Assessment of the severity of organophosphate (fenitrothion) poisoning based on its serum concentration and clinical parameters.

BACKGROUND: Fenitrothion (MEP) is the most frequent cause of organophosphate pesticides (OP) poisoning in Japan, but clinical parameters to predict its severity remain uncertain. METHOD: We evaluated 26 cases (12 males and 14 females) of MEP poisoning brought to our critical care center. Regarding acute lung injury (ALI) as a hallmark complication leading to poor recovery, we divided patients into two groups: cases without ALI (Grp1, n = 14), and cases who developed ALI (Grp2, n = 12) at various points after the poisoning. Serial changes in clinical parameters and laboratory test results were compared between them. RESULTS: The median MEP concentrations on arrival (min~max) for Grp1 and Grp2 were 2.3 (0.5-5.1) and 4.6 (1.1-14.0) µg/ml, respectively. Serum pseudo-cholinesterase (PChE) levels on arrival were 21(< 10-59) U/L in Grp1 and < 10 in Grp2. Based on individual patient kinetics, we estimated MEP concentration at 2 and 24 hours after ingestion, and determined cutoff values for differentiating the two groups for each time point as 4.0 µg/ml and 0.5 µg/ml, respectively. By logistic regression analysis, two groups were distinguished with accuracy of 92.3% based on their time of arrival after ingestion and initial MEP concentration. Clinical parameters associated with ALI were days with miosis, days with PChE below 100 U/L, and days requiring administration of atropine. CONCLUSION: The severity of MEP poisoning is closely associated with both time to presentation after ingestion and initial MEP concentration. Serial monitoring of MEP concentrations in the first 24 hours is also useful in predicting the clinical course.

Prognostic factors and toxicokinetics in acute fenitrothion self-poisoning requiring intensive care.

OBJECTIVE: We aimed to evaluate prognostic factors and toxicokinetics in acute fenitrothion self-poisoning. METHODS: We reviewed 12 patients with fenitrothion self-poisoning admitted to the intensive care unit between 2003 and 2006. We compared the characteristics, initial vital signs, physiological scores, corrected QT interval on electrocardiogram and laboratory data (serum fenitrothion concentration and cholinesterase activity) of non-survivors and survivors. Furthermore, we evaluated the correlation between the prognostic factors and severity of poisoning (lengths of intensive care unit and hospital stays), and the toxicokinetics of the patients. RESULTS: In the 2 non-survivors, the estimated fenitrothion ingestion dose and the serum fenitrothion concentration at the emergency department and at 24 h after ingestion were significantly higher than those in the 10 survivors. (P = 0.008, 0.003, and 0.04, respectively). In the 10 survivors, the serum fenitrothion concentration at 24 h after ingestion was significantly correlated with the lengths of intensive care unit and hospital stays (P = 0.004 and 0.04, respectively); however, the initial vital signs, physiological scores, corrected QT interval on electrocardiogram at the emergency department, and serum cholinesterase activity did not show any correlation. In five patients successfully fitted to a two-compartment model, the distribution and elimination half-lives were 2.5 and 49.8 h, respectively, which is compatible with the slow and prolonged clinical course of fenitrothion poisoning. CONCLUSION. Estimated fenitrothion ingestion dose and serum fenitrothion concentration at the emergency department and at 24 h after ingestion may be useful prognostic factors in acute fenitrothion self-poisoning. Furthermore, we should take care for the patients whose serum fenitrothion concentration is high.

[Serum fenitrothion concentration and toxic symptom in acute intoxication patients].

The serum drug concentrations were measured by HPLC or GC/MS in 15 patients of acute fenitrothion (MEP), an organophosphorus insecticide, intoxication. There was no fatal case. The patients were admitted 0.5 approximately 12 hours after the ingestion of 5 approximately 50g MEP. The range of serum MEP concentrations were from undetectable level (< 0.01 microg/mL) to 9.73 microg/mL. Toxic symptoms were correlated with the serum MEP levels. About < 7 microg/mL of the serum MEP levels associated with mild cases and about > 7 microg/mL associated with serious cases. The elimination curves in mild cases were successfully simulated by the one-compartment model and the elimination half-lives (T1/2) were 9.9 +/- 7.7hr (mean +/- S.D.). The serum MEP concentrations declined below the detectable level in 48hr. The elimination curves in two serious cases were successfully simulated by the two-compartment model. The T1/2 in the alpha phase were 5.3hr and 6.7hr (under the direct hemoperfusion), and the T1/2 in the beta phase were 35hr and 52hr. The serum MEP concentrations declined below the detectable level in 300hr.

