Organophosphorus poisoning induced delayed neurotoxicity: a report of two cases.

INTRODUCTION: Organophosphorus compounds (OPC) are one of the most commonly used pesticides worldwide and are often misused for suicidal poisoning due to their easy availability. Acute manifestations and management of organophosphorus (OP) poisoning have been reported several times. Organophosphorus-induced delayed neurotoxicity (OPIDN) is a rare delayed presentation of OP poisoning that involves central-peripheral distal axonopathy. CASE PRESENTATION: In this study, we report two cases of OPIDN developed after a few weeks of OP poisoning. Clinical features, electrodiagnostic study findings, and rehabilitative measures adopted for the patients and their follow-up have been described in the report. DISCUSSION: Organophosphorus (OP) poisoning may rarely produce features of delayed neurotoxicity, which may gradually appear after acute cholinergic symptoms. This report shows the importance of considering the delayed presentation of possible OPC toxicity in patients with neurological symptoms and a history of OPC exposure.

Biochemical and haematological abnormalities in severe acute organophosphorus poisoning / Anomalías bioquímicas y hematológicas en la intoxicación grave por organofosforados. Estudio prospectivo en un solo centro

Background: Organophosphorus insecticides are considered one of the commonest causes of morbidity and mortality due to poisoning worldwide. Severe organophosphorus poisoning can lead to multiple sometimes lethal metabolic and haematological abnormalities. Methods: A total of 141 OP poisoning patients were admitted during the study period and their blood samples were collected on admission and analysed for the biochemical abnormalities. Results: Out of 141 patients 76 were males (53.9%) and 65 were females (46.1%). Bradycardia with Pulse rate of less than 60 was seen in in 21 patients (14.7). Hypoxemia with oxygen saturation of less than 94% was seen in 32 (22.7%). leucocytosis with TLC o 11000 or more was seen in 19 patients (13.5%).101 patients (83.5%) had low serum choline esterase levels less than 1.5kU/L. Hypokalaemia with K+ of less than 3.5 was seen in 16 patients (9.9%). Five patients died out of 141 (3.5%). Hypoxemia Spo2 of less than 90% was seen in 3 (60%) patients who died and hypoglycaemia with blood glucose of less than 70mg/dl was seen in 2 out of 5 Patients (40%). Conclusions: low choline esterase levels less than 1.5kU/L was the most common abnormality indicating severe poisoning followed by hypoxemia. Both Hypoxemia and low acetylcholine esterase levels are bad prognostic signs and result in high mortality in organophosphorus poisoning. (AU)

Introducción: De entre todos los procesos de intoxicación, el envenenamiento por organofósforados se considera una de las causas más comunes de morbilidad y mortalidad en todo el mundo. La intoxicación grave por organofósforo puede provocar múltiples anomalías metabólicas y hematológicas, a veces letales. Métodos: Un total de 141 pacientes intoxicados por organofósforados fueron ingresados durante el periodo de estudio y sus muestras e sangre fueron recogidas al ingreso y analizadas para detectar las anomalías bioquímicas. Resultados: De los 141 pacientes, 76 eran varones (53,9%) y 65 mujeres (46,1%). Se observó bradicardia con una frecuencia de pulso inferior a 60 en 21 pacientes (14,7). Se observó hipoxemia con una saturación de oxígeno inferior al 94% en 32 (22,7%). Leucocitosis con un recuento total de leucocitos de 11.000 o más en 19 pacientes (13,5%). 101 pacientes (83,5%) tenían niveles bajos de colina esterasa sérica inferiores a 1,5 kU/L. Se observó hipopotasemia con K+ inferior a 3,5 en 16 pacientes (9,9%). Cinco pacientes fallecieron de un total de 141 (3,5%). Se observó hipoxemia Spo2 inferior al 90% en 3 (60%) pacientes que fallecieron e hipoglucemia con glucemia inferior a 70 mg/dl en 2 de 5 pacientes (40%). Conclusiones: Los niveles bajos de colinesterasa inferiores a 1,5 kU/L fueron la anomalía más frecuente que indicaba intoxicación grave, seguida de hipoxemia. La hipoxemia, la hipoglucemia y los niveles bajos de acetilcolinesterasa son signos de mal pronóstico y dan lugar a una elevada mortalidad en la intoxicación por organofosforados. (AU)

Acute Organophosphate Poisoning Case Review With Consideration of Off-Gassing During Postmortem Examination.

