Methemoglobin measurements are underestimated by the Radical 7 co-oximeter: experience from a series of moderate to severe propanil poisonings.

INTRODUCTION: In Asia methemoglobinemia (MetHb) is commonly caused through self-poisoning with the pesticide propranil. MetHb can cause hypoxia, coma and death, but usually responds to methylene blue. It is therefore vital to have accurate methods to measure blood MetHb to guide appropriate treatments. The gold standard to measure MetHb utilizes a spectrophotometer, but recent bedside tests have been developed e.g., pulse co-oximeter probe and blood color chart. METHODS: Nine propanil poisoned patients had data collected from hospitals in Sri Lanka during 2008. Several MetHb readings were taken from each patient from admission up to 50 hours using spectrophotometry (Unico UV-Vis model no. 2800), pulse co-oximetry (Radical-7, Masimo, CA), and color chart. RESULTS: The co-oximeter underestimated the MetHb percentage when compared with spectrophotometry and the color chart, especially when the average MetHb was greater than 20%. The color chart demonstrated acceptable accuracy compared with formal spectrophotometry with the majority of values showing no more than 10% difference. CONCLUSION: This small cohort highlights the potential for extreme inaccuracy of the Radical-7 co-oximeter, especially with a MetHb greater than 20%. Pulse co-oximeters should be required to be validated for the complete range of MetHb prior to regulatory approval.

A bedside test for methaemoglobinemia improved antidote use in propanil poisoning.

BACKGROUND: In 2008, self-poisoning with the herbicide propanil had a case-fatality of around 11% in Sri Lanka. A simple quantitative methaemoglobinemia bedside test was developed so that treatment could be titrated according to the methaemoglobin level. OBJECTIVE: To determine whether the new method influenced patient management and changed the case fatality of propanil self-poisoning. METHOD: The bedside test (using an inexpensive validated colour chart) was introduced in three hospitals (Anuradhapura, Polonnaruwa and Galle) in Sri Lanka from 2008. Junior ward staff were given a brief training on how to use the chart for quantitative estimation of methaemoglobin in patients with propanil poisoning and utilize the results in the context of the national treatment guidelines for propanil poisoning. It was taught that the bedside test should be done repeatedly from admission until it showed consistently low values of methaemoglobin. Treatment with the antidote methylene blue was suggested for patients whose methaemoglobin was greater than 20%. Limited clinical data on poisoning have been prospectively collected from these hospitals from 2003. The case-fatality and management before and after the change were compared with data up to December 2014. RESULTS: The case-fatality decreased from (38/401) 9.5% to (8/262) 3.1% [difference: -6.4%, 95% CI: -10 to -3]. Methylene blue use increased from under 10% of patients before to 55% of patients after the intervention. More patients received repeat doses and infusions, and few received ascorbic acid and exchange transfusion. CONCLUSION: The simple bedside test for methaemoglobinemia was readily adopted into routine practice and led to large changes in management. A substantial reduction in mortality from propanil poisoning occurred after this intervention.

Exchange transfusion can be life-saving in severe propanil poisoning: a case report.

BACKGROUND: Propanil is an important cause of herbicide poisoning in Sri Lanka, accounting for about 2% of all cases of self-poisoning. The outcome is extremely poor when the poisoning is severe and current medical care is of limited efficacy. Death usually occurs due to the severe and prolonged methaemoglobinaemia. We describe a case of severe Propanil poisoning, successfully treated by exchange transfusion at a tertiary care hospital in Sri Lanka. CASE PRESENTATION: A 17-year old Sri Lankan male (body weight--42 kg), presented to a local hospital 1 hour after self-ingestion of nearly 500 ml (4.3 g/kg) of liquid Propanil (concentration--360 g/l). On admission he had dizziness and peripheral cyanosis. He was given intravenous methylene blue (1 mg/kg) within one hour of admission, which was repeated subsequently due to minimal response. The next day morning, (18 hours after poisoning) the patient was transferred to the National Hospital of Sri Lanka (NHSL) for further management. On admission to NHSL, he was drowsy and confused, had a shallow respiratory effort and marked central and peripheral cyanosis. Respiratory rate was 20/min, with a pulse-oximetry of 77% on room air. The arterial blood gas analysis was as follows; pH--7.24, HCO3(-)--12 mmol/l, pCO2--28 mmHg, pO2--239 mmHg and O2 saturation--100%. Exchange transfusion was commenced within two hours of admission to NHSL. A dramatic improvement in oxygen saturation was observed immediately afterwards, with the saturation in pulse-oximetry rising to >95%. The level of consciousness and respiratory effort also improved. He was discharged subsequently 8 days after the initial poisoning. CONCLUSION: Propanil has potential to produce severe life threatening clinical manifestations, despite categorization as a herbicide with low toxicity. In cases of severe poisoning, exchange transfusion may be life saving. Since methylene blue, intensive care and exchange transfusion facilities are also not readily available in local hospitals, which frequently encounter cases of severe Propanil poisoning, early transfer of patients to tertiary care hospitals should be considered. Exchange transfusion may be helpful even in late stages in patients with severe poisoning.