The effect of plasmapheresis on plasma cholinesterase levels in a patient with organophosphate poisoning.

OBJECTIVE: To describe the role of plasmapheresis in management of organophosphate poisonings. DESIGN: Case report. SETTING: A medical intensive care unit of a medical faculty. PATIENT: A patient with organophosphate poisoning whose cholinesterase levels continuously decline and then increase up to a normal level after plasmapheresis is performed for his sepsis. INTERVENTIONS: Plasmapheresis with fresh frozen plasma. MEASUREMENTS AND MAIN RESULTS: Baseline plasma cholinesterase (ChE) level was 4001 IU/L (normal values: 4000-10000 IU/L). Aspiration pneumonia was developed on day 3, and sepsis occurred on day 5. During this period, ChE levels gradually decreased. On day 5, plasmapheresis was performed for sepsis. Interestingly, plasma ChE levels increased from 2101 IU/L to 6144 IU/L after plasmapheresis. Atropine and pralidoxime were stopped, and a high level of ChE continued during hospitalization. The patient was successfully weaned from mechanical ventilation 3 days after plasmapheresis. CONCLUSION: Plasma exchange therapy may be considered for patients with organophosphate poisoning unresponsive to atropine and pralidoxime.

Effects of sublethal fenitrothion ingestion on cholinesterase inhibition, standard metabolism, thermal preference, and prey-capture ability in the Australian central bearded dragon (Pogona vitticeps, Agamidae).

The central bearded dragon (Pogona vitticeps) is a medium-sized lizard that is common in semiarid habitats in Australia and that potentially is at risk of fenitrothion exposure from use of the chemical in plague locust control. We examined the effects of single sublethal doses of this organophosphate (OP; low dose = 2.0 mg/kg; high dose = 20 mg/kg; control = vehicle alone) on lizard thermal preference, standard metabolic rate, and prey-capture ability. We also measured activities of plasma total cholinesterase (ChE) and acetylcholinesterase before and at 0, 2, 8, 24, 120, and 504 h after OP dosing. Predose plasma total ChE activity differed significantly between sexes and averaged 0.66 +/- 0.06 and 0.45 +/- 0.06 micromol/min/ml for males and females, respectively. Approximately 75% of total ChE activity was attributable to butyrylcholinesterase. Peak ChE inhibition reached 19% 2 h after OP ingestion in the low-dose group, and 68% 8 h after ingestion in high-dose animals. Neither OP doses significantly affected diurnal body temperature, standard metabolic rate, or feeding rate. Plasma total ChE levels remained substantially depressed up to 21 d after dosing in the high-dose group, making this species a useful long-term biomonitor of OP exposure in its habitat.

Changes in the hemodynamic state of patients with acute lethal organophosphate poisoning.

The main cause of death due to acute organophosphate poisoning is believed acute respiratory failure caused by peripheral and central cholinergic actions. Today, advances in respiratory management and intensive care make it possible to maintain the respiratory function of patients with organophosphate poisoning, but it is still difficult to maintain their circulation, and some patients with acute organophosphate poisoning die of metabolic acidosis. The present study clarified the hemodynamics of patients with acute lethal organophosphate poisoning. Subjects were patients with severe acute organophosphate poisoning accompanied by hypotension in whom hemodynamics were monitored by pulmonary artery catheterization. In this study, the medical records of these patients were reviewed. Four patients with severe acute organophosphate poisoning accompanied by hypotension and metabolic acidosis died. In 3/4 patients respiration was maintained favorably. In all 4 patients cardiac output was maintained, but systemic vascular resistance index (SVRI) was significantly reduced. Catecholamine administration was ineffective and did not increase SVRI.

[A case of mixed poisoning by organophosphate and methanol].

