A comprehensive review on experimental and clinical findings in intermediate syndrome caused by organophosphate poisoning

Toxicol Appl Pharmacol. 2012 Feb 1;258(3):309-14. doi: 10.1016/j.taap.2011.11.014. Epub 2011 Dec 2.


Acute organophosphate (OP) intoxication is important because of its high morbidity and mortality and occurrence of muscular paralysis associated by inhibition of acetylcholinesterase (AChE) activity at the neuromuscular junction. Cholinergic crisis, intermediate syndrome (IMS), and OP-induced delayed neuropathy (OPIDN) are the evidences that can be observed in OP intoxication. The main cause of morbidity due to OP poisoning is IMS that occurs 24-96 h after poisoning. Mechanisms underlying the IMS are not fully known. Although the electrophysiological aspects of delayed neuropathy are best characterized, the IMS remain very little studied. The aim of this study was to revisit current knowledge related to OP and the IMS. For this purpose, a systematic review without date limitation was performed. A total of 599 relevant articles were found and reviewed. Data were categorized according to experimental and clinical studies. Occurrences of persistent AChE inhibition, electromyography changes, muscle cell injury, and oxidative stress are the most important pieces of evidence for involvement of IMS in OP toxicity. Delayed AChE inhibition, muscle necrosis, down regulation or desensitization of postsynaptic ACh receptors, failure of postsynaptic ACh release, and oxidative stress-related myopathy are involved in IMS. Toxicokinetic factors, such as a high lipid-solubility, duration of AChE inhibition and metabolite excretion, evolution of alterations on repetitive nerve stimulation (RNS), type and frequency of muscle lesions can estimate the probability of the IMS. Plasma AChE of less than 200 units is a predictor and the 30 Hz RNS decremental response could be a useful marker for the IMS.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Acetylcholinesterase / drug effects*
  • Acetylcholinesterase / metabolism
  • Animals
  • Cholinesterase Inhibitors / poisoning*
  • Electromyography
  • Humans
  • Neuromuscular Junction / pathology
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / physiopathology
  • Organophosphate Poisoning*
  • Oxidative Stress / drug effects
  • Paralysis / chemically induced
  • Syndrome
  • Time Factors


  • Cholinesterase Inhibitors
  • Acetylcholinesterase