Serial repetitive nerve stimulation studies in organophosphorus poisoning indicate two distinct pathophysiological processes occur at the neuromuscular junction in the intermediate syndrome

• Published in: Clinical toxicology (Philadelphia, Pa.) Pa.), 2024-04, Vol.62 (4), p.219-228
• Main Authors: Buckley, Nicholas A, Jayawardane, Pradeepa, Weerasinghe, Vajira, Dawson, Andrew H, Dassanayake, Tharaka Lagath
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Adult; Aged; Clinical Research; Electric Stimulation; Female; Humans; Male; Median Nerve - physiopathology; Middle Aged; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiopathology; Organophosphate Poisoning - physiopathology; Prospective Studies; Respiratory Insufficiency - chemically induced; Respiratory Insufficiency - etiology; Respiratory Insufficiency - physiopathology; Ulnar Nerve - physiopathology; Young Adult
• ISSN: 1556-3650; 1556-9519
• DOI: 10.1080/15563650.2024.2343744

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. Thirty-four consenting symptomatic patients with acute organophosphorus pesticide poisoning with intermediate syndrome (  = 10) or a milder intermediate syndrome (  = 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). 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 (partial) intermediate syndrome (median 55 per cent versus 16 per cent,  = 0.0001). Similar large differences were found for rate-dependent block (30 per cent versus 7 per cent,  = 0.001), which was uncommon in 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];