We encountered a case of mixed poisoning by organophosphate and methanol. Each poisoning was comparatively frequent but we reviewed no cases of mixed poisoning of them. A 49-year-old woman was transferred to our hospital because of oral ingestion of organophosphorous compound (about 14 g of fenitrothion) and glass cleaner (about 40 g of methanol) for suicidal purpose. She underwent general antioverdose treatment including gastric lavage, activated charcoal and cathartics. For fenitrothion poisoning, she received atropine and pralidoxime. For methanol poisoning, she was treated with hemodialysis. Three days later, she moved to psychiatric ward from emergency ward without aftereffects and was given a diagnosis of depression.

Pharmacokinetics and dosage regimen of 2-pyridine aldoxime in Bubalus bubalis intoxicated with fenitrothion.

In the present study, the pharmacokinetics of 2-pyridine aldoxime (2-PAM, 30 mg/kg, i.v.) alone and in conjunction with atropine (0.3 mg/kg; 1/4 i.v., 3/4 i.m.) was investigated in 10 Bubalus bubalis intoxicated with a single oral lethal dose of fenitrothion (435 mg/kg). Based on the kinetic parameters, an appropriate dosage regimen of 2-PAM in B. bubalis was calculated. There was no significant difference between plasma levels and pharmacokinetic parameters of 2-PAM in the two groups of animals, given 2-PAM alone and in conjunction with atropine. The peak plasma concentration of 2-PAM at 1 min was in the range of 189.5-196.6 microg/mL which declined to 9.22-9.98 microg/mL at 4 h. The values of elimination half-life, Vd(area) and total body clearance were 2.41-2.67 h, 0.77-0.95 L/kg and 227.5-245.7 mL/kg/h, respectively. The binding capacity of 2-PAM to plasma proteins of fenitrothion-intoxicated buffalo calves and dissociation rate constant of protein drug complex were 0.015 x 10(-6) mol/g and 2.367 x 10(-6) mol, respectively. Approximately 63% of 2-PAM was bound with plasma proteins. In the treatment of organophosphate insecticide (OPI) toxicity in B. bubalis, an appropriate i.v. dosage regimen of 2-PAM in conjunction with atropine would be 18 mg/kg followed by 15 mg/kg at 4 h interval.

Severe fenitrothion poisoning complicated by rhabdomyolysis in psychiatric patient.

Non-traumatic rhabdomyolysis associated with organophosphate intoxication has not been generally reported. We report here in a severe case of fenitrothion poisoning complicated by rhabdomyolysis. A 43-year-old woman ingested approximately 100 ml of fenitrothion emulsion (50%) in an attempt to commit suicide. On day 3 after admission, her creatine phosphokinase (CPK) peaked at 47,762 IU/L. She received supportive treatment included sodium bicarbonate and fluid resuscitation. However, muscarinic symptoms including excessive miosis and salivation developed on day 5 when her CPK levels decreased. The delay in cholinergic symptoms might have been due to the trihexyphenidyl she took with the antipsychotic drugs. Fortunately, the present patient recovered from the acute cholinergic crisis, and acute renal failure was prevented by early diagnosis. This is a case of organophosphate poisoning complicated by rhabdomyolysis in a psychiatric patient. The masking of acute cholinergic symptoms should be taken into consideration in such patients.

Accidental fenitrothion intoxication in young broilers.

Death from fenitrothion intoxication in young broiler chicks has never been reported. The mortality in this instance was 16.4% in the first week. The dead birds were found lying in a ventral position resting their heads on the floor. Prior to death dyspnea and paralysis occurred. A concentration of 120 mg fenitrothion/kg of litter (dry weight) was found.

Determination of organophosphorous pesticides in biological samples of acute poisoning by HPLC with diode-array detector.

We have developed a simple and rapid method for measuring 11 organophosphorous pesticides (dichlorvos, methidathion, salithion, malathion, fenitrothion, fenthion, parathion, diazinon, ethylthiometon, O-ethyl O-(4-nitrophenyl)phenylphosphonothioate (EPN) and chlorpyrifos) and one metabolite (3-methyl-4-nitrophenol) of fenitrothion in serum and urine of acute poisoning patients by HPLC with a diode-array detector. An aliquot of the biological sample after deproteinization by acetonitrile was injected into C18 column using acetonitrile-water as a mobile phase. The detection limits in serum and urine ranged from 0.05 to 6.8 micrograms/ml at a wavelength of 230 nm. This method was successfully applied to two actual cases of acute poisoning.

