Clinical Profile and Outcome of Organophosphorus Poisoning in a Tertiary Hospital.

Organophosphorus compound (OPC) poisoning is common in Bangladesh. The toxicity of the agent and paucity of appropriate medical services has resulted in high mortality rates. To find out the clinical profile and outcome of OPC poisoning patients is the main aim of my study. This descriptive cross-sectional study was conducted in the Department of Medicine, Mymensingh Medical College Hospital, Bangladesh from September 2016 to November 2018. In this study, mean age of the study subjects was 25.90±11.24 years. Males (70.8%) were predominant than female (29.2%). In this study, most of the poisoning was done by ingestion (98.3%) and only two (1.7%) by inhalation. Regarding features, most muscarinic effect was constricted pupil and bronchospasm (65.0%). Common nicotinic effect was fasciculation (25.0%) and central effect was headache (61.67%). Mean amount of OPC ingestion was 26.30±17.24 ml in this study. Regarding circumstances of poisoning, familial disharmony (38.3%) and quarrel with other family members (37.5%) were the major reason followed by failure of personal affairs (15.0%) and other reasons (9.2%). Regarding complications, aspiration pneumonia was found in 6.7% cases, cardiac arrhythmia was in 6.7% cases and intermediate syndrome was in 1.7% cases. Most of the study subjects (95.0%) recovered fully. Most of the patients were from rural area. Suicidal was the common motive and familial disharmony and quarrel with other family members are the common circumstances of poisoning. Mortality rate was 5.0%.

Atypical organophosphate poisoning and a successful case of prolonged intubation in a low-resource newly developed intensive care unit in rural Zambia.

Organophosphate poisoning is a common, under-reported cause of attempted and completed suicide worldwide. Following the resolution of the acute cholinergic syndrome, patients may develop respiratory muscle and proximal limb weakness, known as intermediate syndrome. A young man was brought to our rural hospital unconscious, in extremis, due to organophosphate pesticide poisoning. He developed atypical intermediate syndrome with global paralysis, persistent fasciculations and prolonged cholinergic symptoms, differing from the recognised presentation. He was intubated for fifteen days in our newly developed intensive care unit. Limited treatment options and the absence of blood gases, electrolyte testing, ECGs, invasive monitoring and imaging, in conjunction with regular disruptions to electricity and oxygen, and complications including seizures and pneumonia, all made this prolonged intubation an ambitious and challenging endeavour. We offer learning points for the acute physician and rural intensivist, and a summary of our reflections and hints for best care when adapting to a resource-limited setting.

Lack of cholinergic features in healthcare workers caring for a patient with organophosphate poisoning.

INTRODUCTION: Controversy exists with regard to risk of secondary exposure of health care workers caring for patients who have ingested an organophosphate insecticide. We aim to report clinical effects of staff members caring for an organophosphate poisoned patient. INCIDENT: A 76-year-old male presented to the Emergency Department exhibiting a cholinergic toxidrome requiring atropine, intubation and mechanical ventilation. METHODS: We undertook a retrospective chart review of any Emergency Department presentations for medical assessment in relation to the incident and conducted telephone interviews of any healthcare workers who did not present but were deemed to be closely involved with patient care. We collected data including age, gender, symptoms reported and plasma cholinesterase activity measurement. RESULTS: We collected data from 13 individuals, of whom nine presented for medical assessment, including the patient's spouse. Five additional staff members were interviewed, having been identified via Emergency Department rostering documentation. The 13 healthcare workers comprised five nurses, four paramedics and four doctors. Dizziness and nausea were reported in two and the patient's spouse reported one episode of vomiting. Of the nine patients who had plasma cholinesterase activity measured, none were below the laboratory reference range, including those who experienced symptoms. CONCLUSIONS: We found no clinical nor biochemical evidence of toxicity in healthcare workers caring for a critically ill patient with organophosphate ingestion. These findings are consistent with previously published guidelines advocating standard/Level D personal protective equipment. We believe that emergency departments should not be closed as a safety measure.

Efficacy and Safety of Plasma Exchange Combined with Hemoperfusion in the Treatment of Organophosphorus Poisoning: A Meta-Analysis.

