Ventajas del bloqueo neuromuscular con bromuro de rocuronio en infusión vs bromuro de rocuronio en bolos en laparotomías, Hospital Vicente Corral Moscoso, Hospital José Carrasco Arteaga, Cuenca, 2010 /

Objetivo. Comparar los resultados de dos métodos de administración de un relajante muscular no despolarizante, y los requerimientos de droga total.Materiales y Método. Es un estudio clínico controlado aleatorizado a simple ciego. Se incluyeron 120 pacientes de ambos sexos ASA I y II, en un grupo se administra B. de Rocuronio a 0.6mg/kg para la inducción e intubación, posterior a esto se monitoriza cada 10 minutos, cuando se requiera se administra el relajante en Bolos a 0.15mg/kg, el otro grupo se administra B. de Rocuronio a 0.6mg/kg para la inducción e intubación, posterior a esto mediante Bomba de Infusión el relajante a dosis de 0.3mg/kg/hora e igualmente se monitoriza, al final de la cirugía se cuantifica la dosis utilizada de Relajante Muscular y en cual grupo se logra condiciones operatorias óptimas. Resultados. Los grupos fueron comparables en las variables de control. Las condiciones operatorias fue significativamente mayor en el grupo que recibió B de Rocuronio en Infusión. El porcentaje de pacientes con condiciones operatorias (TOF 0 y 1) óptimas fue significativamente mayor en el grupo que recibió la infusión (P = 0.001). El promedio de B. de Rocuronio administrado durante todo el procedimiento fue de 8,3 ± 1,32 ug/kg/min en el grupo que presentó condiciones operatorias óptimas, (TOF 0 y 1), en tanto que en el grupo que presentó malas condiciones fue de 9,13 ± 1,8 ug/kg/min. Implicaciones. La administración de B de Rocuronio en Infusión está sugerida para mantener una relajación adecuada y permanente evitando las dosis excesiva o sub óptimas.au

Sugammadex: su eficacia y seguridad en la reversión selectiva del vecuronio

Introducción: En 1979, con la monitorización del uso rutinario de los relajantes neuromusculares, se determinó incidencia en la relajación neuromuscular residual del 45%, con múltiples complicaciones respiratorias que incrementan la estancia hospitalaria. No es conocida la eficacia y seguridad del manejo del vecuronio y su reversión con el uso del sugammadex dentro del manejo rutinario de anestesia. Métodos: Revisión sistemática de artículos sobre el comportamiento del sugammadex cuando se realiza reversión para el efecto del vecuronio, por ser la primera droga que ha demostrado eficacia y seguridad frente a relajantes musculares no despolarizantes esteroideos, que ayuda a prevenir bloqueo residual en el posoperatorio. Resultados: Búsqueda en las bases de datos de EMBASE, EBSCO y MEDLINE y Pubmed (desde enero 2000-diciembre 2012), con palabras MeSH, sugammadex, vecuronium, binding reversal agents, neuromuscular blocking agents; artículos en idioma inglés de estudios clínicos controlados en pacientes humanos adultos en los cuales el sugammadex fue comparado con placebo u otro medicamento. Se aprecia disminución del tiempo de recuperación de la relajación neuromuscular en el bloqueo moderado con un rango de 1,5 a 2,3min con el sugammadex vs 18,9 a 66,2min con la neostigmine y en un bloqueo profundo desde 35,5-68,4min, con dosis de 0,5mgrs/kg de sugammadex hasta 1,4-1,7min con 8mgrs/kg. Discusión: Resultados favorables en el suministro de dosis mayores a 2mgrs/kg en pacientes que presentaban bloqueo neuromuscular moderado y mayores de 4mgrs/kg en bloqueo neuromuscular profundo. Existe necesidad de nuevos estudios clínicos que soporten estos hallazgos. Conclusión: La evidencia sugiere que sí existe una adecuada reversión de la relajación neuromuscular del vecuronio con el uso de sugammadex a 2mgrs/kg, con disminución importante del tiempo y mayor recuperación del paciente sin presencia de relajación residual.

Evaluación del Rocuronio Mediante Aceleromiografía en Pacientes con Sobrepeso u Obesidad

