PDF(Pubmed)
Abstract：
UNASSIGNED: Intermediate syndrome is an important cause of respiratory failure following acute organophosphorus pesticide poisoning. The objective of this study was to examine the pathophysiology of this syndrome by analysis of sequential repetitive nerve stimulation studies in patients with acute organophosphorus pesticide poisoning.
UNASSIGNED: Thirty-four consenting symptomatic patients with acute organophosphorus pesticide poisoning with intermediate syndrome (n = 10) or a milder forme fruste intermediate syndrome (n = 24) were assessed prospectively with daily physical examination and repetitive nerve stimulation done on the right and left median and ulnar nerves. The compound muscle action potential at 1, 3, 10, 15, 20 and 30 Hertz was measured with a train of ten stimuli. The amplitudes of the resulting stimuli were normalized to the first stimulus (100 per cent) and plotted against time. The decrease in the area under the curve of all the second stimulus compound muscle action potentials in the first 0.3 seconds was measured as a means of quantifying the refractory block. The decrease in the area under the curve under the 10, 15, 20 and 30 Hertz compound muscle action potentials relative to this pooled second stimulus compound muscle action potentials-area under the curve indicated the extent of additional rate-dependent block (decreasing compound muscle action potential-area under the curve over the first 0.3 seconds after the first stimulus with increasing Hertz).
UNASSIGNED: These new measurements strongly correlated with the severity of weakness. Refractory block was seen in most patients but was more severe in those with intermediate syndrome than those with forme fruste (partial) intermediate syndrome (median 55 per cent versus 16 per cent, P = 0.0001). Similar large differences were found for rate-dependent block (30 per cent versus 7 per cent, P = 0.001), which was uncommon in forme fruste intermediate syndrome but found in nine out of 10 patients with intermediate syndrome. Rate dependent block was generally only observed after 24 hours. The simplest strong predictor was total block at 30 Hertz repetitive nerve stimulation (89 per cent [interquartile range 73 to 94 per cent] versus 21 per cent [4 to 55 per cent]; P < 0.0001), which was very similar to total block calculated by summing other calculations.
UNASSIGNED: These findings likely represent depolarization and desensitization block from prolonged excessive cholinergic stimulation but it is not clear if these are from pre- or post-synaptic pathology. An animal model of intermediate syndrome with repetitive nerve stimulation studies might enable a better pathophysiological understanding of the two types of block.
UNASSIGNED: The limited number of repetitive nerve stimulation studies performed were sufficient to demonstrate proof-of-concept, but further studies with more patients are needed to better define the correlates, clinical relevance and possible diagnostic/prognostic roles for the use of this technique.
UNASSIGNED: There are two easily distinguishable pathophysiological abnormalities in the neuromuscular block in intermediate syndrome. While they often coincide, both may be observed in isolation. The total and rate-dependent block at 30 Hertz are strongly associated with more severe weakness.
UNASSIGNED: Thirty-four consenting symptomatic patients with acute organophosphorus pesticide poisoning with intermediate syndrome (n = 10) or a milder forme fruste intermediate syndrome (n = 24) were assessed prospectively with daily physical examination and repetitive nerve stimulation done on the right and left median and ulnar nerves. The compound muscle action potential at 1, 3, 10, 15, 20 and 30 Hertz was measured with a train of ten stimuli. The amplitudes of the resulting stimuli were normalized to the first stimulus (100 per cent) and plotted against time. The decrease in the area under the curve of all the second stimulus compound muscle action potentials in the first 0.3 seconds was measured as a means of quantifying the refractory block. The decrease in the area under the curve under the 10, 15, 20 and 30 Hertz compound muscle action potentials relative to this pooled second stimulus compound muscle action potentials-area under the curve indicated the extent of additional rate-dependent block (decreasing compound muscle action potential-area under the curve over the first 0.3 seconds after the first stimulus with increasing Hertz).
UNASSIGNED: These new measurements strongly correlated with the severity of weakness. Refractory block was seen in most patients but was more severe in those with intermediate syndrome than those with forme fruste (partial) intermediate syndrome (median 55 per cent versus 16 per cent, P = 0.0001). Similar large differences were found for rate-dependent block (30 per cent versus 7 per cent, P = 0.001), which was uncommon in forme fruste intermediate syndrome but found in nine out of 10 patients with intermediate syndrome. Rate dependent block was generally only observed after 24 hours. The simplest strong predictor was total block at 30 Hertz repetitive nerve stimulation (89 per cent [interquartile range 73 to 94 per cent] versus 21 per cent [4 to 55 per cent]; P < 0.0001), which was very similar to total block calculated by summing other calculations.
UNASSIGNED: These findings likely represent depolarization and desensitization block from prolonged excessive cholinergic stimulation but it is not clear if these are from pre- or post-synaptic pathology. An animal model of intermediate syndrome with repetitive nerve stimulation studies might enable a better pathophysiological understanding of the two types of block.
UNASSIGNED: The limited number of repetitive nerve stimulation studies performed were sufficient to demonstrate proof-of-concept, but further studies with more patients are needed to better define the correlates, clinical relevance and possible diagnostic/prognostic roles for the use of this technique.