INTRODUCTION: The aim of the study was to systematically evaluate the efficacy and safety of plasma exchange combined with hemoperfusion in the treatment of organophosphorus poisoning. METHODS: PubMed, Embase, the Cochrane Library, China National Knowledge Internet, Wanfang database, and Weipu database were searched for articles about this subject. Literature screening and selection were conducted in strict accordance with the inclusion and exclusion criteria. RESULTS: 14 randomized controlled trials with 1,034 participants were included in this meta-analysis study, including 518 cases in plasma exchange combined with hemoperfusion group (the combination treatment group) and 516 cases in hemoperfusion group (the control group). Compared with the control group, the combination treatment group was associated with a higher effective rate (relative risk [RR] = 1.20, 95% confidence interval [CI] [1.11, 1.30], p < 0.00001) and lower fatality rate (RR = 0.28, 95% CI [0.15, 0.52], p< 0.0001); reduced TNF-α (standardized mean difference [SMD] = -1.95, 95% CI [-2.42, -1.48], p < 0.00001), IL-6 (SMD = -1.94, 95% CI [-3.08, -0.80], p = 0.0009), and C-reactive protein (CRP) (SMD = -1.94, 95% CI [-2.86, -1.03], p < 0.0001); shorten coma time (SMD = -1.99, 95% CI [-2.75, -1.24], p < 0.00001), recovery time of cholinesterase activity (SMD = -1.71, 95% CI [-1.90, -1.53], p < 0.00001), and hospital stay (SMD = -1.29, 95% CI [-1.59, -0.98], p < 0.00001). The incidence of complications in the combination treatment group such as liver and kidney damage (RR = 0.30, 95% CI [0.18, 0.50], p < 0.00001), pulmonary infection (RR = 0.29, 95% CI [0.18, 0.47], p < 0.00001), and intermediate syndrome (RR = 0.32, 95% CI [0.21, 0.49], p < 0.00001) was lower than that in the control group. CONCLUSIONS: The current evidence suggests that the combination of plasma exchange with hemoperfusion therapy can reduce the mortality of patients with organophosphorus poisoning, shorten the recovery time of cholinesterase activity and the time of coma, reduce the average length of hospital stay, and reduce the levels of IL-6, TNF-α, and CRP, but high-quality randomized double-blind controlled trials are still required to confirm the current findings in the future.

Intoxicación por organofosforados / Organophosphorus poisoning

El panorama de las intoxicaciones es muy amplio y abarca un sin número de sustancias potencialmente mortales. Se estiman alrededor de 13 millones de químicos, incluyendo los naturales y los sintéticos, dentro de este último grupo se encuentran los plaguicidas, los cuales surgen como armas químicas probadas en insectos. Son una de las familias de productos químicos más ampliamente utilizadas por el hombre e independientemente de sus beneficios, es evidente que son sustancias deliberadamente tóxicas y carecen de selectividad real. Afectan simultáneamente a la «especie blanco como a otras categorías de seres vivos, particularmente al ser humano Pueden clasificarse en función de algunas de sus características principales, como son la toxicidad aguda, la vida media, la estructura química y su uso o de acuerdo a su estructura química se clasifican en diversas familias. Los reportes de la organización mundial de la salud (OMS) muestran que anualmente a nivel mundial, hay aproximadamente un millón de intoxicaciones accidentales y dos millones de intoxicaciones provocadas (suicidios) con plaguicidas, de las cuales aproximadamente 200.000 terminan en la muerte. En este trabajo abordaremos la intoxicación aguda por organofosforados ya que en la actualidad estos productos tienen una amplia aplicación en la actividad agrícola, provocando la muerte de cientos de personas. La mayor parte de las intoxicaciones ocurren en países en desarrollo y México no es la excepción, motivo por el cual se realiza este trabajo con la finalidad de ofrecer herramientas para un diagnóstico correcto, un tratamiento oportuno con el fin de evitar posibles complicaciones asociadas y preservar la vida del paciente