Introducción El rocuronio es un relajante muscular utilizado en la práctica anestésica diaria en la que la dosis depende del peso corporal. Se ha demostrado que en el paciente obeso se debe calcular en base a el peso ideal y no al peso real; sin embargo, no hay claridad de como esto modifica el tiempo de latencia y recuperación del medicamento en esta población. Metodología Se realizó un estudio observacional prospectivo para evaluar los resultados de la aceleromiografía en pacientes con sobrepeso u obesidad comparados con pacientes con IMC normal. Los desenlaces fueron tiempo de latencia, tiempo duración 25 y tiempo de recuperación de la función neuromuscular. Resultados Se incluyeron 40 pacientes por medio de muestreo por conveniencia con una relación de 1:1 según peso corporal. No hubo diferencias significativas en las condiciones de la población a diferencia de la clasificación de ASA y el IMC (p=0,03). En el tiempo de latencia no hubo diferencias significativas (p=0.31) ni en el tiempo duración 25, y al evaluar los tiempos de recuperación del bloqueo neuromuscular se encontró una diferencia significativa en los pacientes con sobrepeso (p=0.01). Ningún paciente requirió reversión farmacológica del rocuronio. Discusión Se puede afirmar que existe una disminución en la duración de acción del rocuronio en pacientes con IMC elevado, significativamente menor a la descrita en la literatura para las dosis aplicadas. La dosificación basada en peso ideal puede realmente ser insuficiente en el paciente con sobrepeso u obesidad para alcanzar la duración clínica de este medicamento.

Tempo de latência e duração do efeito do rocurônio, atracúrio e mivacúrio em pacientes pediátricos

JUSTIFICATIVA E OBJETIVOS: Os bloqueadores neuromusculares (BNM) são freqüentemente utilizados em anestesia pediátrica e não existe aquele considerado ideal. O objetivo deste trabalho foi avaliar o rocurônio, o atracúrio e o mivacúrio, em crianças, quanto ao tempo de latência e de recuperação, à interferência sobre as variáveis hemodinâmicas e às condições de intubação traqueal. MÉTODO: Sessenta e sete crianças, estado físico ASA I e II, com idade variando de 2 anos e 6 meses a 12 anos, foram anestesiadas com alfentanil (50 µg.kg-1), propofol (3 mg.kg-1), sevoflurano e N2O/O2 e divididas em três grupos: G1 = rocurônio 0,9 mg.kg-1 (n = 22); G2 = atracúrio 0,5 mg.kg-1 (n = 22) e G3 = mivacúrio 0,15 mg.kg-1 (n = 23). A monitorização do bloqueio neuromuscular foi realizada com o método de aceleromiografia no trajeto do nervo ulnar. Foram estudados: o tempo de latência (TL), a duração clínica (T25), o tempo de relaxamento (T75) e o índice de recuperação (T25-75). A pressão arterial média (PAM) e a freqüência cardíaca (FC) foram registradas em seis momentos, bem como as condições encontradas no momento da intubação traqueal. RESULTADOS: A mediana do TL foi de 0,6 minutos em G1, 1,3 minutos em G2 e 1,9 minutos em G3. A mediana do T25 foi em G1 = 38 minutos, G2 = 41,5 minutos e G3 = 8,8 minutos. A mediana do T75 foi em G1 = 57,7 minutos, G2 = 54,6 minutos e G3 = 13,6 minutos. A mediana do índice de recuperação (T25-75) foi em G1 = 19,7 minutos, G2 = 13,1 minutos e G3 = 4,8 minutos. As condições de intubação traqueal foram consideradas excelentes na maioria dos pacientes de ambos os grupos. Não houve modificações clínicas importantes da PAM e da FC. CONCLUSÕES: O rocurônio, 0,9 mg.kg-1, teve o menor tempo de latência e o mivacúrio, 0,15 mg.kg-1, o menor tempo de recuperação nos pacientes pediátricos anestesiados com sevoflurano. Também, o rocurônio, o mivacúrio e o atracúrio não determinaram alterações hemodinâmicas de importância clínica relevante e proporcionaram excelentes condições de intubação traqueal.

Neuromuscular imbalances in the track sprinter

Athletic coaching can involve observation of a motor control task and then proposing guidance to an athlete about how the task performance can be developed. Coaches can identify the technique elements that seem to hinder performance and then provide instruction. Recently, a variety of training methods were proposed to enhance sprint performance, however a number of authors have identified these methods as characterised by low scientific evaluation or support (Brown & Vescovi, 2012; Jones, Bezodis, & Thompson, 2009). This article will outline a scientifically robust neuromuscular theory underlying poor movement techniques that may be visible when coaches observe sprint performance. The goal of this article is to inform the sprint coach of a method to identify and correct suboptimal biomechanics to enhance athletic performance.

The role of neuromuscular inhibition in hamstring strain injury recurrence

Hamstring strain injuries are amongst the most common and problematic injuries in a wide range of sports that involve high speed running. The comparatively high rate of hamstring injury recurrence is arguably the most concerning aspect of these injuries. A number of modifiable and nonmodifiable risk factors are proposed to predispose athletes to hamstring strains. Potentially, the persistence of risk factors and the development of maladaptations following injury may explain injury recurrence. Here, the role of neuromuscular inhibition following injury is discussed as a potential mechanism for several maladaptations associated with hamstring re-injury. These maladaptations include eccentric hamstring weakness, selective hamstring atrophy and shifts in the knee flexor torque-joint angle relationship. Current evidence indicates that athletes return to competition after hamstring injury having developed maladaptations that predispose them to further injury. When rehabilitating athletes to return to competition following hamstring strain injury, the role of neuromuscular inhibition in re-injury should be considered.