ABSTRACT: Although self-harm via ingestion of organophosphorus compounds is relatively common in the developing world, it is rare in the United States. This article reviews the signs and symptoms associated with acute organophosphate poisoning and highlights the effects of organophosphate off-gassing during postmortem examinations to increase awareness of this potentially dangerous workplace exposure.Paramedics responded to a 42-year-old man with pulseless electrical activity. Spontaneous circulation was restored after aggressive resuscitation. Before loss of consciousness, the patient exhibited diaphoresis, vomiting, and diarrhea. Upon admission, the patient had a Glasgow Coma Scale score of 3. Significant laboratory values included a pH of 6.8, p co2 of 72 mm Hg, and lactic acid of 21.8 mmol/L. Electrocardiography suggested inferior ST-elevation myocardial infarction. Electroencephalogram revealed severe cerebral dysfunction. The patient died shortly thereafter.Scene investigation revealed suicidal ideations, which included a snapshot of a bottle containing granular sediment associated with statements that he had imbibed fertilizer. During the postmortem examination, the decedent exuded a petroleum-like odor. In addition, autopsy personnel developed symptoms consistent with organophosphate exposure.A reported history of suspected organophosphate exposure in a decedent should prompt increased safety practices to avoid potential harm to autopsy personnel.

Opsoclonus-myoclonus syndrome caused by organophosphate poisoning.

Opsoclonus-myoclonus syndrome is a combination of involuntary, arrhythmic, conjugate saccadic eye movements with myoclonus. The most common cause in adults is paraneoplastic encephalitis. Rarer causes include infections such as scrub typhus, and toxins such as organophosphates and cocaine. Organophosphates are one of the common poisonings in tropical countries such as India, causing both central and peripheral nervous system manifestations. We describe a middle-aged male farmer with unexplained altered consciousness and respiratory depression. After 2 days, he developed opsoclonus-myoclonus, and then bronchorrhoea and bradycardia, raising suspicion of organophosphate poisoning. After we had identified a very low serum cholinesterase concentration, he disclosed having consumed organophosphates.

Neuroleptic malignant syndrome associated with acute organophosphate poisoning: Case report / Síndrome neuroléptico maligno asociado con intoxicación aguda por un organofosforado: reporte de caso.

Neuroleptic malignant syndrome is a rare and potentially fatal clinical condition frequently associated with the use of antipsychotics. In the literature, there is only one case report associated with the intake of organophosphates. We present the case of a patient who presented with a clinical picture compatible with neuroleptic malignant syndrome, after the ingestion of an organophosphate (chlorpyrifos). A 57-year-old man who consulted for attempted suicide, acute deterioration of consciousness, torpid neurological evolution, and associated autonomic instability associated with rigidity, persistent hyperthermia, and elevated CPK. Bromocriptine treatment was offered, which resolved the clinical picture. The association with the ingestion of an organophosphate was established, and he was discharged without sequelae. The diagnosis of neuroleptic malignant syndrome is clinical and should be considered in any case of exposure to substances that may lead to dysregulation of dopaminergic neurotransmission in order to initiate timely therapy and impact outcomes.

El síndrome neuroléptico maligno es una condición clínica rara y potencialmente letal que frecuentemente se asocia con el uso de antipsicóticos. En la literatura especializada se encontró únicamente un reporte de caso relacionado con la ingestión de organofosforados. Se presenta un paciente con un cuadro clínico correspondiente al síndrome neuroléptico maligno posterior a la ingestión de clorpirifós. Como resultado de un intento de suicidio con el mencionado organofosforado, el hombre de 57 años presentó deterioro agudo del estado de consciencia, evolución neurológica tórpida e inestabilidad autonómica asociada a rigidez e hipertermia persistentes, así como incremento de la creatina-fosfocinasa (creatine phosphokinase, CPK). Se le administró tratamiento con bromocriptina, con lo cual el cuadro clínico remitió, y fue dado de alta sin secuelas. El diagnóstico del síndrome neuroléptico maligno es clínico y debe contemplarse en cualquier caso de exposición a sustancias que puedan resultar en una desregulación de la neurotransmisión dopaminérgica, con el fin de iniciar el tratamiento oportuno y contrarrestar efectivamente los efectos.