The panorama of poisoning is very wide and covers a number of potentially mortal substances. About 13 million chemicals are estimated, including the natives and synthetic, within the latter group are pesticides, which arise as chemical weapons in insects. They are one of the most widely used chemical families and regardless of their benefits, it is evident that they are deliberately toxic substances and lack real selectivity. They simultaneously affect the "white species as other categories of living beings, particularly the human being can be classified according to some of its main characteristics, such as acute toxicity, half -life, chemical structure and its use or according to Its chemical structure are classified into various families. The reports of the World Health Organization (WHO) show that worldwide, there are approximately one million accidental poisonings and two million poisoning caused (suicides) with pesticides, of which approximately 200,000 end up in death. In this work we will address acute organophosphate poisoning since these products are currently a wide application in agricultural activity, causing the death of hundreds of people. Most poisoning occur in developing countries and Mexico is no exception, which is why this work is done in order to offer tools for a correct diagnosis, timely treatment in order to avoid possible associated complications and preserve The patient's life

Prevalence, clinical manifestations, laboratory findings, treatment, and outcome of intermediate syndrome in anticholinesterase pesticide intoxication of dogs: A retrospective study.

Organophosphates and carbamates are important anticholinesterase intoxicants of humans and dogs. Intermediate syndrome (IMS) typically occurs 7-96 h following a toxicity-associated acute cholinergic crisis (ACC), and manifests clinically as weakness of the proximal limb, respiratory, and neck flexor muscles. The aim of this study was to describe the prevalence, clinical findings, and outcome of IMS in dogs. The medical records of a veterinary teaching hospital were searched for dogs diagnosed with ACC, IMS, or both, between 2017 and 2021. Case files were retrospectively reviewed. Six historical IMS cases were additionally reviewed. Thirty-two dogs were diagnosed with anticholinesterase intoxication during the search period, of which 23 (72 %) were only diagnosed with ACC, seven (22 %) progressed from ACC to IMS, and two (6 %) were only diagnosed with IMS. Duration of hospitalisation was longer in the IMS group compared to the ACC only group (P = 0.005). When all dogs with IMS (n = 15, including the six historical cases) were considered, survival was 100 %, including four (27 %) that required positive pressure mechanical ventilation following respiratory failure. Serum butyrylcholine esterase activity, a marker of cholinesterase activity, was below reference interval when first measured in 14 (93 %) of dogs; however, was not a useful as a recovery marker. IMS should be suspected in dogs demonstrating respiratory, neck, and proximal limb muscle paresis or paralysis, especially following clinical signs consistent with ACC. Absence of clinical signs consistent with ACC or butyrylcholine esterase activity within the reference interval does not exclude IMS as a differential.

Clinical Analysis of Acute Organophosphorus Pesticide Poisoning and Successful Cardiopulmonary Resuscitation: A Case Series.

Acute organophosphorus pesticide poisoning (AOPP) with cardiac arrest has an extremely high mortality rate, and corresponding therapeutic strategies have rarely been reported. Therefore, this study aimed to explore the prognostic factors and effective treatments of AOPP-related cardiac arrest. This retrospective study was conducted in our department in the years 2018-2021. We conducted a descriptive analysis of the clinical manifestations, rescue strategies, and prognosis of patients with AOPP who had experienced cardiac arrest and successful cardiopulmonary resuscitation. This study included six cases of patients with AOPP in addition to cardiac arrest; in four cases, cardiac arrest occurred <12 h after ingestion, and in two, cardiac arrest occurred more than 48 h after ingestion. Five patients had not undergone hemoperfusion therapy before cardiac arrest, and all six were treated with atropine during cardiopulmonary resuscitation and subsequent pralidoxine. Four patients recovered and were discharged from the hospital, one died in our department, and one was transferred to a local hospital and died there 2 h later. The last two patients had severe pancreatic injuries and disseminated intravascular coagulation. This, along with their death, might have been related to their prognosis. Cardiac arrest can occur in patients with severe AOPP for whom antidote administration was insufficient or not timely. Application of atropine and pralidoxine in a timely manner after cardiac arrest following AOPP is the key to successful treatment. This study provides useful guidelines for the treatment of similar cases in the future.

Guillain-Barre Syndrome: A Rare Complication of Organophosphate Poisoning.