Post-match changes in neuromuscular function and the relationship to match demands in amateur rugby league matches

Objectives: The current study investigated the change in neuromuscular contractile properties following competitive rugby league matches and the relationship with physical match demands. Design: Eleven trained, male rugby league players participated in 2–3 amateur, competitive matches (n = 30). Methods: Prior to, immediately (within 15-min) and 2 h post-match, players performed repeated counter-movement jumps (CMJ) followed by isometric tests on the right knee extensors for maximal voluntary contraction (MVC), voluntary activation (VA) and evoked twitch contractile properties of peak twitch force (Pt), rate of torque development (RTD), contraction duration (CD) and relaxation rate (RR). During each match, players wore 1 Hz Global Positioning Satellite devices to record distance and speeds of matches. Further, matches were filmed and underwent notational analysis for number of total body collisions. Results: Total, high-intensity, very-high intensity distances covered and mean speed were 5585 ± 1078 m, 661 ± 265, 216 ± 121 m and 75 ± 14 m min−1, respectively. MVC was significantly reduced immediately and 2 h post-match by 8 ± 11 and 12 ± 13% from pre-match (p < 0.05). Moreover, twitch contractile properties indicated a suppression of Pt, RTD and RR immediately post-match (p < 0.05). However, VA was not significantly altered from pre-match (90 ± 9%), immediately-post (89 ± 9%) or 2 h post (89 ± 8%), (p > 0.05). Correlation analyses indicated that total playing time (r = −0.50) and mean speed (r = −0.40) were moderately associated to the change in post-match MVC, while mean speed (r = 0.35) was moderately associated to VA. Conclusions: The present study highlights the physical demands of competitive amateur rugby league result in interruption of peripheral contractile function, and post-match voluntary torque suppression may be associated with match playing time and mean speeds.

Young men utilise limited neuromuscular prepartion to regulate post-impact knee mechanics during step landing

Purpose The neuromuscular mechanisms determining the mechanical behaviour of the knee during landing impact remain poorly understood. It was hypothesised that neuromuscular preparation is subject-specific and ranges along a continuum from passive to active. Methods A group of healthy men (N = 12) stepped-down from a knee-high platform for 60 consecutive trials. Surface EMG of the quadriceps and hamstrings was used to determine pre-impact onset timing, activation amplitude and cocontraction for each trial. Partial least squares regression was used to associate pre-impact preparation with post-impact knee stiffness and coordination. Results The group analysis revealed few significant changes in pre-impact preparation across trial blocks. Single-subject analyses revealed changes in muscle activity that varied in size and direction between individuals. Further, the association between pre-impact preparation and post-impact knee mechanics was subject-specific and ranged along a continuum of strategies. Conclusion The findings suggest that neuromuscular preparation during step landing is subject-specific and its association to post-impact knee mechanics occurs along a continuum, ranging from passive to active control strategies. Further work should examine the implications of these strategies on the distribution of knee forces in-vivo.

Neuromuscular hamstring function in response to intermittent running and previous injury

This thesis examined the impact of previous hamstring injury and fatigue on the function of the hamstring muscles and their neural control. The work established the role of neuromuscular inhibition after hamstring injury and involved the development of a new field testing device for eccentric hamstring strength, which is now in high demand in elite sport worldwide. David has four peer-reviewed publications from this doctoral work.

Analysis of the neuromuscular activity during rising from a chair in water and on dry land

PURPOSE: The purpose of the present study was to analyze the neuromuscular responses during the performance of a sit to stand [STS] task in water and on dry land. SCOPE: 10 healthy subjects, five males and five females were recruited for study. Surface electromyography sEMG was used for lower limb and trunk muscles maximal voluntarty contraction [MVC] and during the STS task. RESULTS: Muscle activity was significantly higher on dry land than in water normalized signals by MVC from the quadriceps-vastus medialis [17.3%], the quadriceps - rectus femoris [5.3%], the long head of the biceps femoris [5.5%], the tibialis anterior [13.9%], the gastrocnemius medialis [3.4%], the soleus [6.2%]. However, the muscle activity was higher in water for the rectus abdominis [-26.6%] and the erector spinae [-22.6%]. CONCLUSIONS: This study for the first time describes the neuromuscular responses in healthy subjects during the performance of the STS task in water. The differences in lower limb and trunk muscle activity should be considered when using the STS movement in aquatic rehabilitation.