Expression of Hypersensitive Troponin I and Soluble ST2 in Acute Organophosphorus Pesticide Poisoning.

The role of soluble growth stimulating gene 2 protein and highly sensitive cardiac troponin in the diagnosis of early myocardial injury caused by acute organophosphorus pesticide poisoning was studied. 171 inpatients with AOPP were divided into three experimental groups according to their mild, moderate, and severe conditions. 20 healthy people were selected as the control group. The levels of cTnI, HS-CTNI, NT proBNP, and ST2 were measured at the 4th and 12th hours after the experiment. The measured data were expressed by mean standard deviation. The independent sample t-test was used for the detection between the two groups, and one-way ANOVA was used for the analysis and comparison between multiple groups. The relevant data were analyzed by Spearman correlation test (P < 0.05). The levels of cTnI and HS cTnI in the experimental group increased with the extension of time and the deepening of poisoning degree; four hours after admission, ST2 and NT proBNP water in the control group and the experimental group increased significantly on average. According to the analysis of the data, there was a positive correlation between HS TnI and ST2 in patients with AOPP (r = 0.938, P < 0.001, r = 0.827, P < 0.001). The more serious the disease, the higher the concentrations of HS TnI and ST2, and the more serious the myocardial injury.

Mean Serum Creatine Kinase among Organophosphate Poisoning Cases in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Major cases of poisoning are associated with organophosphates. Cholinergic effects and an intermediate phase seen with organophosphate poisoning may implicate myopathy. Creatine kinase is a marker of muscle tissue damage. This study aimed to find out the mean serum creatine kinase among organophosphate poisoning cases in a tertiary care centre. Methods: A descriptive cross-sectional study was carried out among organophosphate poisoning cases in a tertiary care hospital from 13 October 2017 to 30 March 2018. Ethical approval was taken from the Institutional Review Committee [Reference number: 117(6-11-E) 2/074/075]. Blood samples were assayed for serum acetylcholinesterase in the pharmacology laboratory and for serum creatine kinase and lactate dehydrogenase in the biochemistry laboratory. Low serum acetylcholinesterase was taken as the basis for the establishment of organophosphate poisoning. A convenience sampling technique was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 103 organophosphate poisoning cases, the mean serum creatine kinase was 931.35±446.60 IU/l (845.10-1017.60, 95% Confidence Interval). Conclusions: The mean serum creatine kinase level among organophosphate poisoning cases was higher than in other studies done in similar settings. Keywords: acetylcholinesterase; creatine kinase; organophosphate poisoning; rhabdomyolysis.

Successful treatment of severe myocardial injury complicated with refractory cardiogenic shock caused by AOPP using extracorporeal membrane oxygenation: A case report.

RATIONALE: Acute organophosphorus pesticide poisoning (AOPP) is a common critical illness observed in clinical practice, and severe AOPP can cause serious cardiac toxicity. PATIENT CONCERNS: This patient was a 43-year-old woman who was admitted to the emergency department with acute respiratory failure and hypotension 13 hours after oral consumption of 300 mL of phoxim pesticide. DIAGNOSES: Acute organophosphorus pesticide poisoning, cardiogenic shock. INTERVENTIONS: We conducted veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy as the patient did not respond to conventional measures. OUTCOMES: This patient was successfully rescued with VA-ECMO therapy and discharged. LESSONS: We suggest that for patients with severe myocardial injury complicated with cardiogenic shock caused by AOPP, the use of VA-ECMO therapy can improve the prognosis.

Prolonged apnea after ECT in organophosphorus poisoning - the need to redefine norms.

BACKGROUND: Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency ward and the ICU. OP compounds act by irreversibly binding to pseudocholinesterase enzyme and hence prolong the apnea in patients being given suxamethonium. We present a unusual case of OP poisoning (OPP) in which prolonged apnea ensued in a patient of severe depression following MECT (modified electroconvulsive therapy) in which suxamethonium was used as muscle relaxant, in whom we were cautious of the side-effect of prior organophosphorus poisoning. Since the cases of OPP are very high worldwide, a thorough knowledge of the interaction of the action of the drug and the receptors on which it acts takes pride of place. This article highlights the nuances in the field of psychiatry and anaesthesia in diagnosis and management of prolonged apnea after ECT. CASE PRESENTATION: A 53/F patient consumed OP 38 days prior to MECT. Since existing literature recommend a delay of 4 weeks and a subminimal dose of suxamethonium to prevent prolonged apnea, both these points were taken into consideration. Despite 38 days post exposure to OP, and a dose of succinylcholine of < 0.3 mg/kg, the patient remained apneic for 3 h. Suxamethionum apnea was managed with elective ventilation. After recovery, patient had no residual effect. Subsequently her pseudocholinesterase levels were done which were found to be very low. CONCLUSION: This case is being presented to emphasize that behaviour of post synaptic receptors cannot be relied upon after OP poisoning and pseudocholinesterase levels needs to be mandatorily checked, irrespective of duration post-exposure. In strong suspects dibucaine number and fluoride number also needs to be estimated.