Organophosphate poisoning is common following accidental or suicidal ingestion. Cases have been reported with different neurological consequences including acute cholinergic excess, intermediate syndrome (IMS), organophosphate-induced delayed neuropathy (OPIND), and organophosphate-induced chronic neuropsychiatric disorder (COPIND). Cases of Guillain-Barre syndrome (GBS) have also been reported as a consequence of delayed toxic effects of organophosphate poisoning. Here, we report a case of a 17-year male with accidental organophosphate ingestion, who developed acute onset of neuropathy and subsequently was diagnosed as GBS. The patient was treated with plasmapheresis and recovered successfully. Key Words: Guillain-barre syndrome, Organophosphate poisoning, Plasmapheresis.

Study of Organophosphorus Compound Poisoning in a Tertiary Care Hospital and the Role of Peradeniya Organophosphorus Poisoning Scale as a Prognostic Marker of the Outcome.

Organophosphate compounds (OPC) cause most selfpoisoning deaths in India due to their easy availability and lack of stringent laws. AIM: To evaluate the clinical profile and outcome of the patients presenting with OPC poisoning and to study the prognostic value of Peradeniya Organophosphorus Poisoning Scale (POPS) in predicting the clinical outcomes. MATERIAL: This was a prospective study involving 100 patients of OPC poisoning admitted to Tata Main Hospital from June 2018 to May 2020 based on the inclusion criteria. Demographic profile, clinical features, treatment details, and need for ventilatory support were noted. POPS was applied on admission, and the patients were followed up for the outcome in terms of morbidity and mortality. OBSERVATION: Of the 100 patients, most patients were between 20 and 29 years with male to female ratio being 1.2:1. Vomiting (94%), followed by excessive secretions (84%) were the most common symptoms. Overall mortality was 22%. On grading of severity as per the POP scale, 27% of the patients had mild poisoning, 37% patients had moderate, whereas 36% had severe poisoning. Only 11.11% of the patients with POPS 0-3 required ventilator support, whereas 16.2% of the patients with POPS 4-7, and 100% of patients with POPS 8-11 required ventilator assistance (P < 0.0001). Similarly, the total dose of atropine required (P < 0.0001), length of intensive care unit (ICU) stay, complications, and mortality (P < 0.0001) were significantly associated with higher POPS. CONCLUSION: POPS at admission, correlated well with the need for ventilator support, the total dose of atropine required, length of stay in the ICU, complications, and mortality. It can thus be used for prognostication and risk stratification of patients with OPC poisoning.

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.

Cell membrane enveloped polymeric nanosponge for detoxification of chlorpyrifos poison: In vitro and in vivo studies.

Organophosphates are highly toxic compounds as they are involved in irreversible inhibition of acetylcholinesterase, causing various neurotoxic effects via acetylcholine accumulation throughout the nervous system. Traditional treatments for organophosphate poisoning are not effective enough to overcome all the toxic effects. There is a need for alternate treatment of life threatening poisoning of organophosphates. For this purpose a biomimetic nanosponge of poly (lactic-co-glycolic acid) is prepared, characterized and analysed as an antidote for organophosphate poisoning. In this nanosponge red blood cell membranes are used for coating poly lactic co-glycolic acid nanoparticles. In vitro studies are conducted to investigate the retention of acetylcholinesterase activity on the prepared nanosponge as well as to assess the scavenging ability of prepared nanosponge for model organophosphate, chlorpyrifos. In vivo studies are conducted to evaluate the detoxification potential of nanosponge in rabbit model, poisoned with chlorpyrifos. Hepatotoxicity and renal toxicity of nanosponge/chlorpyrifos complex is also studied in survived rabbits and the data is analysed statistically.

Efficacy of fresh frozen plasma transfusion in comparison with conventional regimen in organophosphate poisoning treatment: a meta-analysis study.

