Caffeine reduces organophosphate-induced respiratory failure: Effect of caffeine on dichlorvos-induced central respiratory failure in a rat model

Organophosphate (OP) poisoning is a serious global health concern responsible for more than three million poisonings worldwide each year. OP- induced respiratory failure is associated with an unacceptably high mortality rate. Caffeine has been successfully used in other cases of central respiratory failure. We hypothesized that caffeine administration would mitigate respiratory failure in an animal model of OP poisoning. We used a previously validated animal model of OP-induced central apnea with detailed physiologic respiratory recordmgs. The model consisted of Wistar rats that were anesthetized but spontaneously breatlung 100% oxygen. Airflow, respiratory rate, tidal volume, mean arterial pressure and pulse rate were digitally recorded for 120 min following OP exposure or until death. The two study groups mcluded dichlorvos and saline (n = 8) or dichlorvos and caffeine (n = 8). In all groups, dichlorvos was given as a single subcutaneous dose of 100 mg/kg (3x rat LD50). In each group caffeme (20 mg/kg) or saline (same volume) was given as a smgle intravenous (IV) mjection 1 mm prior to exposure to dichlorvos. Pmnary outcome was tune to apnea. Data are presented as mean (stdev). Comparison between groups was performed using Student's t Test and analysis of variation (ANOVA). There was no difference between group respiratory- parameters during the baseline period. There was no difference in mortality between the groups (100% both) but the tune to apnea differed significantly (p < 0.001). Animals pre-Treated with caffeine demonstrated apnea 30.6 (8.7) mm post dichlorvos exposure. Animals pre-Treated with saline demonstrated apnea 12.2 (3.9) nun post exposure. The rate of decline in respiratory rate and tidal volume was less in animals pre-Treated with caffeine. In conclusion, in a rat model of dichlorvos poisoning with central apnea, caffeine exposure prior to dichlorvos did not prevent OP-mduced central apnea, but it did prolong the tune to apnea after dichlorvos exposure.