Clinical outcomes and kinetics of propanil following acute self-poisoning: a prospective case series.

BACKGROUND: Propanil is an important cause of death from acute pesticide poisoning, of which methaemoglobinaemia is an important manifestation. However, there is limited information about the clinical toxicity and kinetics. The objective of this study is to describe the clinical outcomes and kinetics of propanil following acute intentional self-poisoning. METHODS: 431 patients with a history of propanil poisoning were admitted from 2002 until 2007 in a large, multi-centre prospective cohort study in rural hospitals in Sri Lanka. 40 of these patients ingested propanil with at least one other poison and were not considered further. The remaining 391 patients were classified using a simple grading system on the basis of clinical outcomes; methaemoglobinaemia could not be quantified due to limited resources. Blood samples were obtained on admission and a subset of patients provided multiple samples for kinetic analysis of propanil and the metabolite 3,4-dichloroaniline (DCA). RESULTS: There were 42 deaths (median time to death 1.5 days) giving a case fatality of 10.7%. Death occurred despite treatment in the context of cyanosis, sedation, hypotension and severe lactic acidosis consistent with methaemoglobinaemia. Treatment consisted primarily of methylene blue (1 mg/kg for one or two doses), exchange transfusion and supportive care when methaemoglobinaemia was diagnosed clinically. Admission plasma concentrations of propanil and DCA reflected the clinical outcome. The elimination half-life of propanil was 3.2 hours (95% confidence interval 2.6 to 4.1 hours) and the concentration of DCA was generally higher, more persistent and more variable than propanil. CONCLUSION: Propanil is the most lethal herbicide in Sri Lanka after paraquat. Methylene blue was largely prescribed in low doses and administered as intermittent boluses which are expected to be suboptimal given the kinetics of methylene blue, propanil and the DCA metabolite. But in the absence of controlled studies the efficacy of these and other treatments is poorly defined. More research is required into the optimal management of acute propanil poisoning.

Immunomodulatory effects of the herbicide propanil on cytokine production in humans: In vivo and in vitro exposure.

Propanil, 3,4-dichloropropionanilide, a commonly used herbicide, has been shown to induce effects on the mouse immune system. The aim of this study was to assess the immunotoxicity of propanil in occupationally exposed agricultural workers and to characterize its molecular mechanism of action. Seven agricultural workers intermittently exposed to propanil and 7 healthy matched controls entered the study. Data were collected through physical examination, and laboratory investigations addressed at the main serum, cellular, and functional immune parameters. The levels of exposure were assessed by determining the urine concentration of the major propanil metabolite, 3,4-dichloroaniline. The investigation of serum, cellular, and functional immune parameters suggested that propanil exposure results in a modest immunomodulatory effect, characterized by an increase in the plasma level of IgG(1) and in LPS-induced IL-6 release and, by a reduction in PHA-induced IL-10 and IFN release, associated with a reduced IFN/IL-4 ratio. As observed, following in vivo exposure, in vitro treatment of human peripheral blood leukocytes with propanil resulted in a dose-dependent reduction in PHA-induced IFN-gamma and IL-10 production, while LPS-induced TNF-alpha production was not affected indicating a direct effect of propanil on selected immune parameters. We demonstrated that propanil interfering with PHA-induced intracellular calcium increase modulated IL-10 and IFN-gamma transcription and translation, which indicates that propanil acts on early events triggered by PHA. Overall, our results suggest that human exposure to propanil has slight immunomodulatory effects, and point out that the inhibition of the PHA-induced intracellular calcium rise is an important target of propanil. These findings improve our understanding of the mechanism underlying propanil-induced immunotoxicity.

[Simultaneous determination of propanil, carbaryl and 3,4-dichloroaniline in human serum by HPLC with UV detector following solid phase extraction].

In case of poisoning by herbicide compounded with Propanil (DCPA) and Carbaryl (NAC), we attempted simultaneous solid-phase extractions of DCPA, NAC, and 3,4-dichloroaniline (DCA), a metabolite of DCPA, from the patient's serum, and quantitative analytical method using HPLC-UV detection. With this HPLC method, the quantitative detection limits in the serum are 0.005 microgram/ml for DCPA and DCA and 0.001 microgram/ml for NAC, and the UV spectra of all three compounds could easily be obtained using a diode-array detection limit of 0.05 microgram/ml. When the three compounds were added to serum at concentrations ranging from 0.1-10.0 micrograms/ml, the recovery rates were satisfactory at between 91.1% and 101.9%. On analysis of the serum of patient who had ingested Kusanon A Emulsion, the ingested substance apparently caused an increase in the DCA concentration, which led to the appearance of methemoglobinemia. The possibility that the DCA concentration might be used for prognostic purposes was suggested.