OBJECTIVE: To evaluating the efficacy of fresh frozen plasma (FFP) in comparison with conventional regimen in the treatment of organophosphate (OP) poisoning. METHODS: PubMed, ScopeMed, Cochrane, Scopus, and Google Scholar databases were searched. The search strategy used the following key words "organophosphate" and "poisoning or toxicity", "(atropine and oxime)", "fresh frozen plasma", "clinical trial", "outcome". The treatment with atropine or/and oxime was considered conventional therapy. The length of hospitalization, the length of ICU admission, need for mechanical ventilation and its duration, clinical recovery point, choline esterase level, mortality rate, and intermediate syndrome (IMS) occurrence were the key outcomes of interest. Databases were searched during the period of 2003-2019. Five studies were included in the analysis. RESULTS: Pooling of data showed that the relative risk (RR) of mortality in OP poisoning for five included trials comparing FFP-treated group with conventional regimen therapy was [0.563 (95% CI (0.252, 1.255)]. The summary of RR for IMS in two studies was [RR: 1.34, 95% CI (0.655, 2.742)]. In addition, there was a non-significant mean difference (MD) in hospital stay [MD: -0.106, 95% CI (-0.434, 0.223)] in three included trials. A significant MD was observed in the length of ICU admission in two trials between FFP-treated group compared to the conventional treatment group [MD: -2.672, 95% CI (-4.189, -1.154)], but after random effects meta-analysis, the changes were not significant [MD: -2.015, 95% CI (-6.308, 2.277)]. The summary of fixed-effect meta-analysis for choline esterase level in three trails was [MD: -0.117, 95% CI (-0.468, 0.234)]. The RR of ventilation requirement for two included trials in the FFP-treated group comparing to the conventional regimen therapy was [0.84, 95% CI (0.691, 1.022)] while for ventilation duration in two studies was [MD: -0.183, 95% CI (-0.567, 0.201)]. CONCLUSION: The addition of FFP to conventional therapy did not improve the outcomes of mortality, IMS, hospital length of stay, cholinesterase levels, need or duration of mechanical ventilation, and only the length of ICU stay could affect in the treated group.

Combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by chlorpyrifos.

The aim of this study was to investigate the combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by CPF. 64 adult male albino rats were randomly selected and devided into eight groups of eight including: control, exercise (EXE), chlorpyrifos (CPF), Control + Oil (Co + Oil), Control + DMSO (Co + DMSO), chlorpyrifos + eugenol (CPF + Sup), chlorpyrifos + exercise (CPF + Exe) and, chlorpyrifos + exercise + eugenol (CPF + Exe + Eu). Four experimental groups received intraperitoneal injection (5 days a week) of 3.0 mg/kg body weight CPF in DMSO for 6 consecutive weeks. The exercise groups performed aerobic 5 days per week over 4 weeks. Eugenol were administered by gavage. Finally, the animals were sacrificed using CO2 gas (a half of the rats were anesthetized with ketamine and xylazine and then perfused) to evaluate hippocampus histology and parameters. The results of this study showed that CPF injection significantly decreased BDNF, AChE and ATP in CA1 area of the hippocampus (p ˂ 0.05). Also, CA1 apoptosis by tunnel assay, it was found that CPF receiving groups with different dosage, showed a significant increase compared to other groups, which was confirmed by increasing cytochrome C and procaspase-3 in CPF groups (p ˂ 0.05). The result of this study show that 4 weeks of exercise training and eugenol supplementation does not improve the destructive effects of CPF in CA1 area of the hippocampus. As a result, it is recommended that future studies longer periods for treatment with exercise and eugenol supplementation.

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.

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.

Adeno-associated virus-mediated expression of human butyrylcholinesterase to treat organophosphate poisoning.

Rare diseases defined by genetic mutations are classic targets for gene therapy. More recently, researchers expanded the use of gene therapy in non-clinical studies to infectious diseases through the delivery of vectorized antibodies to well-defined antigens. Here, we further extend the utility of gene therapy beyond the "accepted" indications to include organophosphate poisoning. There are no approved preventives for the multi-organ damage resulting from acute or chronic exposure to organophosphates. We show that a single intramuscular injection of adeno-associated virus vector produces peak expression (~0.5 mg/ml) of active human butyrylcholinesterase (hBChE) in mice serum within 3-4 weeks post-treatment. This expression is sustained for up to 140 days post-injection with no silencing. Sustained expression of hBChE provided dose-dependent protection against VX in male and female mice despite detectable antibodies to hBChE in some mice, thereby demonstrating that expression of hBChE in vivo in mouse muscle is an effective prophylactic against organophosphate poisoning.

