clinically relevant aspects of the management of inpatients with RSV infection. Patients with clinically relevant NMI were identified according to the specific comments of the attending physicians and compared with those without NMI. RESULTS: This study covers 6 consecutive seasons; the surveillance took place in 14 pediatric hospitals in Germany from 1999 to 2005. In total, 1568 RSV infections were prospectively documented in 1541 pediatric patients. Of these, 73 (4.7%) patients displayed a clinically relevant NMI; 41 (56%) NMI patients had at least 1 additional risk factor for a severe course of the infection (multiple risk factors in some patients; prematurity in 30, congenital heart disease in 19, chronic lung disease 6 and immunodeficiency in 8). Median age at diagnosis was higher in NMI patients (14 vs. 5 months); NMI patients had a greater risk of seizures (15.1% vs. 1.6%), and a higher proportion in the NMI group had to be mechanically ventilated (9.6% vs. 1.9%). Eventually, the attributable mortality was significantly higher in the NMI group (5.5% vs. 0.2%; P < 0.001 for all). Multivariate logistic regression confirmed that NMI was independently associated with pediatric intensive care unit (PICU) admission (OR, 4.94; 95% CI, 2.69-8.94; P < 0.001] and mechanical ventilation (OR, 3.85; 95% CI, 1.28-10.22; P = 0.017). CONCLUSION: This is the first prospective multicenter study confirming the hypothesis that children with clinically relevant NMI face an increased risk for severe RSV-disease. It seems reasonable to include NMI as a cofactor into the decision algorithm of passive immunization.

Monitoring of neuromuscular blockade at the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting

BACKGROUND: Electrical stimulation of the P6 acupuncture point reduces the incidence of postoperative nausea and vomiting (PONV). Neuromuscular blockade during general anesthesia can be monitored with electrical peripheral nerve stimulation at the wrist. The authors tested the effect of neuromuscular monitoring over the P6 acupuncture point on the reduction of PONV. METHODS: In this prospective, double-blinded, randomized control trial, the authors investigated, with institutional review board approval and informed consent, 220 women undergoing elective laparoscopic surgery anesthetized with fentanyl, sevoflurane, and rocuronium. During anesthesia, neuromuscular blockade was monitored by a conventional nerve stimulator at a frequency of 1 Hz over the ulnar nerve (n = 110, control group) or over the median nerve (n = 110, P6 group) stimulating at the P6 acupuncture point at the same time. The authors evaluated the incidence of nausea and vomiting during the first 24 h. RESULTS: No differences in demographic and morphometric data were found between both groups. The 24-h incidence of PONV was 45% in the P6 acupuncture group versus 61% in the control group (P = 0.022). Nausea decreased from 56% in the control group to 40% in the P6 group (P = 0.022), but emesis decreased only from 28% to 23% (P = 0.439). Nausea decreased substantially during the first 6 h of the observation period (P = 0.009). Fewer subjects in the acupuncture group required ondansetron as rescue therapy (27% vs. 39%; P = 0.086). CONCLUSION: Intraoperative P6 acupuncture point stimulation with a conventional nerve stimulator during surgery significantly reduced the incidence of PONV over 24 h. The efficacy of P6 stimulation is similar to that of commonly used antiemetic drugs in the prevention of PONV.

Neuromuscular issues in cavovarus foot

Differential muscle weakness can cause a cavus foot deformity. Presenting complaints in the hindfoot may include ankle instability, secondary arthritis, or peroneal tendonitis. Presenting complaints in the forefoot may include stress fractures, callus formation over the lateral border of the foot, claw toes, first ray overload, and metatarsalgia. More general presenting complaints can include a drop-foot gait, decreased walking tolerance, and difficulty with shoe or orthotic fitting. To surgically correct the foot shape, soft tissue contractures need to be released, bone deformity corrected, and muscles balanced to optimize their strength and prevent recurrence of the deformity. This article reviews the diagnosis and management of the cavovarus foot secondary to longstanding muscle imbalance.

