Comparative Study of Continuous Pralidoxime Infusion versus Intermittent Dosing: Application of High-Performance Liquid Chromatography Method on Serum of Organophosphate Poisoned Patients

Background: The effective therapeutic dose of pralidoxime methylsulphate for organophosphate (OP) poisoning is necessary to be clarified. This study was designed to comparatively assess the blood level of pralidoxime (BPL) and clinical outcomes in OP poisoned patients treated with intermittent dosing and patients treated with continuous infusion. Methods: This was a prospective, open labelled, cross-sectional, nonrandomized observational study which was done from 2009 to 2012 in a tertiary care hospital in Manipal, India. A high-performance liquid chromatography (HPLC) method with prominence diode array (PDA) detector was developed to measure BPL. Patients were categorized into study and control groups. Patients in study group were divided into 3 subgroups as they were treated with (a) intermittent pralidoxime dosing (1 g/q8h) or (b) continuous pralidoxime infusion (500 mg/h) or (c) continuous pralidoxime infusion (1 g/h). Patients who were not treated with pralidoxime were considered as the control group. The level of acetylcholinesterase (AChE) was measured before and pralidoxime therapy. Results: The developed HPLC method was linear over the range of 0.5-50 µg/mL and the correlation coefficient was found to be greater than 0.99. The median (IQR) of BPL in intermittent dosing (4.63 (5.26)) was comparatively lower than patients treated with continuous infusion. The highest BPL was maintained in 1 g/h group with median (IQR) serum level of 38.86 (16.75). The reactivation rate of AChE was higher in continuous infusion groups compared to intermittent dosing. Comparison of AChE before and after pralidoxime therapy showed that higher BPL was associated with greater reactivation of AChE. Conclusion: HPLC can be used as alternative method for measurement of pralidoxime level in blood. Continuous infusion of pralidoxime maintained a steady higher blood concentration compared to intermittent dosing with vast fluctuations. The reactivation rate of AChE was higher in continuous infusion compared to intermittent dosing. Hence, continuous infusion of pralidoxime can more rapidly recover the OP poisoned patients with less morbidity. 

Keywords:

Chromatography , High Pressure Liquid , Organophosphate Poisoning , Pralidoxime Compounds