Organophosphate induced delayed neuropathy after an acute cholinergic crisis in self-poisoning.

INTRODUCTION: Despite organophosphate pesticide is the most prevalent cause of acute poisoning in low- and middle-income countries, data on organophosphate induced delayed neuropathy (OPIDN) are limited. We aimed to characterize organophosphates' long-term effects on the peripheral nervous system after an acute cholinergic crisis in adults. METHODS: We performed a prospective observational study in an academic hospital of north India in patients aged 13-40 years with acute organophosphate ingestion. After resolving the cholinergic crisis, the patients were followed for six months with neurologic assessments, including history, neurologic examination, and nerve conduction study (NCS). RESULTS: Twenty-three patients were recruited to the study. All but one had normal neurological examination and NCS at discharge from hospital a median duration of six days (interquartile range, 3-10) after self-poisoning. Eight (34.8%) developed OPIDN during the six-month follow-up. Three patients had symptomatic neuropathy, and NCS detected subclinical peripheral nerve involvement in five. All cases were associated with chlorpyrifos ingestion (8/17 total chlorpyrifos cases). Two OPIDN cases had foot drop and gait ataxia at three-month which persist at six-month. One patient had distal paresthesia at three months, which improved at a six-month follow-up. NCS in OPIDN cases invariably revealed axonal degeneration, injury to motor fibers more than sensory fibers, and frequent peroneal nerve involvement. None of the baseline characteristics, including the ingested amount, predicted clinical or subclinical OPIDN in chlorpyrifos self-poisoned patients on a univariant analysis. CONCLUSION: Peripheral nerve involvement is not uncommon after recovery from a cholinergic crisis in chlorpyrifos self-poisoning and debilitating in some patients. Detection of subclinical injury on NCS may provide an early window to prevent severe symptomatic neuropathy.

Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death.

With millions of intoxications each year and over 200,000 deaths, organophosphorus (OP) compounds are an important public health issue worldwide. OP poisoning induces cholinergic syndrome, with respiratory distress, hypertension, and neuron damage that may lead to epileptic seizures and permanent cognitive deficits. Existing countermeasures are lifesaving but do not prevent long-lasting neuronal comorbidities, emphasizing the urgent need for animal models to better understand OP neurotoxicity and identify novel antidotes. Here, using diisopropylfluorophosphate (DFP), a prototypic and moderately toxic OP, combined with zebrafish larvae, we first showed that DFP poisoning caused major acetylcholinesterase inhibition, resulting in paralysis and CNS neuron hyperactivation, as indicated by increased neuronal calcium transients and overexpression of the immediate early genes fosab, junBa, npas4b, and atf3. In addition to these epileptiform seizure-like events, DFP-exposed larvae showed increased neuronal apoptosis, which were both partially alleviated by diazepam treatment, suggesting a causal link between neuronal hyperexcitation and cell death. Last, DFP poisoning induced an altered balance of glutamatergic/GABAergic synaptic activity with increased NR2B-NMDA receptor accumulation combined with decreased GAD65/67 and gephyrin protein accumulation. The zebrafish DFP model presented here thus provides important novel insights into the pathophysiology of OP intoxication, making it a promising model to identify novel antidotes.

Mechanism of central hypopnoea induced by organic phosphorus poisoning.

