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Introduction
Organophosphates (OP) are the most frequently involved pesticides in acute poisoning. Paraquat
(PQ) poisoning has the highest case fatality.
As the mechanism of PQ toxicity includes free radical generation, antioxidants have been tried as
a treatment. Neurotoxic effects of acute OP/PQ poisoning (OP/PQ-P) have been hitherto underexplored.
Objectives
The aims of the study were to assess the effects of acute OP/PQ-P on peripheral nerves, neuromuscular
junction (NMJ), brain-stem, cognition and psychological status. Other aims were to
evaluate adherence to existing management guidelines for OP/PQ-P and to find out efficacy of
antioxidant therapy in acute PQ-P.
Materials and methods
A cohort study was conducted with matched controls. Patients with acute OP/PQ-P were
recruited. Nerve conduction studies, autonomic function tests, repetitive nerve stimulation
(RNS), brain-stem auditory evoked potentials (BAEP), Mini Mental State Examination (MMSE)
and administration of General Health Questionnaire (GHQ) were performed to assess peripheral
nerves, NMJ, brain-stem, cognition and psychological status respectively. Assessments were
performed at one and six weeks after the exposure.
A randomized double-blind placebo controlled clinical trial was conducted. Patients received
intravenous vitamin C for 5 days. Half of them received N-acetylcysteine (NAC) and other half
received 5% dextrose for 3 days.
Results i
There were 70 OP (70 controls) and 28 PQ patients (56 controls).
In OP patients, motor nerve conduction velocity (MCV), amplitude and area of compound
muscle action potential on distal stimulation (CMAP-D), sensory nerve conduction velocity
(SCV) and F-wave occurrence were significantly reduced. At one week the significant
impairment in autonomic functions were change of diastolic blood-pressure 3 min after standing,
heart rate variation during deep breathing (HR-DB), amplitude of sympathetic skin response
(SSR-A), post-void urine volume and size of pupil. All except HR-DB were reversed at six
weeks. There was no effect on RNS.
In PQ patients, amplitude of ulnar nerve CMAP-D, CMAP-D area of median nerve and F-wave
occurrence of median, ulnar and tibial nerves, blood-pressure variation after standing and SSR-A
were significantly reduced at six weeks. All but F- wave occurrence remained impaired at six
weeks. A significant decrement response in RNS was observed following exercise in both
assessments.
There was no significant difference between BAEP and MMSE of OP/PQ-P patients and
controls. GHQ showed high prevalence of psychological distress among the patients with
OP/PQ-P.
There were 40 test, 24 historical-controls and 80 parallel-controls in the clinical trial. The median
survival time was significantly longer in the patients treated with vitamin C when compared with
the historical controls, but not with the parallel controls. NAC had no significant effect on
median survival.
Atropine was commenced in 44% of patients without cholinergic features. 73% of patients
developed atfopine toxicity. None of the patients received the maintenance therapy of
pralidoxime for the recommended duration. Of 90% PQ-P patients who received Fuller’s earth,
15% did not receive it in adequate amounts.
Conclusions
The effects of OP/PQ on nervous system persist at least for six weeks. Antioxidant therapy did
not show promising effects on acute PQ-P. Guidelines were not adhered to when administering
antidotes in OP/PQ-P. |
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