Neuromuscular disuse and atrophy: {\it In vivo\/} magnetic resonance studies of intramuscular lipid metabolism and fluid shift changes

We postulated that neuromuscular disuse results in deleteriously affected tissue-vascular fluid exchange processes and subsequently damages the important oxidative bioenergetic process of intramuscular lipid metabolism. The in-depth research reported in the literature is somewhat limited by the ex vivo nature and sporadic time-course characterization of disuse atrophy and recovery. Thus, an in vivo controlled, localized animal model of disuse atrophy was developed in one of the hindlimbs of laboratory rabbits (employing surgically implanted tetrodotoxin (TTX)-filled mini-osmotic pump-sciatic nerve superfusion system) and tested repeatedly with magnetic resonance (MR) throughout the 2-week period of temporarily induced disuse and during the recovery period (following explantation of the TTX-filled pump) for a period of 3 weeks. Controls consisted of saline/"sham"-implanted rabbit hindlimbs. The validity of this model was established with repeated electrophysiologic nerve conduction testing using a clinically appropriate protocol and percutaneously inserted small needle stimulating and recording electrodes. Evoked responses recorded from proximal (P) and distal (D) sites to the sciatic nerve cuff in the TTX-implanted group revealed significantly decreased (p $<$ 0.001) proximal-to-distal (P/D) amplitude ratios (as much as 50-70% below Baseline/pre-implanted and sham-implanted group values) and significantly increased (p $<$ 0.01) differential latency (PL-DL) values (as much as 1.5 times the pre- and sham-implanted groups). By Day 21 of recovery, observed P/D and PL-DL levels matched Baseline/sham-implemented levels. MRI-determined cross-sectional area (CSA) values of Baseline/pre-implanted, sham- or TTX-implanted, and recovering/explanted and the corresponding contralateral hindlimb tibialis anterior (TA) muscles normalized to tibial bone (TB) CSA (in TA/TB ratios) revealed that there was a significant decline (indicative of atrophic response) from pre- and sham-implanted controls by as much as 20% (p $<$ 0.01) at Day 7 and 50-55% (p $<$ 0.001) at Day 13 of TTX-implantation. In the non-implanted contralaterals, a significant increase (indicative of hypertrophic response) by as much as 10% (p $<$ 0.025) at Day 7 and 27% (p $<$ 0.001) at Day 13 + TTX was found. The induced atrophic/hypertrophic TA muscles were observed to be fully recovered by Day 21 post-explantation as evidenced by image TA/TB ratios. End-point biopsy results from a small group of rabbits revealed comprehensive atrophy of both Type I and Type II fibers, although the heterogeneity of the response supports the use of image-guided, volume-localized proton magnetic resonance spectroscopy (MRS) to noninvasively assess tissue-level metabolic changes. MRS-determined results of a 0.25cc volume of tissue within implanted limb TA muscles under resting/pre-ischemic, ischemic-stressed, and post-ischemic conditions at timepoints during and following disuse atrophy/recovery revealed significantly increased intramuscular spectral lipid levels, as much as 2-3 times (p $<$ 0.01) the Baseline/pre-implanted values at Day 7 and 6-7 times (p $<$ 0.001) at Day 13 + TTX, which approached normal levels (compared to pre- and sham-implanted groups) by Day 21 of post-explanation recovery. (Abstract shortened by UMI.) ^