Effects of increasing neuromuscular electrical stimulation current intensity on cortical sensorimotor network activation: A time domain fNIRS study

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O₂Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O₂Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O₂Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Mitochondrial Malfunction in Tumor Formation and Neuromuscular Diseases : Consequences of defects in fumarate hydratase and in the respiratory chain

The mitochondrion is an organelle of outmost importance, and the mitochondrial network performs an array of functions that go well beyond ATP synthesis. Defects in mitochondrial performance lead to diseases, often affecting nervous system and muscle. Although many of these mitochondrial diseases have been linked to defects in specific genes, the molecular mechanisms underlying the pathologies remain unclear. The work in this thesis aims to determine how defects in mitochondria are communicated within - and interpreted by - the cells, and how this contributes to disease phenotypes. Fumarate hydratase (FH) is an enzyme of the citrate cycle. Recessive defects in FH lead to infantile mitochondrial encephalopathies, while dominant mutations predispose to tumor formation. Defects in succinate dehydrogenase (SDH), the enzyme that precedes FH in the citrate cycle, have also been described. Mutations in SDH subunits SDHB, SDHC and SDHD are associated with tumor predisposition, while mutations in SDHA lead to a characteristic mitochondrial encephalopathy of childhood. Thus, the citrate cycle, via FH and SDH, seems to have essential roles in mitochondrial function, as well as in the regulation of processes such as cell proliferation, differentiation or death. Tumor predisposition is not a typical feature of mitochondrial energy deficiency diseases. However, defects in citrate cycle enzymes also affect mitochondrial energy metabolism. It is therefore necessary to distinguish what is specific for defects in citrate cycle, and thus possibly associated with the tumor phenotype, from the generic consequences of defects in mitochondrial aerobic metabolism. We used primary fibroblasts from patients with recessive FH defects to study the cellular consequences of FH-deficiency (FH-). Similarly to the tumors observed in FH- patients, these fibroblasts have very low FH activity. The use of primary cells has the advantage that they are diploid, in contrast with the aneuploid tumor cells, thereby enabling the study of the early consequences of FH- in diploid background, before tumorigenesis and aneuploidy. To distinguish the specific consequences of FH- from typical consequences of defects in mitochondrial aerobic metabolism, we used primary fibroblasts from patients with MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) and from patients with NARP (neuropathy, ataxia and retinitis pigmentosa). These diseases also affect mitochondrial aerobic metabolism but are not known to predispose to tumor formation. To study in vivo the systemic consequences of defects in mitochondrial aerobic metabolism, we used a transgenic mouse model of late-onset mitochondrial myopathy. The mouse contains a transgene with an in-frame duplication of a segment of Twinkle, the mitochondrial replicative helicase, whose defects underlie the human disease progressive external ophthalmoplegia. This mouse model replicates the phenotype in the patients, particularly neuronal degeneration, mitochondrial myopathy, and subtle decrease of respiratory chain activity associated with mtDNA deletions. Due to the accumulation of mtDNA deletions, the mouse was named deletor. We first studied the consequences of FH- and of respiratory chain defects for energy metabolism in primary fibroblasts. To further characterize the effects of FH- and respiratory chain malfunction in primary fibroblasts at transcriptional level, we used expression microarrays. In order to understand the in vivo consequences of respiratory chain defects in vivo, we also studied the transcriptional consequences of Twinkle defects in deletor mice skeletal muscle, cerebellum and hippocampus. Fumarate accumulated in the FH- homozygous cells, but not in the compound heterozygous lines. However, virtually all FH- lines lacked cytoplasmic FH. Induction of glycolysis was common to FH-, MELAS and NARP fibroblasts. In deletor muscle glycolysis seemed to be upregulated. This was in contrast with deletor cerebellum and hippocampus, where mitochondrial biogenesis was in progress. Despite sharing a glycolytic pattern in energy metabolism, FH- and respiratory chain defects led to opposite consequences in redox environment. FH- was associated with reduced redox environment, while MELAS and NARP displayed evidences of oxidative stress. The deletor cerebellum had transcriptional induction of antioxidant defenses, suggesting increased production of reactive oxygen species. Since the fibroblasts do not represent the tissues where the tumors appear in FH- patients, we compared the fibroblast array data with the data from FH- leiomyomas and normal myometrium. This allowed the determination of the pathways and networks affected by FH-deficiency in primary cells that are also relevant for myoma formation. A key pathway regulating smooth muscle differentiation, SRF (serum response factor)-FOS-JUNB, was found to be downregulated in FH- cells and in myomas. While in the deletor mouse many pathways were affected in a tissue-specific basis, like FGF21 induction in the deletor muscle, others were systemic, such as the downregulation of ALAS2-linked heme synthesis in all deletor tissues analyzed. However, interestingly, even a tissue-specific response of FGF21 excretion could elicit a global starvation response. The work presented in this thesis has contributed to a better understanding of mitochondrial stress signalling and of pathways interpreting and transducing it to human pathology.