Severe propanil [N-(3,4-dichlorophenyl) propanamide] pesticide self-poisoning.

BACKGROUND: Propanil pesticide poisoning can produce methemoglobinemia, tissue hypoxia, and depression of central nervous system and respiratory system. It has been recorded only rarely worldwide and most current poison texts consider propanil to be of low toxicity. However, propanil self-poisoning is a significant clinical problem in parts of Sri Lanka and an occasional cause of death. AIM OF STUDY: To report the clinical features and management of severe propanil poisoning. PATIENTS AND METHODS: We report a retrospective case series of patients who were treated in the intensive care unit of and/or died in Anuradhapura General Hospital between 1998 and early 2002. RESULTS: Sixteen patients were identified. Common manifestations of toxicity included confusion, reduced conscious level, cyanosis, and respiratory depression. Marked hemolysis was noted in several patients. Nine deaths occurred due to respiratory depression and cardiorespiratory arrest. Management was difficult given the lack of i.v. methylene blue, inability to measure methemoglobin levels, and paucity of intensive care unit beds. CONCLUSIONS: This series indicates that propanil poisoning can be a severe form of self-poisoning, particularly in resource-poor settings. We have now initiated the establishment of a prospective series of propanil poisoned patients to further describe its clinical features, responsiveness to therapy, and case fatality rate.

Pesticide poisoning initially suspected as a natural death.

A pesticide poisoning victim suspected initially as having died a natural death was autopsied. The victim was a 47-year-old male. Macroscopically, signs of acute death and, in particular, general erosion in the mucosa of the airways and esophagus were observed. In the gastric contents, which had a pungent smell and a greenish-brown color, 5.00 g/L of propanil, 1.27 g/L of carbaryl, 0.38 g/L of ethylbenzene, and 0.32 g/L of xylene were detected. In the blood (serum), 21.6 mg/L of propanil, 8.1 mg/L of carbaryl, 1.7 mg/L of ethylbenzene, and 4.0 mg/L of xylene were identified. Postmortem methemoglobinemia (45%) was recognized. The cause of death was considered to have been pesticide poisoning; propanil was probably most responsible for his death. The police considered the case to be "death with illness as the suspected cause." By performing an autopsy, however, we were able to clarify that the cause of death was pesticide poisoning.

Propanil poisoning.

OBJECTIVE: To document clinical features of propanil poisoning and discuss treatment. DESIGN, SETTING AND PATIENTS: Five patients treated in the University medical unit at the Karapitiya teaching hospital over the past two years. INTERVENTIONS AND MEASUREMENTS: Relevant laboratory investigations were done. The patients were treated on accepted lines. RESULTS: All had methaemoglobinaemia. The first patient died after severe poisoning in spite of intensive treatment. The second had severe poisoning requiring exchange transfusion and treatment with methylene blue. The third, fourth and fifth patients had mild poisoning which responded readily to oral methylene blue. The last patient had taken a combination of propanil and oxydiazone. The first and second patients had features of haemolysis and the second patient had acute hepatitis. CONCLUSIONS: Propanil poisoning is uncommon. Lower levels of methaemoglobin than were previously thought may be associated with a fetal outcome. Methylene blue is used in the treatment as it reduces blood methaemoglobin but in severe poisoning exchange transfusion may be necessary as a life saving measure.

Propanil-chloracne and methomyl toxicity in workers of a pesticide manufacturing plant.

In a survey of occupationally acquired disease in workers at a pesticide plant, we found that 11 (11%) of 102 workers had been hospitalized for illness related to chemical exposures; highest hospitalization rates occurred in packaging (27%), production (22%), and maintenance (9%) workers. Commonest causes of hospitalization were intoxication by the carbamate pesticide methomyl [1-(methylthio)ethylideneamino methyl carbamate], a reversible cholinesterase inhibitor, and methemoglobinemia following exposure to 3,4-dichloroaniline. On clinical evaluation, five (46%) of 11 packaging workers, the group with the highest exposure to methomyl, had experienced blurred vision or pupillary constriction. Seventeen (61%) of 28 production workers with exposure to dichloroaniline and propanil (3'4'-dichloropropionanilide) had chloracne, an acne-form dermatosis caused by the contaminant tetrachlorazobenzene in propanil and dichloroaniline. The chloracnegenic potentials of propanil and dichloroaniline were verified by rabbit ear tests. These findings reemphasize the hazards inherent in the the manufacture and formulation of pesticides and herbicides.