Expression of neuromuscular junction messenger RNAs and protein in aged rats

The loss of skeletal muscle mass is believed to be the dominant reason for reduced strength in aging humans. The purpose of this investigation was to gain some information as to why skeletal muscles lose mass as we age. Since nervous system innervation is essential for skeletal muscle fiber viability, incomplete regional reinnervation during normal synaptic junction turnover has been hypothesized to result in selective muscle fiber loss. Examined here was the age-related association in skeletal muscle between atrophy and the expression of mRNAs encoding the γ- and ϵ-subunits of the nicotinic acetylcholine receptor, myogenin, and muscle specific receptor kinase (MuSK). Gastrocnemius and biceps brachii muscles were collected from young (2 month), adult (18 month), and old (31 month) Fischer 344 cross brown Norway F 1 male rats. In the gastrocnemius, muscles of old vs. young and adult rats, lower muscle mass was accompanied by significantly elevated acetylcholine receptor γ-subunit, myogenin, and MuSK mRNA levels. In contrast, the biceps brachii muscle in the same animals exhibited neither atrophy nor a change in acetylcholine receptor γ-subunit, myogenin, or MuSK mRNA levels. Expression of the acetylcholine receptor ϵ-subunit mRNA did not change with age in either gastrocnemius or biceps brachii muscles. Since acetylcholine receptor γ-subunit, myogenin, and MuSK mRNA levels are upregulated in surgically denervated skeletal muscles of young rats while expression of the acetylcholine receptor ϵ-subunit does not change, the findings of the current investigation suggest that a select fiber population within atrophied skeletal muscles of old rats may be in a denervated-like state. I speculate that increases in γ-subunit, myogenin, and MuSK mRNA levels in atrophied muscles of old rats are compensatory responses to nerve terminal retraction. Indeed, a prolongation of denervation in these muscle fibers would subsequently result in their atrophy and death, ultimately leading to a decline in the number of force generating elements present in the muscle. ^

The craniosacral progression of muscle development influences the emergence of neuromuscular junction alterations in a severe murine model for spinal muscular atrophy.

AIMS As 4-day-old mice of the severe spinal muscular atrophy (SMA) model (dying at 5-8 days) display pronounced neuromuscular changes in the diaphragm but not the soleus muscle, we wanted to gain more insight into the relationship between muscle development and the emergence of pathological changes and additionally to analyse intercostal muscles which are affected in human SMA. METHODS Structures of muscle fibres and neuromuscular junctions (NMJs) of the diaphragm, intercostal and calf muscles of prenatal (E21) and postnatal (P0 and P4) healthy and SMA mice were analysed by light and transmission electron microscopy. NMJ innervation was studied by whole mount immunofluorescence in diaphragms of P4 mice. RESULTS During this period, the investigated muscles still show a significant neck-to-tail developmental gradient. The diaphragm and calf muscles are most and least advanced, respectively, with respect to muscle fibre fusion and differentiation. The number and depth of subsynaptic folds increases, and perisynaptic Schwann cells (PSCs) acquire a basal lamina on their outer surface. Subsynaptic folds are connected to an extensive network of tubules and beaded caveolae, reminiscent of the T system in adult muscle. Interestingly, intercostal muscles from P4 SMA mice show weaker pathological involvement (that is, vacuolization of PSCs and perineurial cells) than those previously described by us for the diaphragm, whereas calf muscles show no pathological changes. CONCLUSION SMA-related alterations appear to occur only when the muscles have reached a certain developmental maturity. Moreover, glial cells, in particular PSCs, play an important role in SMA pathogenesis.

Incidencia de la aplicación de un programa de fútbol en actividades que se basan en el incremento de las unidades motoras activas, utilizando como herramienta un adecuado entrenamiento de la fuerza de tipo neuromuscular en niños de 6-8 años

El presente trabajo es un macro ciclo de cinco meses que se realizó en la ACADEMIA DE FUTBOL ARNOLDO IGUARAN con niños en edades de los 6 a los 8 años pertenecientes al Municipio de La Villa de San Diego de Ubaté, Colombia; el objetivo principal fue determinar Incidencia de la aplicación de un programa de futbol, en actividades que se basan en el incremento de las unidades motoras activas, utilizando como herramienta un adecuado entrenamiento de la fuerza de tipo neuromuscular, haciendo énfasis en las acciones intermitentes y fundamental mente donde el niño este obligado a desarrollar fuerza y a entrenar con sobre cargas significativas

Incidencia de la aplicación de un programa de fútbol en actividades que se basan en el incremento de las unidades motoras activas, utilizando como herramienta un adecuado entrenamiento de la fuerza de tipo neuromuscular en niños de 6-8 años

