Neurophysiological monitoring of pharmacological manipulation in acute organophosphate (OP) poisoning. The effects of pralidoxime, magnesium sulphate and pancuronium.
OBJECTIVE
The neuromuscular transmission failure in acute organophosphate (OP) poisoning occurs because of the irreversible inactivation of the enzyme acetylcholinesterase located in the neuromuscular junction, and is distinguished neuroelectrophysiologically by single electrical stimulus-induced repetitive responses and either a decremental or a decrement-increment response upon high-rate repetitive nerve stimulation (RNS). Understandably, the administration of pharmacological agents with actions at different sites in the neuromuscular junction would alter the neuroelectrophysiological findings in acute OP poisoning.


METHODS
The effect of several pharmacological agents including pralidoxime (10 patients), magnesium sulphate (4 patients) and pancuronium (7 patients) on the neuroelectrophysiological abnormalities was studied in 21 patients with acute OP poisoning.


RESULTS
Pralidoxime administration produced neurophysiological amelioration in 11 out of 15 occasions. In those cases where it produced a beneficial effect, pralidoxime administration was continued and its neuroelectrophysiological effects were studied daily. The efficacy of pralidoxime administration was demonstrated by neuroelectrophysiological testing for a maximum of 6 days after poisoning. Three types of neuroelectrophysiological responses to pralidoxime were noted: (i) lack of neuroelectrophysiological improvement (two patients); (ii) initial improvement with subsequent lack of improvement (two patients); and (iii) initial improvement with subsequent normalisation of neuromuscular transmission (5 patients). Normalisation of the electrodiagnostic tests and the failure of pralidoxime to ameliorate the neuromuscular transmission abnormalities were neuroelectrophysiological indications for the discontinuation of pralidoxime treatment. The administration of magnesium sulphate (MgSO4.7H2O, 4 g intravenous) resulted in a decrease in the CMAP amplitude, loss of the repetitive response and conversion of the decrement-increment response at high-rate RNS to an incremental response. Repetitive responses and the decremental response at high-rate RNS also disappeared after the administration of pancuronium (0.5 mg intravenous) to 6 patients. However, in one case where pancuronium administration was preceded by pralidoxime, there occurred a dramatic worsening of the neuromuscular transmission defect.


CONCLUSIONS
While the administration of all 3 agents-- pralidoxime, magnesium sulphate and pancuronium-- resulted in the reversion of the neuroelectrophysiological defects, only pralidoxime is contended to be therapeutically useful. The therapeutic benefit due to its administration is limited by a short duration of action, and hence it is recommended that it should be administered for a longer period of time under neuroelectrophysiolgical guidance.
Singh
G
G
Department of Medicine, Dayanand Medical College, Ludhiana, India.
Avasthi
G
G
Khurana
D
D
Whig
J
J
Mahajan
R
R
D000208:Acute Disease; D000931:Antidotes / Q000008:administration & dosage*; D004569:Electroencephalography; D006801:Humans; D007306:Insecticides / Q000506:poisoning*; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008991:Monitoring, Physiologic; D009468:Neuromuscular Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D009469:Neuromuscular Junction / Q000503:physiopathology; D018733:Nicotinic Antagonists / Q000008:administration & dosage*; D009943:Organophosphorus Compounds; D010197:Pancuronium / Q000008:administration & dosage*; D011220:Pralidoxime Compounds / Q000008:administration & dosage*; D009435:Synaptic Transmission / Q000187:drug effects; D016896:Treatment Outcome
D000931:Antidotes; D007306:Insecticides; D018733:Nicotinic Antagonists; D009943:Organophosphorus Compounds; D011220:Pralidoxime Compounds; D008278:Magnesium Sulfate; D010197:Pancuronium; C028797:pralidoxime