pralidoxime and Acute-Kidney-Injury

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan-Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P < 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045-166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.

Topics: Acute Kidney Injury; Affect; Aged; Antidotes; Atropine; Chlorpyrifos; Female; Humans; Insecticides; Male; Mevinphos; Middle Aged; Organophosphate Poisoning; Organothiophosphorus Compounds; Pneumonia, Aspiration; Pralidoxime Compounds; Psychotic Disorders; Respiratory Insufficiency; Retrospective Studies; Seizures; Shock; Survival Analysis; Treatment Outcome

There is a trend towards increasing doses of pralidoxime to treat human organophosphate poisonings that may have relevance in subpopulations. Indeed, pralidoxime is eliminated unchanged by the renal route. This study assesses the effect of renal failure on the kinetics of pralidoxime in a rat model of acute renal failure induced by potassium dichromate administration. On the first day, Sprague-Dawley rats received subcutaneously potassium dichromate (study) or saline (control). Forty-eight hours post-injection, animals received pralidoxime methylsulfate (50mg/kg of pralidoxime base) intramuscularly. Blood specimens were sampled during 180min after the injection. Urine was collected daily during the 3 days of the study. Plasma pralidoxime concentrations were measured by liquid chromatography with electrochemical detection. There was a 2-fold increase in mean elimination half-life and a 2.5-fold increase in mean area under the curve in the study compared to the control group. The mean total body clearance was halved in the study compared to the control group. Our study showed acute renal failure does not modify the distribution of pralidoxime but significantly alters its elimination from plasma. These results suggest that dosages of pralidoxime should be adjusted in organophosphate-poisoned humans with renal failure when using high dosage regimen of pralidoxime.

Topics: Acute Kidney Injury; Animals; Antidotes; Area Under Curve; Chromatography, Liquid; Half-Life; Male; Metabolic Clearance Rate; Pralidoxime Compounds; Rats; Rats, Sprague-Dawley

We recently showed in a rat model of dichromate-induced acute renal failure (ARF) that the elimination but not the distribution of pralidoxime was altered resulting in sustained plasma pralidoxime concentrations. The aim of this study was to compare the efficiency of pralidoxime in normal and acute renal failure rats against paraoxon-induced respiratory toxicity. Ventilation at rest was assessed using whole-body plethysmography after subcutaneous administration of either saline or paraoxon (50% of the LD(50)), in the control and ARF rats. Thirty minutes after administration of paraoxon, either saline or 50mg/kg of pralidoxime was administered intramuscularly. ARF had no significant effects on the ventilation at rest. The effects of paraoxon on respiration were not significantly different in the control and ARF group. Paraoxon increased the total time (T(TOT)), expiratory time (T(E)) and tidal volume (V(T)), and decreased the respiratory frequency (f). In paraoxon-poisoned rats with normal renal function, pralidoxime had a significant but transient effect regarding the T(TOT) and V(T) (p<0.05). In the ARF group, the same dose of pralidoxime significantly decreased the T(TOT), T(E), and V(T) and increased f during 90 min (p<0.01). In conclusion, pralidoxime had partial and transient effects towards paraoxon-induced respiratory toxicity in control rats; and a complete and sustained correction in ARF rats.

Topics: Acute Kidney Injury; Animals; Antidotes; Disease Models, Animal; Insecticides; Lethal Dose 50; Male; Paraoxon; Plethysmography, Whole Body; Pralidoxime Compounds; Rats; Rats, Sprague-Dawley; Respiration; Respiration Disorders

Severe organophosphate poisoning (OPP) has a high mortality rate. Respiratory and neurological complications are common in OPP. Multiple organ distress syndrome (MODS) and renal impairment are relatively rare but correlated with death. In previous publications, in patients who did not survive OPP, their deaths were due to MODS or acute renal failure. A case of intentional ingestion of an organophosphate with renal and multiple organ complications is described. In addition to the standard atropine/oxime regimen, continuous venous-venous haemofiltration (CVVH) therapy was started; the patient survived this intoxication. The pathogenesis of renal injury by OPP is unclear and more insight is required. In our experience, CVVH can be a valid therapy, considering in particular the toxicokinetics of the organophosphate.

Topics: Acute Kidney Injury; Adult; Antidotes; Atropine; Hemofiltration; Humans; Insecticides; Male; Organothiophosphorus Compounds; Pralidoxime Compounds; Suicide, Attempted; Treatment Outcome