El presente trabajo es un macro ciclo de cinco meses que se realizó en la ACADEMIA DE FUTBOL ARNOLDO IGUARAN con niños en edades de los 6 a los 8 años pertenecientes al Municipio de La Villa de San Diego de Ubaté, Colombia; el objetivo principal fue determinar Incidencia de la aplicación de un programa de futbol, en actividades que se basan en el incremento de las unidades motoras activas, utilizando como herramienta un adecuado entrenamiento de la fuerza de tipo neuromuscular, haciendo énfasis en las acciones intermitentes y fundamental mente donde el niño este obligado a desarrollar fuerza y a entrenar con sobre cargas significativas

Incidencia de la aplicación de un programa de fútbol en actividades que se basan en el incremento de las unidades motoras activas, utilizando como herramienta un adecuado entrenamiento de la fuerza de tipo neuromuscular en niños de 6-8 años

El presente trabajo es un macro ciclo de cinco meses que se realizó en la ACADEMIA DE FUTBOL ARNOLDO IGUARAN con niños en edades de los 6 a los 8 años pertenecientes al Municipio de La Villa de San Diego de Ubaté, Colombia; el objetivo principal fue determinar Incidencia de la aplicación de un programa de futbol, en actividades que se basan en el incremento de las unidades motoras activas, utilizando como herramienta un adecuado entrenamiento de la fuerza de tipo neuromuscular, haciendo énfasis en las acciones intermitentes y fundamental mente donde el niño este obligado a desarrollar fuerza y a entrenar con sobre cargas significativas

Controlo de estufagem do Vinho Madeira em escala piloto

Um dos processos de envelhecimento do Vinho Madeira é a “Estufagem” realizada através da circulação de água aquecida a uma determinada temperatura por um sistema de serpentina existente no interior de cada estufa. De modo a tornar o processo de estufagem eficiente e preservar a qualidade do Vinho Madeira, a monitorização, registo e controlo da temperatura reveste-se da maior importância sendo, atualmente, todo esse processo realizado, por norma, manualmente, quer no sistema de dez estufas de aço inox existente no laboratório de enologia da Universidade da Madeira (UMa), quer nos sistemas das cooperativas de Vinho Madeira. Existem, no mercado, alguns sistemas que solucionam, com menor ou maior limitação, este problema. Porém, nenhum desses sistemas implementa um sistema de controlo “inteligente” capaz de se adaptar automaticamente a diferentes períodos de temperaturas predefinidos e manter o aquecimento das estufas de acordo com essas temperaturas com uma margem de erro inferior a ±0,5℃, bem como o custo associado aos mesmos é elevado o que dificulta a sua implementação neste setor. O sistema implementado, nesta tese, consiste em duas aplicações: uma aplicação web e uma Windows Forms Application. A aplicação web foi desenvolvida em C# com recurso à framework ASP.NET Web Pages e implementa toda a lógica necessária à monitorização gráfica e à gestão do sistema, nomeadamente a definição do setpoint para cada estufa. A Windows Forms Application, também desenvolvida em C# devido à necessidade de interligação com a biblioteca fornecida pela CAREL para conexão aos controladores de temperatura IR32, efetua o registo e controlo automático da temperatura, de acordo com o setpoint definido para cada estufa através da aplicação web. O controlo de temperatura realiza-se com recurso às redes neuronais, nomeadamente através dum controlador DIC (Direct Inverse Controller) que obteve, de entre os vários controladores testados, o melhor Erro Quadrático Médio (MSE) e o melhor Coeficiente de Correlação (R). Através da utilização do sistema implementado conseguiu-se eliminar a limitação física de erro com ± 1℃ em torno do setpoint tendo-se conseguido, para o melhor caso, uma margem de erro de ± 0,1℃ relativamente ao setpoint reduzindo-se, assim, a margem de variação de temperatura até um máximo de 1,8ºC e, consequentemente, o erro associado.