391 Paralysis Following Acute Organophosphate Poisoning Improves Survival and Decreases Pulmonary Secretion Production in a Rat Model

Abstract

Acute organophosphate poisoning (OP) produces profound pulmonary secretions. Standard treatment therapy includes anticholinergic medications aimed to reduce the volume of pulmonary secretion and mechanical ventilation for pulmonary support. Neuromuscular weakness termed intermediate syndrome attributes to morbidity and mortality related to OP poisoning in about 25% of cases. We have previously found that adding pancuronium to comprehensive medical treatment can preserve nicotinic acetylcholine receptors at the neuromuscular junction. The ideal timing of the first dose of pancuronium may have profound impacts on survival. Our objective was to compare the survival rates following acute OP poisoning in a rats model. Rats were intubated, anesthetized with isoflurane, and ventilated on a mechanical ventilator prior to exposure to intravenous OP (parathion 40mg/kg). Paralysis was initiated at 1, 4 and 7 hours post OP poisoning. Oxygenation saturation, pulse rate, and end-tidal CO2, peak inspiratory pressure (PIP), lung capacity (LC), and lung elastance (LE) were continuously monitored. Treatment with 2-PAM (90 mg/kg), midazolam (0.125mg/kg) and atropine (0.25mg/kg) were initiated at 1) point where pulse rate fell by 25% or 2) 40 minutes post poisoning. 2-PAM was repeated at 6 and 12 hours. Animals remained mechanically ventilated for 16 hours with atropine dosage titrated to volume of pulmonary secretions. All rats received equivalent medications, ventilator support and suctioning practices during the experiment. Pulmonary secretion volume was recorded using graduated suction catheters. Our study was powered to determine a 50% difference in mortality between groups with 10 animals in each group and 23% mortality difference with 22 animals in each group. Overall survival was higher when paralysis was initiated earlier. Baseline physiologic variables did not differ between study groups at the baseline period prior to poisoning. Animals paralyzed at 1 (n=10) and 4 hours (n=11) demonstrated 100% survival, but animals paralyzed at hour 7 hours (n=22) demonstrated 63.6% survival (p=0.035). Prominent respiratory secretions were seen in all animals post poisoning, but secretions were increased in group 3 with delayed paralysis. The average pulmonary secretion volume for each group is in Table 1. Animals with increased volume of pulmonary secretions were treated with higher doses of atropine.Tabled 1Average total pulmonary secretion volume (ul) and total atropine dose (mg) administered in 16 hourGroup 1: 1hr*Group 2: 4hr*Group 3: 7hr*Total Volume of Pulmonary Secretions (ul)122.95123.68276.82Total Atropine Dose1.741.732.17* Delay time of first dose of pancuronium (10mg/kg) Open table in a new tab * Delay time of first dose of pancuronium (10mg/kg)