Whether central apnoea or hypopnoea can be induced by organophosphorus poisoning remains unknown to date. By using the acute brainstem slice method and multi-electrode array system, we established a paraoxon (a typical acetylcholinesterase inhibitor) poisoning model to investigate the time-dependent changes in respiratory burst amplitudes of the pre-Bötzinger complex (respiratory rhythm generator). We then determined whether pralidoxime or atropine, which are antidotes of paraoxon, could counteract the effects of paraoxon. Herein, we showed that paraoxon significantly decreased the respiratory burst amplitude of the pre-Bötzinger complex (p < 0.05). Moreover, pralidoxime and atropine could suppress the decrease in amplitude by paraoxon (p < 0.05). Paraoxon directly impaired the pre-Bötzinger complex, and the findings implied that this impairment caused central apnoea or hypopnoea. Pralidoxime and atropine could therapeutically attenuate the impairment. This study is the first to prove the usefulness of the multi-electrode array method for electrophysiological and toxicological studies in the mammalian brainstem.

Occupational exposure to organophosphate pesticides and hematologic neoplasms: a systematic review. / Exposição ocupacional a agrotóxicos organofosforados e neoplasias hematológicas: uma revisão sistemática.

OBJECTIVE: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies. METHODOLOGY: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RESULTS: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin's lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control). CONCLUSION: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.

Temporal Effects of 2% Pilocarpine Ophthalmic Solution on Human Pupil Size and Accommodation.

INTRODUCTION: First responders and those who work with organophosphate (OP) compounds can experience ocular symptoms similar to those caused by exposure to low levels of nerve agents. This study was designed to examine the efficacy of a safe, clinically available, simulant that reproduces ocular symptoms associated with low-level OP exposure. Among these ocular symptoms are a constriction of the pupils (miosis), decreased visual acuity, and changes in accommodation. MATERIALS AND METHODS: Volunteers aged 18-40 were assigned to groups receiving either a two-drop or three-drop dose of FDA approved 2% pilocarpine ophthalmic solution. Baseline visual performance measurements were taken before eye drop instillation and a timer was started following the first drop of pilocarpine. Once eye drops were administered, visual performance including distant and near vision, pupil size, and accommodation were measured every 5 minutes for 2 hours. RESULTS: Both groups experienced significant miosis in excess of 90 minutes. Visual acuity was significantly reduced because of accommodative changes. The three-drop group experienced longer lasting combined effects when compared to the two-drop group. CONCLUSIONS: 2% pilocarpine ophthalmic solution can safely simulate major ocular symptoms of OP exposure for behavioral research studies for at least 60 minutes.

Acute encephalopathy followed by delayed myelopathy: A rare presentation of organophosphate poisoning.

Organophosphorus compounds (OPC) are commonly used pesticides and suicidal ingestion is a common mode of poisoning. The manifestation of OPC poisoning and its severity depend upon the type, dose and potency of the OPC consumed. Neurological presentations are well defined clinical syndromes consisting of early, intermediate and delayed manifestations (rare), categorised on the basis of time elapsed since OPC exposure. We report a rare delayed manifestation of organophosphorus poisoning in the form of pure motor spastic paraparesis due to dorsal myelopathy. A possibility of delayed manifestations of toxicity should be considered in individuals presenting with features suggestive of myelopathy and a previous history of organophosphate exposure.

Differences between organophosphates in respiratory failure and lethality with poisoning post the 2011 bans in Sri Lanka.

Introduction: Self-poisoning with organophosphorus pesticides (OPs) has high morbidity and mortality. The most toxic OP formulations have been progressively banned in Sri Lanka over the past three decades. However, respiratory failure (RF) requiring ventilation remains a major contributor to fatalities. Therefore, this study was conducted to examine the frequency of RF and death after poisoning with the currently available OPs to determine if further bans might be warranted to reduce the burden of OP poisoning in Sri Lanka.Methods: Five hundred and forty patients with confirmed OP self-poisoning were prospectively observed throughout their hospital stay following admission to Peradeniya hospital in the Central Province of Sri Lanka. Clinical data including the time and duration of intubation were documented prospectively in structured datasheets.Results: One hundred and forty-nine patients required ventilation (27%), and 34 (23%) of those died. Males with alcohol co-ingestion were more likely to develop RF. Compared to other OPs, profenofos (Odds Ratio [OR] = 2.5, 95% CI: 1.5-3.9), and quinalphos (OR = 4.5, 95% CI: 1.6-12.6) were more likely to, and chlorpyrifos (OR = 0.2, 95% CI: 0.1-0.4) less likely to lead to RF than other OPs. Profenofos was also associated with higher mortality (OR = 2.3, 95% CI: 1.1-4.6) than other OPs. The median time to intubation was longer for profenofos, but the duration of intubation was similar for all OP formulations.Conclusion: RF and deaths following OP ingestion continue to be a major problem in Sri Lanka, with profenofos being the major current agent of concern. Strategies to replace profenofos and quinalphos use with less toxic insecticides should be explored. Doctors should be alert to the high probability of delayed and prolonged RF after profenofos poisoning.