UNASSIGNED: There are two easily distinguishable pathophysiological abnormalities in the neuromuscular block in intermediate syndrome. While they often coincide, both may be observed in isolation. The total and rate-dependent block at 30 Hertz are strongly associated with more severe weakness.
摘要：
■中间综合征是急性有机磷农药中毒后呼吸衰竭的重要原因。这项研究的目的是通过分析急性有机磷农药中毒患者的顺序重复神经刺激研究来检查该综合征的病理生理学。
■对34名同意有症状的急性有机磷农药中毒合并中间综合征（n=10）或轻度的中间综合征（n=24）的患者进行了前瞻性评估，每天进行体格检查并对左右正中和尺神经进行重复神经刺激。用一组十种刺激测量1、3、10、15、20和30赫兹的复合肌肉动作电位。将所得刺激的振幅标准化为第一刺激(100%),并对时间作图。测量在前0.3秒内所有第二刺激复合肌肉动作电位的曲线下面积的减少,作为量化难治性阻滞的手段。在10、15、20和30赫兹复合肌肉动作电位下的曲线下面积相对于该汇集的第二刺激复合肌肉动作电位-曲线下面积的减少表明额外的速率依赖性阻滞的程度(在第一刺激后的前0.3秒内,随着赫兹的增加,复合肌肉动作电位-曲线下面积减少)。
■这些新的测量结果与虚弱的严重程度密切相关。难治性阻滞在大多数患者中可见，但在患有中间综合征的患者中比患有男性（部分）中间综合征的患者更严重（中位数为55％对16％，P=0.0001)。在速率依赖性区块中发现了类似的巨大差异(30%对7%，P=0.001),这在水果中间综合征中并不常见，但在10例中间综合征患者中有9例发现。通常仅在24小时后观察到速率依赖性阻断。最简单的强预测指标是30赫兹重复神经刺激时的总阻滞（89％[四分位距73％至94％]与21％[4％至55％]；P<0.0001），这与通过求和其他计算计算得出的总块非常相似。
■这些发现可能代表了长期过度胆碱能刺激引起的去极化和脱敏阻滞，但尚不清楚这些是来自突触前还是突触后病理。具有重复神经刺激研究的中间综合征动物模型可能使对两种类型的阻滞有更好的病理生理学理解。
■进行的有限数量的重复神经刺激研究足以证明概念验证，但是需要对更多患者进行进一步的研究来更好地定义相关性，使用该技术的临床相关性和可能的诊断/预后作用。
■在中间综合征中，神经肌肉阻滞存在两种易于区分的病理生理异常。虽然它们经常重合，两者都可以单独观察。30赫兹的总阻滞和速率依赖性阻滞与更严重的虚弱密切相关。
■对34名同意有症状的急性有机磷农药中毒合并中间综合征（n=10）或轻度的中间综合征（n=24）的患者进行了前瞻性评估，每天进行体格检查并对左右正中和尺神经进行重复神经刺激。用一组十种刺激测量1、3、10、15、20和30赫兹的复合肌肉动作电位。将所得刺激的振幅标准化为第一刺激(100%),并对时间作图。测量在前0.3秒内所有第二刺激复合肌肉动作电位的曲线下面积的减少,作为量化难治性阻滞的手段。在10、15、20和30赫兹复合肌肉动作电位下的曲线下面积相对于该汇集的第二刺激复合肌肉动作电位-曲线下面积的减少表明额外的速率依赖性阻滞的程度(在第一刺激后的前0.3秒内,随着赫兹的增加,复合肌肉动作电位-曲线下面积减少)。
■这些新的测量结果与虚弱的严重程度密切相关。难治性阻滞在大多数患者中可见，但在患有中间综合征的患者中比患有男性（部分）中间综合征的患者更严重（中位数为55％对16％，P=0.0001)。在速率依赖性区块中发现了类似的巨大差异(30%对7%，P=0.001),这在水果中间综合征中并不常见，但在10例中间综合征患者中有9例发现。通常仅在24小时后观察到速率依赖性阻断。最简单的强预测指标是30赫兹重复神经刺激时的总阻滞（89％[四分位距73％至94％]与21％[4％至55％]；P<0.0001），这与通过求和其他计算计算得出的总块非常相似。
■这些发现可能代表了长期过度胆碱能刺激引起的去极化和脱敏阻滞，但尚不清楚这些是来自突触前还是突触后病理。具有重复神经刺激研究的中间综合征动物模型可能使对两种类型的阻滞有更好的病理生理学理解。
■进行的有限数量的重复神经刺激研究足以证明概念验证，但是需要对更多患者进行进一步的研究来更好地定义相关性，使用该技术的临床相关性和可能的诊断/预后作用。
■在中间综合征中，神经肌肉阻滞存在两种易于区分的病理生理异常。虽然它们经常重合，两者都可以单独观察。30赫兹的总阻滞和速率依赖性阻滞与更严重的虚弱密切相关。
