Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

Abstract

Organophosphorus (OP) compound poisoning is a major global public health problem. Acute OP insecticide self-poisoning kills over 200,000 people every year, the majority from self-harm in rural Asia. Highly toxic OP nerve agents (e.g., sarin) are a significant current terrorist threat, as shown by attacks in Damascus during 2013. These anticholinesterase compounds are classically considered to cause an acute cholinergic syndrome with decreased consciousness, respiratory failure, and, in the case of insecticides, a delayed intermediate syndrome that requires prolonged ventilation. Acute respiratory failure, by central and peripheral mechanisms, is the primary cause of death in most cases. However, preclinical and clinical research over the last two decades has indicated a more complex picture of respiratory complications after OP insecticide poisoning, including onset of delayed neuromuscular junction dysfunction during the cholinergic syndrome, aspiration causing pneumonia and acute respiratory distress syndrome, and the involvement of solvents in OP toxicity. The treatment of OP poisoning has not changed over the last 50 years. However, a better understanding of the multiple respiratory complications of OP poisoning offers additional therapeutic opportunities.

The clinico-demographic study of morbidity and mortality in patients with organophosphate compound poisoning at tertiary care hospital in rural India

“…This observation was in line with many other researchers. 7,11,16,19,[29][30][31] Senanayake and Karalliedde classified "type II Paralysis" 33 as "intermediate syndrome" and described it as a distinct clinical entity on the basis of electromyographic (EMG) findings of postsynaptic neuromuscular junction (NMJ) failure that had occurred between 24 and 96 h after the resolution of the initial cholinergic crisis and prior to the onset expected for delayed neuropathy. 32 The respiratory muscles are often affected and patients require prolonged periods of ventilatory support and are associated with its complications.…”

Antiseizure and neuroprotective effects of delayed treatment with midazolam in a rodent model of organophosphate exposure

“…The accumulation of acetylcholine in peripheral synapses after cholinesterase inhibition results in muscle tremors, cardiovascular dysfunction, hypotension, and bronchial spasms. 1,2 The mortality immediately after exposure is most commonly due to respiratory failure after OP/NA-induced bronchospasm, bronchorrhea, and paralysis of respiratory muscles. 2,3 The accepted therapy to ameliorate these lethal peripheral responses is administration of the antidote compounds atropine, pyridostigmine, and an oxime, such as pralidoxime (2-pyridine aldoxime methyl chloride or 2-PAM).…”

A rodent model of human organophosphate exposure producing status epilepticus and neuropathology

“…Accidental or deliberate exposure to these OP-containing compounds is a major, worldwide health problem. OPs are potent inhibitors of cholinesterase (Lotti, 2001); therefore, OP exposure induces the accumulation of acetylcholine in peripheral synapses, which results in muscle tremors, cardiovascular dysfunction, hypotension, and bronchial spasms (Hulse et al, 2014, Lotti, 2001). OP-related morbidity most frequently results from respiratory failure due to brochospasm, bronchorrhea, and paralysis of respiratory muscles (Karalliedde and Senanayake, 1989, Lotti, 2001).…”