Novel therapeutics for treating organophosphate-induced status epilepticus co-morbidities, based on changes in calcium homeostasis.

Organophosphate (OP) chemicals include pesticides such as parathion, and nerve gases such as sarin and soman and are considered major chemical threat agents. Acute OP exposure is associated with a cholinergic crisis and status epilepticus (SE). It is also known that the survivors of OP toxicity exhibit neurobehavioral deficits such as mood changes, depression, and memory impairment, and acquired epilepsy. Our research has focused on addressing the need to develop effective therapeutic agents that could be administered even after prolonged seizures and would prevent or lessen the chronic morbidity associated with OP-SE survival. We have developed rat survival models of OP pesticide metabolite paraoxon (POX) and nerve agent sarin surrogate diisopropyl fluorophosphate (DFP) induced SE that are being used to screen for medical countermeasures against an OP attack. Our research has focused on studying neuronal calcium (Ca2+) homeostatic mechanisms for identifying mechanisms and therapeutics for the expression of neurological morbidities associated with OP-SE survival. We have observed development of a "Ca2+ plateau" characterized by sustained elevations in neuronal Ca2+ levels in OP-SE surviving rats that coincided with the appearance of OP-SE chronic morbidities. These Ca2+ elevations had their origin in Ca2+ release from the intracellular stores such that blockade with antagonists like dantrolene, carisbamate, and levetiracetam lowered OP-SE mediated Ca2+ plateau and afforded significant neuroprotection. Since the Ca2+ plateau lasts for a prolonged period, our studies suggest that blocking it after the control of SE may represent a unique target for development of novel countermeasures to prevent long term Ca2+ mediated OP-SE neuropsychiatric comorbidities such as depression, anxiety, and acquired epilepsy (AE).

A pilot clinical study of the neuromuscular blocker rocuronium to reduce the duration of ventilation after organophosphorus insecticide poisoning.

Background: A common manifestation of organophosphorus insecticide self-poisoning is prolonged respiratory failure due to neuromuscular junction dysfunction and likely nicotinic receptor overstimulation. We aimed at collecting preliminary data on whether addition of the competitive nicotinic antagonist rocuronium to standard early therapy might be clinically feasible and associated with reduced duration of ventilation.Methods: A pilot three-arm dose-response phase II trial was set up to compare bolus doses of rocuronium bromide titrated to produce initial >95% or 50% inhibition of neuromuscular function, measured using acceleromyography, plus standard treatment, versus standard treatment alone. After attaining inhibition, patients receiving bolus rocuronium then received rocuronium infusions for a maximum of 120 h. Primary outcome was duration of intubation; secondary outcome was case fatality. Plasma butyrylcholinesterase activity was measured throughout the inpatient stay. Blood was analysed to confirm the organophosphorus insecticide ingested.Results: Forty-five patients were randomised to receive: rocuronium to initially attain 95% inhibition (Roc>95, n = 15), rocuronium to initially attain 50% inhibition (Roc50, n = 14), or no rocuronium (control, n = 16). The most commonly ingested pesticide was profenofos (29/45, 64.4%). Butyrylcholinesterase activity remained severely inhibited for the duration of the study for most patients. Case fatality was 9/45 (20%) and similar across study arms: control 3/16 (18.8%), Roc50 4/14 (28.6%) and Roc>95 2/15 (13.3%) (p = .5842). When excluding patients who died, median [IQR] duration of intubation was significantly longer in the Roc50 (259.5 [176-385] h) and Roc>95 (226.8 [186-355] h) groups compared to controls (88.5 [47-160] h, p = .0162 and p = .0016, respectively).Conclusions: In this pilot dose-response study, we found no evidence that rocuronium in addition to standard therapy reduced the duration of intubation. It is possible that it worsened neuromuscular junction function. Further clinical research, including testing of shorter duration regimens, needs to be performed before nicotinic antagonists can be used in the clinical management of OP poisoning.