Clinical manifestations, laboratory findings, treatment and outcome of acute organophosphate or carbamate intoxication in 102 dogs: A retrospective study.

Organophosphates (OP) and carbamates are commonly used insecticides and important intoxication sources of humans and animals. Nevertheless, large scale studies of these intoxications in dogs are unavailable. The medical records of dogs presented to a veterinary hospital were reviewed retrospectively. The study included 102 dogs definitely diagnosed with acute OP or carbamate intoxication. The most common presenting clinical signs included muscle tremor, hypersalivation, miosis, weakness, vomiting and diarrhea. Hypersalivation, muscle tremor and tachypnea were significantly (P < 0.05) associated with survival to discharge; while weakness, mental dullness, anorexia, pale mucous membranes and paddling were significantly associated with death. Common laboratory abnormalities included decreased butyrylcholine esterase activity, acidemia, increased total plasma protein, leukocytosis, hypochloridemia, hyperbilirubinemia, increased creatinine and alanine transaminase (ALT), aspartate transaminase (AST) and creatine kinase activities, and prolonged activated partial thromboplastin time (aPTT). Compared to the survivors, the non-survivors showed significantly: higher frequencies of thrombocytopenia, hypocarbemia, prolonged prothrombin time (PT), hypernatremia, hyperkalemia, hypocholesterolemia, hypoproteinemia, hypertriglyceridemia, increased ALT activity and increased urea concentration; lower median concentrations of venous blood bicarbonate, serum chloride and total CO2; and higher medians of PT, serum total bilirubin and urea concentrations, and ALT and AST activities. Intoxicated dogs were commonly treated with diphenhydramine, atropine-sulfate, antibiotics, diazepam and pralidoxime, while some (19.2%) required general anesthesia and mechanical ventilation. The survival rate of dogs treated by gastric lavage was higher (P = 0.041) compared to that of the remaining dogs. Development of respiratory failure and mechanical ventilation requirement were significantly associated (P < 0.001) with death. The mortality rate was 17%.

Organophosphorus nerve agent poisoning: managing the poisoned patient.

Organophosphorus (OP) nerve agent poisoning made the headlines in 2018 with the nerve agent 'Novichok' poisonings in Salisbury, England. This event highlighted a gap in the knowledge of most clinicians in the UK. In response, this special article aims to enlighten and signpost anaesthetists and intensivists towards the general management of OP nerve agent poisoned patients. Drawing on a broad range of sources, we will discuss what OP nerve agents are, how they work, and how to recognise and treat OP nerve agent poisoning. OP nerve agents primarily act by inhibiting the enzyme acetylcholinesterase, causing an acute cholinergic crisis; death usually occurs through respiratory failure. The antimuscarinic agent atropine, oximes (to reactivate acetylcholinesterase), neuroprotective drugs, and critical care remain the mainstays of treatment. The risk to medical staff from OP poisoned patients appears low, especially if there is a thorough decontamination of the poisoned patient and staff wear appropriate personal protective equipment. The events in Salisbury in the past year were shocking, and the staff at Salisbury District General Hospital performed admirably in treating those affected by Novichok nerve agent poisoning. We eagerly anticipate their future clinical publications so that the medical community might learn from their valuable experiences.

[Organophosphorus poisoning: Towards enzymatic treatments]. / Intoxication aux organophosphorés : vers des traitements enzymatiques.

Organophosphorus compounds (OP) are toxic molecules developed as insecticides and chemical warfare nerve agents (CWNAs). Most OP are neurotoxic and act as nervous system disruptors by blocking cholinergic transmission. They are therefore responsible for many poisonings worldwide. OP toxicity may result either from acute or chronic exposure, and their poisoning effect were evaluated using several animal models. These latter were also used for evaluating the efficacy of antidotes. Strategies based on enzymes that can trap (stoichiometric bioscavengers) or degrade (catalytic bioscavengers) OP, were particularly studied since they allow effective decontamination, without toxicity or environmental impact. This review summarizes the results obtained in vivo with enzymes through three levels: prophylaxis, treatment and external decontamination. The efficiency of enzymatic treatments in different animal models is presented and the relevance of these models is also discussed for a better extrapolation to humans.