Human mortality in organophosphate poisonings.

We reviewed 130 admissions of organophosphate poisoning and analyzed the causes of death. Fenitrothion, malathion, dichlorvos, trichlorfon and fenitrothion/malathion were the most frequent chemicals involved. Mortality was 25% (32/130); delay in discovery and transport (18 cases), insufficient respiratory management (8 cases), and severe underlying or co-existing diseases (6 cases) were noted in the lethalities. Insufficient respiratory management consisted of delay in endotracheal intubation (5 cases) and failure in weaning (3 cases). About 3/4 of the severely serum cholinesterase-depressed cases needed ventilators. This suggests that better respiratory management would improve the outcome of organophosphate poisonings. Close observation of the clinical symptoms is essential, and detection of changes in serum cholinesterase may be helpful.

Relapse and elevation of blood urea nitrogen in acute fenitrothion and malathion poisoning.

We observed 6 patients with severe fenitrothion and/or malathion poisoning necessitating artificial ventilation and intensive care monitoring. Three developed relapse following acute cholinergic crisis. In these patients the blood urea nitrogen (BUN) abnormally elevated before the development of relapse and the initial high concentration of plasma organophosphate (OP) decreased only gradually. However, the patients who did not develop relapse showed no elevation of BUN and a relatively low concentration of plasma OP. This observation was confirmed in a retrospective search of 14 patients. In addition, erythrocyte cholinesterase (EChE) activities were more helpful to diagnose the development of relapse than plasma cholinesterase activities. Therefore, careful monitoring of BUN in addition to plasma OP concentration may be useful to predict the development of relapse.

Physiological stress responses of Anguilla anguilla to fenitrothion.

The present communication deals with the effect of fenitrothion (0.04 ppm) on the carbohydrate metabolism of the european eel Anguilla anguilla and its recovery from intoxication. Analysis of various parameters such as glycogen, lactate and glucose was made on different eel tissues after 2, 8, 12, 24, 32, 48, 56, 72 and 96 hr of fenitrothion exposure. Subsequently, the fish were allowed recovery periods of 8, 12, 24, 48, 72, 96, 144 and 192 hr in clean water, and the same parameters were evaluated. Muscle glycogen content decreased significantly during the exposure time, while blood glucose levels increased markedly. Gill, muscle and blood lactate values increased during pesticide exposure. Most of the metabolic disorders did not persist after allowing recovery in clean water during less than a week. The observed effects of fenitrothion on fish metabolism are discussed in relation to a stress syndrome and probable reasons for alterations have been exposed.

Intermediate syndrome in acute fenitrothion poisoning.

Fenitrothion has been reported as one of the organophosphates causing so called "intermediate syndrome"--clinical entity of still unclear reasons. That is why we decided to perform a retrospective examination of oral intoxication with this compound. Clinical course of 16 cases were analysed. Clinical state on admission, AChE activity and pesticide concentration in blood were considered. Gastric lavage, atropine and oximes were included in the treatment. 6 patients died in the period of 5 to 22 days (mean 11.8) from poison intake. All 6 revealed slight signs of poisoning at the time of admission (first 24th). AChE was moderately inhibited. Patients' clinical state was deteriorating and AChE activity was decreasing during next 48 h even though oximes therapy was applied. Intubation and mechanical ventilation was required. Fenitrothion concentration in blood varied from 470 to 8350 ng/ml (mean 2823 ng/ml). In 3 fatal cases toxicological examination of autopsy tissue was done. High fenitrothion concentration was found in adipose tissue and also in the brain. In the group of 10 recovered patients "intermediate syndrome" was not observed in 3 only. AChE activity returned to normal quickly. Fenitrothion concentration ranged from 96 to 360 ng/ml (mean 202 ng/ml). In the remaining 7 clinical state became worse during next 48-72 hours after temporary improvement. Respiratory failure and increasing AChE activity inhibition were major signs. Fenitrothion concentration varied from 180 to 3020 ng/ml (mean 1690 ng/ml). AChE inhibition persisted even for 30 days from poisoning.